The Peripheral giant cell granuloma (PGCG) is an asymptomatic, non-neoplastic and proliferative lesion of unknown etiology. Some possible pre-disposing factors such as hormonal changes dur-ing pregnancy, have been suggested. However, the association between PGCG and pregnancy is controversial. There are few reported clinical cases of pregnancy-associated PGCG in the litera-ture, and they occurred only in the lower jaw. The present report is on a 35-year-old female pa-tient at 36 weeks of gestation who presented with a PGCG in the central and lateral incisors of the upper jaw. The management consisted of surgical excision, along with curettage of the affected bony walls. The diagnosis was based on clinical results and imaging examinations, and it was histopathologically confirmed. The patient underwent postoperative follow-up evaluations at 3, 6 and 12 months, and there were no signs of recurrence.

Plant stem cell cultures have so far been established in only a few plant species using cambial meristematic cells. The presence of stem cells or stem cell-like cells in other organs and tissues of the plant body, as well as the possibility of de novo generation of meristematic cells from differentiated cells, allows to consider the establishment of stem cell cultures in a broader range of species. Therefore, this study aimed to establish a stem cell culture of the medicinal plant Calendula officinalis L. Callus tissues were induced from explants taken from leaves and roots. Appropriate combinations of plant growth regulators and light parameters for in vitro cultivation were selected. Already at this stage, stem and dedifferentiated cells could be identified, and cell suspension cultures were established from specific parts of the formed callus. Cell suspension cultures with a high proportion of stem cells originating from roots (92–93%) or leaves (72–73%) were developed. The amount of stem cells derived from the roots in the cell suspension reached a plateau at a level of 5.60–5.72105.

The idea of CUAD (contact unmodified antisense DNA) biotechnology and the use of oligonucleotide insecticides (briefly, olinscides, or DNA insecticides) was proposed on lepidopterans and gradually disseminated on hemipteran pests. As the next-generation platform for creation of insecticides, it has a number of unique characteristics (short unmodified antisense DNA as contact insecticide, insect rRNAs as target, DNA containment as mechanism of action) that distinguish it from existing classes of chemical insecticides. Oligonucleotide insecticides possess low carbon footprint, high safety for non-target organisms, rapid biodegradability, avoidance of target-site resistance, ensuring prosperity for agricultural countries that will implement this innovation. As the next-generation class of insecticides olinscides create opportunities that have never existed before in crop protection. Using flexible CUAD platform, any farmer, botanical garden or pest control company is capable of creating its own unique arsenal of insecticides, well-tailored for a particular population of insect pest. Most technological innovations start out very expensive and don't work well, but eventually start working well and become very cheap. CUAD biotechnology has come a long way for 16 years and is very close to the point to be implemented on a large scale against certain groups of pests. In this article we provide basic knowledge of use of oligonucleotide pesticides and list pests (mainly from suborder Sternorrhyncha, Hemiptera) which were successfully controlled by us recently.

The classical human satellite DNAs, also referred to as human satellites 1, 2 and 3 (HSat1, HSat2, HSat3, collectively HSat1-3) constitute the largest individual arrays of tandemly repeated DNA sequences in the genome. Even though they were among the first human DNA sequences to be isolated and characterized at the dawn of molecular biology, HSat1-3 have been left behind in the genomics era and remain among the most enigmatic sequences in the human genome. Although HSat1-3 total roughly 3% of the genome on average, they were almost entirely missing from the human genome reference assembly for 20 years. Recently, the Telomere-to-Telomere Consortium produced the first truly complete assembly of a human genome, including the enormous HSat1-3 arrays, opening them up for a new wave of discovery. Towards this end, here, I provide an account of the history and current understanding of HSat1-3 genomics, evolution, and roles in disease.

The identification of floral visitation by pollinators provides an opportunity to improve our understanding of the fine-scale ecological interactions between plants and pollinators, contributing to biodiversity conservation and promoting ecosystem health. In this review we outline the various methods which can be used to identify floral visitation, providing a comparison between molecular and non-molecular methods. We review the literature covering the ways in which DNA metabarcoding has been used to answer ecological questions relating to plant use by pollinators and discuss the findings of this research. We present detailed methodological considerations for each step of the metabarcoding workflow, from sampling through to amplification and finally bioinformatic analysis. Detailed guidance is provided to researchers for utilization of these techniques, emphasizing the importance of standardization of methods and improving the reliability of results. Future opportunities and directions of using molecular methods to analyze plant-pollinator interactions are then discussed.

Conventional plaque assays rely on the use of overlays to restrict viral infection allowing the formation of distinct foci that grow in time as the replication cycle continues leading to counta-ble plaques that are visualized with standard techniques such as crystal violet, neutral red or immunolabeling. This classical approach takes several days until large enough plaques can be visualized and counted with some variation due to subjectivity in plaque recognition. Since plaques are clonal lesions produced by virus-induced cytopathic effect, we applied DNA fluores-cent dyes with differential cell permeability to visualize them by live cell imaging. We could observe different stages of that cytopathic effect corresponding to an early wave of cells with chromatin-condensation followed by a wave of dead cells with membrane permeabilization within plaques generated by different animal viruses. This approach enables an automated plaque identification using image analysis to increase single plaque resolution compared to crystal violet counterstaining and allows its application to plaque tracking and plaque reduction assays to test compounds for both antiviral and cytotoxic activities. This fluorescent real-time plaque assay sums to those next-generation technologies by combining this robust classical method with modern fluorescence microscopy and image analysis approaches for future applica-tions in virology.

Reduced-order electrothermal models play a key role in the design and control of lithium- ion cell stacks, calling for accurate model parameter calibration. This paper presents a complete electrical and thermal experimental characterization procedure for coupled modeling of cylindrical lithium-ion cells in order to implement them in a prototype Formula SAE hybrid racing car. The main 4goal of the tests is to determine cell capacity variations with temperatures and discharge currents, to predict the open circuit voltage of the cell and its entropic component. A simple approach for the characterization of the battery equivalent electrical circuit and a two-steps thermal characterization method are also shown. The investigations are carried out on four commercial 18650 NMC lithium cells. The model demonstrated to predict the battery voltage at a RMS error lower than 20mV and the temperature to a RMS error equal to 0.5 ◦C. The authors hope that this manuscript can contribute to the development of standardized characterization techniques for such cells, while offering experimental data and validated models that can be used by researchers and BMS designers in different applications.

This article explores the geothermal resources of Kazakhstan's Zharkent Basin, with a specific focus on the high-temperature geothermal sources in the Almaty region of Southern Kazakhstan. The research aims to analyze the energy characteristics of the Organic Rankine Cycle (ORC) for harnessing low-enthalpy geothermal energy for small-scale electricity generation. A detailed thermodynamic model was developed, employing R134a as the working fluid. An in-depth analysis of the Zharkunak field (Zharkent, Almaty region) revealed that well 5539, with its notably high temperatures, offers the highest potential for geothermal electricity production, achieving an annual output of approximately 10,371 MWh. The total electric power output from the studied wells in the region is estimated at 20,111 MWh annually, representing a significant contribution towards sustainable energy production and reducing reliance on traditional coal-fired power plants. The study concludes that the Organic Rankine Cycle is not only a viable and efficient technology for utilizing low-enthalpy geothermal resources to generate electricity on a small scale, but also a key player in enhancing energy independence. By leveraging local geothermal energy, the Almaty region can significantly reduce its reliance on external energy sources, thereby fostering sustainable development and reducing environmental impacts.

By virtue of the knowledge of the beneficial effect of the warm and dry storage, for the growth of the chincuya seed embryo, defined as morphological dormancy. The effect of the same type of storage was studied for the seed viability and germination by soaking gibberellic acid. Also, fatty acids and their kinetics were identified during the warm and dry storage. The following treatments were evaluated: storage time (0, 3, 6, 9 and 12 months), seed soaking in gibberellic acid at 350 mg L-1, and for the control, imbibition in distilled water, both for 72 h. The seed viability was evaluated through the stain test with tetrazolium chloride. The embedded seeds were germinated on absorbent paper towels and incubated at different temperatures of 30 ° C during the day and 25 ° C at night and 12 hours of photoperiod. The lipid profile was developed by gas chromatography. Seeds were held at constant temperature of 25 ± 3 ° C, in darkness, during the storage time. Results demon-strated that the high initial viability was maintained until the ninth month, when it decreases and is statisti-cally different from the other treatments. The smaller germination percentage (26.1 %) was observed in the freshly harvested seeds and, the higher one corresponded to the six months (65.6 %), with these differences being statistically significant. Regarding the identified fatty acids and their average content, it was found that 33.41 % corresponded to palmitic acid, 7.72 % to stearic acid; the arachidic acid with 1.30 %, making a total of saturated fatty acids of 42.44 %. The detected unsaturated fatty acids were: palmitoleic acid 1.52 %, oleic acid 43.37 % and linoleic acid 7.24 %, in total, 52.15 %. No significative changes were observed in the fatty acids content that are the largest part of the total seed reserves; although the higher concentrations matched with the longest germination (three months), with an average of 92.84 % total fatty acids. Specified regressions indi-cated with statistical robustness that palmitoleic and palmitic acids increased while the oleic acid decreased during the dry storage. The arachidic acid showed a slightly downward trend. Also, the concentrations of fat-ty acids were significatively different between unstored and unincubated seeds (intact) and unstored and in-cubated, but without germinating seeds (dormant), in the latter, the total fatty acids content was significantly lower. Given that the application of gibberellic acid and warm dry storage favored germination, as well as the change in fatty acid content during warm dry storage, added to the results already reported on morphological changes and embryonic growth as an effect of the same type of storage, it is established that Annona purpurea seeds present morphophysiological dormancy, also this is the first identification report of arachidic and pal-mitoleic acids in chincuya seeds and the higher germination percentage reported (65.6 %).

The study conducts a comparative life cycle assessment (LCA) analysis to assess the environmental impact of two different manufacturing processes used to produce transparent dental aligners. The former method consists of thermoforming a polymeric disc over 3D printed, customized models, while the second, more innovative approach involves the direct printing of aligners using additive manufacturing (AM), specifically applying digital light processing (DLP) technology. The analysis results highlight how adopting direct printing through AM brings significant advantages in terms of environmental sustainability, thanks to the substantial reduction in raw materials and electricity consumption. These drops translate into decreased potential environmental impacts across all impact categories considered within the EF 3.1 method. Furthermore, lowering the amount of raw materials needed in the direct printing process contributes to a notable decrease in the overall volume of waste generated, emphasising the environmental benefits of this innovative technique.

1) Background: The influence of estrogen on cognitive and perceptual functions is debated. Some research suggests that estrogen increases arousal, improving cognitive function, while others propose that increased arousal might reduce performance on certain tasks. This study investigates the effects of menstrual cycle phase and estrogen levels on lightness perception in cycling women and hormonal contraceptive (HC) users. (2) Methods: Estrogen levels were determined from saliva samples collected at three sessions aligned with different menstrual phases in 16 women (9 with natural cycles, 7 HC users). The effects of wavelength and menstrual cycle phase on lightness perception were analyzed, followed by post-hoc comparisons and correlations between lightness perception and estrogen levels for both cycling women and HC users. (3) Results: Lightness varied by menstrual phase (MCP) in cycling women and was slightly higher during the low estrogen menstrual phase compared to peri-ovulation or luteal phases. In HC users, lightness measures were equivalent across phases. For cycling women, lightness was negatively correlated with estrogen for the green and green-yellow stimuli. There were no such associations among HC users. (4) Conclusions: This report challenges the concept that high estrogen phases of the menstrual cycle always positively influence perception. Conversely, the present results revealed that—at least in cycling, non-hormonal contraceptive users—lightness perception was both at a maximum during the low estrogen menstrual phase and negatively associated with estrogen levels across all tested wavelengths.

The concentrations and fluxes of arsenic (As) and cadmium (Cd) were examined in the hydrological cycle (bulk, throughfall deposition and percolation water), litterfall and soils in a maquis broadleaved evergreen forest stand in western Greece. It was found that the enrichment of As in the atmosphere was both due to suspended geogenic material and long range transfer, whereas for Cd the long range transfer was the predominant way for deposition in the ecosystem. Three models were assessed to find the volumes of percolation water and therefore the fluxes of As and Cd in the water that leave the ecosystem permanently. When calculating the total amounts of the heavy metals in soils, the statistical uncertainty derived from every soil layer has to be taken into account.

This study investigates the impact of financial integration on international dynamics from the perspective of volatility shocks. To achieve this, I employ an IRBC model with time-varying volatilities, recursive preferences, and a global bank. The model demonstrates that volatility shocks trigger precautionary saving incentives, but the specific effects vary based on the type of shock. In the presence of productivity volatilities, countries with a higher level of financial integration exhibit greater divergence in their business cycles, while financial integration tends to result in more synchronized business cycles in the face of financial volatilities. Disregarding volatility shocks would underestimate the impact of financial integration on the comovement of business cycles across countries. Furthermore, welfare analysis also indicates that financial markets play a crucial role in enhancing social welfare, regardless of the type of volatility.

The global construction sector contributes a significant share of total greenhouse gas (GHG) emissions. In Australia, infrastructure activity alone generates 18% of the GHG emissions budget. The use of low-embodied carbon building materials is crucial to achieving sustainability in the construction sector and to fulfill national and international climate goals. Industrial hemp (Cannabis sativa L.) is considered a promising feedstock for sustainable construction materials because of its biogenic carbon content, fast-growing cycles with low agricultural input requirements, and technical functionality which is comparable to traditional materials. This study has applied the life cycle assessment (LCA) guideline of ISO 14040:2006 to estimate the carbon footprint (CF) expressed in carbon dioxide equivalent (CO2eq) emissions of hemp-based building materials in Western Australia. The functional unit is 1 m2 of hemp-based board, and the system boundary includes cradle-to-gate stages, i.e., pre-farm, on-farm, and post-farm activities. The production of 1 m2 of hemp-based board is estimated to be - 2.302 kgCO2eq. Electricity from the public grid for lignin extraction during the post-farm stage is the main contributor to total CO2eq emissions (26%), followed by urea production (14%) during the pre-farm stage. Overall, the use of electricity from the SWIS during the post-farm stage accounts for 45% of total emissions. Sensitivity analysis shows that the CF of hemp-based boards is highly sensitive to the source of energy, i.e., total replacement of the SWIS by solar power decreases the CF from - 2.30 to -6.07 kgCO2eq (164%). The results suggest that hemp-based boards exhibit lower embodied GHG emissions compared to traditional materials, such as gypsum plasterboards.

Results of profile loss measurements, including trailing edge flow details, are presented for the flow of an organic vapor through a linear turbine cascade. The so-called VKI-I blade profile from the open literature was chosen for the cascade, and the working fluid was NOVEC 649. Pitot probes and hot wire anemometry were employed to measure the flow field up and downstream of the cascade. Details of the unsteady flow caused by the trailing edge of the blades and the turbulent spectrum were investigated using hot-wire anemometry. The new organic vapor flow results were compared with literature data obtained for air and with the prediction of conventional literature loss models. It was found that under certain thermodynamic conditions, specific traditional loss models can reasonably predict organic Rankine cycle (ORC) turbines' profile loss. Still, significant deviations between the loss models and the experimental data can also occur.

We investigated rainfall patterns in India over during the 60-year period from 1951 to 2010 and predicted changes for the next century (2051-2100) with an assumed 4K warming from large ensemble experiments (190 members). We focused on rainfall patterns during two periods of present-day climate (1951-1980 and 1981-2010) and their projected changes for the near and far future (2051-2080 and 2081-2110). Our analysis revealed that the northeastern region of India and some southern regions received higher rainfall during the period of 1951-2010. This finding is consistent with daily observations from the Asian Precipitation Highly Resolved Observational Data Integration Towards Evaluation (APHRODITE). In a warming climate, rainfall events in India are predicted to carry more precipitation, with the northeast and southern regions experiencing stronger rainfall events. The frequency and intensity of these events (with more than 20mm of rainfall per day, on average) are also expected to increase. Overall, our study suggests that water-related disasters such as flooding and landslides could be much worse in India in the future due to climate warming.

Understanding the molecular underpinnings of the evolution of complex (multi-part) systems is a fundamental topic in biology. One unanswered question is the extent to which similar or different genes and regulatory interactions underlie similar complex systems across species. Animal eyes and phototransduction (light detection) are outstanding systems to investigate this question because some of the genetics underlying these traits are well-characterized in model organisms. However, comparative studies using non-model organisms are also necessary to understand the diversity and evolution of these traits. Here, we compare the characteristics of photoreceptor cells, opsins, and phototransduction cascades in diverse taxa, with particular focus on cnidarians. In contrast to the common theme of deep homology, whereby similar traits develop mainly using homologous genes, comparisons of visual systems - especially in non-model organisms - are beginning to highlight a “deep diversity” of underlying components, illustrating how variation can underlie similar complex systems across taxa. Although using candidate genes from model organisms across diversity was a good starting point to understand the evolution of complex systems, unbiased genome-wide comparisons and subsequent functional validation will be necessary to uncover unique genes that comprise complex systems of non-model groups to better understand biodiversity and its evolution.

The paper describes a model of subjective goal-oriented semantics extending standard "view-from-nowhere" approach. Generalization is achieved by using a spherical vector structure essentially supplementing the classical bit with circular dimension, organizing contexts according to their subjective causal ordering. This structure, known in quantum theory as qubit, is shown to be universal representation of contextual-situated meaning at the core of human cognition. Subjective semantic dimension, inferred from fundamental oscillation dynamics, is discretized to six process-stage prototypes expressed in common language. Predicted process-semantic map of natural language terms is confirmed by the open-source word2vec data.

The SARS-Cov-2 virus, which causes COVID 19, uses the cell surface protein ACE2 as receptor for entry into cells. Critically ill COVID-19 patients often require prolonged mechanical ventilation which can cause mechanical stress to lung tissue. In vitro studies have shown that expression of ACE2 in alveolar cells is increased following mechanical stretch and inflammation. Therefore, we analyzed transcriptome datasets of 480 (non-COVID-19) lung tissues in the GTex tissue gene expression database. We found that mechanical ventilation of the tissue donors increased the expression of ACE2 by more than two-fold (p<10^-6). Analyses of transcriptomes of mechanically ventilated mice in the GEO database indicate that this alveolar cell response to stretch and inflammation is mediated by the chemokine midkine. Using a novel big knowledge network approach (SPOKE) we also found in transcriptomes of pharmacological perturbations (LINCS) that corticosteroids down-regulate midkine in pulmonal cells, and confirmed this in GEO transcriptomes of animal studies. Thus, mechanical ventilation of patients with COVID-19 pneumonia may eo ipso facilitate viral propagation in the lung, further accelerating the pulmonal pathology that has necessitated mechanical ventilation in the first place. This vicious cycle presents a rationale for the temporary treatment with corticosteroids to modulate the midkine-ACE2 axis in ventilated COVID19 patients and for gentler ventilation protocols.

Abstract-Digital Phase Plane is presented in this paper. For constant input second order digital systems with arbitrary initial conditions for arbitrary quantizaters, this digital phase plane shows, in plot form, the state trajectory and the asymptotic stability, including the existence and the position of arbitrary period limit cycles.

The isoenergetic cycle is a purely mechanical cycle comprised of adiabatic and isoenergetic processes. In the latter the system interacts with an energy bath keeping constant the expectation value of the Hamiltonian. This cycle has been mostly studied in systems consisting of particles confined in a power-law trap. In this work we study the performance of the isoenergetic cycle for a system described by the quantum Rabi model for the case of controlling the coupling strength parameter, the resonator frequency and the two-level system frequency. For the cases of controlling either the coupling strength parameter or the resonator frequency, we find that it is possible to closely approach to maximal unit efficiency when the parameter is sufficiently increased in the first adiabatic stage. In addition, for the first two cases the maximal work extracted is obtained at parameter values corresponding to high efficiency which constitutes an improvement over current proposals of this cycle.

Like living organisms, cancer cells require energy to survive and interact with their environment. Mitochondria are the main organelles for energy production and cellular metabolism. Recently, investigators demonstrated that cancer cells can hijack mitochondria from immune cells. This behavior sheds light on a pivotal piece in the cancer puzzle, the ‘dependence’ on the normal cells. This article illustrates the benefits of new, functional mitochondria for cancer cells that urge them to hijack mitochondria. It describes how functional mitochondria help cancer cells’ survival in the harsh tumor microenvironment, immune evasion, progression, and treatment resistance. Recent evidence has put forward the pivotal role of mitochondria in cancer stem cells’ metabolism. This theory highlights the mitochondria in cancer biology and explains how targeted anti-mitochondrial treatments can improve oncological outcomes.

In this study, we investigate the influence of control type and strain rate on the lifetime of specimens manufactured from 50CrMo4. This influence is described by a strain rate dependent method that uses cyclic stress strain curves to correct displacement controlled cyclic test results. The objective of this correction is to eliminate the stress related differences between displacement controlled cyclic test results and force controlled cyclic test results. The method is applied to the results of ultrasonic fatigue tests of six different combinations of heat treatment, specimen geometry (notch factor) and atmosphere. The corrected results show an improved agreement with test results obtained on conventional fatigue testing equipment with similar specimens: the standard deviation in combined data sets is significantly reduced (p=4.1%). We discuss the literature on intrinsic and extrinsic strain rate effects in carbon steels.

Colony-stimulating factor 1 receptor (CFS-1R) is a myeloid receptor with a crucial role in monocyte survival and differentiation. Its overexpression is associated with aggressive tumor characterized by an immunosuppressive microenvironment and poor prognosis. CSF-1R ligands, IL-34 and M-CSF, are produced by many cells in the tumor microenvironment (TME), suggesting a key role for the receptor in the crosstalk between tumor, immune and stromal cells in the TME. Recently, CSF-1R expression was reported at the cell membrane of cancer cell from different solid tumors, capturing the interest of various research group interested in investigating the role of this receptor in non-myeloid cells. This review summarizes current data available on the expression and activity of CSF-1R in different tumor types. Notably, CSF-1R+ cancer cells have been shown to produce CSF-1R ligands, indicating that CSF-1R signaling is positively regulated in autocrine manner in cancer cells. Recent research demonstrated that CSF-1R signaling enhances cell transformation by supporting tumor cell proliferation, invasion, stemness and drug resistance. In addition, this review covers recent therapeutic strategies, including monoclonal antibodies and small molecule inhibitors, targeting the CSF-1R and designed to block the pro-oncogenic role of CSF-1R in cancer cell.

This comprehensive review delves into the multifaceted aspects of ERK signaling and the intricate mechanisms underlying distinct cellular fates. ERK1 and ERK2 (ERK) govern proliferation, transformation, epithelial-mesenchymal transition, differentiation, senescence, or cell death, con-tingent upon activation strength, duration, and context. The biochemical mechanisms underlying these outcomes are inadequately understood, shaped by signaling feedback and the spatial localization of ERK activation. Generally, ERK activation aligns with the Goldilocks principle in cell fate determination. Excessive or insufficient ERK activity inhibits growth, whereas moderated activation supports proliferation and survival. Unraveling the intricacies of how the degree of ERK activation dictates cell fate requires deciphering mechanisms encompassing protein stability, transcription factors downstream of ERK, and the chromatin landscape.

Psoriasis is a multi-factorial immune-mediated disease that affects approximately 2% of the UK population and 2.5% worldwide. The condition can impact multiple organs, including the skin and joints. In moderate to severe cases, systemic and topical medications may not provide adequate relief, and as a result, biologic treatments are often administered as a monotherapy or in combination with other treatments. While biologic treatments are more effective than systemic and topical medications in treating psoriasis, patients require close supervision and monitoring while receiving this type of treatment. Liposomes are highly versatile and can be employed for therapy and research applications. They enhance drug retention at the site of administration, thereby reducing systemic side effects. Our study was the first to investigate the genotoxicity of secukinumab, an ideal biologic treatment for psoriasis (a human IgG1k antibody, anti-IL17A), in bulk and liposome nanoparticles on the lymphocytes of psoriasis patients compared to healthy individuals. We evaluated and com-pared the genotoxicity of secukinumab in bulk and liposomal form using the Comet and micronucleus assays. Both assays demonstrated that secukinumab in both forms did not ex-hibit genotoxicity and reduced DNA damage following treatment of the lymphocytes from healthy individuals and psoriatic patients with secukinumab bulk and liposomes format. Both concentrations of secukinumab used (2.1 and 2.8 µg/mL) effectively decreased H2O2-induced DNA damage in both groups to nearly the level of the negative control. Secukinumab bulk and liposome form significantly decreased H2O2-induced damage and efficiently attenuated its adverse effects both in the Comet (p<0.0001) and micronucleus assays (p<0.01). Overall, secukinumab in both forms exhibited protective and an-ti-genotoxic effects by demonstrating its potential to reduce DNA damage caused by oxida-tive stress and by not inducing any further damage in the lymphocytes of either healthy in-dividuals or patients.

There is no routine approach to identify patients with gynecologic malignancies at high risk for chemotherapy-resistance. Circulating tumor DNA (ctDNA) tumor fraction (TFx) represents a minimally-invasive approach to tumor profiling, with as yet limited data on utility in gynecologic malignancies. The objective was to investigate the use of ctDNA TFx in a cohort of patients with ovarian and endometrial cancer. Plasma samples from patients with biopsy-proven ovarian or endometrial cancer collected between 4/2018 and 4/2020 were subjected to shallow whole genome sequencing with determination of TFx via ichorCNA package. The association of TFx to continuous and categorical baseline clinicopathologic factors and progression-free survival was assessed. 210 plasma samples from 78 patients with gynecologic cancers were analyzed. Mean TFx for ovarian cancer was 5.5% and endometrial cancer 2.4% and there was no significant difference in TFx among histology either for endometrial or ovarian cancers. Grade was associated with significant difference in ‘sentinel’ TFx among ovarian cancers but not endometrial cancers. ctDNA TFx dynamics over time demonstrated rapid clearance of ctDNA in most patients with ovarian cancer, while endometrial cancer had consistently low TFx. ctDNA TFx is feasible in ovarian and endometrial cancers and may be a valuable important tool for prognostication.

The European white birch, scientifically known as Betula pendula, and its variant, B. pendula 'Dalecarlica' are characterized by a serrated leaf margin that enhances their aesthetic appeal. However, the lobed leaf trait can undergo random and spontaneous reversion to the typical ovoid or cordate shape during asexual reproduction. Investigating and elucidating the molecular mechanisms underlying this unpredictable reversion mutation is essential for comprehending the birch leaf development process. In this research, we employed a non-lobed-leaf mutant derived from a lobed-leaf birch clone during plant tissue culture. We adopted a multi-omics approach, including whole-genome resequencing, transcriptome sequencing, and methylation profiling, to analyze and compare genomic variations and gene expression modifications. The study revealed that the 24 variant genes affected by 1464 SNP/InDel sites in the genome of the non-lobed-leaf mutant are not associated with leaf development. While the overall methylation level in the mutant's genome closely resembles that of the serrated-leaf birch, ten genes exhibit differential methylation accompanied by differential expression. Transcriptome sequencing demonstrated that the differentially downregulated genes in the mutant are significantly enriched in the GO:0009733 (response to auxin) and GO:0009734 (auxin-activated signaling) pathways. Validation through McrBC-PCR and qRT-PCR confirmed differential methylation and expression of BpIAA9 in the reversion mutant. The elevated methylation level in the BpIAA9 promoter leads to reduced expression, resulting in changes in the expression of auxin-responsive genes. This, in turn, leads to a transcriptional downregulation enrichment effect in auxin-related pathways in the reversion mutant, ultimately inhibiting the regulation of leaf veins by auxin during their development.

Pediatric brain tumors are the leading cause of cancer-related death in children. Diagnosis cur-rently relies on surgical biopsy to obtain tumor tissue for histological analysis. There is a great need for less invasive approaches to molecularly profile tumors and monitor therapeutic response. Liquid biopsy analysis of circulating tumor biomarkers in biofluids like cerebrospinal fluid (CSF) and blood offers a promising minimally invasive strategy. This review discusses recent advances in developing liquid biopsy assays using next-generation sequencing, digital PCR, and emerging techniques to detect circulating tumor DNA (ctDNA), cells (CTCs), and exosomes in pediatric brain tumors. The ability to use these circulating biomarkers for non-invasive diagnosis, thera-peutic targeting, tracking response to therapy, and understanding resistance mechanisms is ex-amined. Technical and clinical validation challenges to translate liquid biopsies into routine clin-ical practice are also discussed.

Pharmacogenetics and DNA methylation influence therapeutic outcomes and provide insights into potential therapeutic targets for brain-related disorders. To understand the effect of genetic polymorphisms on drug response and disease risk, we analyzed the relationship between global DNA methylation, drug-metabolizing enzymes, transport genes, and pathogenic gene phenotypes in serum samples from two groups of patients: Group A, which showed increased 5-methylcytosine (5mC) levels during clinical follow-up, and Group B, which exhibited no discernible change in 5mC levels. We identified specific SNPs in several metabolizing genes, including CYP1A2, CYP2C9, CYP4F2, GSTP1, and NAT2 that were associated with differential drug responses. Specific SNPs in CYP had a significant impact on enzyme activity, leading to changes in phenotypic distribution between the two patient groups. Group B, which contained a lower frequency of normal metabolizers and a higher frequency of ultra-rapid metabolizers compared to patients in Group A, did not show an improvement in 5mC levels during follow-up. Furthermore, there were significant differences in phenotype distribution between patient Groups A and B for several SNPs associated with transporter genes (ABCB1, ABCC2, SLC2A9, SLC39A8, and SLCO1B1) and pathogenic genes (APOE, NBEA, and PTGS2). These findings appear to suggest that the interplay between pharmacogenomics and DNA methylation has important implications for improving treatment outcomes in patients with brain-related disorders.

Background: Oxygen exists in two gaseous (dioxygen and ozone) and six solid allotropic modifications. An additional allotropic modification of oxygen, the cyclooctaoxygen, was predicted to exist in 1990. The first synthesis and characterization of cyclooctaoxygen as its sodium crown complex, isolated in the form of three cytosine nucleoside hydrochloride complexes, was reported in 2016.Results: The sperminium hydrogen phosphate/cyclooctaoxygen sodium complex is calculated to cover the actively transcribed regions (2.6%) of bovine lymphocyte interphase genome. Cyclooctaoxygen seems to be naturally absent in hypoxia-induced highly condensed chromatin, taken as a model for eukaryotic metaphase/anaphase/early telophase mitotic chromatin. Hence, it is proposed that the cyclooctaoxygen sodium-bridged sperminium hydrogen phosphate and selenite coverage serves as an epigenetic shell of actively transcribed gene regions in eukaryotic ‘open’ euchromatin DNA. Cyclooctaoxygen sodium-bridged sperminium hydrogen selenite was calculated to serve as a marker shell component at ATG start codons in human euchromatin DNA mRNA genes, both at the translation initiation triplet and at 5'-untranslated region upstream ATGs. The total herbicide glyphosate (ROUNDUP®) and its metabolite (aminomethyl)phosphonic acid (AMPA) are proved to represent ‘epigenetic poisons’, since they both selectively destroy the cyclooctaoxygen sodium complex. This definition is of reason, since the destruction of cyclooctaoxygen is certainly sufficient to bring the protection shield of human euchromatin into collateral epigenetic collapse.Conclusions: The total herbicide glyphosate and its environmental metabolite (aminomethyl)phosphonic acid (AMPA) can be associated in vitro with catalytic detoriation of eukaryotic euchromatin genetic information.General Significance: The epigenetic shell of eukaryotic euchromatin is susceptible to decay induced by catalytic epigenetic poisons threatening eukaryotic genomic heritage.

Background: Strongyloidiasis, a neglected disease caused by intestinal nematodes of the genus Strongyloides, is endemic to tropical and subtropical areas such as Vietnam. The morphological diagnosis of larvae by Hara Mori culture technique and microscopicare are considered the standard diagnostic procedures in the endemic areas of Strongyloides spp. However, they could only identify the genus, not the species of Strongyloides. DNA-molecular techniques which are highly sensitive and more cost-effective have been increasingly utilized in detection of Strongyloides species. This study aims to determine prevalence and the species of Strongyloides among resident population in Duc Hoa district, Long An province, Southern Vietnam. Methods: A cross-sectional study was conducted using 1,190 stool samples collected in Duc Hoa district, Long An province, Vietnam, from July, 2017 to November 2018. The stool specimens were transported to the Laboratory of Medical Parasitology, Pham Ngoc Thach University of Medicine within two hours of collection at an appropriate temperature of 25 oC. All samples were stored at 2 - 8°C and processed within 48 hours for microscopic examination. Molecular detection was carried out at Laboratory of Molecular Biology, Pham Ngoc Thach University of Medicine, Hochiminh city, VietNam. Results: Of the 1,190 samples tested, Strongyloides spp. larvae were detected in 79 specimens (6.6%) by two classical parasitological methods, namely direct microscopy and the modified Harada-Mori filter paper culture. DNA was extracted from 70 of the 79 samples of Strongyloides spp. larvae, which was subsequently characterized by real-time PCR amplification of the 18S and 28S regions of the rDNA gene. The results showed that 97.1% of the DNA samples were S. stercoralis, 2.9% were co-infections with S. ratti and S. stercoralis, and 2.9% belonged to S. ratti. For all 14 isolates, nucleotide sequencing was compared with other human pathogenic species of Strongyloides whose sequences are available in GenBank. The identity of 12/14 sequences were confirmed as S. stercoralis with a high level of similarity (91.3% - 100%) and over 98% for S. ratti. Between the two co-infection samples, the higher similarity belonged to S. stercoralis. Conclusion: A molecular amplification of small subunit ribosome RNA followed by sequence analysis has been proved to be a suitable method for discrimination of Strongyloides spp. retrieved from stool samples.

Gastric cancer (GC) is one of the most common malignancies around the world, and the incidence of GC is increasing in the past decades. In addition to genetic modifications, epigenetic alterations catalyzed by DNA methyltransferases (DNMTs) are a well-characterized epigenetic hallmark in gastric cancer. Nowadays, DNA methylation landscape is essential for maintaining the silence of tumor suppressor genes (TSGs). As an important group of peptide, TFF family has been confirmed to function as a TSG in various kinds of cancers. However, whether TFFs could be modified by DNA methylation in gastric cancer remains unknown. In this study, we initially screened out two expression profiles about GC from Gene Expression Omnibus (GEO) database. The higher expressions of TFF1 and TFF2 were observed in GC tumor tissues than normal tissues. Additionally, we illustrated that the expressions of TFF1/TFF2 were associated to the overall survival (OS) and tumor free survival (TFS) of GC patients via through the Kaplan-Meier analysis. Subsequently, the integrative analysis was performed to estimate the DNA methylation level of each site in TFF1/TFF2 CpG islands. Importantly, our findings indicated that hyper-methylation of cg01886855 and cg26403416 were separately responsible for the downregulation of TFF1 and TFF2 in GC samples. Besides, utilizing the gain of function assay, we demonstrated that TFF1/TFF2 could suppress the proliferation of GC cells. Based on these results, We identified that TFF1 and TFF2 acted as the putative tumor suppressors in gastric cancer, which suggested that TFFs could be two candidate biomarkers for predicting tumor recurrence in gastric cancer patients. Furthermore, these findings highlight a potential therapeutic approach in targeting the TFFs for the treatment of gastric cancer.

Wildfires have continued to increase in frequency and severity in Southern California due in part to climate change. To gain a further understanding of microbial soil communities’ response to fire and functions that may enhance post-wildfire resilience, soil fungal and bacterial microbiomes were studied from different wildfire areas in the Gold Creek Preserve within the Angeles National Forest using 16S, FITS, 18S, 12S, PITS, and CO1 amplicon sequencing. Sequencing datasets from December 2020 and June 2021 samplings were analyzed using DNA Subway, ranacapa, stats, vcd, EZBioCloud, and mixomics. Significant differences were found among bacterial and fungal taxa associated with different fire areas in the Gold Creek Preserve. There was evidence of seasonal shifts in the alpha diversity of the bacterial communities. In the sparse partial least squares analysis, there were strong associations (r>0.8) between longitude, elevation, and a defined cluster of Amplicon Sequence Variants (ASVs). The Chi-square test revealed differences in fungi:bacteria (F:B) proportions between different trails (p=2*10^-16). sPLS results focused on a cluster of Green Trail samples with high elevation and longitude. Analysis revealed the cluster included the post-fire pioneer fungi Pyronema, and Tremella. Chlorellales algae, and pathogenic Fusarium sequences were elevated. Bacterivorous Corallococcus, which secretes antimicrobials, and bacterivorous flagellate Spumella, were associated with the cluster. There was functional redundancy in clusters that were differently composed, but shared similar ecological functions. These results implied a set of traits for post fire resiliency. These included photo-autotrophy, mineralization of pyrolyzed organic matter and aromatic/oily compounds, pathogenicity and parasitism, antimicrobials, and N-metabolism.

The deadliest disease in the world, cancer, kills many people every year. The early detection is the only hope for the survival of malignant cancer patients. As a result, in the preliminary stages of , the diagnosis of cancer biomarkers at the cellular level is critical for improving cancer patient survival rates. For decades, scientists have focused their efforts on the invention of biosensors. Biosensors, in addition to being employed in other practical scenarios, can essentially function as cost effective and highly efficient devices for this purpose. Traditional cancer screening procedures are expensive, time-consuming, and inconvenient for repeat screenings. Biomarker-based cancer diagnosis, on the other hand, is rising as one of the most potential tools for early detection, disease progression monitoring, and eventual cancer treatment. As Biosensor is an analytical device, it allows the selected analyte to bind to the biomolecules being studied (– for example RNA, DNA, tissue, proteins, cells). They can be divided based on the kind of biorecognition or transducer elements on the sensor. Most biosensor analyses necessitate the analyte being labeled with a specific marker. In this review article, the application of distinct variants of biosensors against cancer has been described.

Two-dimensional silicon allotrodes– also called Sinicene– have recently experienced intensive scientific research interest due to their unique electrical, mechanical, and sensing characteristics. A novel silicene based nano-material has been enticed great amenities, partially because of its uniformity with graphene. Silicene is a highly sensitive for numerous sensors based on molecular sensing as pH sensor, gas sensor, ion sensor and biosensing are Deoxyribonucleic acid (DNA) nucleobase sensor, photonic sensor, cell-based biosensor, glucose sensor, and bioelectric nose sensor. Nowadays genetic research based on DNA hybridization, which is a vital tools for sensing material and it has various detection methods. Among of them, the detection method is frequency readout used to a label-free detection of DNA hybridization. In this paper we have compared the graphene and silicene quantum capacitance that has been proposed for a DNA hybridization detection method on wireless readout. These method shows, the strands of mismatched and complementary DNA have in different range of frequency to identify output efficiency. With respect to DNA concentration the output of silicene is almost sharply linear than graphene. In addition of field effect transistor, silicene opens a new opportunities due to its band gap whereas graphene indicates zero band gap. It can be stated that silicene is much more reliable as well as much stronger than multi-layered graphene.

This review article offers an in-depth look at DNA, its discovery, structure, functions, and the significant role it plays in modern biomedical research. It begins by revisiting the landmark discovery of the DNA double helix by scientists Watson and Crick, a structure resembling a twisted ladder that forms the blueprint of life. The review explains the basic processes of DNA replication (copying DNA), transcription (converting DNA to RNA), and translation (turning RNA into proteins), which are fundamental to understanding how genetic information is passed on and used by living organisms. The article then explores gene regulation and epigenetics, which involve how genes are turned on or off and how environmental factors can affect gene expression without changing the DNA sequence itself. It examines how DNA interacts with various proteins and modifiers, which play crucial roles in these processes. A major focus is on the advancements in DNA sequencing technologies. From the initial Sanger sequencing method, which was labor-intensive and time-consuming, to the highly efficient next-generation sequencing (NGS) and the latest single-molecule sequencing techniques, the review covers how these technologies have revolutionized genomics and personalized medicine. It also highlights the importance of computational genomics and bioinformatics, fields that deal with analyzing and interpreting the vast amounts of data generated by DNA sequencing. The review discusses DNA's crucial role in understanding human diseases. It covers DNA-based research in cancer, rare genetic disorders, infectious diseases, and pharmacogenomics (how genes affect a person's response to drugs). It emphasizes studies that have led to new ways of diagnosing and treating diseases. The article looks at the future of DNA research. It talks about emerging technologies like CRISPR-Cas9, a revolutionary gene-editing tool that allows scientists to modify DNA with high precision. Synthetic biology, an interdisciplinary field that combines biology and engineering for designing and constructing new biological parts and systems, is also discussed. Furthermore, DNA nanotechnology, which involves designing DNA molecules for technological uses, is explored. Finally, the review addresses ethical issues in DNA research, such as privacy concerns and debates over genome editing.

The initiation reactions of DNA synthesis are central processes during human chromosomal DNA replication. They are separated into two main processes: the initiation events at replication origins, the start of the leading strand synthesis for each replicon, and the numerous initiation events taking place during lagging strand DNA synthesis. In addition, a third mechanism is the re-initiation of DNA synthesis after replication fork stalling, which takes place when DNA lesions hinder the progression of DNA synthesis. The initiation of leading strand synthesis at replication origin is regulated at multiple levels, from the origin recognition to the assembly and activation of replicative helicase, the Cdc45-MCM2-7-GINS (CMG) complex. In addition, the multiple interactions of the CMG complex with the eukaryotic replicative DNA polymerases such as DNA polymerase α-primase (Pol α), DNA polymerase δ and ε at replication forks play pivotal roles in the mechanism of initiation reactions including the initiation of signalling unperturbed and stalled replication forks, ‘replication stress’ events, via ATR (ATM-Rad 3-related protein kinase). All these processes are essential for the accurate transfer of the cells’ genetic information to their daughters. Failures and dysfunctions in these processes gives rise to genome instability followed by genetic diseases including cancer. Thus, in their review ‘Hallmarks of Cancer: New Dimensions‘ Hanahan and Weinberg (2022) called genome instability a fundamental function in the development process of cancer cells. In recent years, the understanding of the initiation processes and mechanisms of human DNA replication has made substantial progress at all levels which will be discussed in the review.

Tdp1 and Tdp2 are DNA repair enzymes that repair DNA damages caused by various agents, including anticancer drugs. Thus, these enzymes resist anticancer therapy and could be the reasons of resistance to such widely used drugs as topotecan and etoposide. In the present work, we found compounds capable of inhibiting both enzymes among derivatives of (-)-usnic acid. Both (+)- and (-)-enantiomers of compounds act equally effectively against Tdp1, and only (-)-enantiomers inhibited Tdp2. Surprisingly, the compounds protect HEK293FT wild type cells from the cytotoxic effect of etoposide but potentiate it against Tdp2 knockout cells. We assume that the sensitizing effect of the compounds in the absence of Tdp2 is associated with effective inhibition of Tdp1, which could take over the functions of Tdp2.

This article is devoted to the results of in-depth analysis of the system of binary-oppositional structures in DNA n-plet alphabets and their algebraic-matrix representations. These results show that the molecular complementary replication of DNA strands is accompanied by the presence of an algebraic version of the principle "like begets like" in matrix representations of DNA alphabets having internal structures. This algebraic version is based on binary-oppositional structures in the genetic molecular system, which can be represented by binary numbers and corresponding matrices of DNA alphabets. The received results allow thinking that the phenomenon "like begets like" (or a complementary replication in a wide sense) is systemic in the genetic organization and is connected with algebraic features of biological organization. Correspondingly, the biological principle "like begets like" can be additionally modeled by algebraic-matrix methods and approaches. Such algebra-matrix modeling of the genetic coding system gives new ways for studying and understanding the key role of the named principle in genetic and other inherited physiological complexes. On this way, the author discovered general rules of stochastic organization of information binary sequences of genomic DNAs of eukaryotes and prokaryotes. The presented rules are connected with information dichotomies of probabilities and corresponding fractal-like trees of probabilities, which fundamentally differ from constructional dichotomies in biological bodies. The received phenomenological data and rules lead to new biological ideas.

A sustainable, scalable source of energy‐dense chemical fuel is urgently needed to ensure the security of our energy supply for future generations. Solar energy is the only renewable energy source of sufficient scale to replace fossil fuels and meet rising environmental demand. Hydrogen is expected to play a key role as an energy carrier in future energy systems of the world. As fossil fuel supplies become scarcer and environmental concerns increase, hydrogen is likely to become an increasingly important chemical energy carrier and eventually may become the principal chemical energy carrier. When most of the world’s energy sources become non-fossil based, hydrogen and electricity are expected to be the two dominant energy carriers for the provision of end-use services. Photocatalytic hydrogen evolution from water by solar energy over semiconductors offers a promising way for clean and renewable production of hydrogen. The TiO2-based materials have received considerable attention in recent years due to their extensive application in photocatalysis for hydrogen evolution. Though TiO2 is the most widely investigated photocatalyst for hydrogen evolution, it still provides low photocatalytic activity due to the wide bandgap that results in photocatalytic activity only under ultraviolet (UV) irradiation. Modification of TiO2 photocatalysts with several transition metals has been extensively studied to extend the absorbance capacity of TiO2 into the visible range. The effect of different photocatalytic deposition and reaction parameters also play major roles in enhancing the photostability of photoanode and increasing the hydrogen gas output, respectively.

The response of building elements during earthquakes has been an area of concern for different researchers around the world. The NSEs are the first elements to attain failure, the buildings after damages in safety priority are classified as in “Life Safety” mode, but in reality, they are in “Collapse Safety” mode and the occupants inside the buildings are in a state of “Non-Life Safety” as a result of falling of the hazardous NSE’s like cladding's, partitions, hanging objects. In addition to the Life Cycle Cost Assessment (LCCA), the Social Life Cycle Assessment (SLCA) is overlooked by the majority of the researchers, the community must be prepared to respond to an event more efficiently without any major casualties or loss of life. It is expected that by the end of 2050, almost double the construction will take place, the embodied energy during the pre-construction, post-construction and demolition generates a lot of CO2s into the environment, hence sustainability should be given due importance, helping in the achievement of Sustainable Developmental Goals (SDGs).

Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underly chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei followed by incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA-repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in Sonic-Hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA-repair genes resulting in chromosome instability and chromothripsis-like rearrangements.

The presence of mutated genes strongly correlates with the incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprits, we need to look at the biochemistry of cancer, with a focus on enzymes which invariably facilitate transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active-site by various carcinogens, its role in initiating retinoblastoma and HPV-related cervical cancers is well documented. Blocking the activity of malignant RnR is a certain way to arrest cancer.

Although agricultural crops production systems in subtropical plateau regions currently pose high environmental risks, especially in developing countries, their environmental impacts and emission-reduction potentials remain unclear, and the development potential of such systems is likely huge. We conducted a case study in Yunnan Province, China, to quantify the environmental impacts from crop production during 2002–2021. The life cycle assessment method was employed to identify factors driving the environmental impacts, and potential mitigation strategies were proposed. The yield and total nutrient input of grain crops in Yunnan Province increased over the 20-year period, and environmental footprint of crops production in Yunnan Province was higher than that of other regions. Average annual mean greenhouse gas (GHG) emissions and soil acidification potentials (AP) and water eutrophication potentials (EP) of crops production during 2002–2021 were 732 kg CO2-eq·Mg-1, 15.8 kg SO2-eq·Mg-1, and 2.7 kg PO4-eq Mg-1, respectively. GHG emissions from g crops mainly originated from applying agricultural materials during the crop life cycle. There was a significant correlation between surplus nitrogen and environmental impacts. Scenario testing showed that through crop sowing, nutrient regulation, and crop management, the crop yield could be increased and environmental costs could be reduced. The greatest reductions were found in wheat production: 53.1%, 67.9%, and 67.7% for GHG emissions, AP, and EP, respectively. Adopting comprehensive agricultural management measures could reduce the negative impact of crops production on the environment in subtropical plateau areas and achieve sustainable agricultural development.

Wolfenden and his coworkers observed the astronomical numbers for the catalytic proficiency of some enzymes. We connected that pinnacle of biological evolution to the universal thermodynamic evolution. We added or multiplied a random noise with chosen rate constants to explore the correlation between dissipation and enzyme efficiency for ten enzymes: beta-galactosidase, glucose isomerase, β-lactamases from three bacterial strains, ketosteroid isomerase, triosephosphate isomerase, and carbonic anhydrase I, II, and T200H. The turnover number kcat and catalytic efficiency kcat/KM are proportional to the overall entropy production – the main parameter from irreversible thermodynamics. For most enzymes with the Michaelis-Menten type cycle kinetics, the best increase in the forward kcat/KM follows after increasing the equilibrium constant of substrate-enzyme association. The Discussion section emphasizes the role of biological evolution in harvesting order (high enzyme efficiency) from disorder (high noise and dissipation). It also connects the applications of the maximum partial entropy production theorem in optimizing enzyme kinetics (D. Juretić "Bioenergetics - A Bridge across Life and Universe") with the present total entropy production role analysis. De novo enzyme design and various attempts to speed up the rate-limiting catalytic steps may profit from our theoretical insights.

Certain services can help avoid environmental impact in larger contexts. However, there is no commonly agreed bottom-up methodology for calculation of the total net reduction effect of specific digital services. Life Cycle Assessment (LCA) is a common denominator for most methodologies. The most common method is the Attributional LCA (ALCA), and recently the emerging handprint ALCA estimating so-called positive environmental impacts. Moreover, Consequential LCA (CLCA) can be used to capture market effects. The third conceptual approach is Input-Output LCA. The purpose is to propose and test a new method based on some of the existing ones. The existing concepts are compared and a synthesis is made to create a practical but still useful method. The new method is applied to two illustrative cases in the Information and Communication Technology (ICT) domain; the introduction of a 5G enabled drone for pipe inspection and the 5G enabled health consultation. Compared to simplified ALCA, the difference between the absolute score for the baseline system and the target system changes up to 15% when the proposed simplified CLCA (SCLCA) method is used. The results show that SCLCA, when combined with analytical methods for expressing digital ICT services’ own impact, is a fruitful approach which is both practical and feasible.

Background: Leishmaniasis is a neglected disease with a global spread that affects both domestic and wild animals in addition to people. Leishmania donovani is the suspected anthroponotic cause of VL in India, where it is an endemic disease. The reservoir hosts play a crucial role in the life cycle of the Leishmania parasite. The complicated connection between the pathogen, vector, and reservoir exhibits geographical and temporal diversity. Human-to-human and, to a lesser extent, human-to-animal transmission is the principal mechanism for the maintenance of anthroponotic diseases. Scope and approach: A deliberate, systematic search was conducted on PubMed, Science Direct, and Google Scholar using keywords such as "Leishmania donovani," "zoonotic visceral leishmaniasis," and "wild animal reservoir for leishmania donovani." 530 potentially significant references were obtained from these 507 were disallowed due to copy avoidance, irrelevant titles, research publications from nations other than India, or modified compositions. The remaining 20 investigations were later rejected because they did not meet the criteria for inclusion. Finally 3 research papers with 867 goats, 161 cattles, 106 chickens, 26 sheep, 3 buffaloes, 406 dogs and 309 rats were reported. Conclusion: According to the review, goats are the epidemic's primary host and possible reservoir in several regions of India. In the endemic regions of the disease, some species of rodents along with the canines appear to be maintaining the L. donovani transmission cycle.

Nonequilibrium work switching simulations and Jarzynski’s equation are a reliable method to compute free energy differences, ΔAlow→high, between two levels of theory, such as a pure molecular mechanical (MM) and a quantum mechanical/molecular mechanical (QM/MM) description of a system of interest. Despite the inherent parallelism, the computational cost of this approach can quickly get very high. This is particularly true for systems where the core region, the part of the system to be described at different levels of theory, is embedded in an environment, such as explicit solvent water. We find that even for relatively simple solute–water systems, switching lengths of at least 5 ps are necessary to compute ΔAlow→high reliably. In this study, we investigate two approaches towards an affordable protocol, with emphasis on keeping the switching length well below 5 ps. Inserting a hybrid charge intermediate state with modified partial charges which resembles the charge distribution of the desired high level makes it possible to obtain reliable calculations with 2 ps switches. Attempts using step-wise linear switching paths, on the other hand, did not lead to improvement, i.e., faster convergence for all systems. To understand these findings, we analyzed the solutes’ properties as a function of partial charges used, the number of waters in direct contact with the solute, and studied the time needed for water molecules to reorient themselves upon a change in the solute’s charge distribution.

The purpose of this study was to determine changes in the mechanical properties of the thigh and lower leg musculature during the early follicular and ovulatory phases. Subjects were 15 female university students with normal menstrual cycles. The early follicular and ovulatory phases were estimated by the basal body temperature method, ovulation kits, and salivary estradiol concentration measurement. The MyotonPRO digital palpation device (Myoton AS, Tallinn, Estonia) was used to measure muscle and tendon stiffness in the early follicular and ovulatory phases. Measurement sites were the rectus femoris (RF), vastus medialis (VM), patellar tendon (PT), medial head of gastrocnemius, soleus, and Achilles tendon. No significant differences in stiffness of all muscle tendons were identified between the early follicular and ovulatory phases. In the ovulatory phase, a significant positive correlation was seen between stiffness of RF and PT, and between stiffness of VM and PT. These results suggest that the stiffness of muscles and tendons of anterior sites of the thigh and posterior sites of the lower leg may not change between the early follicular and ovulatory phases. During the ovulatory phase, tendons may also be stiffer in individuals with stiffer anterior thigh muscles.

Grill-specific footprints for common fuels/grill types in the USA are estimated from public information and data from a major grill manufacturer. These are a function of both 1) a fuel’s footprint and 2) a grill’s efficiency of cooking. In 2022, grill-specific footprints vary by 9:1. A typical gas grill is highest at 3.6 lb CO2e/grill session, nine times that of a wood-pellet grill, lowest at 0.4 lb. Charcoal briquettes, electricity and super-efficient gas grills come in-between. Pellets are lowest, because they are made from waste wood and their production burden is modest. Electricity has the highest fuel footprint, yet the second-lowest grill-specific footprint, thanks to its high efficiency. Briquettes come in fourth, because their production involves fossil gas, and they contain some fossil coal. Grill efficiency is key for gas (natural gas or propane): a typical gas grill has twice the footprint of a super-efficient one. In 2027, with bio substitution, the super-efficient gas grill would move ahead of pellets. Electricity and charcoal could improve but would still place fifth and sixth. The range of grill-specific footprints could fall to 4.5:1, within a much-lower range, the highest footprint in 2027 almost 60% lower than 2022’s highest.

The paper proposes a mechanism for the impact of changes in the key rate on the volume of newly issued loans. The volume depends on the price (interest rates on loans), and the price depends on the key rate and the actual consumption of loans in the previous period (generalized cobweb cycle). The model was estimated by a Kalman filter, adequacy was confirmed by simulation. It is possible to forecast the average rate on loans for a month in advance according to the information published by the Central Bank of the Russian Federation (CB). By playing various scenarios for changing the key rate, it was found that in quiet periods of economic development, the usual laws of supply and demand operate in the loan market and by raising the key rate, you can reduce inflation. In the turbulent (overheated) state of the economy, an increase in the key rate can, on the contrary, provoke an increase in the issuance of loans and unconventional manipulations with the key rate are required.

The increasing amount of municipal sludge in China requires safe and effective management to protect human health and ensure environmental sustainability. Pyrolysis is a thermochemical process that that decompose organic matter at elevated temperature and under anaerobic conditions, and it has attracted an increasing attention in sludge treatment in the recent years. However, comprehensive environmental and economic assessment of sludge pyrolysis in China's context is rare, due to the small quantities of full-scale sludge pyrolysis plant. In this paper, we applied our design and operation parameters of full-scale sludge pyrolysis plants to generate the material and energy consumptions of the pyrolysis system under various of conditions, including sludge organic content and moisture content, system size, system energy distribution, and whether or not heat substitution is applied. Life cycle assessment and techno-economic assessment were then applied to investigate the environmental and economic performance of the system Our results demonstrate the significant environmental and economic impacts associated with sludge properties and system size. Generally, sludge with higher organic content and lower moisture content requires less natural gas consumption, which leads to a simultaneous improvement of the system environmental and economic performance. The system economic performance is more sensitive to the system size, and centralized sludge handling using a larger pyrolysis is more economic favorable. In the most ideal case, the average global warming potential and minimum sludge handling price of sludge pyrolysis could be as low as -32.5 kg CO₂-Eq/t DS and 188.8 $/t DS, respectively. Based on these results, we discussed the pathways that could be taken to further optimize the environmental and economic performances of the pyrolysis system.

I wish to suggest a hypothesis regarding the physiological function of alpha-synuclein, a protein implicated in Parkinson disease, whose cell biology is still debated. The essence is the concept of Carnot cycle of refrigeration in which membrane fluidity depends on the heat produced by mitochondria. The hypothesis has the potential to explain the diverse phenotypes attributed to alpha-synuclein under both physiological and pathological conditions.

In this paper, our goal is to perform a virtual restoration of an ancient coin from its image. The present work is the first one to propose this problem, and it is motivated by two key promising applications. The first of these emerges from the recently recognised dependence of automatic image based coin type matching on the condition of the imaged coins; the algorithm introduced herein could be used as a pre-processing step, aimed at overcoming the aforementioned weakness. The second application concerns the utility both to professional and hobby numismatists of being able to visualise and study an ancient coin in a state closer to its original (minted) appearance. To address the conceptual problem at hand, we introduce a framework which comprises a deep learning based method using Generative Adversarial Networks, capable of learning the range of appearance variation of different semantic elements artistically depicted on coins, and a complementary algorithm used to collect, correctly label, and prepare for processing a large numbers of images (here 100,000) of ancient coins needed to facilitate the training of the aforementioned learning method. Empirical evaluation performed on a withheld subset of the data demonstrates extremely promising performance of the proposed methodology and shows that our algorithm correctly learns the spectra of appearance variation across different semantic elements, and despite the enormous variability present reconstructs the missing (damaged) detail while matching the surrounding semantic content and artistic style.

The importance of the contribution from tourism to climate change was pointed out by the International Tourism Organization (UNWTO). By combining process-based Life Cycle Assessment (LCA) and Input-output analysis, several researches have tried to evaluate the impacts of the tourism industry as well as its products and services. Indeed, the tourism sector has a wide range of industries including travel and tour, transportation, accommodation, food and beverage, amusement, souvenirs etc. However, the existing cases did not show a breakdown of the impact on climate change. In this paper, the carbon footprint (CFP) of the Japanese tourism industry was calculated based on tourist consumption, using the Japanese Input-output table and the Japanese tourism industry. It was shown that the total emissions were approximately 136 million t-CO2 per year. The contribution ratio of each stage is as follows: Transport 56.3%, Souvenirs 23.2%, Petrol (direct emissions) 16.9%, Accommodation 9.8%, Food and Beverage 7.5%, Activities 3.0%. Then, in the breakdown, the impact is high in the following order Air transport 24.7%, Petrol (direct emissions) 16.9%,Accommodation 9.8%, Food and Beverage 7.5%, Petrol 6.1%, Textile products 5.3%, Food items 4.9%, Confectionery 4.8%, Rail transport 3.9%, Cosmetics 1.9%, Footwear 1.8%, etc. In addition to transportation, this research also highlighted especially the contribution from souvenirs, accommodation, food and beverages.

In this paper, a thermodynamic investigation is done on a Kalina-flash cycle. This work is initially validated with the Kalina cycle power plant, Wich is commissioned in Husavic. Low-temperature Kalina-flash is considered for this study. This cycle is working with the ammonia-water mixture. The Kalina-flash cycle was optimized in the view of exergy and thermal efficiency. A multi-objective genetic algorithm is used to accomplish optimization. The optimum values of the objective functions are observed to be 40.20 and 11.70% respectively. At last, The influence of the separator inlet dryness fraction, basic ammonia mass fraction, temperature and flash pressure ratio on the first and second law efficiencies are analysed.

Plant trichomes are specialized unicellular structures that originate and project from above ground epidermal tissues on the surfaces of leaves, petals, stems, petioles, peduncles, and seed coats depending on species. Trichomes (also called ‘hairs’) play well-recognized roles in defense against insect herbivores, both as a physical barrier that obstructs herbivore movement and by mediating chemical defenses. By virtue of their physical properties (size, density), trichome hairs can directly operate to protect buds of plants from insect damage, reduce leaf temperature, increase light reflectance, prevent water loss, and decrease leaf abrasion. Great variety of trichomes and their accessibility makes them a useful model for studying the molecular processes of cell fate determination, cell cycle control and cellular morphogenesis. In leaves, the developmental control of the trichomatous complement has highlighted a regulatory network based on four fundamental elements: (i) genes that activate and/or modify the normal cell cycle of epidermal cells (i.e. endoreduplication cycles); (ii) transcription factors that create activator/repressor complexes with a central role in determining cell fate, initiation and differentiation of an epidermal cell in trichome; (iii) evidences that point out the interplay of the aforesaid complexes with various phytohormones; (iv) epigenetic mechanisms involved in trichome development. Here, we describe trichome development in leaves, commonly subjected to environmental injury, and where most genetic regulators have been characterized.

In this paper we analyze the relationship between bankruptcy risk and the corporate life cycle in Pakistan from 2005 to 2014. For this purpose, we run a Hierarchical Linear Mixed Model (HLM) for a sample of 301 non-financial listed firms in 12 different sectors. The empirical outcomes reveal that firms during introduction, growth and, decline stages (mature stage) of life-cycle experience higher (lower) bankruptcy risk. Moreover, in juxtaposition with growth stage, bankruptcy risk is higher at the introduction stage of life-cycle. These findings suggest that financial managers should be cautious about the financial fragility of the firm at each stage of corporate life-cycle. The results also entail that Pakistani firms do not follow a sequential pattern in their life-cycle rather they have the tendency to revert to a previous stage or jump to the next stage of life-cycle. This is the first study that empirically examines the association between firm life-cycle stage and corresponding bankruptcy risk and asserts that managers must incorporate the life-cycle effects into their financial planning and decision making for sustainable working of an enterprise.

Natural gas combined cycle power plants (CCPPs) are widely used to meet peak loads in electric energy production. Continuous monitoring of the output electrical power of CCPPs is a requirement for power performance. In this study, the role of ambient temperature change having the greatest effect on electric production is investigated for a natural gas CCPP. The plant has generated electricity for fourteen years and setup at 240 MW in Aliağa, İzmir, Turkey. Depending on the seasonal temperature changes, the study data were obtained from each gas turbine (GT), steam turbine (ST) and combined cycle blocks (CCBs) in the ambient temperature range of 8-23°C. It has been found that decreases of the electric energy in the GTs because of the temperature increase and indirectly diminishes of the electricity production in the STs. As a result, the efficiency of each GT, ST and CCB reduced, although the quantity of fuel consumed by the controllers in the plant was decreased. As a result of this data, it has been recommended and applied that additional precautions have been taken for the power plant to bring the air entering the combustion chamber to ideal conditions and necessary air cooling systems have been installed.

The attention to sustainable-related issues has grown fast in recent decades. The experience gained with these themes reveals the importance of considering this topic in the construction industry, which represents an important sector in the world. This work consists on conducting a multicriteria analysis of four cement powders, with the objective of calculating and analysing the environmental, human health and socio-economic effects of their production processes. The economic, technical, environmental and safety performances of the examined powders result from official, both internal and public, documents prepared by the producers. The Analytic Hierarchy Process permitted to consider several indicators (i.e. environmental, human health related and socio-economic parameters) and to conduct comprehensive and unbiased analyses which gave the best, most sustainable cement powder. As assumed in this study, the contribution of each considered parameter to the overall sustainability has a different incidence, therefore the procedure could be used to support on-going sustainability efforts under different conditions. The results also prove that it is incorrect to consider only one parameter to select the ‘best’ cement powder, but several impact categories should be considered and analysed if there is an interest for pursuing different, often conflicting interests.

This paper proposes that intelligent processes can be completely explained by thermodynamic principles. They can equally be described by information-theoretic principles that, from the standpoint of the required optimizations, are functionally equivalent. The underlying theory arises from two axioms regarding distinguishability and causality. Their consequence is a theory of computation that applies to the only two kinds of physical processes possible—those that reconstruct the past and those that control the future. Dissipative physical processes fall into the first class, whereas intelligent ones comprise the second. The first kind of process is exothermic and the latter is endothermic. Similarly, the first process dumps entropy and energy to its environment, whereas the second reduces entropy while requiring energy to operate. It is shown that high intelligence efficiency and high energy efficiency are synonymous. The theory suggests the usefulness of developing a new computing paradigm called Thermodynamic Computing to engineer intelligent processes. The described engineering formalism for the design of thermodynamic computers is a hybrid combination of information theory and thermodynamics. Elements of the engineering formalism are introduced in the reverse-engineer of a cortical neuron. The cortical neuron provides perhaps the simplest and most insightful example of a thermodynamic computer possible. It can be seen as a basic building block for constructing more intelligent thermodynamic circuits.

In this paper, a method of charging lead acid battery with solar power by flyback converter is proposed. The basic system consists of a buffer circuit, auxiliary power circuit, control circuit, voltage feedback circuit and current feedback circuit. The system is capable of monitoring battery voltage and the current, charging the coupling inductor and automatic control of output duty cycle, overcharging and over-discharging protection. The experiment proves that the charging efficiency is improved by about 83% at full load.

Background. Currently, most of the research in breast cancer has been carried out in conventional two-dimensional (2D) cell culture due to its practical benefits, however, the three-dimensional (3D) cell culture is becoming the model of choice in cancer research because it allows cell-cell and cell-extracellular matrix (ECM) interactions, mimicking the native microenvironment of tumors in vivo. Methods. in this work, we evaluated the effect of 3D cell organization on the expression pattern of miRNAs (by Small-RNAseq) and mRNAs (by microarrays) in the breast cancer SKBR3 cell line and analyzed the biological processes and signaling pathways regulated by the differ-entially expressed protein-coding genes (DE-mRNAs) and miRNAs (DE-microRNAs) found in the organoids. Results. We obtained well-defined cell-aggregated organoids with a grape cluster-like morphology with a size up to 9.2×105 μm3. The transcriptomic assays showed that cell growth in organoids significantly affected (all p < 0.01) the gene expression patterns of both, miRNAs and mRNAs, finding 20 upregulated and 19 downregulated DE-microRNAs, as well as 49 upregulated and 123 downregulated DE-mRNAs. In silico analysis showed that a subset of 11 upregulated DE-microRNAs target 70 downregulated DE-mRNAs. These genes are involved in 150 gene on-tology (GO) biological processes such as regulation of cell morphogenesis, regulation of cell shape, regulation of canonical Wnt signaling pathway, morphogenesis of epithelium, regulation of cy-toskeleton organization, as well as in the MAPK and AGE-RAGE signaling KEGG-pathways. In-terestingly, hsa-mir-122-5p (Fold Change (FC)=15.4), hsa-mir-369-3p (FC=11.4), and hsa-mir-10b-5p (FC=20.1) regulated up to the 81 % of the 70 downregulated DE-mRNAs. Conclu-sion, the organotypic 3D cell-organization architecture of breast cancer SKBR3 cells impacts the expression pattern of miRNAs-mRNAs network mainly through overexpression of hsa-mir-122-5p, hsa-mir-369-3p, and hsa-mir-10b-5p. All these findings suggest that the interaction between cell-cell and cell-ECM as well as the change in the culture architecture impacts gene ex-pression, and therefore, support the pertinence of migrating breast cancer research from conven-tional cultures to 3D models.

Solar power innately has issues with weather, grid demand and time of day, which for the case of concentrating solar power (CSP) can be mitigated through use of thermal energy storage. Nuclear reactors, including lead-cooled fast reactors (LFRs), can load follow, but have high fixed and low operating costs which can make this economically unattractive. We investigate potential synergies through coupling CSP and LFR together in a single supercritical CO$_2$ Brayton cycle and/or using the same thermal energy storage. Combining these cycles allows for the LFR to thermally charge the salt storage in the CSP cycle during low demand periods to be dispatched when grid demand increases. The LFR/CSP coupling into one cycle is modeled to find the preferred location of the LFR heat exchanger, CSP heat exchanger, sCO$_2$-to-salt heat exchanger (C2S), turbines, and recuperators within the supercritical CO$_2$ Brayton cycle. Three cycle configurations have been studied: two-cycle configuration, which uses CSP and LFR heat for dedicated turbocompressors, has the highest efficiencies but with less component synergies; a combined cycle with CSP and LFR heat sources in parallel is the simplest with the lowest efficiencies; and a combined cycle with separate high temperature recuperators for both the CSP and LFR is a compromise between efficiency and component synergies. Additionally, four thermal energy storage charging techniques are studied: the turbine positioned before C2S, requiring a high LFR outlet temperature for viability; the turbine after the C2S, reducing turbine inlet temperature and therefore power; the turbine parallel to the C2S producing moderate efficiency; and a dedicated circulator loop. While all configurations have pros and cons, use of a single cycle offers component synergies with limited efficiency penalty. Using a turbine in parallel with the C2S heat exchanger is feasible but results in a low charging efficiency, while a dedicated circulator loop offers flexibility and near perfect heat storage efficiency but increasing cost with additional cycle components.

Despite the remarkable success of Carnot’s heat engine cycle in founding the discipline of thermodynamics two centuries ago, false viewpoints of his use of the caloric theory in the cycle still linger, limiting his legacy. An action revision of the Carnot cycle can correct this, showing that the heat flow powering external mechanical work is compensated internally with configurational changes in the thermodynamic or Gibbs potential of the working fluid, differing in each stage of the cycle quantified by Carnot as caloric. Action (@) is a property of state having the same physical dimensions as angular momentum (mrv=mr2ω). However, this property is scalar rather than vectorial, including a dimensionless phase angle (@=mr2ωδφ). We have recently confirmed with atmospheric gases that their entropy is a logarithmic function of the relative vibrational, rotational and translational action ratios with Planck’s quantum of action ħ. The Carnot principle shows that the maximum rate of work (puissance motrice) possible from the reversible cycle is controlled by the difference in temperature of the hot source and the cold sink, the colder the better. This temperature difference between the source and the sink also controls the isothermal variations of the Gibbs potential of the working fluid, that Carnot identified as reversible temperature-dependent but unequal exchanges in caloric. Importantly, the engine’s inertia ensures that heat from work performed adiabatically in the expansion phase is all restored to the working fluid during the adiabatic recompression, less the net work performed. This allows both the energy and the thermodynamic potential to return to the same values at the beginning of each cycle, a point strongly emphasized by Carnot. Our action revision equates Carnot’s calorique, or the non-sensible heat later described by Clausius as ‘work-heat’ exclusively to negative Gibbs energy (-G) or quantum field energy. This action field complements the sensible energy or vis-viva heat as molecular kinetic motion and its recognition should have significance for designing more efficient heat engines or better understanding of the heat engine powering the Earth’s climates.

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

This study investigates the microbial composition of a commercially available Swiss fermented milk and colostrum product with a history of use in chronic condition management since 2014. The analysis, performed using the Axiom Microbiome Array, identified a high number of targets corresponding to microbial species classified as probiotics belonging to the Bifidobacteriaceae family. The array provided 28 unique targets, each corresponding to a specific microbe. Next, the amino acid sequences of beta-galactosidase and sialidase from Bifidobacteria and humans were studied because these enzymes are responsible for the production of GcMAF (Gc protein-derived Macrophage Activating Factor) from the Gc protein that is abundant in colostrum. The Bifidobacterial enzymes showed striking functional similarities with their human counterparts. In addition, the study explores the potential health benefits of this product with a focus on GcMAF and chondroitin sulfate, a glycosaminoglycan highly represented in milk and colostrum. The high concentration of specific Bifidobacteria strains contributes to these benefits through two mechanisms: enhanced GcMAF production and activation of chondroitin sulfate, which in turn exhibits GcMAF-like activity. These findings suggest that the Bifidobacteria-rich Swiss product could offer health benefits through these combined mechanisms.

This study introduces the MuhdoAge clock, a novel saliva-based epigenetic clock, designed to predict biological age with strong correlations in a healthy, disease-free cohort. Leveraging a comprehensive dataset from Muhdo Health, this research analyses saliva samples utilising the Illumina MethylationEPIC array. Through robust statistical methods, 237 significant CpG sites were identified that correlate with age-related methylation changes, exhibiting a coefficient of determination (R²) of 0.652 after outlier removal, with tiered algorithmic design improving this further to 0.726 in a new dataset that combined pathologic and healthy individuals (n=2682). Comparatively, the MuhdoAge clock was evaluated against other known epigenetic clocks, demonstrating high precision in predicting biological age within healthy individuals (R² = 0.878, n=1844), emphasising its potential utility in non-invasive, large-scale applications. The clock shows promise for integration into public health strategies for monitoring and potentially mitigating age-related decline, facilitated by its ease of use and accessibility through saliva sampling. Furthermore, this study highlights the impact of lifestyle and environmental factors on biological ageing, highlighting the importance of personalised health interventions. Future research is to focus on longitudinal studies to validate these findings and explore the mechanisms underlying epigenetic age acceleration.

East Lake in Wuhan, China, harbors a high number of freshwater fish species of great conservation value, concurrently serving as vital resources for local livelihoods. However, the ecosystem is threatened by an array of anthropogenic activities, thus requiring consistent monitoring of the local fish community to enable more efficacious conservation management. In place of conventional surveying methods, we undertook the first analysis of the fish distribution within East Lake via metabarcoding of environmental DNA (eDNA). The accuracy and efficacy of eDNA metabarcoding relies heavily upon selecting an appropriate primer set for PCR amplification. Given the varying environmental conditions and taxonomic diversity across distinct study systems, it remains a challenge to propose an optimal genetic marker for universal use. Thus, it becomes necessary to select PCR primers suitable for the composition of fish in the East Lake. Here, we evaluated the performance of two primer sets, Mifish-U and Metafish, designed to amplify 12S rRNA barcoding genes in fishes. Our results detected a total of 116 taxonomic units and 51 fish species, with beta diversity analysis indicating significant differences in community structure diversity between the 6 sampling locations encompassing East Lake. While it was difficult to accurately compare the species-level discriminatory power and amplification bias of the two primers, Mifish outperformed Metafish in terms of taxonomic specificity for fish taxa and reproducibility. These findings will assist with primer selection for eDNA-based fish monitoring and biodiversity conservation in the East Lake and other freshwater ecosystems.

Autism spectrum disorder (ASD) is a common condition with lifelong implications. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV) additionally were in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes (P=0.0002), validating that most are indeed disease related. Sequence reanalysis increased diagnostic yield from 28% to 68%, mostly by inclusion of de novo PDVs in genes not yet reported as ASD associated. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate high yield of trio-WGS for revealing molecular diagnoses in ASD that is greatly enhanced by re-analyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.

Telomeres are specialized structures at the ends of linear chromosomes that protect them from degradation and fusion. Telomere replication is a complex process that involves both DNA polymerases and a specialized enzyme called telomerase. Telomerase is a ribonucleoprotein complex that synthesizes telomeric DNA by using an internal RNA template. However, telomerase alone cannot fully replicate the telomeric DNA, and requires the cooperation of other factors, such as shelterin, CST, and DNA repair proteins. Moreover, telomere replication is tightly regulated by various mechanisms, such as cell cycle checkpoints, telomere length homeostasis, and telomere position effect. Dysregulation of telomere replication can lead to genomic instability, cellular senescence, and cancer. Therefore, understanding the molecular details of telomere replication is crucial for elucidating the role of telomeres in aging and disease.

Epigenetic changes are changes in gene expression that do not involve alterations to the basic DNA sequence. These changes lead to establishing a so-called epigenetic code that dictates which and when genes are activated, thus orchestrating gene regulation and playing a central role in development, health, and disease. The brain, being for the most formed by cells that do not undergo a renewal process through life, is highly prone to the risk of alterations leading to neuronal death and neurodegenerative disorders, mainly at late age. Here we review the main epigenetic modifications that have been described in the brain, with particular attention to those related to the onset of developmental anomalies or neurodegenerative conditions and/or occurring in old age. DNA methylation and several types of histone modifications (acetylation, methylation, phosphorylation, ubiquitination, sumoylation, lactylation, and crotonylation) are major players in these processes. They are directly or indirectly involved in the onset of neurodegeneration in Alzheimer’s or Parkinson’s disease. Therefore, this review briefly describes the role of these epigenetic changes in the mechanisms of brain development, maturation, and aging and some of the most important factors dynamically regulating or contributing to these changes such as oxidative stress, inflammation, and mitochondrial dysfunction.

A Bacille Calmette-Guérin (BCG) is still the only licensed vaccine for the prevention of tuberculosis, providing limited protection against Mycobacterium tuberculosis infection in adulthood. New advances in delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-days intervals. We demonstrated that intramuscular electroporated DNA-hsp65 vaccine immunization of cynomolgus macaques was safe, and there were no vaccine-related effects on hematological, renal, or hepatic profiles, compared to the pre-vaccination parameters. No tuberculin skin test conversion nor lung X-ray alteration was identified. Further, low, and transient peripheral cellular immune response and cytokine expression were observed, primarily after the third dose of the DNA-hsp65 vaccine. Electroporated DNA-hsp65 vaccination is safe but provided limited enhancement of peripheral cellular immune responses. Preclinical vaccine trials with DNA-hsp65 delivered via EP may include a combination of plasmid cytokine adjuvant and/or protein prime-boost regimen, to help the induction of a stronger cellular immune response.

Autism spectrum disorder (ASD) is a common condition with lifelong implications and a strong hereditary component suggesting genetic underpinnings. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV) additionally were in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes not associated with ASD (P = 0.0002, odds ratio 29), validating that most are indeed disease related. Only 14/34 (41%) of PDV cases had the variant listed on the laboratory report, and reanalysis increased diagnostic yield from 28% to 68%. Variants that we assigned as PDVs yet not on the report were predominately de novo in genes not yet reported as ASD associated. Many subjects both with and without a PDV had inherited Qualifying variants in known ASD-associated genes, suggesting polygenic inheritance. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate high yield of trio-WGS for revealing molecular diagnoses in ASD that is greatly enhanced by re-analyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.

cGAS is a cytosolic DNA sensor that activates innate immune responses through production of the second messenger 2’3’-cGAMP, which activates the adaptor STING. cGAS senses dsDNA in a length-dependent but sequence-independent manner, and it cannot discriminate self-DNA from foreign DNA. In normal physiological conditions, cellular DNA is sequestered in the nucleus by nuclear envelope and in mitochondria by mitochondrial membrane. When self-DNA leaks into the cytosol during cellular stress, or during mitosis, the cGAS can be exposed to self-DNA and be activated. Recently, many studies have investigated how cGAS keeps inactive and avoids to be aberrantly activated by self-DNA. Thus, the aim of this narrative review is to summarize the mechanisms by which cGAS avoids to sense self-DNA under normal physiological conditions.

Currently available DNA detection techniques frequently require compromises between simplicity, speed, accuracy, and cost. Here, we propose a simple, label-free and cost-effective DNA detection platform developed at screen printed carbon electrodes (SPCEs) modified with reduced graphene oxide (RGO) and gold nanoparticles (AuNPs). The preparation of the detection platform involved a two-step electrochemical procedure based on GO reduction onto SPCEs followed by the electrochemical reduction of HAuCl4 to facilitate the post-grafting reaction with AuNPs. The final sensor was fabricated by the simple physical adsorption of a single-stranded DNA (ssDNA) probe onto AuNPs-RGO/SPCE electrode. Each preparation step was confirmed by morphological and structural characterization using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy, respectively. Furthermore, the electrochemical properties of the modified electrodes have been investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The results demonstrated that the introduction of AuNPs onto RGO/SPCEs led to an enhancement in surface conductivity, characteristic that favored an increased sensitivity in detection. The detection process relied on the change in the electrochemical signal induced by the binding of target DNA to the bioreceptor, and was monitored particularly by the change in the charge transfer resistance of a [Fe(CN)6]4−/3− redox couple added in the test solution.

The Botryosphaeriales order are best known for the diseases they cause in woody plants, as primary pathogens or latent pathogens residing in the woody tissue of asymptomatic hosts. In the first instance, Botryosphaeriales species have been identified in Venezuela using morphological de-scriptions in the 80's and 90's, and later, the mid-2000s using molecular techniques. The mor-phological descriptions of the asexual morphs were initially used for the identification of Botry-osphaeriales genera and species. Lasiodiplodia spp., (as L. theobromae) was the most isolated fungus in Venezuela within the Botryosphaeriales and has been found in more than 50% of the hosts in native and non-native plants, followed by Diplodia, Dothiorella, Fusicoccum, Lasiodiplodia, Micro-diplodia, Macrophomina, Neofusicoccum, Sphaeropsis, and Botryosphaeria, considered all of them cosmopolitan group. With molecular studies, that included DNA sequence data from multiple genes, such as the internal transcribed spacer of rDNA (ITS), translation elongation factor-1α (tef1), and β-tubulin (btub) used on the fungi isolated from woody plants, mainly trees or forest species, resulted in the presence of two families within the Botryosphaeriales order for Venezuela. Botryosphaeriaceae family with the genera: Botryosphaeria, Cophinforma, Diplodia, Lasiodiplodia and Neofusicoccum, and the Pseudofusicoccumaceae family that includes the genus Pseudofusicoccum. In Botryosphaeriaceae family was again the Lasiodiplodia genus the most predominant in most hosts, and the specie L. theobromae the most isolated in native and non-native plants; Botryosphaeria dothidea, Cophinforma atrovirens, Diplodia scrobiculata (syn. Diplodia guayanensis), Lasiodiplodia brasi-liensis, L. crassispora, L. pseudotheobromae, Neofusicoccum arbuti (syn. N. andinum), N. parvum, and N. ribis are cosmopolitan species, and they were isolated from native and non-native plants; while Pseudofusicoccum stromaticum was found in plantations non-native of Acacia mangium, E. urophylla x E. grandis, Eucalyptus urophylla, and reported exclusively in South America; Lasiodiplodia venezue-lensis has only been reported in Venezuela, from native and non-native plants. The presence, distribution, diversity, and symptoms of these fungi, mainly of the new genus, new species, and reports found in Venezuela and other parts of the world, were also reviewed.

DNA markers have high occurrence and mutation rates and are generally located around the controlling regions of some tissue-specific genes and housekeeping genes that can change the expression pattern. Microsatellites and CpG islands are stretches of DNA with repeats and are known to influence gene expression. Microsatellites are more prone to mutations than the rest of the genomic DNA which allows the straightforward genomic nucleotide evolutionary transformation rate in different species. In the present study, these DNA markers are mined and an in-silico comparison was carried out to understand their occurrence pattern and distribution frequency in sex chromosomes (X and Y) of 12 different animal species using Perl and R programming pipelines. It was found that female-dominant X chromosomes had higher occurrence and distribution frequencies for these DNA markers than that of male-dominant sex chromosome i.e. Y which means that the former has a higher number of the evolutionary sites. The density of DNA markers however, showed remarkable variation for different animal species The results obtained need validation through wet-lab experimentation. Tri- and hexa-nucleotide repeats are more abundant in exons, whereas other repeats are more abundant in non-coding regions.

More than 50% of patients with non-small cell lung cancer (NSCLC) are treated with radiotherapy (RT) during different phases of treatment. However, radiation pneu-monitis (RP) and resistance often lead to RT failure in NSCLC patients. JWA, a tumor suppressor gene, is known to enhance DNA damage in gastric cancer cells while protect normal cells from DNA damage induced by cisplatin. Recently, we have re-ported that JWA agonist compound 4 (JAC4) effectively protects intestinal epithelium from RT triggered damage in mice. However, the potential synergistic and attenuated effects of JAC4 in chest RT of lung cancer are not been illuminated. The aim of this study was to investigate the effects of JAC4 on the radiotoxicities of both NSCLC and normal lung tissue. CCK-8 and colony formation assays showed that JAC4 played a bidirectional role in radiation-treated SPCA-1 and BEAS-2B cells. Western blotting and immunofluorescence assays showed that JAC4 in combination with RT increased DNA damage and apoptosis in SPCA-1 cells, while the opposite effect was observed in BEAS-2B cells. Mechanistically, JAC4 inhibited homologous recombination repair (HR) and non-homologous end joining (NHEJ) in SPCA-1 cells, but not in normal cells. JAC4 increased antioxidant capacity, and reduced oxidative stress and inhibited nu-clear factor Kappa-B (NF-κB, P65) translocation to the nucleus in BEAS-2B cells. Im-portantly, the bidirectional roles of JAC4 on RT were reversed by siJWA in both SPCA-1 and BEAS-2B cells. Finally, the bidirectional effects of JAC4 in combination with RT were further validated in NSCLC xenograft model mice. In conclusion, JAC4 enhanced effect of RT on tumor growth while alleviated RP and lung injury. Our re-sults may provide new strategy for optimizing RT regimen for NSCLC.

Different types of disasters, whether natural or human character, lead to the significant loss of human lives. In the latter case, the quick action of identification of corpses and human remains is mandatory. There are a variety of protocols to identify victims, however, genetics is one of the tools that allow an exact identification of the victim. However, several factors may interfere with this identification, from the biological samples’ degradation not allowing the analysis of nuclear information, to failure to dispose of biological samples from family members. Access to certain family members could be a determinant of the proper choice of genetic markers that allow the identification of the victim, or his/her inclusion in a given genetic maternal or paternal lineage. With the new advances in the genetic field, it is expected to allow soon the identification of victims from disasters only with his/her biological postmortem samples, being possible to draw a robot portrait and its most likely physical characteristics. In all cases, genetics is the only modern tool with universal character and can be used in essentially all biological samples, giving and identification of more or less accurate statistical character, depending on whether nuclear or lineage markers are used.

Understanding epigenome paths through which smoking contributes to cardiometabolic traits is important for downstream applications. In this study, I used a SNP-based analytical pipeline to integrate several publicly available datasets and identify CpG sites that mediate the impact of smoking on cardiometabolic traits. After applying stringent statistical criteria, 11 CpG sites were detected that showed significant association (P<5e-8) with cardiometabolic traits at both discovery and replication stage. By integrating eQTL data, I identified genes behind a number of these associations. cg05228408 was hypomethylated in smokers and contributed to higher blood pressure by lowering the expression of CLCN6 gene. cg08639339 was hypermethylated in smokers and lowered metabolic rate by increasing the expression of RAB29; furthermore, I noted TMEM120A mediated the impact of smoking-cg17325771 on LDL, and LTBP3 mediated the smoking-cg07029024 effect on heart rate. This study provides a list of CpG sites that mediates the impact of smoking on cardiometabolic traits and a framework to investigate epigenome path through which a lifestyle habit modifies disease risks.

The purpose of this study is to provide an accurate formula for calculating entropy for short DNA sequences and to demonstrate how to use it to examine leukemia patient surviving. We used IDIBAPS leukemia patient’s data base with 117 anonymized records. The generalized form of the Robust Entropy Estimator (EnRE) for short DNA sequences was proposed and key EnRE futures was showed. The Survival Analysis has been done using statistical package IBM SPSS. Entropy EnRE were calculated for leukemia patients for two samples: A. 2 groups divided by median EnRE and B. 2 groups of patients were formed according to their belonging to 1st and 4th quartiles of EnRE. The result of survival analysis are statistically significant: A. p &lt; 0.05; B. p &lt; 0.005. The death hazard for a patient with EnRE below median is 1.556 times that of a patient with EnRE over median and that the death hazard for a patient of 1st quartile (lowest EnRE) is 2.143 times that of a patient of 4th quartile (highest EnRE). The transition from median to quartile patients’ groups with more EnRE differentiation confirmed the unique significance of the entropy of DNA sequences for leukemia patients surviving.

Reliable species identification is critical for detection and monitoring of biological invasions. In this study, we propose four sets of primers for efficient amplification of several loci, including the mitochondrial cytochrome oxidase-c (COI) subunit I gene which is a basis for DNA barcoding. This set of primers gives a shorter product which can be used in high-throughput sequencing systems for metabarcoding purposes. Another mitochondrial locus encoding the large ribosomal subunit (16S) may be useful to study the population structure and as an additional source of information in the metabarcoding of communities. We propose to use a set of primers for the nuclear locus of the small ribosomal subunit (18S) as a positive control and to verify the results of the barcoding. Our proposed sets of primers demonstrate a high amplification efficiency and a high specificity both for freshwater alien and indigenous fishes. The proposed research design makes it possible to carry out extremely cheap studies on the assessment of biological diversity using genetic analysis without expensive equipment, and with the technique for conducting laboratory work and processing of the results available to any researcher. The paper also presents original data on the genetic polymorphism of all mass alien fish species in the Volga-Kama region. High efficiency of DNA identification based on our primers is shown as compared to traditional monitoring of biological invasions.

Pancreatic cancer is the third leading cause of cancer-related deaths in the United States. Pancreatic ductal adenocarcinoma (PDA) is the most common (90%) and aggressive type of pancreatic cancer. Genomic analyses of PDA specimens have identified the recurrent genetic mutations that drive PDA initiation and progression. However, the underlying mechanisms that further drive PDA metastasis remain elusive. Despite many attempts, no recurrent genetic mutation driving PDA metastasis has been found, suggesting that PDA metastasis is driven by epigenetic fluctuations rather than genetic factors. Therefore, establishing epigenetic mechanisms of PDA metastasis would facilitate the development of successful therapeutic interventions. In this review, we provide a comprehensive overview on the role of epigenetic mechanisms in PDA as a critical contributor on PDA progression and metastasis. In particular, we explore the recent advancements elucidating the role of nucleosome remodeling, histone modification, and DNA methylation in the process of cancer metastasis.

Proteins and DNA exhibit key physical chemical properties that make them advantageous for building nanostructures with outstanding features. Both DNA and protein nanotechnology have growth notably and proved to be fertile disciplines. The combination of both types of nanotechnologies is helpful to overcome the individual weaknesses and limitations of each one, paving the way for the continuing diversification of the structural nanotechnologies. Recent studies have implemented a synergistic combination of both biomolecules to assemble unique and sophisticate protein-DNA nanostructures. These hybrid nanostructures are highly programmable and display remarkable features that create new opportunities to build in the nanoscale. This review focuses on the strategies deployed to create hybrid protein-DNA nanostructures. Here, we will discuss strategies such as polymerization, spatial directing and organizing, coating, rigidizing or folding DNA into particular shapes or moving parts. The enrichment of structural DNA nanotechnology by incorporating protein nanotechnology has been clearly demonstrated and still shows a large potential to create useful and advanced materials with cell-like properties or dynamic systems. It can be expected that structural protein-DNA nanotechnology will open new avenues in the fabrication of nano-assemblies with unique functional applications and enrich the toolbox of bionanotechnology.

Non-homologous end-joining (NHEJ) is a major DNA repair pathway in mammalian cells that recognizes, processes and fixes DNA damages throughout the cell cycle, and is specifically important for homeostasis of post-mitotic neurons and developing lymphocytes. Neuronal apoptosis increases in the mice lacking NHEJ factors Ku70 and Ku80. Inactivation of other NHEJ genes, either Xrcc4 or Lig4, leads to massive neuronal apoptosis in the central nervous system (CNS) that correlates with embryonic lethality in mice. Inactivation of either Paxx, Mri or Dna-pkcs NHEJ gene results in normal CNS development due to compensatory effects of Xlf. Combined inactivation of Xlf/Paxx, Xlf/Mri and Xlf/Dna-pkcs, however, results in late embryonic lethality and high levels of apoptosis in CNS. To determine the impact of NHEJ factors on early stages of neurodevelopment, we isolated neural stem and progenitor cells from mouse embryos and investigated proliferation, self-renewal and differentiation capacity of these cells lacking either Xlf, Paxx, Dna-pkcs, Xlf/Paxx or Xlf/Dna-pkcs. We found that XLF, DNA-PKcs and PAXX maintain the neural stem and progenitor cell populations and neurodevelopment in mammals, which is particularly evident in the double knockout models.

The world has now entered into a replacement era of genomics due to the continued advancements within the next generation high throughput sequencing technologies, which incorporates sequencing by synthesis-fluorescent in place sequencing (FISSEQ), pyrosequencing, sequencing by ligation using polony amplification, supported oligonucleotide detection (SOLiD), sequencing by hybridization alongside sequencing by ligation, and nanopore technology. Great impacts of those methods are often seen for solving the genome related problems of plant and Animalia which will open the door of a replacement era of genomics. This might ultimately overcome the Sanger sequencing that ruled for 30 years. NGS is predicted to advance and make the drug discovery process more rapid.

By introducing a suitable renormalization process the charge carrier and phonon dynamics of a double-stranded helical DNA molecule is expressed in terms of an effective Hamitonian describing a linear chain, where the renormalized transfer integrals explicitly depend on the relative orientations of the Watson-Crick base pairs, and the renormalized on-site energies are related to the electronic parameters of consecutive base pairs along the helix axis, as well as to the low-frequency phonons dispersion relation. The existence of synchronized collective oscillations enhancing the π-π orbital overlapping among different base pairs is disclosed from the study of the obtained analytical dynamical equations. The role of these phonon-correlated, long-range oscillation effects on the charge transfer properties of double standed DNA homopolymers is discussed in terms of the resulting band structure.

DNA sequencing methods were first developed more than 20 years ago with the publication of two approaches to sequencing methodology that became known as Sanger sequencing (1), based on enzymatic synthesis from a single-stranded DNA template with chain termination using dideoxynucleotides (ddNTPs) and Maxim-Gilbert sequencing (2),which involved chemical degradation ofend-radio-labeled DNA fragments. Both methods relied on four-lane,high resolution polyacrylamide gel electrophoresis to separate the labeled fragment and allow the base sequence to be read in a staggered ladder-like fashion. Sanger sequencing was technically easier and faster, and thus became the main DNA sequencing method for the vast majority of applications.

For its microtubule-binding properties, the expression level of the neurodegeneration-associated protein Tau is pondered as a potential modifier of cancer resistance to chemotherapy since decades. Indeed, Tau binds microtubules at the same site as taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network in order to stall cell division and to induce tumor cell death. Whilst independent studies report the association between low Tau expression and superior taxane response, the data were refused by a meta-analysis, suggesting interference of other parameters. Unpredictably, Tau expression level was identified as a prognostic cancer marker, whereby its positive or negative predictive value for survival depended on the cancer type. With recent experimental evidence linking Tau to P53 signaling, DNA stability and protection and to the implication of Tau in cancer is strengthened. The identification of a role of Tau at the interface between two major aging-related disorder families, neurodegeneration and cancer, offers clues for the epidemiological observation inversely correlating these disorders. Elucidating how Tau is mechanistically implicated in cellular pathways common to these devastating illnesses may extend the Tau-targeting therapeutic opportunities to cancer.

Herein, we describe a highly efficient, non-complicated, and non-organic procedure to overcome the negative effect of chemotherapeutic drugs on the quality of the extracted DNA by applying several modulations in cell washing, suspension, and lysis of cells treated with these drugs. In this protocol, 500µl were extracted from patients who received systemic sessions of chemotherapy. The validity of this protocol for digestion with restriction endonucleases and both conventional and real-time polymerase chain reaction were tested. This protocol proved obvious purity (1.8±0.02 and 2.1±1.2, for A_260/280 and A_260/230, respectively) and adequate yields (10±2.24) µg/100 ml. The positive results of validation experiments proved the validity of the extracted DNA for downstream applications of molecular biology. In addition to the proven efficiency of this protocol to extract DNA from normal samples, its validity was also confirmed from patients who were exposed to chemotherapy. This entails a novel approach to extract a molecular biology grade DNA without having inhibitors against enzymes used in digestion, amplification, and subsequent sequencing even after the systemic sessions with several doses of chemotherapy.

Introduction: The tumour suppressor protein p53 commonly referred to as guardian of the genome plays important role in preserving the genome through the regulation of programmed cell death, DNA repair, energy metabolism, cell cycle entry or exit and senescence. Mutations in p53 can either result to a loss of tumour suppressor function or gain of oncogenic properties. Hence, mutations in p53 are the most frequent genetic mutational alteration in human cancers, associated with worse prognosis and more aggressive disease outcome. Methods: To assess the mutational hotspots and conserved regions of p53, I analyzed 76 complete p53 protein sequences covering whole exons from the NCBI GenBank database. Multiple sequence alignment (MSA) was done using ClustalX version 2.1. Results: Thirty-five (19) mutations were identified with more frequent mutations in amino acid (aa) position 72 and 79 (Exon 4), amino acid deletion in codon 112-122 (Exon 4), codon 213 (Exon 6), codon 248 (Exon 7), codon 273 (Exon 8) and codon 278 (Exon 8). Mutations at amino acid position 79, 248, 278 located in the DNA-binding domain exhibited more than one alteration in same position. Conclusions: Findings from this study revealed the prevalence of mutations in the DNA binding domain of p53 and the structure-function effect of the mutations. Assessing the pattern and frequency of p53 alterations, and analyzing it thoroughly for each carrier, could help in identifying correlations between p53 status and outcome and possible candidate for gene therapy.

Chan and colleagues in their paper titled “Human origins in a southern African palaeo-wetland and first migrations” (https://www.nature.com/articles/s41586-019-1714-1) report 198 novel whole mitochondrial DNA (mtDNA) sequences and infer that ‘anatomically modern humans’ originated in the Makgadikgadi–Okavango palaeo-wetland of southern Africa around 200 thousand years ago. This claim relies on weakly informative data. In addition to flawed logic and questionable assumptions, the authors surprisingly disregard recent evidence and debate on human origins in Africa. As a result, the emphatic and high profile conclusions of the paper are unjustified.

The use of circulating cell-free (cf) DNA to monitor cancer progression and response to therapy has significant potential but there is only limited data on whether this technique can detect the presence of low frequency subclones that may ultimately confer therapy resistance. In this study, we sought to evaluate whether whole-exome sequencing of cfDNA can accurately profile the mutation landscape of metastatic melanoma. We used whole-exome sequencing (WES) to identify variants in matched tumor-derived genomic (g) DNA and plasma-derived cfDNA isolated from a cohort of 10 metastatic cutaneous melanoma patients. WES parameters such as sequencing coverage and total sequencing reads were comparable between gDNA and cfDNA. There was significant concordance between gDNA and cfDNA based on the total number of variants identified and the degree of overlap in variants which was independent of the site of tumor biopsy. The mutant allele frequency of common single nucleotide variants was lower in cfDNA reflecting lower read depth and dilution of circulating tumor DNA in the circulation by other cfDNA species. In addition to known melanoma driver mutations, several other melanoma-associated mutations were found to be concordant between matched gDNA and cfDNA. This study highlights that WES of cfDNA can capture clinically-relevant mutations present in melanoma metastases, but does not appear to provide any additional unique information on tumor heterogeneity. Targeted deep sequencing may be required to detect low frequency genomic aberrations known for predicting therapy resistance.

Here we describe ARSA-16S, a tool and accompanying reference database for the analysis of bacterial 16S amplicons. Among other features, ARSA-16S is based on a new model, approach, and algorithm for sequence-level assignment of reads understood as probability distributions, assigns reads individually, and is designed with non-overlapping amplicons covering two non-contiguous regions. A new set of primers for the amplification and sequencing of the V4 and V6 regions is also provided.

Current understanding of mechanisms of cellular resistance to genotoxic stress is incomplete but is critical for a variety of medical applications. Recent developments in the CRISPR/Cas technologies open new opportunities for targeted interrogation of resistance genes and pathways. In the present work, we used nuclease dead Cas9 constructs to achieve targeted overexpression of endogenous genes encoding two essential subunits of DNA damage sensor complex, XPC and HR23B, in HEK293T cells. Both individual and simultaneous overexpression of the two genes was achieved and the effects on cellular resistance to ionizing radiation and paraquat was examined. Using the fluorometric microculture cytotoxicity assay, we showed that simultaneous, but not separate overexpression of the two genes lead to a 30% increase in survivability. Irradiated cells that overexpressed both XPC and HR23B genes showed higher clonogenic capacity and proliferation rate compared to the irradiated transfection control as revealed by the clonogenic survival assay. Modulation of the gene expression did not affect cell resistance to paraquat. In summary, our results demonstrate a high potential of CRISPR/dCas9-enabled multiplex overexpression of stress-response genes in functionally justified combinations, exemplified here by the XPC-HR23B complex, for achieving an enhanced cellular radioresistance.

Genetics plays an integral role in athletic performance and is increasingly becoming recognised as an important risk factor for injury. Ankle and knee injuries are the most common injuries sustained by soccer players. Often these injuries result in players missing training and matches, which can incur significant costs to clubs. This study aimed to identify genotypes associated with ankle and knee injuries in soccer players and how these impacted the number of matches played. 289 soccer players including 46 professional, 98 semi-professional and 145 amateur players were genetically tested. Ankle and knee injuries and the number of matches played were recorded during the 2014/15 season. Four genes were assessed in relation to injury. Genotypes found to be associated with injury included the TT genotype of the GDF5 gene, TT and CT genotypes of AMPD1 gene, TT genotype of COL5A1 and GG genotype of IGF2 gene. These genes were also associated with a decrease in the number of matches played.

Background Glioblastoma (GBM) is a poor prognosis malignant grade 4 glioma. After surgical resection, standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. The DC vaccination increased the amount of intratumoral-activated cytotoxic T lymphocytes and decreased the number of FoxP3-positive regulatory T cells. Based on these da-ta, we have developed a phase II protocol with the DC vaccine concomitant to standard RT-CT in patients undergoing surgery for GBM. Methods This is a single-arm, monocentric, phase II trial evaluating progression-free survival (PFS) and the safety of a DC vaccination integrated with standard therapy in resected GBM patients. The vaccine administration begins at the end of the RT-CT (Induction Phase) and is subsequently al-ternated with TMZ cycles (Maintenance Phase). The primary endpoints are PFS and safety. Among the secondary endpoints, are the in vitro and in vivo Immune response evaluations. Results By December 2022 , nine patients had been enrolled in the first step. Two patients progressed within three months after leukapheresis and none had experienced DC vaccine-related G3-4 tox-icity. Five patients had a positive DTH test against KLH. By June 2023. The median OS from leu-kapheresis was 23.1 months and 24.7 from surgery. Conclusions This combination therapy is well-tolerated, and we have achieved the two endpoints required for the first step. Therefore, the study will proceed to enroll the remaining 19 patients.

Biological parameters extracted from electrical signals from various body parts have been used for many years to analyze the human body and its behavior. In addition, electrical signals from cancer cell lines, normal cells, and viruses, among others, have been widely used for the detection of various diseases. Single-cell parameters such as cell and cytoplasmic conductivity, relaxation frequency, and membrane capacitance are important. There are many techniques available to characterize biomaterials, such as scanning tunneling microscopy (STM), nanotechnology, microstrip cavity resonance measurement, dielectric impedance measurement (DEPIM), etc. This article reviews the single cell isolation and sorting techniques, summarizes the common single cell operations such as impedance flow cytometry, cell electrical impedance, electrical impedance sensing, and summarizes the current single cell analysis techniques and their applications.