The science‐policy interface in climate change adaptation became better managed over the past decades. However, the scientists and other knowledge producers, as well as policy makers still need to take bolder steps to more effectively engage with others to apply science and shape up policies. This paper aims to provide practical recommendations, intended to promote conversations between science and policy sectors to address climate change issues. Here, I used two different approaches to synthesize experiences and identify recommendations: a literature review and a case study. The paper stress main findings: (1) The linear communication model is still commonly involved in the science - policy dialogue and proved to be useful to increase the relevance of science and data products to decision makers. (2) When a gap between knowledge producer and knowledge user or decision maker exists, the need for a third party to specialize in bridging the gap become essential. (3) Indigenous people and knowledge must be involved in adaptation policy making based on legitimation local and traditional knowledge, designing the consultation process to broadly engage local and indigenous people, facilitating meaningful dialogues between traditional knowledge and science, and developing initiatives to strengthen skills and capacity of indigenous communities.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

One method of estimating the evaporation rate (ER) is to use a variety of evaporation pans, such as the Class A standard evaporation pan (CASEP) and the Colorado Sanken standard evaporation pan (CSSEP). In this study, the rate of evaporation of CASEP and CSSEP have been investigated and compared with each other. This study was conducted in Semnan, Iran. CSSEP was used as a test pan, which was performed in an open space around the Faculty of Civil Engineering, Semnan University. Evaporation was recorded daily for 123 days. The evaporation of the CASEP pan was obtained from the synoptic station of Semnan, which is located at a distance of 2.39 km from the test site. Meteorological data were also obtained from the synoptic station of Semnan and compared with experimental evaporation data. The results of this study showed that the daily ER from CASEP and CSSEP in the tested time periods were not significantly different. Based on the Klomogorov-Sminrov method, the best statistical distributions for CASEP and CSSEP were calculated as Error and Gamma, respectively. The coefficient of determination (R 2 ) between the two pans was estimated to be about 93%. Also, by examining the ER with other meteorological data, it was observed that the ER has the highest correlation with the average daily air temperature.

The ZIPs (ZRT/IRT-like proteins) play critical roles in the absorption, transport, and intracellular balance of metal ions essential for various physiological processes in plants. However, little is known about the pan-genomic characteristics and properties of ZIP genes in cucumber (Cucumis sativus L.). In this study, we identified 10 CsZIP genes from the pan-genome of 13 C. sativus accessions. Among them, only CsZIP10 showed no variation in protein sequence length. We analyzed the gene structure, conserved domains, promoter cis-elements, and phylogenetic relationships of these 10 CsZIP genes derived from "9930". Based on phylogenetic analysis, the CsZIP genes were classified into three branches. Amino acid sequence comparison revealed the presence of conserved histidine residues in the ZIP proteins. Analysis of promoter cis-elements showed that most promoters contained elements responsive to plant hormones. Expression profiling in different tissues showed that most CsZIP genes were expressed at relatively low levels in C. sativus leave, stem, and tendril, and CsZIP7 and CsZIP10 were specifically expressed in root, indicating their potential involvement in the absorption and transport of metal ions. Transcriptomic data indicated that these 10 ZIP genes displayed responses to both downy mildew and powdery mildew, and CsZIP1 were significantly downregulated after both salt and heat treatments. In conclusion, this study deepens our understanding of the ZIP gene family and enhances our knowledge of the biological functions of CsZIP genes in C. sativus.

Our paper examines the place of Pan-Africanism as an educational, political, and cultural movement which had a lasting impact on the on the relationship between liberation and people of African descent, in the continent of Africa and the Diaspora. We also show its evolution, beginning with formerly enslaved Africans in the Americas, to the colonial borders of the 1884 Berlin Conference, and conclude with the independence movements in Africa. For formerly enslaved Africans, Pan-Africanism was an idea that helped them see their commonalities as victims of racism. That is, they realized that they were enslaved because they came from the same continent and shared the same racial heritage. They associated the continent of Africa with freedom. The partitioning of Africa at the Berlin Conference (colonialism) created pseudo-nation states out of what was initially seen as an undivided continent. Pan-Africanism provided an ideology for rallying Africans at home and abroad against colonialism, and the creation of colonial nation-states did not erase the idea of a united Africa. As different African nations gained political independence, they took it upon themselves to support those countries fighting for their independence. The belief, then, was that as long as one African nation was not free, the continent could not be viewed as free. The existence of nation-states did not imply the negation of Pan-Africanism. The political ideas we examine include those of Marcus Garvey, W.E.B. Du Bois, Kwame Nkrumah, and Thabo Mbeki.

Fungi play an increasingly important role in the biological control of insect pests. Aspergillus oryzae XJ1 is highly virulent to locusts, which are a destructive economic pest worldwide. Because of its host association with locusts, which is unique in Aspergillus, in this study we examined the genetic relationships of A. oryzae XJ1 within Aspergillus. We sequenced the genome of A. oryzae XJ1 and compared it with the genomes of other Aspergillus species. The complete genome of A. oryzae XJ1 is 37.9 Mb, comprising 11,720 putative genes, assembled into eight chromosomes. The genome size is similar to that of other A. oryzae strains. Phylogenomic analysis indicated that A. oryzae XJ1 was most closely related to A. flavus. Core/pan-genome analysis of A. oryzae XJ1 and other Aspergillus species revealed that A. oryzae XJ1 had 704 strain-specific genes, whereas A. flavus NRRL 3357, A. oryzae KDG 21, and A. parasiticus NRRL 2999 had 646, 955, and 779 unique genes, respectively. These results indicate that A. oryzae XJ1 is genetically distinct at the genome level from other Aspergillus species, including A. oryzae and A. flavus, and its recognition as a distinct species is supported.

One of the hallmarks of the Alternative Lengthening of Telomeres (ALT) is the association with Promyelocytic Leukemia (PML) Nuclear Bodies, known as APBs. In the last years, APBs have been described as the main place where telomeric extension occurs in ALT positive cancer cell lines. A different set of proteins have been associated with APBs function, however, the molecular mechanisms behind their assembly, colocalization, and clustering of telomeres, among others, remain unclear. To improve the understanding of APBs in the ALT pathway, we integrated multi-omics analyses to evaluate genomic, transcriptomic and proteomic alterations, and functional interactions of 71 APBs-related genes/proteins in 32 PanCancer Atlas studies from The Cancer Genome Atlas Consortium (TCGA). As a result, we identified 13 key proteins which showed distinctive mutations, interactions, and functional enrichment patterns across all the cancer types and proposed this set of proteins as candidates for future ex vivo and in vivo analyses that will validate these proteins to improve the understanding of the ALT pathway, fill the current research gap about APBs function and their role in ALT, and be considered as potential therapeutic targets for the diagnosis and treatment of ALT positive cancers in the future.

Aging is the important risk factor for tumorigenesis. Metabolic reprogramming is hallmark of both aging and tumor initiation. However, how the crosstalk between aging and metabolic reprogramming affects the tumor microenvironment (TME) to promote tumorigenesis was poorly explored. We utilized a computational approach proposed by our previous work, termed as MMP3C (Modeling Metabolic Plasticity by Pathway Pairwise Comparison), to depict age-related metabolic plasticity using pan-cancer bulk RNA-seq data. Through MMP3C analysis across 17 age-related cancer types, a high metabolic organized heterogeneity was found across those cancer types. Subsequent analysis revealed a higher degree of glycolysis and impaired oxidative phosphorylation in older patients. Similar phenomenon was also observed at the single cell resolution. Many energy generation pathways, i.e., TCA cycle, oxidative phosphorylation were weakened in activated T cells and macrophages, while it increased in exhausted T cells, immunosuppressive macrophages, and Tregs in older patients. It was suggested that aging-induced metabolic switches alter the utilization of glucose, thereby influencing immune function and resulting in the remodeling of the tumor microenvironment. This study provides new insights into the associations between tumor metabolism and TME mediated by aging, linking with novel strategies for cancer therapy.

Bidirectional gene promoters affect the transcription of two genes, leading to the hypothesis that they should exhibit protection against genetic or epigenetic changes in cancer. Therefore, they provide an excellent opportunity to learn about promoter susceptibility to somatic alteration in tumors. We tested this hypothesis using data from genome-scale DNA methylation (14 cancer types), simple somatic mutation (10 cancer types), and copy number variation profiling (14 cancer types). For DNA methylation, the difference in rank differential methylation between tumor and tumor-adjacent normal matched samples based on promoter type was tested by Wilcoxon rank sum test. Logistic regression was used to compare differences in simple somatic mutations. For copy number alteration, a mixed effects logistic regression model was used. The change in methylation between non-diseased tissues and their tumor counterparts was significantly greater in single compared to bidirectional promoters across all 14 cancer types examined. Similarly, the extent of copy number alteration was greater in single gene compared to bidirectional promoters for all 14 cancer types. Furthermore, among 10 cancer types with available simple somatic mutation data, bidirectional promoters were slightly more susceptible. These results suggest that selective pressures related with specific functional impacts during carcinogenesis drive the susceptibility of promoter regions to somatic alteration.

Inflammation is widely acknowledged as a significant characteristic of cancer, playing a substantial function in both the initiation and advancement of cancers. In this research, we planned to investigate the comparison among pan-immune inflammation markers and other well-known markers (systemic immune inflammation index and neutrophil to lymphocyte ratio) to predict prognosis in individuals treated with radical cystectomy for bladder cancer. Methods: In this retrospective analysis, we focused on preoperative PIV, systemic immune inflammation index (SII), and neutrophil-lymphocyte ratio (NLR) in 193 individuals managed with radical cystectomy for bladder cancer between January 2016 and November 2022. Multivariable logistic regression assessments were perfomred to assess the predictive capabilities of PIV, SII, and NLR for infiltration of lymph nodes (N), aggressive tumor stage (pT3/pT4), and any non-organ limited disease at the time of RC. Multivariable Cox regression analyses were conducted to assess the predictive impact of PIV on Relapse-free survival (RFS), Cancer-specific survival (CSS), and Overall survival (OS). Results: Our individuals were divided into high PIV and low PIV cohorts using the optimal cut-off value (340.96 x 109/ L) based on receiver operating characteristic curve analysis for relapse-free survival. In multivariable preoperative logistic regression models, only SII and PIV correlated with the infiltration of lymph nodes, aggressive disease, and any non-organ confined disease. In multivariable Cox regression models considering presurgical clinicopathological variables, an higher PIV was associated with diminished RFS (p = 0.017) and OS (p = 0.029). In addition, in multivariable Cox regression models for postoperative outcomes, a high PIV correlated with both RFS ( p = 0.034) and OS ( p= 0.048). Conclusions: Our study suggests that PIV and SII are two very similar markers that may serve as an independent and significant predictor of aggressive disease and worse survival impacts on individuals undergoing radical cystectomy for bladder neoplasm.

Polyarteritis nodosa (PAN), also known as panarteritis nodosa, represents a form of necrotizing vasculitis that predominantly affects medium-sized vessels, although it is not restricted to them and can also involve smaller vessels. The clinical presentation is heterogeneous and characterized by a significant number of patients exhibiting general symptoms including asthenia, fever, and unintended weight loss. Although PAN can involve virtually any organ, it preferentially affects the skin, nervous system, and the gastrointestinal tract. Orchitis is a rare but specific manifestation of PAN. The absence of granulomas, glomerulonephritis and ANCA serves to distinguish PAN from other type of vasculitis. Major complications consist of hemorrhagic and thrombotic events occurring in mesenteric, cardiac, cerebral, and renal systems. Historically, PAN was frequently linked to hepatitis B virus (HBV) infection, but this association has dramatically changed in recent years due to declining HBV prevalence. Current epidemiological research often identifies connection between PAN and genetic syndromes as well as neoplasia. This article provides a comprehensive review of PAN, specifically focusing on the progression of its clinical manifestations over time.

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is in its 5th year and is being maintained by the inability of current spike-alone based COVID-19 vaccines to prevent transmission leading to the continuous emergence of variants and sub-variants of concern (VOCs). This underscores the critical need for next-generation broad-spectrum pan-Coronavirus vaccines (pan-CoV vaccine) to break this cycle and end the pandemic. The development of a pan-CoV vaccine offering protection against a wide array of VOCs requires two key elements: (1) identifying protective antigens that are highly conserved between passed, current and future VOCs; and (2) developing a safe and efficient antigens deliver system for induction of broad-based B- and T-cell immunity. This review will (1) present the current state of antigen delivery platforms involving a multifaceted approach, including bioinformatics, molecular and structural biology, immunology, and advanced computational methods; (2) discuss the challenges facing development of safe and effective antigen delivery platforms; and (3) highlight the potential of nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP) as the platform that is well suited to the needs of a next-generation pan-CoV vaccine, such as the ability to induce broad-based immunity and amenable to large-scale manufacturing to safely provide durable protective immunity against current and future Coronavirus threats.

Evaporation from surface water plays a key role in water accounting of basins, water resources management, and irrigation systems management, so simulating evaporation with high accuracy is very important. In this study, two methods for simulating pan evaporation under different climatic conditions in Iran were developed. In the first method, six experimental relationships (linear, quadratic, and cubic, with two input combinations) were determined for Iran’s six climate types, inspired by a multilayer perceptron neural network (MLP-NN) neuron and optimized with the genetic algorithm. The best relationship of the six was selected for each climate type, and the results were presented in a three-dimensional graph. In the second method, the best overall relationship obtained in the first method was used as the basic relationship, and climatic correction coefficients were determined for other climate types using the genetic algorithm optimization model. Finally, the accuracy of the two methods was validated using data from 32 synoptic weather stations throughout Iran. For the first method, error tolerance diagrams and statistical coefficients showed that a quadratic experimental relationship performed best under all climatic conditions. To simplify the method, two graphs were created based on the quadratic relationship for the different climate types, with the axes of the graphs showing relative humidity and temperature, and with pan evaporation was drawn as contours. For the second method, the quadratic relationship for semi-dry conditions was selected as the basic relationship. The estimated climatic correction coefficients for other climate types lay between 0.8 and 1 for dry, semi-dry, semi-humid, Mediterranean climates, and between 0.4 and 0.6 for humid and very humid climates, indicating that one single relationship cannot be used to simulate pan evaporation for all climatic conditions in Iran. The validation results confirmed the accuracy of the two methods in simulating pan evaporation under different climatic conditions in Iran.

The availability of multiple sequenced genomes from a single species made it possible to explore intra- and inter-specific genomic comparisons at higher resolution and build clade-specific pangenomes of several crops. The pan-genomes of crops constructed from various cultivars/accessions, landraces, and wild ancestral species represent a compendium of genes and structural variations and allow researchers to search for the novel genes and alleles that were inadvertently lost in domesticated crops during the historical process of crop domestication or in the process of extensive plant breeding. Fortunately, many valuable genes and alleles associated with desirable traits like disease resistance, abiotic stress tolerance, plant architecture, and nutrition qualities exist in landraces, ancestral species, and crop wild relatives. The novels genes from the wild ancestors and landraces can be introduced back to high-yielding varieties of modern crops by implementing classical plant breeding, genomic selection, and transgenic/gene editing approaches. Thus, pan-genomic represents a great leap in plant research and offers new avenues for targeted breeding for mitigating the impact of global climate change. Here we summarize the tools used for pangenome assembly and annotations, web-portals hosting plant pangenomes. Furthermore, we highlight a few discoveries made in crops using the pan-genomic approach and its future potential.

This study investigated the optimal treatment conditions to improve the quality of white pan bread by applying high-voltage pulsed electric fields (PEF) technology with varying electric field treatment times to bread dough. The treatment was conducted at an electric field strength of 2 kV/cm, frequency of 10 Hz, and a pulse width of 100 µs, with varying treatment time of 10, 20, and 30 min. When PEF was applied for 10 min, the treatment dough’s fermentation expansion rate was significantly higher. Bread made with the 10 min treated dough also exhibited higher weight, volume, specific volume, and moisture content, along with lower oven spring and baking loss rate. During storage, the 10 min treated samples maintained higher moisture content, while the 20 and 30 min treated samples showed no significant difference. In terms of texture profile analysis, the treated samples had lower hardness and chewiness compared to the control, while springiness, cohesiveness, and resilience tended to be slightly higher. In terms of texture, the treated samples had lower hardness and chewiness, but higher springiness, cohesiveness, and resilience compared to the control group.

Cucumber (Cucumis sativus L.) is a vital economic vegetable crop, and TRM (TONNEAU1 Recruiting Motif) gene plays a key role in cucumber organ growth. However, the pan-genomic characteristics of the TRM gene family and their expression patterns under different stresses have not been reported in cucumber. In this study, we identified 29 CsTRMs from the pan-genomes of 13 cucumber accessions, with CsTRM29 existing only in PI183967. Most CsTRM proteins exhibited differences in sequence length, except five CsTRMs having consistent protein sequence lengths among the 13 accessions. All CsTRM proteins showed amino acid variations. Analysis of CsTRM gene expression patterns revealed that six CsTRM genes strongly changed in short-fruited lines compared with long-fruited lines. And four CsTRM genes strongly responded to salt and heat stress, while CsTRM14 showed responses to salt stress, powdery mildew, gray mold and downy mildew. Some CsTRM genes were induced or suppressed at different treatment timepoint, suggesting that cucumber TRM genes may play different roles in responses to different stresses, with expression patterns varying with stress changes. Remarkably, the expression of CsTRM21 showed considerable change between long and short fruit and in responses to abiotic stresses (salt stress, heat stress) as well as biotic stresses (powdery mildew, gray mold), suggesting a dual role of CsTRM21 in both fruit shape determination and stress resistance. Collectively, this study provided a base for further functional identification of CsTRM genes in cucumber plant growth and stress resistance.

G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan GPCR involving HIV infection, colonic inflammation and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability of inhibiting cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) than in normal tissues. And among 33 cancer types, GPR15 expression is significantly correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD) positively and stomach adenocarcinoma (STAD) negatively. This study also revealed that commonly upregulated gene set in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted the structure-based virtual screening. The top 8 hits compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provided novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.

Recent studies suggest that PEBP1/RKIP and YY1, despite having distinct molecular functions, may interact and mutually influence one another's activity. They exhibit reciprocal control over each other's expression through regulatory loops, prompting the hypothesis that their interplay could be pivotal in cancer advancement and resistance to drugs. To delve into this interplay's functional characteristics, we conducted a comprehensive analysis using bioinformatics tools across a range of cancers. Our results confirm the association between elevated YY1 mRNA levels and varying survival outcomes in diverse tumors. Furthermore, we observed differing degrees of inhibitory or stimulatory effects of these two genes in various cancer pathways, along with correlations between their mRNA expression and immune infiltration. Additionally, YY1/PEBP1 expression (or methylation) displayed connections with genomic alterations across cancer types. Notably, we uncovered links between YY1/PEBP1 and different indicators of immunosuppression, such as immune checkpoint blockade response, and T-cell dysfunction/exclusion levels, across different patient groups. Overall, our findings underscore the significant role of the interplay between YY1 and PEBP1 in cancer progression, influencing genomic changes, tumor immunity or the tumor microenvironment. Additionally, these two gene products appear to impact the sensitivity of anticancer drugs, opening new avenues for cancer therapy.

INTRODUCTION There have been several advances in the treatment of hepatitis C virus (HCV) infection which have resulted in major reductions in the morbidity and mortality from liver-associated disease. These are not widely available in the Caribbean, due in part, to lack of knowledge of the epidemiology of infections with HCV. As efforts are made to eliminate HCV from the region, these and other existing barriers such as lack of an established database on HCV must be addressed. This review seeks to identify gaps in the knowledge of HCV in the Caribbean with respect to seroprevalence, genotype distribution and general epidemiologic characteristics. MATERIALS AND METHODS The literature for the period January 1, 2005, to October 2022, was reviewed to gather country specific data on HCV across the Caribbean. References were identified through indexed journals accessed through established databases. The usage pattern of HCV drugs was determined from data obtained from Pharmacists and Infectious Diseases Specialists across the region. RESULTS The prevalence of HCV in the Caribbean was 1.5%; the region should therefore be considered an area of moderate prevalence. Notably, data from specific countries were limited. The prevalence of HCV among intravenous drug users (21.9-58.8%); persons living with HIV/AIDS (0.8 to 58.5%); prisoners (32.8-64%) and men who have sex with men (MSM) (0.8-6.9%) was generally higher than in the general population (0.8-2.3%). Genotype 1 (83% was most prevalent followed by genotypes 2 (7.2%) and 3(2.1%), respectively. Drugs currently being used for treatment of HCV infections across the Caribbean include Epclusa (Sofosbuvir/velpatasvir), and Harvoni (Ledipasvir/sofosbuvir). Some of these drugs, are only available in the private sector and are sourced externally whenever needed. CONCLUSION There is a paucity of current data on the seroprevalence of HCV in the Caribbean and well-designed prospective studies are indicated to drive the implementation of treatment and control programs for HCV in the region. Barriers which need to be first overcome include unavailability and high cost of drugs used to treat HCV infections, injecting drug use and limited access to medical care and laboratory testing.

Background Cancer is one of the most concerning public health issues in the world. One of cancer hallmarks wildly accepted is sustaining proliferative signaling, which involved most of the cell cycle biological activities. Centromeric histone, Centromere Protein A (CENPA), a variant of canonical histone H3, plays an essential role in selective chromosome segregation in the cell cycle. However, so far, a systematic pan-cancer bioinformatic analysis has not been done yet. Methods We accessed genome, transcriptome, and clinical information from open databases. The genetic alteration, mRNA expression, functional enrichment, stemness, mutation association, expression in cell populations and cellular locations, cell cycle association, survival association of CENPA, and immune association were analyzed. A prognostic model for glioma patients was constructed as an example application of CENPA as a biomarker. Drugs targeting CENPA in cancer cells were also screened and predicted by the CENPA correlation of drug sensitivity and protein-ligand docking. Results CENPA had low gene mutation in cancers. CENPA was overexpressed in almost all cancer types in TCGA compared to their normal control. CENPA was highly expressed in the nucleus of malignant cells. CENPA was associated with the cell cycle of cancer cells. CENPA is a biomarker for the cell cycle G2 phase in cancer cells. CENPA was a diagnostic and prognostic biomarker across multiple cancer types. The prognosis of glioma with CENPA was reliable and can be applied with other prognostic factors. CENPA was associated with the immune microenvironment. Drugs CD-437, 3-Cl-AHPC, Trametinib, BI-2536, and GSK461364 were predicted to target CENPA in cancer cells. Conclusion CENPA was a cell cycle biomarker in cancers with diagnostic and prognostic value.

Viruses continue to provide vital insights into the field of control of gene expression. Viral transactivators, in concert with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to trans-acting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the Replication-Transcription complex might, therefore, transactivate viral and cellular RNAs in transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution, constituting a potential pan-coronaviral therapeutic target. Here, we show by using primary and secondary structural comparisons that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3, the coronaviral nucleocapsid C-terminal domains (N-CTDs) harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and the coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain similar to that in lentiviral Tat proteins.

Blood-based circulating cell free DNA(cfDNA) detection offers a non-invasive and easily accessible way for early cancer detection. Despite the extensive utility of cfDNA, there are still many challenges to develop the clinical biomarkers. For example, cfDNA with genetic alterations often compose a small portion of the DNA circulating in plasma, which can be confounded by cfDNA contributed by normal cells. Therefore, filtering out the potential false-positive cfDNA mutations from health population will be important for the cancer-based biomarkers. Additionally, many low-frequency genetic alterations are easily overlooked in small amount of cfDNA-based cancer test. We hypothesize that, the combination of diverse types of cancer studies on cfDNA can provide us a new insight to identify low-frequency genetic variant across cancer types for early clinical detection of cancers. By building a standardized computational pipeline for 1358 cfDNA samples across seven cancer types, we prioritize 129 shard genetic variants in the major cancer types. Further functional analysis of the 129 variants found that they are mainly enriched in ribosome pathways such as cotranslational protein targeting to membrane, some of which are tumor suppressor, oncogene and related to cancer initiation. In summary, our integrative analysis revealed the important roles of ribosome proteins as the common biomarkers in early cancer diagnosis.

Increased mitotic activity is associated with the genesis and aggressiveness of many cancers. To assess the clinical value of mitotic activity as prognostic biomarker, we performed a pan-cancer study on the mitotic network activity index (MNAI) constructed based on 54-gene mitotic apparatus network. Our pan-cancer assessment on TCGA (33 tumor types, 10,061 patients) and validation on other publicly available cohorts (23 tumor types, 9,209 patients) confirmed the significant association of MNAI with overall survival, progression-free survival and other prognostic endpoints in multiple cancer types, including Lower-Grade Gliomas (LGG), Breast Invasive Carcinoma (BRCA) and many others. We also showed significant association of MNAI with genetic instability, which provides a biological explanation of its prognostic impact at pan-cancer landscape. Futhermore, we found that patients with high MNAI benefit more from anti-PD-1 and Anti-CTLA-4 treatment. In addition, we demonstrated on LGG and BRCA that the multimodal integration of MNAI and the AI-empowerd Cellular Morphometric Subtypes (CMS) significantly improved the predictive power of prognosis compared to MNAI and CMS alone. Our results suggest that MNAI can be used as a potential prognostic biomarker for different tumor types toward different clinical endpoints, and multimodal integration of MNAI and CMS exceeds individual biomarker for precision prognosis.

The Rev. Martin Luther King Jr. and Nelson Mandela were two of the world's most iconic civil (political) (human) rights advocates and leaders of all time. Both advocated for, and to varying degrees, applied elements of peaceful protests to the achievement of their goals. Both spent time in jail, often concurrently, but eventually forced their respective countries to extend the same rights that white populations had denied Africans and African Americans. For the US, civil rights, voting rights, right to education, housing and housing loans suggested that equality had been achieved, capped in South Africa by the election of Nelson Mandela as the first majority-rule president, and in the US, by Barack Obama’s election to the presidency. Yet the historical over-policing, police mistreatment and more generally, the judicial system’s inordinate ‘targeting’ of African Americans, with egregious cases running from Emmett Till to Rodney King to Walter Scott to Breonna Taylor to George Floyd to Rayshard Brooks and thousands of others shows the danger of such magical thinking. The now-persistent global wave pursuing human rights, civil rights and the right to be treated equally, primarily driven by the loosely-organized Black Lives Matter (BLM) movement, has become the leading voice in pursuit of equality. Riots such as those in LA, protests in Ferguson and everywhere in summer 2020 has ushered new civil rights campaign. In the US and elsewhere, it has morphed to include historical issues such as monuments to colonialism, the US civil war, slavery and slave owners and traders, institutions, companies and people whose wealth and existence has links to slavery. Instructively, the protests persisted even as COVID-19, the hundred-year plague, continues to ravage the world. Lost in the moment is the absence of central leadership and leaders such as MLK or Mandela. Their charisma and effectiveness has been lacking for 50 years. This paper evaluates whether this has led to inconsistent civil and human rights pursuit for equality, or whether perchance, Mandela and MLK were extraordinary, once-in-a-lifetime transformative leaders uniquely selected by history for their time.

The increase in pandemics caused by RNA viruses of zoonotic origin highlights the urgent need for broad-spectrum antivirals against novel and re-emerging RNA viruses. Broad-spectrum antivirals could be deployed as first-line interventions during an outbreak while virus-specific drugs and vaccines are developed and rolled out. Viruses depend on the host’s protein synthesis machinery for replication. Several natural compounds that target the cellular DEAD-box RNA helicase eIF4A, a key component of the eukaryotic translation initiation complex eIF4F, have emerged as potential broad-spectrum antivirals. Rocaglates, a group of flavaglines of plant origin that clamp mRNAs with highly structured 5’UTRs onto the surface of eIF4A through specific stacking interactions, exhibit the largest selectivity and potential therapeutic indices among all known eIF4A inhibitors. Their unique mechanism of action limits the inhibitory effect of rocaglates to the translation of eIF4A-dependent viral mRNAs and a minor fraction of host mRNAs exhibiting stable RNA secondary structures and/or polypurine sequence stretches in their 5´UTRs, resulting in minimal potential toxic side effects. Maintaining a favorable safety profile while inducing efficient inhibition of a broad-spectrum of RNA viruses makes rocaglates into primary candidates for further development as pan-antiviral therapeutics.

The challenge posed by multi-drug resistance (MDR) of pathogenic organisms, spectacularly manifested in the 6 “ESKAPE” bacterium (two Gram-positive, four Gram-negative) species, should invoke new comprehensive strategies, and needs cooperation of scientists with medical, veterinary and natural science background. This review is aimed at informing newcomers, coming from the field of biology and genetics, about problems related to rapidly emerging, new multi-drug resistant, pathogenic, bacteria. Unlike persistence, the antibiotic resistance is inherited. A functioning “resistance gene” makes a susceptible organism resistant to a given antibiotic, encoding for polypeptides capable of acting either as decomposing enzymes, or acting as trans-membrane pumps, or membrane structure components capable of modifying the permeability implementing a «by pass» mechanism enabling the antibiotic molecule to reach its cellular target(s). A functioning “sensitivity gene” encode for a polypeptide, capable (directly or indirectly) of transferring toxic molecules into target cells, or of metabolizing non-transferable to transferable, or non-toxic molecules to toxic derivatives. A gene of a normal function could act as a “sensitivity” gene in the presence of antibiotics of chemical structures similar to the natural substrate of the gene product, (enzyme or binding/ trans-membrane protein). The Agrocin 84 story is a good example. Multi-drug resistance is a phenotypic consequence of the sequential accumulation of mutations, and/or up-take of plasmids or genomic islands carrying resistance genes from the environment via horizontal gene transfer, mediated by conjugative plasmid or bacteriophage carrying mobile genetic elements. Both multi-drug resistance and collateral sensitivity are evolutionary products. Some revealed evolutionary process and their Lamarckian and Darwinian interpretations are discussed. Toolkits of comparative full-genome sequencing, genomics, experimental evolution and population genetics may provide perspectives for overcoming the invincibility of multi-drug panresistance. The status of some recently emerging pathogenic bacterium species with zoonic features and of veterinary background is also discussed.

The advent of high throughput sequencing has enabled researchers to systematically evaluate the genetic variations in cancer, resulting in identifying many cancer-associated genes. Although cancers in the same tissue are widely categorized in the same group, they demonstrate many differences concerning their mutational profiles. Hence there is no “silver bullet” for the treatment of a cancer type. This reveals the importance of developing a pipeline to identify cancer-associated genes accurately and re-classify patients with similar mutational profiles. Classification of cancer patients with similar mutational profiles may help discover subtypes of cancer patients who might benefit from specific treatment types. In this study, we propose a new machine learning pipeline to identify protein-coding genes mutated in a significant portion of samples to identify cancer subtypes. We applied our pipeline to 12270 samples collected from the International Cancer Genome Consortium (ICGC), covering 19 cancer types. Here we identified 17 different cancer subtypes. Comprehensive phenotypic and genotypic analysis indicates distinguishable properties, including unique cancer-related signaling pathways, in which, for most of them, targeted treatment options are currently available. This new subtyping approach offers a novel opportunity for cancer drug development based on the mutational profile of patients. We also comprehensive study the causes of mutations among samples in each subtype by mining the mutational signatures, which provides important insight into their active molecular mechanisms. Some of the pathways we identified in most subtypes, including the cell cycle and the Axon guidance pathways, are frequently observed in cancer disease. Interestingly, we also identified several mutated genes and different rates of mutation in multiple cancer subtypes. In addition, our study on “gene-motif” suggests the importance of considering both the context of the mutations and mutational processes in identifying cancer-associated genes. The source codes for our proposed clustering pipeline and analysis are publicly available at: https://github.com/bcb-sut/Pan-Cancer.

This paper presents the development and implementation of a Pan-Tilt-Zoom (PTZ) camera interfaced with a Jetson processor hosting Artificial Intelligence (AI) algorithms, designed to address the challenges of traditional biometric capture for first-time passport photos of young children. The system enhances the accuracy, efficiency, and adaptability of facial biometric capture by recognizing and accommodating the dynamic and diverse behaviors of children. Utilizing AI, the system detects faces and analyzes facial features using 68 landmark points, ensuring high-quality images that meet ISO standards. These technical specifications, implementation process, and performance evaluations of the developed system are provided in this paper, demonstrating the potential of the proposed AI Face-Capture to advance biometric identification and verification for young children.

Whenever vegetated areas are monitored over time, phenological changes in land cover should be decoupled from changes in acquisition conditions, like atmospheric components, sun and satellite heights, and imaging instrument. This especially holds when the multispectral (MS) bands are sharpened for spatial resolution enhancement by means of a panchromatic (Pan) image of higher resolution, a process referred to as pansharpening. In this paper, we provide evidence that pansharpening of visible/near-infrared (VNIR) bands takes advantage from a correction of the path radiance term introduced by the atmosphere, during the fusion process. This holds whenever the fusion mechanism emulates the radiative transfer model ruling the acquisition of the Earth’s surface from space, that is, for methods exploiting a multiplicative, or contrast-based, injection model of spatial details extracted from the panchromatic (Pan) image into the interpolated multispectral (MS) bands. The path radiance should be estimated and subtracted from each band before the product by Pan is accomplished. Both empirical and model-based estimation techniques of MS path radiances are compared within the framework of optimized algorithms. Simulations carried out on two GeoEye-1 observations of the same agricultural landscape at different dates highlight that the de-hazing of MS before fusion is beneficial for an accurate detection of seasonal changes in the scene, as measured by the normalized differential vegetation index (NDVI).