CCCTC-binding factor (CTCF) is a conserved transcription factor that performs diverse roles in transcriptional regulation and chromatin architecture. Cancer genome sequencing reveals diverse acquired mutations in CTCF, which we have shown, functions as a tumour suppressor gene. While CTCF is essential for embryonic development, little is known of its absolute requirement in somatic cells and the consequences of CTCF haploinsufficiency. We examined the consequences of CTCF depletion in immortalised human and mouse cells using shRNA knockdown and CRISPR/Cas9 genome editing and examined the growth and development of heterozygous Ctcf (Ctcf^+/-) mice. We also analysed the impact of CTCF haploinsufficiency by examining gene expression changes in CTCF-altered endometrial carcinoma. Knockdown and CRISPR/Cas9-mediated editing of CTCF reduced the cellular growth and colony-forming ability of K562 cells. CTCF knockdown also induced cell cycle arrest and a pro-survival response to apoptotic insult. However, in p53 shRNA-immortalised Ctcf^+/- MEFs we observed the opposite: increased cellular proliferation, colony formation, cell cycle progression and decreased survival after apoptotic insult compared to wild type MEFs. CRISPR/Cas9-mediated targeting in Ctcf^+/- MEFs revealed a predominance of in-frame microdeletions in Ctcf in surviving clones, however protein expression could not be ablated. Examination of CTCF mutations in endometrial cancers showed locus-specific alterations in gene expression due to CTCF haploinsufficiency, in concert with downregulation of tumour suppressor genes and upregulation of estrogen-responsive genes. Depletion of CTCF expression imparts a dramatic negative effect on normal cell function. However, CTCF haploinsufficiency can have growth-promoting effects consistent with known cancer hallmarks in the presence of additional genetic hits. Our results confirm the absolute requirement for CTCF expression in somatic cells and provide definitive evidence of CTCF’s role as a haploinsufficient tumour suppressor gene. CTCF genetic alterations in endometrial cancer indicate that gene dysregulation is a likely consequence of CTCF loss, contributing to, but not solely driving cancer growth.

Keywords: green spaces, NDVI, level of greenness, urban environment, Aktobe

The development of U.S. Army and NATO data link systems is introduced first, and then the development trend of future intelligent data link is summarized into integration, generalization, multifunctionality and high security. A unit-level combat system architecture based on the global combat cloud, which is capable of realizing the flexible scheduling of global combat resources and maximizing the overall combat effectiveness, is proposed. Intelligent data link is an important part of this solution, providing strong information support for future urban unit-level warfare.

Abstract: Rural digital governance is an inevitable requirement to improve the efficiency of rural governance, and is also an important means to realize the modernization of rural governance. In the context of the digital rural development strategy, the index measurement system of rural digital governance level is built around five key governance areas of "digital economy, digital ecology, digital culture, digital people's livelihood, and digital government affairs". The entropy weight Topsis model is used to measure and evaluate the level of rural digital governance in 31 provinces in China in 2021. The results show that there is a large gap in the level of digital governance in China's counties and villages, and the level of each region presents a decreasing spatial distribution from "east - middle - west". In terms of digital economy, the eastern region has a high score and good development, while the central and western regions have poor development. In terms of digital ecology, only the eastern region is higher than the national average; In terms of digital culture, only the central region is higher than the national average; In terms of digital livelihood and digital government, the central and eastern regions are slightly higher than the national average; The top three provinces in overall scores are Zhejiang, Guangdong and Jiangsu.

Flood disasters have become an annual occurrence along the East Coast of North Sumatra (ECNS) and Medan City. Numerous studies have examined the causal factors flood disasters in this area, such as changes in land use, drainage issues, and population growth, but the intensity of flood disasters continues to rise. In this research, we focused on evaluating the unexplored factors of land subsidence and rising sea levels in this region. Our investigation uses multi-sensor satellite data and field surveys to conduct an assessment of the rate of land subsidence and sea level rise and assess their implications on flood disasters. This study highlights the potential of multi-sensor satellite data as a primary resource for assessing flood disasters in coastal areas and densely populated large cities. Furthermore, we propose a solution to reduce the negative impact of flood disasters by by engaging local communities and environmental enthusiasts in mangrove reforestation along the coastline.

The creation of crop-type maps from satellite data has proven challenging, often impeded by a lack of accurate in-situ data. This paper aims to demonstrate a method for crop-type (ie. Maize, Wheat and Other) recognition based on Convolutional Neural Networks using a bottom-up approach. We trained the model with a highly accurate dataset of crowdsourced labelled street-level imagery. Classification results achieved an AUC of 0.87 for wheat, 0.85 for maize and 0.73 for other. Given that wheat and maize are the two most common food crops globally, combined with an ever-increasing amount of available street-level imagery, this approach could help address the need for improved crop-type monitoring globally. Challenges remain in addressing the noisy aspect of street-level imagery (ie. buildings, hedgerows, automobiles, etc.), where a variety of different objects tend to restrict the view and confound the algorithms

Smoking have been linked to male infertility by affecting the sperm epigenome and genome. In this study, we aimed to determine possible changes in the transcript levels of the PTPRN2, PGAM5, and TYRO3 genes in heavy smokers compared with non-smokers; and to investigate their association with fundamental sperm parameters. One hundred eighteen sperm samples (63 heavy-smokers (G1) and 55 non-smokers (G2) were included in this study. Semen analysis was performed according to WHO guidelines. After total RNA extraction, RT-PCR was used to quantify the transcript levels of studied genes. In G1 a significant decrease in standard semen parameters in comparison to non-smokers has been shown (p<0.05). Moreover, PGAM5 and PTPRN2 were differentially expressed (P≤0.03 and P≤0.01, respectively), and downregulated in spermatozoa of G1 compared to G2. In contrast, no difference was observed for TYRO3 (p≤0.3). In G1, mRNA expression level of studied genes correlated negatively with motility, sperm count, normal form, vitality, and sperm membrane integrity (p<0.05). Therefore, smoking may affect gene expression and male fertility by altering DNA methylation patterns in genes associated with fertility and sperm quality, including PGAM5, PTPRN2, and TYRO3.

Memristor has attracted a lot of interest due to its high processing speed, low power consumption and high integration ability, which is critical for electronic systems and memory-centric computing. However, the memristor programming circuit and strategy are still inflexible and complex, since the signal generator/collector and stimulate pulse must be carefully matched and designed based on memristor intrinsic characteristics without reconfigurable. Here, a simple and effective circuit only consists a parallel reference-resistor-and-NMOS is designed to program memristor with a more than 99% memristance precision. And the amplitude and width of stimulate pulse are fixed to ±4V and 5ms, respectively. In order to cope with the device variation, such as ±10% tolerance of transition voltage, an optimized programming strategy was proposed and demonstrated great robustness. Additionally, a set of reference resistors and NMOSs have been added to facilitate multi-level memristance operation without requiring any changes to the circuit structure. This program circuit was also employed to program memristor crossbar remains 99% precision. In the end, a memristor-based convolutional neural network which controlled by our optimized programming circuit was used for image recognition, and 89.36% accuracy can be achieved even under 15.8% memristance tolerance. This novel circuit demonstrates a simple and flexible strategy in memristor programming, providing a new way to control memristor crossbar for practical application.

Structured extraction of emergency event information can effectively enhance the ability to re-spond to emergency events. This article focuses on the extraction of Chinese document-level emergency events, which mainly faces two key issues in this field: first, related datasets; Secondly, existing DEE (document-level event extraction) studies mostly use sequence annotation to extract candidate entities in the subtask of candidate entity extraction without considering the problem of role overlapping between candidate entities. On the one hand, this article constructs a Chinese document-level emergency extraction dataset, CDEEE, which first annotates the issues of argu-ment scattering, multiple events, and role overlapping. On the other hand, this article proposes a model RODEE for the problem of role overlapping in DEE tasks. This model first uses two in-dependent modules to represent the head and tail positions of candidate entities, then uses a multiplication attention mechanism to interact with the two to obtain a scoring matrix. Finally, role-overlapping candidate entities are predicted to assist in completing DEE tasks. Experiments were conducted on our manually annotated dataset, CDEEE, and the results showed that RODEE can effectively solve the problem of role overlapping in candidate entities and improve the performance of the DEE model.

When there is uncertainty in the value of parameters of the input random components of a stochastic simulation model, two-level nested simulation algorithms are used to estimate the expectation of performance variables of interest. In the outer level of the algorithm (n) observations are generated for the parameters, and in the inner level (m) observations of the simulation model are generated with the value of parameters fixed at the value generated in the outer level. In this article, we consider the case in which the observations at both levels of the algorithm are independent, showing how the variance of the observations can be decomposed into the sum of a parametric variance and a stochastic variance. Next, we derive central limit theorems that allow us to compute asymptotic confidence intervals to assess the accuracy of the simulation-based estimators for the point forecast and the variance components. Under this framework, we derive analytical expressions for the point forecast and the variance components of a Bayesian model to forecast sporadic demand; and we use these expressions to illustrate the validity of our theoretical results by performing simulation experiments using this forecast model.

Abstract: This work is presenting a water level control and monitoring system in a tank, by using the development boards Arduino Uno, NodeMCU ESP8266 and the ultrasonic sensor HC-SR04. The water tank is supplied through a pump controlled by the development board Arduino Uno by means of a relay. The author has issued a control algorithm for controlling the water level and a program in the development environment Arduino IDE that has been implemented and validated on the experimental stand. For monitoring the development board NodeMCU ESP8266 has been used that takes the information from the ultrasonic sensor HC-SR04 and sends it through Wi-Fi to the platform ThingSpeak. Based on the experimental results it has been found out that the water level control system in the tank provides the performances imposed through the designing stage, and the pump running has been automatically stopped when the limit, settled through the program for the water maximum level in the tank, has been reached. The measured value of the water level is shown on the LCD 1602 display. In the water circuit of the home consumers or irrigation systems supplied from the tank a pump controlled by means of a mobile phone has been installed. In order to implement this control system, the author has issued a program for another development board Arduino Uno, whilst for the mobile phone he used the application Arduino Bluetooth Control. The advantage of this water level control and monitoring system in the tank is given by the very low costs in comparison to the cost of an industrial type control system.

Mangrove forests, which are essential for the maintenance of terrestrial and marine biodiversity on tropical coasts and constitute the main blue-carbon ecosystems for the mitigation of global warming, are among the world’s most threatened ecosystems. Mangrove conservation can greatly benefit from paleoecological and evolutionary studies, as past analogs documenting the responses of these ecosystems to environmental drivers such as climate change, sea level shifts and anthropogenic pressure. A database (CARMA) encompassing nearly all studies on mangroves from the Caribbean region, one of the main mangrove biodiversity hotspots, and their response to past environmental shifts has recently been assembled and analyzed. The dataset contains over 140 sites and ranges from the Late Cretaceous to the present. The Caribbean was the cradle of Neotropical mangroves, where they emerged in the Middle Eocene (~50 million years ago; Ma). A major evolutionary turnover occurred in the Eocene/Oligocene transition (34 Ma) that set the bases for the shaping of modern-like mangroves. However, the diversification of these communities leading to their extant composition did not occur until the Pliocene (~5 Ma). The Pleistocene (the last 2.6 Ma) glacial-interglacial cycles caused spatial and compositional reorganization with no further evolution. Human pressure on Caribbean mangroves increased in the Middle Holocene (~6000 years ago), when pre-Columbian societies began to clear these forests for cultivation. In recent decades, deforestation has significantly reduced Caribbean mangrove cover and it has been estimated that, if urgent and effective conservation actions are not undertaken, these 50 million-year-old ecosystems might disappear in a few centuries. A number of specific conservation and restoration applications based on the results of paleoecological and evolutionary studies are suggested.

Reliable and accurate flood prediction is a challenging task in poorly gauged basins due to data scarcity. Data is an essential component of any AI/ML model today, and the performance of such models hugely depends on the availability of sufficient amount of trusted, representative data. However, unlike a few well-studied rivers, most of the rivers in developing countries are still insufficiently monitored, which significantly hinges the design and development of advanced flood prediction models and early warning systems. This paper presents a multi-modal, sensor-based and near-real time river monitoring system to produce a multi-feature data set for the Kikuletwa river in Northern Tanzania, an area that heavily suffers from frequent floods. Our deployed system, which gather information about river depth levels and weather at several locations, aims at widening the ground truth of the river characteristics and eventually improve the accuracy of flood predictions. We provide details on the monitoring system used to gather the data as well as report on the methodology and the nature of the data. Finally, we present the relevance of the data set in the context of flood prediction, discussing the most suitable AI/ML-based forecasting approaches, while also highlighting some applications of the data set beyond flood warning systems.

Anemia is a significant public health problem among children, especially school-age children because their body quickly produces red blood cells to provide sufficient blood volume with plasma expansion to maintain blood concentration. This research aimed to study the anemia situation, knowledge about anemia, food consumption behaviors, and the association between knowledge, food consumption behaviors, and hematocrit level among school-age children in primary school, in Thasala district, Nakhon Si Thammarat Province. This is a descriptive study among 408 students, Grades 4 to 6, aged 9-12 years. Research instruments included the demographic data of the children and their knowledge about anemia, food consumption behaviors, and hematocrit assessment. Data were analyzed using descriptive, Spearman’s rank correlation coefficient, and logistic regression statistics. The results revealed that 23.2% of the samples had anemia, whereas 22.22% had mild anemia and 0.98% had moderate anemia. The children knew about anemia, where the mean score was at a moderate level (Mean= 6.63; SD= 2.51) out of 10. The mean score on food consumption behaviors was in the moderate level (Mean= 17.49; SD= 3.68) out of 24. There were significantly positive correlations between the knowledge about anemia and the hematocrit level at a moderate level (r= 0.45, p< 0.001). Correlation analysis revealed moderate food consumption behaviors with the hematocrit level (r= 0.40, p< 0.001). When confirm with Logistic regression found that knowledge about anemia (OR = 9.15, 95% CI: 4.57-18.34), and food consumption behaviors (OR = 19.09, 95% CI: 9.71-37.53) were significantly associated with the hematocrit level. Conclusions: This study showed that knowledge and appropriate food consumption behaviors are associated with hematocrit levels. Enhancing knowledge about anemia and food consumption behaviors may be reduced the prevalence of anemia in school-age children. The health care providers in primary care should be encouraged children to have health education and eat sufficient food.

Abstract The article discusses about the current situation of Novel Corona Virus also called as the COVID-19 that hinder for all human’s life including the education. Rapidly escalating COVID-19, has caused havoc in quality education and every educational institution are closed. As the UNESCO report it showed that 1.6 billion children being affected due to the close of institution across 191 countries. With the alternative method every education institution started blended learning virtual classes in order to continue learning environment in students. The articles investigate COVID-19 impact on student’s quality education in Nepal and social work implication. The findings of the study shows that the COVID-19 has seriously effects on the students learning environment. It showed the huge gap between getting the good education in Nepal. However, Nepal has also made some policies to provide equal quality education to all the children through the ICT and also encourage social work to actively participate on providing education to all the majority of group children in Nepal. Whereas social work applied the micro, messo, and macro level of implication in practice to provide the education for children in remote area of Nepal.

Yam (Dioscorea spp.) is a monocotyledonous herbaceous vine plant grown in the tropics and subtropics. It is a multi-species plant with varied intra- and interspecific ploidy levels. Of the 600 species, 11 are cultivated staple supporting the livelihood of over 300 million people. The paucity of information on ploidy and the genomic constitution is a significant challenge to the crop’s genetic improvement through crossbreeding. The objective of this study was to investigate the ploidy levels of 236 accessions across six cultivated and two wild species using chromosome counting, flow cytometry and genotyping-based ploidy determination methods. Results obtained from chromosome counting and genotyping-based ploidy determination were in agreement. In majority of the accessions, chromosome counting and flow cytometry were congruent, allowing future rapid screening of ploidy levels using flow cytometry. Among cultivated accessions, 168 (71%) were diploid, 50 (21%) were triploid, and 12 (5%) were tetraploid. Two wild species included in the study were diploids. Resolution of ploidy level in yams offers opportunities for implementing successful breeding programmes through intra- and inter-specific hybridization.

Investigation of sea-level positions during the highly-dynamic Marine Isotope Stage 3 (MIS 3: 29-61 kyrs BP) proves difficult because: i) in stable and subsiding areas, coeval coastal sediments are currently submerged at depths of few to several tens of meters below present sea level; ii) in uplifting areas, the preservation of geomorphic features and sedimentary records is limited due to the erosion occurred during the Last Glacial Maximum (LGM) with sea level at depth of -130 m, followed by marine transgression that determined the development of ravinement surfaces. This study discusses previous research in the Mediterranean and elsewhere, and describes new fossiliferous marine deposits laying on metamorphic bedrock of Cannitello (Calabria, Italy). Radiocarbon ages of marine shells (about 43 kyrs cal BP) indicate that these deposits, presently between 28 and 30 meters above sea level, formed during MIS 3.1. Elevation correction of the Cannitello outcrops (considered in an intermediate-to-far-field position with respect to the ice sheet) with the local vertical tectonic rate and Glacial Isostatic Adjustment (GIA) rate allows to propose a revision of the eustatic depth for this highstand. Our results are consistent with recently proposed estimates based on a novel ice sheet modelling technique.

In a safety-critical system typically not all provided services have the same criticality, which we call mixed-criticality systems. Criticality arithmetic, also called SIL arithmetic, is an approach to lower the development effort of a service by providing redundancy with tasks that are developed for a lower criticality level. In this paper we present ATMP-CA, which is a derivation of the multi-core scheduler ATMP. ATMP-CA is able to take into account the knowledge about the use of criticality arithmetic. ATMP-CA has a modified core allocation and procedure for utility optimisation, considering the context of the replicated tasks. We conducted experiments that show that ATMP-CA is able to provide the services using criticality arithmetic, while the reference schedulers were not.

Evolutionary convergence provides natural opportunities to investigate how, when, and why novel traits evolve. Many convergent traits are complex, highlighting the importance of explicitly considering convergence at different levels of biological organization, or ‘multi‐level convergent evolution’. To investigate multi‐level convergent evolution, we propose a holistic and hierarchical framework that emphasizes breaking down traits into several functional modules. We begin by identifying long‐standing questions on the origins of complexity and the diverse evolutionary processes underlying phenotypic convergence to discuss how they can be addressed by examining convergent systems. We argue that bioluminescence, a complex trait that evolved dozens of times through either novel mechanisms or conserved toolkits, is particularly well suited for these studies. We present an updated estimate of at least 94 independent origins of bioluminescence across the tree of life, which we calculated by reviewing and summarizing all estimates of independent origins. Then, we use our framework to review the biology, chemistry, and evolution of bioluminescence, and for each biological level identify questions that arise from our systematic review. We focus on luminous organisms that use the shared luciferin substrates coelenterazine or vargulin to produce light because these organisms convergently evolved bioluminescent proteins that use the same luciferins to produce bioluminescence. Evolutionary convergence does not necessarily extend across biological levels, as exemplified by cases of conservation and disparity in biological functions, organs, cells, and molecules associated with bioluminescence systems. Investigating differences across bioluminescent organisms will address fundamental questions on predictability and contingency in convergent evolution. Lastly, we highlight unexplored areas of bioluminescence research and advances in sequencing and chemical techniques useful for developing bioluminescence as a model system for studying multi‐level convergent evolution.

This article presents a new method of segmenting images with gray levels. The method is based on determining several thresholds for separation of gray levels. The determination of these thresholds is done using the certainty of the neutrosophic information. The concept of this method can be stated simply: to choose the local maximums for the neutrosophic certainty.

Recent climatic changes have resulted in an increased frequency and prolonged periods of drought and strained water resources affecting plant production. We explored the possibility of reducing irrigation in a container nursery and studied the growth response of seedlings of economically important forest trees: broadleaf deciduous angiosperms Fagus sylvatica, Quercus petraea and evergreen conifers Abies alba and Pinus sylvestris. We also studied markers of water stress including modifications of biomass allocation, leaf anatomy, proline accumulation and expression of selected genes. Growth of the broadleaved deciduous species was more sensitive to the reduced water supply than that of conifers. Remarkably, growth of the shade tolerant Abies was not affected. Adjustment of biomass allocations was strongest in P. sylvestris, with a remarkable increase in allocation to roots. In response to water deficit both deciduous species accumulated proline in leaves and produced leaves with shorter palisade cells, reduced vascular tissues and smaller conduit diameters, but not conifers. Relative transcript abundance of a gene encoding a Zn-finger protein in Q. petraea and a gene encoding a pore calcium channel protein 1 in A. alba increased as water deficit increased. These findings suggest that in container nursery, the genetic selection can be initiated by water deficit. Our study shows major differences between functional groups in response to irrigation, with seedlings of evergreen conifers having higher tolerance than the deciduous species. This suggests that major water savings could be achieved by adjusting irrigation regime to functional group or species requirements.

Multiple studies have shown that hospital settings are poorly cleaned during terminal cleaning. The adequacy of these cleaning methods has been undermined by presence of multi drug resistant bacteria on hospital surfaces. This case is even more serious in developing countries leading to health care- associated infections that pose a great threat to patients, visitors and health care providers in hospital settings.This study used various microbiological techniques to test for antibiotic susceptibility profiles of bacteria present at Thika Level 5 Hospital surfaces, Kenya. A simple random cross sectional study was performed, with a total of 85 samples being collected from five different sites. The sites included male and female wards, health care personnel offices, latrine, and kitchen surfaces. Samples were collected using sterile swabs, dipped in normal saline, and transported to the laboratory within 2Hours for processing.Of the 85 plates cultured, 47 plates showed bacterial growth (55%) on selective media with a significant P value of 0.0357. Seven different species of bacteria were identified biochemically from all sites, Escherichia coli was the most abundant species (28%), and the least was Salmonella typhii (5%). Multiple drug resistance was common in the different bacteria identified. All isolates were resistant to chloramphenical and susceptible to gentamycin. The most resistant microorganism was Staphylococcus aureus (50%), and the least resistant microorganism was Klebsiella pneumoniae (12.5%). The antimicrobial resistant bacterial species identified in this study have been documented to cause serious health care associated infections. These results present a significant public health concern because there is a possibility of patients, staff and visitors contacting nosocomial infections when they come into contact with surfaces at Thika Level 5 Hospital surfaces, Kenya.

Background: Acute appendicitis (AA) is the most common cause of emergency surgery. Perforation is more common than adults. Early diagnosis and new markers are needed. The aim of this study was to investigate the effects of plasma Fetuin-A (FA) levels in patients with the acute abdomen (AB). Material and Method: This prospective study included 107 patients younger than 16 years of age who were admitted to the emergency department for abdominal pain between January 2018 and December 2018. The patients who presented to abdominal pain were divided into two groups as AA and other causes (OC) of AB. T Patients with acute appendicitis; intraperitoneal, retrocolic / retrocecal and appendicitis were divided into three groups. Also, the AA group was divided into two groups as perforated appendicitis and non-perforated appendicitis. Serum FA levels of the patients were evaluated in the emergency department. Results: In the AA group, C-reactive protein (CRP) and white blood cell (WBC) levels were higher, and FA levels were significantly lower than in the AB group. Intraperitoneal localization was 95.2% and perforation was frequent. When significant values in the univariate regression analysis for acute abdomen and perforation were compared in the multivariate regression analysis, CRP, WBC, and FA levels were found to be prognostic. Also, decreased FA levels were associated with AA while too much decreased FA levels were associated with the risk of perforation. Conclusion: While trying to diagnose AA in children, the FA level, CRP and WBC may be predictive values to identify risk factors.

There has been rampant fold-ups, merger and acquisitions occurring in the Ghanaian banking industry. Then, the questions arise: Is the Ghanaian Financial System in Crisis? This study was conducted to find answers to these problems unsolved with prior literature. A sample of seventy customers of the Royal Bank, 8 employees of the Royal Bank and 2 managers of the Royal Bank were selected for a case-survey. The study also monitored the Trend of the Ghanaian Financial System through the reading and monitoring of daily news on the Financial System and reports of banks. The data from the field and the secondary data from news and reports were analysed symmetrically. The study drew on Minsky’s Financial Crisis Theory to explain the phenomenon in the Ghanaian economy and to draw predictions of what would happen in other developing economies. The study found out that: (1) The Ghanaian financial system is fragile and it holds true for most developing economies; (2) The financial system suffers greatly when the confidence level of customers falls significantly; (3) Management information systems raises the confidence level of customers (borrowers and lenders) such that there is a greater fall and impact in times of instability in the economy; (4) The higher the level of MIS adoption in an unstable economy, the more fragile the Financial System becomes and (5) A higher adoption of Management Information Systems in a Fragile Financial System indirectly contributes to Financial Crisis of the Financial System.

Study nature of epidemiological risk factors and patterns of distribution of mortality from Alzheimer's (D_A) in 160 countries. An exponential Malthus model was used to construct adequate approximations of statistical data. Proportionality of average lifetime after 55 years (Δt) to education index (Ψ) was established. Ranking of countries by increasing value of ΨΔt showed that D_A depends exponentially on ΨΔt and all countries can be divided into three groups in accordance with level of their economic development. In series of countries of low, medium and highly developed, their average values of D_A increase exponentially. Growth of D_A in developed countries in post-industrial epoch was explained by emergence of a new risk factor Alzheimer's of a mental nature. A mismatch of complexity or, on contrary, primitiveness of profession with level of mental development of worker, provokes development of chronic stress in him, fraught with pathologies of cognitive function metabolism in elderly. The geography of Alzheimer's disease was explained by the dependence of the human mentality on latitudinal climate change and on the chiral factor of a solar nature acting at night on a sleeping person.

On 5-7 April 2018 a landfalling atmospheric river resulted in widespread heavy precipitation in the Sierra Nevada of California and Nevada. Observed snow levels during this event were among the highest snow levels recorded since observations began in 2002 and exceeded 2.75 km for 31 hours in the northern Sierra Nevada and 3.75 km for 12 hours in the southern Sierra Nevada. The anomalously high snow levels and over 80 mm of precipitation caused flooding, debris flows, and wet snow avalanches in the upper elevations of the Sierra Nevada. The origin of this atmospheric river was super typhoon Jelawat, whose moisture remnants were entrained and maintained by an extratropical cyclone in the northeast Pacific. This event was notable due to its April occurrence, as six other typhoon remnants that caused heavy precipitation with high snow levels (mean = 2.92 km) in the northern Sierra Nevada all occurred during October.

Coastal inundation is an increasing problem. Sea-level rise will greatly increase the frequency and depth of inundation, forcing vulnerable communities to adapt. Communities will need to decide when and how to adapt. The process of decision-making along adaptive pathways is now being used internationally to plan for adaptation over time by anticipating decision points in the future however it unfolds. This process requires risk and uncertainty considerations to be transparent in the scenarios used in such planning. We outline a framework for uncertainty identification and management within coastal hazard assessments which recognizes different types of decision and identifies the types of uncertainty that must be accounted for, such as statistical, scenario and deep uncertainty types. We show how coastal-inundation hazard can be mapped and presented in a way that clearly separates sources of uncertainty, so that they are transparent within a dynamic adaptive pathways planning process. Traditional coastal inundation maps show inundated area only. We present maps of inundation depth and frequency which clearly show the degree of exposure, where that exposure occurs, and how much sea-level rise can be tolerated. The new uncertainty framework and mapping techniques can better identify decision points and their expected time range, which provides more useful input to the adaptation process than traditional coastal inundation assessments.

The paper presents the results of the research concerning an evaluation of information 1 technology of gene expression profiles processing stability with the use of gene expression profiles 2 with different levels of noise component. The information technology is presented as a structural 3 block-chart, which contains all stages of the studied data processing. The hybrid model of objective 4 clustering based on SOTA algorithm and the technology of gene regulatory networks reconstruction 5 have been studied to evaluate the stability to the level of the noise component. The results of the 6 simulation have shown that the hybrid model of objective clustering has high level of stability 7 to noise component and vice versa, the technology of gene regulatory networks reconstruction is 8 very sensitivity to level of noise component. The obtained results indicate the importance of gene 9 expression profiles preprocessing at early stage of gene regulatory network reconstruction in order to 10 remove background noise and non-informative genes in terms of used criteria

(1) Background: Intracortical microelectrodes (IMEs) are an important part of interfacing with the central nervous system (CNS) and recording neural signals. However, recording electrodes have shown a characteristic steady decline in recording performance owing to chronic neuroinflammation. The topography of implanted devices has been explored to mimic the nanoscale three-dimensional architecture of the extracellular matrix. Our previous work used histology to study the implant sites of non-recording probes and showed that a nanoscale topography at the probe surface mitigated the neuroinflammatory response compared to probes with smooth surfaces. Here, we hypothesized that the improvement in the neuroinflammatory response for probes with nanoscale surface topography would extend to improved recording performance. (2) Methods: A novel design modification was implemented on planar silicon-based neural probes by etching nanopatterned grooves (with a 500 nm pitch) into the probe shank. To assess the hypothesis, two groups of rats were implanted with either nanopatterned (n=6) or smooth control (n=6) probes, and their recording performance was assessed over 4 weeks. Postmortem gene expression analysis was performed to compare the neuroinflammatory response from the two groups. (3) Results: Nanopatterned probes demonstrated increased impedance and noise floor compared to controls. However, the recording performance of the nanopatterned and smooth probes was similar, with active electrode yield for control probes and nanopatterned probes being approximately 50% and 45%, respectively by 4 weeks post-implantation. Gene expression analysis showed 1 gene, Sirt1, differentially expressed out of 152 in the panel. (4) Conclusions: This study provides a foundation for investigating novel nanoscale topographies on neural probes.

MADS-box genes play a crucial role in fruit ripening, yet limited research has been conducted on mango. Based on the conserved domains of this gene family, 84 MADS-box genes were identified in the mango genome, including 22 type I and 62 type II MADS-box genes. Gene duplication analysis revealed that both tandem duplication and segmental replication significantly contributed to the expansion of MADS-box genes in the mango genome, with purifying selection playing a vital role in the segmental duplication events within the MiMADS gene family. Cis-acting element analysis demonstrated that most MiMADS genes were hormonally regulated and participated in the growth, development, and stress resistance of mango fruit. Moreover, through expression pattern analysis and phylogenetic tree construction, we identified six MiMADS genes belonging to the SEP1 subfamily and two belonging to the AG subfamily as potential candidates involved in mango ripening regulation. Notably, Mi08g17750 and Mi04g18430 from the SEP1 subfamily were identified as key regulators inhibiting mango fruit maturation; their interaction network was also analyzed. These findings provide a foundation for further investigation into the regulatory mechanisms underlying mango ripening.

Leber’s hereditary optic neuropathy (LHON) is a common mitochondrial genetic disease, causing irreversible blindness in young individuals. Current treatments are inadequate, and there is no definitive cure. This study evaluates the effectiveness of delivering wildtype human NADH ubiquinone oxidoreductase subunit 4 (hND4) gene using mito-targeted AAV(MTSAAV) to rescue LHOH mice. We observed declining pattern electroretinograms amplitudes as mice aged across all groups (P&lt; 0.001), with significant differences among groups (P = 0.023, Control vs. LHON, P = 0.008; Control vs. Rescue, P = 0.228). Inner retinal thickness and intraocular pressure do not change significantly with age or groups. Compared to LHON mice, those rescued with wildtype hND4 exhibit improved retinal visual acuity (0.29± 0.1 cy/deg vs.0.15 ± 0.1 cy/deg) and increased functional hyperemia response (effect of flicker, P&lt;0.001, effect of Group, P=0.004; Interaction Flicker x Group, P&lt;0.001). Postmortem analysis shows a marked reduction in retinal ganglion cell density in the LHON group compared to the other groups (Effect of Group, P&lt;0.001, Control vs. LHON, P&lt;0.001, Control vs. Rescue, P=0.106). These results suggest that MTSAAV-delivered wildtype hND4 gene rescues, at least in part, visual impairment in an LHON mouse model and has the therapeutic potential to treat this disease.

In order to enhance understanding of RNA-binding proteins in rice, a comprehensive investigation was conducted on the RRM1 gene family of rice, encompassing genome-wide identification and exploration of its role in rice blast resistance. Physical and chemical properties of the OsRRM1 gene family in rice was analyzed, including conserved domain, motif, location information, gene structure, phylogenetic tree, collinearity analysis, cis-acting elements, GO, and KEGG. Furthermore, the expression patterns of the OsRRM1 gene were examined at different time intervals following rice blast treatment. Furthermore, the alterations in expression patterns of selected OsRRM1 genes were assessed using quantitative real-time PCR(qRT-PCR). A total of 212 members of the OsRRM1 gene family were identified, which were dispersed across 12 chromosomes. Many of these genes exhibit multiple exons and introns, all of which encompass the conserved RRM1 domain and share analogous motifs. This observation suggests a high degree of conservation within the encoded sequence domain of these genes. Phylogenetic analysis revealed the existence of five subfamilies within the OsRRM1 gene family. Furthermore, the investigation of the promoter region identified homeopathic elements that are involved in nucleic acid binding and interaction with multiple transcription factors. By employing GO and KEGG analysis, four RRM1 genes were tentatively identified as crucial contributors to plant immunity, while the RRM1 gene family was also found to have a significant involvement in the complex of alternative splicing. Additionally, gene expression analysis indicated that the majority of OsRRM1 genes exhibited constitutive expression. The results of the qRT-PCR analysis revealed distinct temporal changes in the expression pattern of the OsRRM1 gene following rice blast treatment. These findings contribute to the existing knowledge of the OsRRM1 gene family, establish a foundation for further investigation into the role of the OsRRM1 gene in response to rice blast infection, and hold theoretical significance for future studies on the functionality of the OsRRM1 gene.

Salvia is a large genus in traditional Chinese medicine with hundreds of species. Tanshinones are a highly representative class of exclusive compounds found in the Salvia genus that exhibit significant biological activity. Tanshinone components have been identified in 16 species of the Salvia genus. The CYP76AH subfamily (P450) is crucial for the synthesis of tanshinone due to its catalytic generation of polyhydroxy structures. 420CYP76AH genes were obtained, clear clustering relationships. In this study 15 CYP76AH genes from 10 Salvia species were cloned and studied from the perspectives of evolution and catalytic efficiency. Structure-function relationship revealed several conserved residues which might be related to the function of CYP76AHs. Amino acids (97I, 116V, and 290T) are conserved in CYP76AH1 group, while amino acids (117G, 208S, 237Y, and 479F) are CYP76AH3 group protein sequence characteristics with unique enzyme function.This research holds significant implications for the classification of the Salvia genus and provide efficient catalytic elements for the synthetic biology production of tanshinones.Keywords: Salvia; CYP76AH; P450; biosynthesis; functional gene

Sheep (Ovis aries) provide a vital source of protein and fibre to human populations. In coming decades, as the pressures associated with rapidly changing climates increase, breeding sheep sustainably as well as producing enough protein to feed a growing human population will pose a considerable challenge for sheep production across the globe. High quality reference genomes and other genomic resources can help to meet these challenges by: 1) informing breeding programmes by adding a priori information about the genome, 2) providing tools such as pangenomes for characterising and conserving genetic diversity, and 3) improving our understanding of fundamental biology using the power of genomic information to link cell, tissue and whole animal scale knowledge. In this review we describe recent advances in the genomic resources available for sheep, discuss how these might help to meet future challenges for sheep production, and provide some insight into what the future might hold.

Antibiotic resistance is a major public health issue that requires a multifaceted approach. One potential source of antibiotic-resistant bacteria is wastewater in developing countries, which often lacks proper treatment infrastructure and can release high levels of antibiotics and antibiotic-resistant bacteria into the environment. This review article summarizes current knowledge on strategies to combat antibiotic resistance in wastewater in developing countries. Our review highlights the importance of improving wastewater treatment infrastructure to effectively remove antibiotics and antibiotic-resistant bacteria, implementing measures to reduce the release of antibiotics into the environment, and monitoring and surveillance to track the presence and spread of antibiotic-resistant bacteria in wastewater. We also discuss the potential challenges and barriers to implementing these strategies and the need for further research to determine their effectiveness in real-world settings. Overall, this review highlights the need for a comprehensive approach to address antibiotic resistance in wastewater in developing countries and underscores the importance of addressing this issue to protect public health.

Therapeutic efficacy of retroviral replicating vector (RRV)-mediated prodrug activator gene therapy has been demonstrated in a variety of tumor models, but clinical investigation of this approach has so far been restricted to glioma and gastrointestinal malignancies. In the present study, we evaluated replication kinetics, transduction efficiency, and therapeutic efficacy of RRV in experimental models of lung cancer. RRV delivering GFP as a reporter gene showed rapid viral replication in a panel of lung cancer cells in vitro, as well as robust intratumoral replication and high levels of tumor transduction in subcutaneous and orthotopic pleural dissemination models of lung cancer in vivo. Toca 511 (vocimagene amiretrorepvec), a clinical-stage RRV encoding optimized yeast cytosine deaminase (yCD) which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU), showed potent cytotoxicity in lung cancer cells upon exposure to 5-FC prodrug. In vivo, Toca 511 achieved significant tumor growth inhibition following 5-FC treatment in subcutaneous and orthotopic pleural dissemination models of lung cancer in both immunodeficient and immunocompetent hosts, resulting in significantly increased overall survival. This study demonstrates that RRV can serve as highly efficient vehicles for gene delivery to lung cancer, and indicates the translational potential of RRV-mediated prodrug activator gene therapy with Toca 511/5-FC as a novel therapeutic strategy for pulmonary malignancies.

Background: Acute hepatopancreatic necrosis disease (AHPND), is a bacterial disease of whiteleg shrimp, which has a high mortality rate (100%) and incurs economic losses. Our objective was to identify the genes which lead to cell and organ damage and investigate bioproducts to prevent and treat. Methods: Litopenaeus vannamei shrimp in Thua Thien Hue province, Vietnam were collected from an infected pond and analysed at the Institute of Biotechnology, Hue University. The PirA gene of Vibrio parahaemolyticus strain K5 was isolated and analyzed for nucleotide sequence and paired with the expression vector pQE30. The expression vector was transformed into E. coli strain M15, the PirA recombinant protein was expressed in the form of 6xHis-PirA fusion protein of about 15 kDa. PirA recombinant protein was purified and determined the PirAvp binding ratio, cloning and sequencing of PirA gene from Vibrio parahaemolyticus strain K5 causing AHPND by PCR method with specific primers and molecular weights of PirAvp and the PirAvp complex. Results: PirA gene from Vibrio parahaemolyticus strain K5 was cloned into pGEM-T easy vector (Promega, USA) and screened E. coli TOP10 colonies containing pGEM T easy/PirA recombinant plasmid on LB agar/ampicillin/IPTG/X-Gal medium. PCR showing a band of about 347 bp, matching the size of PirA gene and two nucleotide sequences (BamHI and HindIII). The results showed that PirA gene has a length of 336 bp and similar to PirA gene on GenBank (Code: KU556825.1). The results of protein extracted from E. coli M15 recombinant cells and 6xHis-PirA target protein was collected in elution fractions from EF2 to EF6, showed that the concentration of 6xHis-PirA protein and EF3 elution fraction collected a highest protein concentration (1,586.54 µg/ml). Conclusions: The purified PirA recombinant protein will provide materials for development research to create biological products to prevent and treat AHPND.

The Wnt pathway plays an essential role in the initiation and progression of various types of cancer. ROR1 and ROR2 are Wnt receptors that are critical for β-catenin-independent (non-canonical) pathways and have been linked to processes driving tumor development and progression, such as cell proliferation, survival, invasion, and therapy resistance. Both receptors have garnered interest as potential therapeutic targets since they are largely absent in adult tissue, are overexpressed in several cancers, and, as members of the receptor tyrosine kinase family, are easier to target than all other components of the pathway. Unlike ROR1 which always promotes tumorigenesis, ROR2 has a very complex role in cancer acting either to promote or inhibit tumor progression in different tumor types. In the present article, we summarize the findings on ROR2 expression in cancer patients and its impact on clinical outcome. Further, we review the biological processes and signaling pathways regulated by ROR2 that explain its dual role in cancer. Finally, we describe the ongoing strategies to target ROR2 in cancer.

The human adenovirus phylogenetic tree is split across seven species (A-G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of preexisting immunity detected across screened populations. However, many aspects of the basic virology of species D, such as their cellular tropism, receptor usage and in vivo biodistribution profile, remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49), a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen whilst avoiding liver interactions, such as intravascular vaccine applications.

The aim of present study was to link the gene expression profile of selected candidate genes with blood profile, growth performance and carcass traits of Barki lambs. Thirty-eight Barki lambs were divided into 3 groups (fast, intermediate and slow growing) according to growth perfor-mance. Body tissues (muscle, liver and fat) were taken from for RNA isolation and Real-time PCR. The results indicated that, the final body weight hot carcass weight were heavier (P ≤ 0.05) in fast (49.9 Kg and 24.57) than intermediate (40.7 and 19.07 Kg) and slow (30.8 and 15.10 Kg) growing animals. The blood profile of total protein, total lipids, calcium, T3 and T4 hormones did not differ among sheep groups. Genes involved in protein biosynthesis (RPL7), fatty acid oxidation (CPT1) and lipolysis (FABP4) were up regulated in fast and intermediate growing lambs in all studied tissues. While, gene-regulating lipogenesis (ADIPOQ) was expressed simi-larly in fat and liver tissues, but increased its expression in muscle of fast and intermediate growing lambs. Expression of CAPN3 was increased in fast and intermediate growing compared to slow growing lambs. In conclusion, the current study providing an evidence for the im-portance of co-expression of these genes in main body tissues linked with growth performance of Barki lambs.

Cyanobacteria are highly diverse, widely distributed photosynthetic bacteria inhabiting various environments ranging from deserts to the cryosphere. Throughout this range of niches, they have to cope with various stresses and kinds of deprivation which threaten their growth and viability. In order to adapt to these stresses and survive, they have developed several global adaptive responses which modulate the patterns of gene expression and the cellular functions at work. Sigma factors, two-component systems, transcriptional regulators and small regulatory RNAs acting either separately or collectively, for example, induce appropriate cyanobacterial stress responses. The aim of this review is to summarize our current knowledge about the diversity of the sensors and regulators involved in the perception and transduction of light, oxidative and thermal stresses and nutrient starvation responses. The studies discussed here point to the fact that various stresses affecting the photosynthetic capacity are transduced by common mechanisms.

Methylenetetrahydrofolate reductase (MTHFR), an enzyme expressed in mammalian testes exerts direct effect on spermatogenesis; however, its protein characteristics in bovine testes remain unknown. Here, we analysed bovine testicular structure, MTHFR bioinformatics profile, mRNA, and protein expression characteristics in yellow-cattle (y-c) and yak testis using histological procedures, bioinformatics analysis, qRT-PCR, and western blot. Testes from 13 bovines, ≤ 2 years juvenile (y-c, n = 3; yak, n=3) and ≥ 3 years adult (y-c, n = 3; yak, n = 4) were collected and analysed. Anatomical characteristics of testis in y-c and yak were similar except the weight or size for which that of y-c was significantly higher or greater than yak. In y-c, an open reading frame (ORF) for 2600 nucleotides sequence, encoding 655 amino acids showed high homology with zebu cattle (99.51%) and wild yak (98.68%). Secondary and 3D protein structures were similar to that of humans with differences in number of nucleotides, amino acids, and some physico-chemical characteristics. MTHFR mRNA expression in y-c and yak were significantly higher in adult testes compared with juvenile ones. However, its protein expression was higher but not statistically significant in adult y-c and yak compared to the juvenile ones. The highlights and inferences of these and other findings are discussed.

MicroRNA (miRNA) is a typical class of small RNAs that could modulate gene expression in trans at the post-transcriptional level. miRNAs bind to the miRNA binding sites (MBSs) in target mRNAs by sequence complementarity. Alternative splicing (AS) is another commonly occurred process in pre-mRNAs that changes the isoforms of a gene. It is hypothesized that there should be an interaction for gene regulation that involves both AS and miRNA targeting. Studies have verified this hypothesis in the model organism Arabidopsis thaliana. High-throughput sequencing data suggested that in Arabidopsis a considerably large fraction of MBSs are affected by AS events. The overlapping between MBS and AS exceeds the randomly simulated number. Functional experiments have indicated that the AS events are required for the gene expression changes of miRNA targets. Therefore, AS and MBS are mutually favored. The observed expression changes caused by miRNAs could also be contributed by AS events. In the present perspective article, we propose that the AS analysis should be incorporated in the differential-expression analysis of miRNA studies. When defining a differentially-expressed gene, it should be clarified whether the change in gene expression is caused by AS events or solely by miRNA targeting.

The NOD2 gene, involved in innate immune responses to bacterial peptidoglycan, has been found to be strongly associated with Crohn’s Disease, with an Odd Ratio ranging from 3 to 36. Families with 3 or more CD affected patients were related to high frequency of NOD2 gene variations as R702W, G908R, 1007fs and were reported in EPIMAD Registry. However, some rare CD multiplex families were described without identification of common NOD2 linked-to-disease variations. In order to identify new genetic variation(s) with a major effect on Crohn’s disease (CD), whole exome sequencing was performed in available subjects comprising 4 patients on 2 generations affected with Crohn’s disease without R702W and G908R variation, and 3 unaffected related subjects. A new rare and not yet reported missense variation of the NOD2 gene, the N1010K, was detected and co-segregated across affected patients. In silico evaluation and modeling highlighted evidences for a deleterious effect of the N1010K variation regarding CD. Moreover cumulative characterization of N1010K and 1007fs as compound heterozygous state in two more severely CD family members strongly suggesting that the N1010K should be a new risk factor involved in Crohn’s disease genetic susceptibility.

Predicting how a genetic change affects a given character is a major challenge in biology, and being able to tackle this problem relies on our ability to develop realistic models of gene networks. However, such models are rarely tractable mathematically. In this paper, we propose a mathematical analysis of the sigmoid variant of the Wagner gene-network model. By considering the simplest case, that is, one unique self-regulating gene, we show that numerical simulations are not the only tool available to study such models: theoretical studies can be done too, by mathematical analysis of discrete dynamical systems. It is first shown that the particular sigmoid function can be theoretically investigated. Secondly, we provide an illustration on how to apply such investigations in the case of the dynamical system representing the one self-regulating gene.

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.

High-grade gliomas are the most common and aggressive adult primary brain tumors with a median survival of only 12-15 months. Current standard therapy consists of maximal safe surgical resection followed by DNA-damaging agents, such as irradiation and chemotherapy that can delay but not prevent inevitable recurrence. Some have interpreted glioma recurrence as evidence of glioma stem cells which persist in a relatively quiescent state after irradiation and chemotherapy, before the ultimate cell cycle re-entry and glioma recurrence. Conversely, latent cancer cells with a therapy-induced senescent phenotype have been shown to escape senescence, giving rise to more aggressive stem-like tumor cells than those present in the original tumor. Therefore, approaches are needed to either eliminate or keep these glioma-initiating cells in a senescent state for a longer time to prolong survival. In our current study, we demonstrate that the radiation-induced cell cycle inhibitor P21 can provide a powerful route to induce cell death in short-term explants of PDXs derived from three molecularly diverse human gliomas. Additionally, cells not killed by P21 overexpression were maintained in a stable senescent state for longer than control cells. Collectively, these data suggest that P21 activation may provide an attractive therapeutic target to improve therapeutic outcomes.

Promoter choice is an essential consideration for transgene expression in gene therapy. The expression of multiple genes requires ribosomal entry or skip sites, or the use of multiple promoters. Promoters systems comprised of two separate, divergent promoters may significantly increase the size of genetic cassettes intended for use in gene therapy. However, an alternative approach is to use a single, compact bidirectional promoter. We identified strong and stable bidirectional activity of the RPBSA synthetic promoter comprised of a fragment of the human Rpl13a promoter, together with additional intron / exon structures. The Rpl13a-based promoter drove long-term bidirectional activity of fluorescent proteins. Similar results were obtained for the EF1-α and LMP2/TAP1 promoters. However, in a lentiviral vector, the divergent bidirectional systems failed to produce sufficient titres to translate into an expression system for dual chimeric antigen receptors (CAR) expression. Although bidirectional promoters show excellent applicability to drive short RNA in Sleeping Beauty transposon systems, their possible use in the lentiviral applications requiring longer and more complex RNA, such as dual CAR cassettes, is limited.

Research in various fields of evolutionary biology has shown that divergence in gene expression is a key driver for phenotypic variation. An exceptional contribution of cis-regulatory evolution has for instance been found to contribute to morphological diversification. In the light of these findings, the analysis of genome-wide expression data has become one of the central tools to link genotype and phenotype information on a more mechanistic level. However, in many studies, especially if general conclusions are drawn from such data, a key feature of gene regulation is often neglected. With our article, we want to raise awareness that gene regulation and thus gene expression is highly context dependent. Genes show tissue- and developmental stage-specific expression. We argue that the regulatory context must be considered when studying evolution of gene expression.

Phylostratigraphic analysis is a way to look anew on phylogenetic data in the evolutionary aspect. It allows counting the evolutionary age based on the analysis of genes, their orthologs and finding the last common ancestor. We performed phylostratigraphic analysis of Arabidopsis thaliana genes associated with several types of abiotic stresses (heat, cold, water-related, light, osmotic, salt, and oxidative) determined by the Gene Ontology annotation. Comparison of the distributions of ages of genes associated with stresses of different type has shown the heat stress to involve older genes while the light stress – younger genes. At the same time, all types of stress are characterized by a significantly higher proportion of old genes (common to all eukaryotes) compared to the whole set of A.thaliana genes. This can be explained by the involvement of basic molecular processes in plant cells into the stress response. Reconstruction and graphical analysis of the gene network of the heat stress educed several clusters associated with different response functions. Some of these clusters contain only ancient genes. The results obtained show that the phylostratigraphic analysis reveals the fundamental features of the organization of gene networks and their evolution.

The sound power LW of wind turbines (WTs) over the past decades has developed in relation to their electric power P as LW ∝ logP. The spectral distribution of the sound did not change significantly over time. This applies to the average performance of wind turbines, with differences between individual WT types. Because of the expected growth of onshore wind energy, a greater number of people will be living close to wind farms. This sustains the need for sound reduction. Sound reduction measures, such as serrations, reduced tip speed and low noise modes, may counteract the development of higher sound power from ever bigger WTs. To investigate this, the sound production of WT types over the last decades is analysed in relation to their size and electric power and the application of sound reduction measures. The analysis includes the broad band A-weighted and low frequency sound power levels as well as more detailed spectral distributions. Results show that the sound power level of wind turbines above 3 MW on average increases less with size than smaller turbines did. This is due to a lower blade tip speed and the use of sound reducing serrations. The spectral content of wind turbine sound, including the lower frequencies, has not changed significantly.

Automated charging technologies are becoming increasingly important in the electrification of heavy road freight transport, especially in combination with autonomous driving. This study provides a comprehensive analysis of automated charging technologies for electric heavy-duty vehicles (HDVs). It encompasses the entire spectrum of feasible technologies, including static and dynamic approaches, with each charging technology evaluated for its advantages, potentials, challenges, and technology readiness level (TRL). Static conductive charging methods such as charging robots, underbody-couplers or pantographs show good potential, with pantographs being the most mature option. These technologies are progressing towards higher TRLs, with a focus on standardization and adaptability. While static wireless charging is operational for some prototype solutions, it encounters challenges related to implementation and efficiency. Dynamic conductive charging through an overhead contact line or contact rails holds promise for high-traffic HDV routes with the overhead contact line being the most developed option. Dynamic wireless charging, although facing efficiency challenges, offers potential for seamless integration into roads and minimal wear and tear. Battery swapping is emerging as a practical solution to reduce downtime for charging, with varying levels of readiness across different implementations. To facilitate large-scale deployment further standardization efforts are required. The study emphasizes the necessity for continued research and development to enhance efficiency, decrease costs, and ensure seamless integration into existing infrastructures. Technologies that achieve this best will have the highest potential to significantly contribute to the creation of an efficiently automated and environmentally friendly transport sector.

Persistent land subsidence or uplift can cause serious latent hazards to urban infrastructure. To thoroughly investigate the causes and impacts of land surface deformation, this study examines the case of Wuxi City, focusing on the land fluctuation patterns in the region following the enforcement of the groundwater abstraction prohibition policy in 2005. This research utilizes the PS-InSAR technique to quantify land surface deformations in the Wuxi region from November 2015 to June 2023 and analyzes 100 SAR images to obtain comprehensive spatiotemporal evolution data of the land surface. Furthermore, this study conducts an in-depth analysis of the effects of various factors, including groundwater, precipitation, and soil geology, on the characteristics of land surface deformation. It pioneers the application of the GARCH (Generalized Autoregressive Conditional Heteroskedasticity) model to analyze the time-series displacement in the study area and innovatively introduces the "amplitude factor" index to assess land surface fluctuations. This study investigates the recent land surface deformation patterns and mechanisms in Wuxi City. By integrating the "amplitude factor", it provides a scientific foundation for future urban development and disaster mitigation strategies in Wuxi City, offering valuable insights for related research.

Improving the level of farmers' participation in collective action is an important way to promote rural revitalization and improve the sustainable livelihood level of farmers in underdeveloped areas. Based on 312 questionnaires of farmers in Shanxi Province, this paper investigates the status of farmers' participation in collective action, their sustainable livelihood level and the sustainable livelihood effect of collective action participation. The results show that: farmers' willingness to participate in collective action is strong, and the participation effect is obvious, but the participation frequency is low, and the participation time is less; The farmers' sustainable livelihood level is relatively low, Empirical research shows that the level of collective action participation will have a significant positive impact on Farmers' livelihood risk prevention, livelihood capital accumulation, livelihood mode selection and livelihood income improvement, and the frequency, time and value perception of participation in collective action will have varying degrees of impact on Farmers' sustainable livelihoods. In order to promote farmers' active participation in collective action, it is proposed to strengthen the construction of collective organizations Provide incentives and improve the quality and skills of farmers to enhance the collective concept and other policy recommendations.

Pressure ulcers carry a significant risk in clinical practice and require effective preventive measures. This paper proposes a practical and interpretable approach to estimate the risk levels of pressure ulcers using decision tree models. In order to address the common problem of imbalanced learning in nursing classification datasets, various oversampling configurations are analyzed to improve data quality prior to modeling. The decision trees built are based on three easily identifiable and clinically relevant pressure ulcer risk indicators: mobility, activity and skin moisture. Their analysis allows nursing professionals to predict the risk levels of pressure ulcer and make informed decisions about patient care. Additionally, this research introduces a novel tabular visualization method to enhance the usability of the decision trees in clinical practice. The approach proposed aims to support nursing professionals in making timely decisions regarding the appropriate preventive interventions according to the risk levels of pressure ulcers, thus improving patient outcomes and healthcare costs. The usefulness and effectiveness of the models presented make them a valuable resource for nursing care in the prevention of pressure ulcers.

The global SARS-Cov-2 which caused the coronavirus disease 2019 (COVID-19) pandemic has had a significant impact over the last 3.5 years, especially among healthcare workers (HCWs) who were constantly in the forefront of the pandemic. Due to the nature of their work, HCWs faced a potential risk of exposure. Therefore, this study investigated the individual-level factors associated with perceived COVID-19 risk among South African HCWs. We used an analytical cross-sectional study design to analyse data from the South African Health Care workers’ response to the Coronavirus (COVID-19) pandemic online survey conducted by the Human Sciences Research Council across the nine provinces in South Africa, from 11th April to 7th May 2020. In this study, only data (n= 5 579) with non-missing values for COVID-19 risk and individual-level factors (age, gender, educational level, occupational category, and race) was analysed. Univariate and Multivariate binomial logistic regression analyses were conducted. The crude and adjusted odds ratio and p-value ≤ 0.05, were used to describe the association between the individual-level factors and perceived COVID-19 risk, from low-medium to high. The binomial logistic regression was used to assess the factors associated with high perceived risk. Perceived COVID-19 risk among HCWs in South Africa was significantly associated with age, race, educational level and occupational category. Being 60 years and older, being “White”, having a Master’s and Doctorate degrees and being a healthcare worker other than a nurse practitioner and medical practitioner, all had higher odds of having high perceived COVID-19 risk. The findings may be used to guide policies and programs aimed at mitigating the impacts of COVID-19 and other similar pandemics.

Accurate forecast of tail water level (TWL) is of great importance for the safe and economic operation and management of hydropower stations. The predictive performance is significantly influenced by the backwater effect of downstream hydropower stations and tributaries, but the explicit quantification method of the backwater effect is lacked. In this study, a deep learning model based forecasting framework for TWL predictions is established and applied to forecast TWL of Xiangjiaba (XJB) hydropower stations, which is influenced by the backwater effect of downstream tributaries including Hengjiang River (HJR) and Minjiang River (MJR). Firstly, the lag time of the backwater effect of HJR and MJR is analyzed based on the permutation importance. The results demonstrate that the lag time of backwater effect on the TWL of XJB is 5-7 hours for the HJR and 1-2 hours for the MJR. Then, the runoff thresholds of the HJR and MJR for impacting the TWL of the XJB station are obtained by scenario comparison, and the results show that the thresholds of HJR and MJR are 700 m3/s and 7000 m3/s respectively. Finally, the deep learning methods based TWL forecasting model is established based on the lag time and threshold analysis. The model is used to forecast the TWL in future 48 hours. The results show that the forecasting model has a good predictive performance with 98.22% of absolute errors less than 20 cm. The mean absolute error over the validation dataset is 5.27 cm and the maximum absolute error is 63.35 cm.

The dairy industry relies heavily on milk pasteurization to ensure the safety and quality of milk products. Pasteurization is a process that involves heating milk to a specific temperature for a set period of time to kill harmful bacteria and other pathogens while preserving its nutritional value. recent years, newer techniques such as High Temperature Short Time (HTST) pasteurization have gained popularity due to their efficiency and effectiveness. HTST pasteurization involves rapidly heating milk to a high temperature for a short duration of time, followed by rapid cooling. This process helps to minimize the loss of flavor and nutrients in milk while ensuring its safety. However, there is still a need in the market for a compact and remotely controlled process plant for milk pasteurization. The proposed work aims to address this need by designing a process plant that is not only compact but also remotely controlled, allowing for efficient and convenient operation. can control the process plant remotely, allowing for flexibility and convenience in monitoring and managing the pasteurization process from anywhere with an internet connection

The Lambousa fishtank, an archaeological structure entirely carved in bedrock, can be easily recognized and measured in plan on Google Earth (GE). We surveyed in situ this excellent archaeological marker in 2016 through direct measurements using traditional field measurements, such as metric tapes and invar rods, and terrestrial photogrammetry, using Structure from Motion (SfM) methods. The bedrock on which the fishtank is founded is an Upper Pleistocene calcarenite also containing Persistrombus Latus. The age of the studied fishtank has not been previously published, but on the basis of the construction technique and the interpretation provided by [1] and references therein . We assume that it was built in the period between 2.1 and 1.8 ka BP, like similar fishtanks in the Mediterarranen area. Architectural structures consist of an evident crepido ora a stone base, and a tunnel which allows for sea water exchange during high tides. The aforementioned hole is well correlated with the crepido which lies around the fishtank. These architectural components allow to evaluate the palaeosea level with significant precision during the time when the fishtank was active. MIS 5.5 coastal deposits that outcrop in the study area are located at a maximum altitude of a few meters, while the inner margin of the MIS 5.5 terrace allows us to hypothesize a “quasi-tectonic stability” also in the long-term. We have also tested several GIA predictions of relative sea level at Lambousa for the past 3.5 kyr according to GIA models ICE-6G (VM5a), ICE-7G (VM7) and to the GIA model by Lambeck and Purcell (2015), obtained with the SELEN4 sea level equation solver.

The hinterland of the Taranto Gulf in Basilicata (southern Italy) provides a great opportunity for the study of coarse-grained coastal systems belonging to a staircase of Quaternary terraced ma-rine-deposits. Among gravelly successions, beach deposits abound in the stratigraphic record, offering exceptional outcrops useful to allow detailed information on their facies features. In this paper, we describe sedimentary facies, textural variations and depositional architecture of these deposits in order to: - demonstrate that the area is an excellent training ground for the study of gravelly beaches in microtidal settings; - discuss about the use of beach deposits as proxy of even small relative sea level variation.

This paper deals with the use of low earth orbit (LEO) satellite links in long-term monitoring of water, ice and snow levels across wide geographic areas, where no other communication links can be applied. Unlike geostationary satellites, LEO satellites do not maintain the same position relative to the ground station, and transmissions need to be scheduled for satellite overfly periods. For our application, the energy consumption optimization is critical, and we develop a learning approach for scheduling the transmission times from the sensors. Our approach is based on online learning, and is applicable to any LEO satellite transmissions.

We investigate the extent to which a two-level quantum system subjected to an external time-dependent drive can be characterized by supervised learning. We apply this approach to the case of bang-bang control and the estimation of the offset and the final distance to a given target state. The estimate is global in the sense that no a priori knowledge is required on the parameters to be determined. Different neural network algorithms are tested on a series of data sets. We point out the limits of the estimation procedure with respect to the properties of the mapping to be interpolated. We discuss the physical relevance of the different results.

An equation for the Fermi level of impurity isotropic semiconductors is considered when the bottom of the conduction band and the top of the valence band are at the center of the first Brillouin zone. The energy of charge carriers in the valence and conduction bands of semiconductors is considered taking into account the real positions of the top of the valence band and the bottom of the conduction band in the first Brillouin zone. A universal equation for determining the Fermi levels of impurity isotropic semiconductors is presented.

The devastating COVID-19 pandemic forced academia to go virtual. Educational institutions around the world have stressed online learning programs in the aftermath of the pandemic. However, because of insufficient access to ICT, a substantial number of students failed to harness the opportunity of online learning. This study explores the latent digital divide exhibited during the COVID-19 pandemic while online learning activities are emphasized among Bangladeshi students. It also investigates the digital divide exposure and the significant underlying drivers of the divide. A cross-sectional survey was employed to collect quantitative data mixed with open-ended questions to collect qualitative information from the student community. The findings revealed that despite the majority of students have physical access to ICT but only 32.5% of students could attend online classes seamlessly, 34.1% of the students reported the data prices as the critical barrier, and 39.8% of students identified the poor network infrastructure is the significant barrier for them to participate in online learning activities. Although most students possess physical access to the device and the Internet, they face the first-level digital divide due to the quality of access and maintaining subscriptions. Consequently, they fail to take advantage of physical access, resulting in the third-level digital divide (Utility Gap) and submerging them into a digital divide cycle. This paper aimed to explore the underlying issues of the digital divide among Bangladeshi students to assist relevant stakeholders (e.g., the Bangladesh government, Educational Institutions, Researchers) in providing the necessary insights and theoretical understanding to arrange adequate support for students to undertake conducive online learning activities.

Dynamical system tools offer a complementary approach to detailed biophysical seizure modeling, with a high potential for clinical applications. This review describes the theoretical framework that provides a basis for theorizing certain properties of seizures and for their classification according to their dynamical properties at onset and offset. We describe various modeling approaches spanning different scales, from single neurons to large-scale networks. This narrative review provides an accessible overview of this field, including non-exhaustive examples of key recent works.

This study aimed to analyze the responsiveness of the 5STS test among stroke patients and to estimate the MCIDs for different severity levels of community ambulation and stages of recovery. The 5STS and comparator instruments [gait speed and Functional Ambulatory Category (FAC)] were evaluated at baseline. These measures were repeated at 4 (Stage 1) and 8 weeks (Stage 2), together with the Global Rating of Change (GROC). The MCIDs were calculated with two anchor-based methods using the GROC as the external criterion. Responsiveness to change for the 5STS was estimated analyzing the correlation with changes in the two comparator instruments and their capacity to discriminate improvement. For the 5STS test, while the MCIDs of the limited community ambulators were similar in the two stages (around 3 s), those of the household ambulators decreased from 1.9 s to 0.72 s. Spearman's rho coefficients showed an acceptable correlation between changes in 5STS and changes for both the FAC and gait speed changes in both stages of recovery. Our study revealed that the 5STS is responsive to functional changes in patients with stroke and that their degree of severity and stage of recovery influence the MCID values of the 5STS.

The investigation of submerged speleothems for sea level studies has made significant contributions to the understanding of the global and regional sea level variations during the Middle and Late Quateranry. This has been especially the case for the Mediterranean Sea, where more than 300 submerged speleothems sampled in 32 caves have been analysed so far. Here, we present a comprehensive review of the results obtained from the study of submerged speleothems since 1978. The studied speleothems cover the last 1.4 Ma and are focused mainly on Marine Isotope Stages (MIS) 1, 2, 3, 5.1, 5.3, 5.5, 7.1, 7.2, 7.3 and 7.5. Results reveal that submerged speleothems represent extraordinary archives providing accurate information on former sea level changes, also considering that the Mediterranean Sea is devoid of any tropical corals since the Miocene. New results from a stalagmite collected at Palinuro (Campania, Italy) characterized by marine overgrowth are also reported. The measured elevations of speleothems are contaminated by the local response to glacial- and hydro-isostatic adjustment (GIA), and thus might significantly deviate from the global eustatic signal. Age and altitude comparation between Mediterranean speleothems, flowstone from Bahamas with local GIA provide a new scenario for MIS 5 and 7 sea level reconstrutions.

COVID-19 is a pandemic with no cure. There is an urgent need for low-cost interventions. Macroclimate work through affecting microclimate. In many situations, man-made microclimate, such as air conditioning, may override the effect of natural macroclimate in determining SARS-CoV-2 pathogenicity. Ambient temperature (AT) has been roughly associated to SARS-CoV-2 transmission. To translate into a feasible practice in controlling COVID-19 pandemic, in-depth and implementable knowledge of AT role in SARS-CoV-2 transmission should be unveiled. This study aimed to determine if there is a ‘safe’ temperature that is comfortable to human beings while significantly inhibitory for SARS-CoV-2 pathogenicity. Data on monthly new deaths or new cases per million population (MDPM or MCPM) and monthly cumulated days with more cases than the previous day (DI) from March 2 to June 30, 2020 were collected from all 118 countries with population over five million. Monthly average AT negatively correlated with the transmission parameters. A significant decrease in transmission was observed when AT reached above 20 ºC. Monthly average (not average high) AT of countries with MDPM <2, MCPM<10, or DI<=7 was found to be between 24.54 and 26.89 ºC (25.18 ºC on average) with average standard error of 4.81. Thus, average AT <20, 20-25, >25 ºC were considered as high, medium, and low risk AT. Furthermore, MDPM in countries with AT <20 ºC were 80.93, 50.23, 13.52, and 5.05 times of those in countries with AT >25 ºC in March, April, May, and June, respectively. MDPM low-risk rates (<2) in countries with AT >25 ºC were 100, 83.33, 52.73, and 52.46%, respectively. In countries with AT <20 ºC, the trends were opposite. Setting indoor temperature to 25 ºC could decrease the need of social distancing for containing SARS-CoV-2 transmission. Ventilation and sanitizing the air with ultraviolet light in nonbusiness hours may be additionally effective. Cooling indoor temperature too low may be a reason of COVID-19 outbreak in some high AT countries. Authorities and the general population can evaluate COVID-19 risk level and manipulate microclimate to reduce the risk anywhere anytime based on local day average AT.

Nowadays, the uses of laser and optics in the medical areas are extremely vivid, especially low-level laser therapy. The light with the wavelength of 633 nm to 1200 nm could penetrate and propagate deep in biological tissue. To develop the low-level laser therapy device, optimizing light delivery is critical to accurately stimulate the biological effects inside the biological tissue. Nevertheless, each form of the tissues at each zone on the body had various refractive optic, absorption, scattering, and anisotropy coefficients. This paper describes the simulation results of low-level laser propagation from skin surface at the lower spine, the knee, the femur and the prostate gland with four wavelengths (633 nm, 780 nm, 850 nm, and 940 nm) by the Monte Carlo method. These simulation results are the base for developing the low-level laser therapy device, that could be used in clinical for treating the fracture, knee osteoarthritis, spinal degeneration, and benign prostatic hypertrophy.

This article presents a new method of segmenting grayscale images by minimizing Shannon's neutrosophic entropy. For the proposed segmentation method, the neutrosophic information components, i.e., the degree of truth, the degree of neutrality and the degree of falsity are defined taking into account the belonging to the segmented regions and at the same time to the separation threshold area. The principle of the method is simple and easy to understand and can lead to multiple thresholds. The efficacy of the method is illustrated using some test gray level images. The experimental results show that the proposed method has good performance for segmentation with optimal gray level thresholds.

Nizatidine is a gastroprotective drug with a short biological half-life and narrow absorption window. This study aimed at developing floating tablets of nizatidine using various HPMC viscosity grades, namely K4M, E4M, K15 and K200M. Directly compressed tablets revealed an excellent uniformity in hardness, thickness and weight and nizatidine was evenly distributed within the matrix floating tablets. Buoyancy study revealed floating lag time as low as 18–38 s, and tablets remain buoyant for upto 24 h. However, the later depended upon viscosity grade of HPMC and that the higher the viscosity, the less was the total floating time. In vitro dissolution indicated viscosity dependent nizatidine release from the floating tablets. HPMC K4M and E4M based floating tablets released almost 100% drug in 12 h, whilst higher viscosity polymers such as K15 and K200M only released 81.88% and 75.81% drug, respectively. The drug release followed non-Fickian diffusion from tablets formulated with K4M, K15 and K200M, whilst super case II transport was observed with E4M based tablets. More interestingly, K4M and E4M polymers have similar viscosity yet exhibited different drug release mechanism. This was attributed to the difference in degree of substitution of methoxyl- and hydroxypropoxyl- groups on polymer backbone.

Lung nodule segmentation in CT images and its subsequent volume analysis can help determinethe malignancy status of a lung nodule. While several efficient segmentation schemes have beenproposed, only a few studies evaluated the segmentation’s performance for large nodules. In thisresearch, we contribute a semi-automatic system which is capable of performing robust 3-D segmen-tations on both small and large nodules with good accuracy. The target CT volume is de-noisedwith an anisotropic diffusion filter and a region of interest is selected around the target nodule ona reference slice. The proposed model performs nodule segmentation by incorporating a mean in-tensity based threshold in Geodesic Active Contour model in level sets. We also devise an adaptivetechnique using image intensity histogram to estimate the desired mean intensity of the nodule.The proposed system is validated on both lung nodules and phantoms collected from publicly avail-able diverse databases. Quantitative and visual comparative analysis of the proposed work withthe Chan-Vese algorithm and statistic active contour model of 3D Slicer platform is also presented.The resulting mean spatial overlap between segmented nodules and reference nodules is 0.855, themean volume bias is 0.10±0.2 ml and the algorithm repeatability is 0.060 ml. The achieved resultssuggest that the proposed method can be used for volume estimations of small as well as large-sizednodules.

Due to an increase in the number of image achieves, Content-Based Image Retrieval (CBIR) has gained attention for research community of computer vision. The image visual contents are represented in a feature space in the form of numerical values that is considered as a feature vector of image. Images belonging to different classes may contain the common visuals and shapes that can result in the closeness of computed feature space of two different images belonging to separate classes. Due to this reason, feature extraction and image representation is selected with appropriate features as it directly affects the performance of image retrieval system. The commonly used visual features are image spatial layout, color, texture and shape. Image feature space is combined to achieve the discriminating ability that is not possible to achieve when the features are used separately. Due to this reason, in this paper, we aim to explore the low-level feature combination that are based on color and shape features. We selected color moments and color histogram to represent color while shape is represented by using invariant moments. We selected this combination, as these features are reported intuitive, compact and robust for image representation. We evaluated the performance of our proposed research by using the Corel, Coil and Ground Truth (GT) image datasets. We evaluated the proposed low-level feature fusion by calculating the precision, recall and time required for feature extraction. The precision, recall and feature extraction values obtained from the proposed low-level feature fusion outperforms the existing research of CBIR.

Unmanned Aerial Vehicles (UAVs) are now filling in the gaps between spaceborne and ground-based observations and enhancing the spatial resolution and temporal coverage of data acquisition. In the realm of hydrological observations, UAVs have a key role to quantitatively characterize the surface flow allowing for remotely accessing the water body of interest. In this paper we propose a technology which uses a sensing platform encompassing a drone and a camera to determine the water level. The images acquired my means of the sensing platform are then analyzed using the Canny method to detect the edges of water level and of Ground Control Points (GCPs) used as reference points. The water level is then retrieved from images and compared to a benchmark value obtained by a traditional device. The method is tested at four locations in an artificial lake in central Italy. Results are encouraging as the overall mean error between estimated and true water level values is around 0.02 m. This technology is well suited to improve hydraulic modeling and thus provide a reliable support to flood mitigation strategies also in uneasy-to-access environments.

The grid nudging technique is often used in regional climate dynamical downscaling to make the simulated large-scale fields consistent with the driving fields. In this study, we focused on two specific questions about grid nudging: (1) which nudged variable had a larger impact on the downscaling results and (2) what was the “optimal” grid nudging strategy for each nudged variable to achieve better downscaling result during summer over the Chinese mainland. To solve this queries, 41 3-month long simulations for the summer of 2009 and 2010 were performed using the Weather Research and Forecasting model (WRF) to downscale National Centers for Environmental Prediction (NCEP) Final Operational Global Analysis (FNL) data to a 30-km horizontal resolution. The results showed that nudging horizontal wind or temperature had significant influence on the simulation of almost all conventional meteorological elements; nudging water vapor mainly affected the precipitation, humidity, and 500 hPa temperature. Moreover, the optimum nudging scheme varied with simulated regions and layers. As a whole, the optimal nudging time was one hour or three hours for nudging wind, three hours for nudging temperature, and one hour for nudging water vapor. The optimal nudged level was above the planetary boundary layer for almost every nudged variable.

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.

The research and development of non-viral gene therapy has been extensive over the past decade and has received a big push thanks to the successful approval of non-viral gene therapy products in recent times. Despite these developments, gene therapy applications in cancer have been limited. One of the main causes of this has been the imbalance in development of delivery vectors as compared to nucleic acid payloads. This paper reviews non-viral vectors that can be used to deliver nucleic acids for cancer treatment. It discusses various types of vectors and highlights their current applications. Additionally, it also discusses perspective on regulatory landscape to facilitate commercial translation of gene therapy.

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

Genes and gene trees have been extensively used to study the evolutionary relationships among populations, species, families and higher systematic clades of organisms. This brought modern Biology into a sophisticated level of understanding about the evolutionary relationships and diversification patterns that happened along the entire history of organismal evolution in Earth. Genes however have not been placed in the center of questions when one aims to unravel the evolutionary history of genes themselves. Thus, we still ignore whether Insulin share a more recent common ancestor to Hexokinase or DNA polymerase. This brought modern Genetics into a very poor level of understanding about sister group relationships that happened along the entire evolutionary history of genes. Many conceptual challenges must be overcome to allow this broader comprehension about gene evolution. Here we aim to clear the intellectual path in order to provide a fertile research program that will help geneticists to understand the deep ancestry and sister group relationships among different gene families (or orthologs). We aim to propose methods to study gene formation starting from the establishment of the genetic code in pre-cellular organisms like the FUCA (First Universal Common Ancestor) until the formation of the highly complex genome of LUCA (Last UCA), that harbors hundreds of genes families working coordinated into a cellular organism. The deep understanding of ancestral relationships among orthologs will certainly inspire biotechnological and biomedical approaches and allow a deep understanding about how Darwinian molecular evolution operates inside cells and before the appearance of cellular organisms.

Zanthoxylum armatum is an forest tree with apomixis characteristic, and RWP-RKs are plant-specific transcription factors known to regulate nitrogen response and embryonic development. However, the genome-wide analysis of RWP-RK family genes in Z.armatum is unclear. In this study, 36 ZaRWP-RK transcription factors were identified in the genome of Z.armatum, among which 15 genes were belonged to the RKD subfamily and 21 belonged to the NLP subfamily. Duplication events of ZaRWP-RK genes were mainly segmental duplication, and synteny analysis revealed close phylogenetic relationship between Z.armatum and Arabidopsis. The analysis of cis-elements indicated that ZaRWP-RK genes may be involved in the regulation of embryonic development of Z.armatum by responding to plant hormones such as abscisic acid, auxin, and gibberellin. Real-time PCR showed that the expression levels of most ZaRWP-RK genes were significantly increased from flowers to young fruits. Protein-protein interaction network analysis further revealed the potential roles of the ZaRWP-RK proteins in apomixis. Collectively, this study provide a theoretical basis for future investigations into the ZaRWP-RK genes and their regulatory mechanisms in the apomixis process of Z.armatum.

Understanding gene expression changes in chicks after vaccination against Newcastle Disease (ND) can reveal vaccine biomarkers. There is limited data on chicks’ early immune response after ND vaccination. Two trials aimed into this knowledge gap. In experiment one, forty-two 13 days-old specific pathogen free (SPF) chicks were used. Harderian glands (Hg) and tracheas (Tc) from five birds per group were sampled at 12, 24, and 48 hours post-vaccination (hpv) to evaluate the gene transcription levels by RNA sequencing (RNA-seq) and RT-qPCR. Results of RNA-seq were compared by glmFTest, while results of RT-qPCR were compared by t-test. With RNA-seq, significant up-regulation of interferon related genes along with JAK-STAT signaling pathways regulation was observed in the Hg at 24- hpv. None of the DEGs identified by RNA-seq were positive for RT-qPCR. Experiment 2 used one-hundred and twelve SPF and commercial chickens at 1 day-old and 14 days-old. Only the commercial birds had maternal antibodies for NDV. By RNA-seq, twenty core DEGs associated with innate immunity and viral genome replication inhibition were identified. Genes previously unlinked to NDV response, such as USP41, were identified. This research present genes with potential as immunity biomarkers for vaccines, yet further investigation is needed to correlate the core gene expression with viral shedding post-vaccination.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures whit bulging calvaria, hypoplasia or aplasia of clavicles permitting abnormal opposition of the shoulders, wide public symphysis, short middle phalanx of the fifth fingers and vertebral, craniofacial and dental anomalies. It is a rare disease, with a prevalence of 1-9/1,000,000, high penetrance, and variable expression. The responsible gene of CCD is the runt-related transcription factor 2 gene (RUNX2). We characterize the clinical, genetic and bioinformatic results of four CCD cases. Two Mexican familial with 6 affected members, 9 asymptomatic individuals, and two sporadic cases with CCD, as well as 100 healthy controls. Genomic DNA analyses of the RUNX2 gene was performed for Sanger sequencing. Bioinformatics tools, used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652del; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability, and structural alterations in RUNX2 protein. Our results show novel mutations that enrich the pool of RUNX2 gene mutations with CCD. In addition, one patient presented clinical data not previously reported that could represent an expanded phenotype of sever expression.

Subclinical inflammation in protocol biopsies relates to tacrolimus exposure and human leukocyte antigen (HLA) matching. We aimed to characterize transcripts associated with rejection and tacrolimus exposure and its association with transplant outcome. We tested whether gene expression is associated with rejection using strictly normal protocol biopsies (n = 17) and biopsies with TCMR or ABMR according to Banff criteria (n = 12). Subsequently, we analyzed these transcripts in a set of 4-month protocol biopsies (n = 137) to assess their association with donor and recipient characteristics, the intensity of immunosuppression, and graft outcome. Differential expression (FDR&gt;3) between normal and rejection biopsies yielded a set of 111 genes. Nineteen out of these 111 genes were correlated with tacrolimus trough levels (TAC-C0) at the time of biopsy in the protocol biopsy cohort (n=137) and allowed us to define 2 clusters of biopsies. The 2 clusters differed in donor age and tacrolimus levels. Subclinical rejection, including borderline lesions, tended to occur in the same cluster. Logistic regression analysis indicated that TAC-C0 at the time of biopsy (OR: 0.83, 95%CI:0.72-0.06, p=0.0117) was associated with cluster 2. In a follow-up averaging 70±30 months, this patient group displayed a significant decline in renal function (p=0.0135). The expression of rejection-associated transcripts in early protocol biopsies is associated with tacrolimus exposure and a faster decline in renal function.

The ability of S. aureus to infect humans and cause a wide range of infections so efficiently is a consequence of the many variant virulence factors that it can produce. Superantigens (SAgs) make up a group of them and include staphylococcal enterotoxins (SE). The main objective of this study was to detect enterotoxin gene cluster (EGC) in S. aureus isolates that caused infections in Paraguayan children in the year 2017, through an observational and cross-sectional study. The detection of the EGC including the seg, sei, sem, sen, seo, and seu genes, was carried out by end-point PCR. 181 S. aureus isolates were collected, most of them caused skin and soft tissue infections (SSTI, n=140, 77%) and came from children under 6 years 50% (n=90). At least one SE gene was detected in 96% (174/181) of isolates and 24% (44/181) carried the entire EGC. An association between methicillin resistance and seg, sei, seo, and seu gene carriage (p ≤0.05) was observed. A high prevalence of EGC was detected in S. aureus isolates collected from infected children attending the main health care centers in Paraguay, its importance is due to the potential of these toxins to aggravate staphylococcal infections.

Sweetpotato is an important miscellaneous grain crop in China, which is threatened by a variety of diseases and insect pests in the process of cultivation and production. sweetpotato stem rot is one of the common sweetpotato diseases, which seriously affects the yield and quality of sweetpotato. However, there are few studies on the mechanism of resistance to stem rot in sweetpotato. In this study, transcriptome sequencing analysis was carried out on the samples at different stages (T1, T2, T3) of stem rot pathogen infecting Xushu 48, and 44839 (T1-VS-T2), 81436 (T1-VS-T2) and 61932 (T2-VS-T3) differentially expressed genes (DEGs) were obtained. The DEGs were mainly concentrated in Alanine, aspartate and glutamate metabolism (ko00250), Carbon fixation in photosynthetic organisms (ko00710) and Amino sugar and nucleotide sugar metabolism (ko00520) and some candidate genes related to plant pathogen infection, such as receptor-like protein kinase (RLK5, RLK7), LRR receptor-like serine/threonine-protein kinase (SERK1), bHLH137, ERF9, MYB73 and NAC053, were screened. The results of this study provide genetic resources for the research on stem rot resistance of sweetpotato and provide theoretical basis for sweetpotato resistance breeding.

Coordination of activities between nuclei and organelles in plant cells involves information exchange, in which phytohormones may play an essential role. Therefore, dissection of the mechanisms of hormone-related integration between phytohormones and mitochondria is an important and challenging task. Here, we found that inputs from multiple hormones may cause changes in transcript accumulation of mitochondrial-encoded genes and nuclear genes encoding mitochondrial (mt) proteins. In particular, treatments with exogenous hormones induced changes in GUS expression in the reporter line possessing a 5'-deletion fragment of the RPOTmp promoter. These changes corresponded in part to up- or downregulation of RPOTmp in wild-type plants, which affected the transcription of mt-encoded genes, implying that promoter fragments of the RPOTmp gene are functionally involved in responses to IAA (indole-3-acetic acid), ACC (1-aminocyclopropane-1-carboxylic acid), and ABA (abscisic acid). Hormone-dependent modulations in the expression of mt-encoded genes can also be mediated through mitochondrial transcription termination factors 15, 17, and 18 of the mTERF family and genes for tetratricopeptide repeat proteins that are coexpressed with mTERF genes, in addition to SWIB5 encoding a mitochondrial SWI/SNF (nucleosome remodelling) complex B protein. These genes specifically responded to hormone treatment, displaying both negative and positive regulation in a context-dependent manner. According to bioinformatic resources, their promoter regions possess putative cis-acting elements involved in responses to phytohormones. Alternatively, hormone-related transcriptional activity of these genes may be modulated indirectly, which is especially relevant for brassinosteroids (BS). In general, the results of the study indicate that hormones are essential mediators that are able to cause alterations in the transcript accumulation of mt-related nuclear genes, which in turn trigger the expression of mt genes.

Monitoring water supply requires, among other quality indicators, the identification of the cyanobacte-ria community taking into account their potential impact in terms of water quality. In this work, cya-nobacteria strains were isolated from Cheffia reservoir and identified based on morphological features, 16S rRNA gene, phylogenetic analysis, and toxin production by PCR screening of the genes involved in the biosynthesis of cyanotoxins (mcyA, mcyE, sxtA, sxtG, sxtI, cyrJ, and anaC). Thirteen strains repre-senting six different genera: Aphanothece, Microcystis, Geitlerinema, Lyngbya, Microcoleus, and Pseudanabaena were obtained. The results demonstrated the importance of morphological features in determining the genus or the species when incongruence between the morphological and phylogenetic analysis occurs and only the utility of the 16S rRNA gene on determining higher taxonomic levels. The phylogenetic analysis confirmed the polyphyly of cyanobacteria for the Microcystis and Oscillatoriales genera. Unexpectedly, Aphanothece sp. CR 11 had the genetic potential to produce microcystins. Our study gives new insight instead of picocyanobacteria toxic genotype in this ecosystem. Thus, conven-tional water treatment methods in this ecosystem have to be adapted.

Water deficit greatly affects global crop growth and productivity, particularly in water-limited environments like upland rice cultivation, leading to reduced grain yield. Plants activate various defense mechanisms during water deficit, involving numerous genes and complex metabolic pathways. Exploring orthologous genes, linked to enhanced drought tolerance, can aid functional validation in target species using genomic data from model organisms. Here, we studied the OsCPK5 gene in upland rice, an AtCPK6 ortholog from A. thaliana, by overexpressing it in the BRSMG Curinga cultivar. Transformants were assessed under two conditions: water deficit applied 79 days after seeding, lasting 14 days, followed by 7 days of irrigation at 80% field capacity. Physiological data and samples were collected at R3, R6, and R8 stages. GM plants consistently exhibited higher OsCPK5 gene expression across stages, peaking during grain filling. During this phase, GM plants displayed reduced stomatal conductance, photosynthetic rate, and increased water use efficiency compared to non-GM plants under drought. GM plants also exhibited higher filled grain percentage in both irrigation conditions. Their drought susceptibility index was 0.9 times lower than NGM plants, and they maintained a higher chlorophyll a/b index, indicating sustained photosynthesis. NGM plants under water deficit exhibited more leaf senescence, while OsCPK5-overexpressing plants retained green leaves. Overall, OsCPK5 overexpression induced diverse drought tolerance mechanisms, hinting at potential for future development of more drought-tolerant rice cultivars.

This paper presents ConF, a novel deep learning model designed for accurate and efficient prediction of non-coding RNA families. NcRNAs are essential functional RNA molecules involved in various cellular processes, including replication, transcription, and gene expression. Identifying ncRNA families is crucial for comprehensive RNA research, as ncRNAs within the same family often exhibit similar functionalities. Traditional experimental methods for identifying ncRNA fam-ilies are time-consuming and labor-intensive. Computational approaches relying on annotated secondary structure data face limitations in handling complex structures like pseudoknots and have restricted applicability, resulting in suboptimal prediction performance. To overcome these chal-lenges, ConF integrates mainstream techniques such as residual networks with dilated convolutions and cross multi-head attention mechanisms. By employing a combination of dual-layer convolu-tional networks and BiLSTM, ConF effectively captures intricate features embedded within RNA sequences. This feature extraction process leads to significantly improved prediction accuracy compared to existing methods. Experimental evaluations conducted on a ten-fold publicly available dataset demonstrate the superiority of ConF in terms of accuracy, sensitivity, and other perfor-mance metrics. Overall, ConF represents a promising solution for accurate and efficient ncRNA family prediction, addressing the limitations of traditional experimental and computational methods.

Heart is composed of muscle cells called cardiomyocytes, including a specialized population, named pacemaker cells, that form the Cardiac Conduction System (CCS), responsible for generating the action potential dictating heart contractions. Failure of the CCS system leads to cardiac arrhythmias requiring complicated therapies and often surgical implantation of electrical pacemakers. However, recent research focusses on development of novel therapies using biological pacemakers aiming to substitute electrical devices. While most signalling pathways and transcription factors involved in the development of the pacemaker cells are known, the upstream regulatory networks need to be predicted through computer-based databases, mathematical modelling as well as functional testing of the regulatory elements in vivo, indicating the need for further research. Here we summarise the current knowledge about the vertebrate myocardial CCS system and development of the pacemaker cells and emphasise areas of future research to clarify the regulation of muscle pacemaker cells and ease development of biological therapies.

The possibility of treating more patients for a longer time, has exploded the concept of anticipation in the systemic treatment of metastatic prostate cancer (mPC). The genetic analysis of Damage DNA Repair (DDR) mutations in pathogenetic variants (PV) and the development of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors led to the first valid precision medicine option tailored for mPC. PARP inhibitors are repeating the same evolutionary path experienced for androgen receptor signaling inhibitors (ARSI), starting from the late stage of second line mCRPC in a limited population and time frame. Inevitably also PARP inhibitors will be absorbed by the concept of anticipation and intensification of care. The anticipation of PARP inhibitors in the first line mCRPC therapy is already underway and further one in mHSPC will soon be verified. According to the crosstalk between androgen receptors (AR) and DNA repair, the new message that is emerging is that the combination of PARP inhibitors with ARSI, disconnects PARP from the genetic analysis. Most of the recent trials analyzing PARP inhibitors plus abiraterone or enzalutamide, enrolled first line mCRPC irrespectively to gene PV. The conclusion of the PROPEL trial was that the advantage was independent to PV status, however the highest advantage was reported in BRCA1/2 mutated subgroup. The conclusion of the MAGNITUDE trial was different, with a significant advantage only in the DDR mutated subgroup and the DDR non-mutated was closed for further enrollment. The combination of PARP inhibitors with ARSI represents a significant strategy in the concept of anticipation and intensification of care in mPC. However, it should not nullify the advantages of precision medicine linked to the genetic analysis of DDR.

Gastrodia pubilabiata is a nonphotosynthetic and mycoheterotrophic orchid belonging to subfamily Epidendroideae. Compared to other typical angiosperm species, the plastome of G. pubilabiata is dramatically reduced in size to be only 30,698 base pairs (bp). This reduction has led to the loss of most photosynthesis-related genes and some housekeeping genes in the plastome, which now only contains 19 protein coding genes, three tRNAs, and three rRNAs. This study decoded the entire mitogenome of G. pubilabiata, which consisted of 44 contigs with a total length of 867,349 bp. Its mitogenome contained 38 protein coding genes, nine tRNAs, and three rRNAs. To determine possible gene transfer events between the plastome and the mitogenome, individual BLASTN searches were conducted, using all available orchid plastome sequences and flowering plant mitogenome sequences. Plastid rRNA fragments were found at a high frequency in the mitogenome. Seven plastid protein coding gene frangments (ndhC, ndhJ, ndhK, psaA, psbF, rpoB, and rps4) were also identified in the mitogenome of G. pubilabiata. Phylogenetic trees using these seven plastid protein coding gene fragments suggested that horizontal gene transfer (HGT) from plastome to mitogenome occurred before losses of photosynthesis related genes, leading to the lineage of G. pubilabiata. Compared to species phylogeny of the lineage of orchid, it was estimated that HGT might have occurred approximately 30 million years ago.

Prostate cancer (PCa) Lung metastases are rarely resected, therefore PCa lung metastases are insufficiently molecularly characterized. We recently identified carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as a potential driver of pulmonary metastatic spread. Here, we show the biological significance of CEACAM6 in PCa cell proliferation, apoptosis and migration. CEACAM6 was silenced by siRNA in PC3 cells. Functional assessment of apoptosis, cell viability, proliferation and migration were performed in siRNA-CEACAM6 PC3 cells. Non-treated and scrambled (scr) RNA PC3 cells were used as control. Following a specific knockdown of CEACAM6 in PC3 cells, the expression of CEACAM6 protein was significantly decreased in comparison to controls. Cell viability and cell counts decreased in CEACAM6 silent PC3 cells. In contrast, caspase-3 activity was highly elevated in siRNA-CEACAM6 PC3. Furthermore, by performing a cell scratch assay, the migration ratio in siRNA-CEACAM6 PC3 cells were significantly diminished compared with the control group after 48 hours of post transfection incubation. CEACAM6 as a cell adhesion molecule has been implicated in promoting metastatic disease in several solid tumours such as colorectal or gastric cancer. We could show that silencing of CEACAM6 has a significant functional effect on PCa cells. CEACAM6 might play an important role in fostering metastatic spread to the lung of PCa patients via enhancing proliferation and suppressing apoptosis. CEACAM6 might therefore pose an attractive therapeutic target to prevent metastatic disease.

Regular physical activity is considered one of the most valid tools able to reduce the risk of on-set of many diseases in humans. However, it is known that intense physical activity is able to induce high levels of genomic damage, while a moderate exercise was found to induce a favora-ble adaptive response by the organism. We evaluated, in a sample of amateur athletes practicing different disciplines, the level of genomic damage by means of the buccal micronuclei assay, comparing obtained data with those of subjects who practiced sport occasionally or that do not practiced any sport. The aim was to evaluate whether physical activity affects background levels of genomic damage and whether the different sports disciplines, as well as some genes poly-morphisms, differentially affect these levels. A total of 206 subjects, 125 athletes and 81 controls, were recruited. Athletes showed significantly lower values of micronuclei, nuclear buds and bi-nucleated cells with respect to controls. Sprinters and martial arts athletes showed significantly higher frequencies of micronuclei than other categories of athletes. Finally, neither sex nor gene polymorphisms seem to influence the levels of genomic damage, confirming that the observed genomic damage is probably due to the type of the sport activity.

At 2.3 megabases in length, the dystrophin gene is enormous: transcription of a single mRNA requires approximately 16 hours. Principally expressed in skeletal muscle, the dystrophin protein product protects the muscle sarcolemma against contraction-induced injury, and dystrophin deficiency results in the fatal muscle-wasting disease, Duchenne muscular dystrophy. This gene is thus of key clinical interest, and therapeutic strategies aimed at eliciting dystrophin restoration require quantitative analysis of its expression. Approaches for quantifying dystrophin at the protein level are well established, however study at the mRNA level warrants closer scrutiny: measured expression values differ in a sequence-dependent fashion, with significant consequences for data interpretation. In this manuscript we discuss these nuances of expression and present evidence to support a transcriptional model whereby the long transcription time is coupled to a short mature mRNA half-life, with dystrophin transcripts being predominantly nascent as consequence. We explore the effects of such a model on cellular transcriptional dynamics, and then discuss key implications for the study of dystrophin gene expression, focussing both on conventional (qPCR) and next-gen (RNAseq) approaches.

Real-time fluorescent quantitative PCR (RT-qPCR) is the most classic and widely used technology for evaluating the expression level of target gene. In order to select the proper internal reference genes for RT-qPCR analysis in Amorphophallus konjac (Araceae), eight candidate internal reference genes, including 25S ribosomal RNA gene (25S rRNA), 18S ribosomal RNA gene (18S rRNA), actin gene (ACT), glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH), Ubiquitin gene (UBQ), β-tubulin gene (β-TUB), eukaryotic elongation factor 1-αgene(eEF-1α), and eukaryotic translation initiation factor 4α-1 gene (eIF-4α) were selected and tested the corresponding expression level in different tissues at different growing stages. The results showed that 25S rRNA, 18S rRNA, and ACT at the reproductive periods, eEF-1α and eIF-4α at the nutritional periods, and eEF-1α, UBQ, and ACT at different leaf developmental periods had a stable level of gene expression, respectively. These results might be useful for the study of gene function in A. konjac.

Charcot–Marie–Tooth disease (CMT) and associated neuropathies constitute the most predominant genetically transmitted neuromuscular conditions; however, effective pharmacological treatments remain elusive. The extensive genetic heterogeneity of CMT, which impacts the peripheral nerves and results in a lifelong disability, presents a significant barrier to the development of comprehensive treatments. An estimated 100 loci within the human genome are linked to various forms of CMT and its related inherited neuropathies. This review delves into prospective therapeutic strategies used for the most frequently encountered CMT variants, namely CMT1A, CMT1B, CMTX1, and CMT2A. Compounds such as PXT3003, which are currently under clinical and preclinical investigation, and a broad array of therapeutic agents and their corresponding mechanisms have been discussed in this review. Furthermore, the progress in established gene therapy techniques, including gene replacement via viral vectors, exon skipping using antisense oligonucleotides, splicing modification, and gene knockdown, has been appraised. Each of these gene therapies has the potential for substantial advancements in future research.

MicroRNAs (miRNAs) regulate plant growth and development and their responses to biotic and abiotic stresses. Although extensive studies show that miR159 family members regulate leaf and flower development in Arabidopsis thaliana, the roles of miRNAs in soybean (Glycine max) are poorly understood. Here, we identified six MIR159 genes in soybean, MIR159aMIR159f, and investigate their expression patterns in plants under low-phosphorus (low-P), NaCl, or abscisic acid (ABA) treatments. In soybean leaves, MIR159e and MIR159f expression was induced by low-P treatment, while in roots, MIR159b, MIR159c, MIR159e, and MIR159f expression was upregulated. In flowers, low-P led to upregulation of MIR159a, MIR159b, MIR159c, and MIR159f, but downregulation of MIR159d and MIR159e. In soybean nodules, MIR159b was upregulated but MIR159a, MIR159c, and MIR159d was downregulated under P deficiency. NaCl treatment induced MIR159a, MIR159b, MIR159c, and MIR159e expression in leaves, and MIR159aMIR159f expression in roots. ABA treatment upregulated MIR159a, MIR159b, and MIR159c but downregulated MIR159d, MIR159e, and MIR159f in leaves. These results suggest that miR159 family members function in plant abiotic stress responses. Moreover, total P content in leaves was significantly lower in plants overexpressing MIR159e than in the wild type, suggesting that miR159e may regulate P absorption and transport in soybean.

Diabetes is a chronic condition that worsens living conditions and causes significant problems, particularly in the vascular system. Many different treatment options are used to prevent these negative effects of diabetes. The most important of these is changing living conditions and exercising regularly.This study aimed todetermining the impacts of a 6-week anaerobic exercise protocol on the blood glucose levels and Glut4 gene expression in the muscle tissues of streptozocin (STZ)-induced diabetic rats. A total of 45 rats were separate control, sedentary, and exercise groups (n=15 each). The STZ used to induce diabetes in rats was applied once with a single intraperitoneal injection. No diabetes was created in the control group, and no exercise was performed, whereas in the sedentary group, diabetes was induced, and no exercise was applied. It was determined that the Glut4 gene expression in the muscle tissue of the exercise group was importantly increased when compared with the sedentary diabetes group.Glut4 gene is an important gene involved in blood glucose regulation and anaerobic exercise significantly increased the expression level of this gene in our study.