Deep learning in structural bioinformatics: current applications and future perspectives.

In this review article, we explore the transformative impact of deep learning (DL) on structural bioinformatics, emphasizing its pivotal role in a scientific revolution driven by extensive data, accessible toolkits and robust computing resources. As big data continue to advance, DL is poised to become an integral component in healthcare and biology, revolutionizing analytical processes. Our comprehensive review provides detailed insights into DL, featuring specific demonstrations of its notable applications in bioinformatics. We address challenges tailored for DL, spotlight recent successes in structural bioinformatics and present a clear exposition of DL-from basic shallow neural networks to advanced models such as convolution, recurrent, artificial and transformer neural networks. This paper discusses the emerging use of DL for understanding biomolecular structures, anticipating ongoing developments and applications in the realm of structural bioinformatics.

Clinical significance of PNO1 as a novel biomarker and therapeutic target of hepatocellular carcinoma.

The RNA-binding protein PNO1 plays an essential role in ribosome biogenesis. Recent studies have shown that it is involved in tumorigenesis; however, its role in hepatocellular carcinoma (HCC) is not well understood. The purpose of this study was to examine whether PNO1 can be used as a biomarker of HCC and also examine the therapeutic potential of PNO1 knockout for the treatment of HCC. PNO1 expression was upregulated in HCC and associated with poor prognosis. PNO1 expression was positively associated with tumour stage, lymph node metastasis and poor survival. PNO1 expression was significantly higher in HCC compared to that in fibrolamellar carcinoma or normal tissues. Furthermore, HCC tissues with mutant Tp53 expressed higher PNO1 than those with wild-type Tp53. PNO1 knockout suppressed cell viability, colony formation and EMT of HCC cells. Since activation of Notch signalling pathway promotes HCC, we measured the effects of PNO1 knockout on the components of Notch pathway and its targets. PNO1 knockout suppressed Notch signalling by modulating the expression of Notch ligands and their receptors, and downstream targets. PNO1 knockout also inhibited genes involved in surface adhesion, cell cycle, inflammation and chemotaxis. PNO1 knockout also inhibited colony and spheroid formation, cell migration and invasion, and markers of stem cells, pluripotency and EMT in CSCs. Overall, our data suggest that PNO1 can be used as a diagnostic and prognostic biomarker of HCC, and knockout of PNO1 by CRISPR/Cas9 can be beneficial for the management of HCC by targeting CSCs.

Pearl millet a promising fodder crop for changing climate: a review.

The agricultural sector faces colossal challenges amid environmental changes and a burgeoning human population. In this context, crops must adapt to evolving climatic conditions while meeting increasing production demands. The dairy industry is anticipated to hold the highest value in the agriculture sector in future. The rise in the livestock population is expected to result in an increased demand for fodder feed. Consequently, it is crucial to seek alternative options, as crops demand fewer resources and are resilient to climate change. Pearl millet offers an apposite key to these bottlenecks, as it is a promising climate resilience crop with significantly low energy, water and carbon footprints compared to other crops. Numerous studies have explored its potential as a fodder crop, revealing promising performance. Despite its capabilities, pearl millet has often been overlooked. To date, few efforts have been made to document molecular aspects of fodder-related traits. However, several QTLs and candidate genes related to forage quality have been identified in other fodder crops, which can be harnessed to enhance the forage quality of pearl millet. Lately, excellent genomic resources have been developed in pearl millet allowing deployment of cutting-edge genomics-assisted breeding for achieving a higher rate of genetic gains. This review would facilitate a deeper understanding of various aspects of fodder pearl millet in retrospect along with the future challenges and their solution. This knowledge may pave the way for designing efficient breeding strategies in pearl millet thereby supporting sustainable agriculture and livestock production in a changing world.

Inhibition of ribosome assembly factor PNO1 by CRISPR/Cas9 technique suppresses lung adenocarcinoma and Notch pathway: Clinical application.

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial-mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with stage, nodal metastasis, and smoking. Lung adenocarcinoma tissues from males expressed higher PNO1 than those from females. Furthermore, lung adenocarcinoma tissues with mutant Tp53 expressed higher PNO1 than those with wild-type Tp53, suggesting the influence of Tp53 status on PNO1 expression. PNO1 knockdown inhibited cell viability, colony formation, and EMT, and induced apoptosis. Since dysregulated signalling through the Notch receptors promotes lung adenocarcinoma, we measured the effects of PNO1 inhibition on the Notch pathway. PNO1 knockdown inhibited Notch signalling by suppressing the expression of Notch receptors, their ligands, and downstream targets. PNO1 knockdown also suppressed CCND1, p21, PTGS-2, IL-1α, IL-8, and CXCL-8 genes. Overall, our data suggest that PNO1 can be used as a diagnostic biomarker, and also can be an attractive therapeutic target for the treatment of lung adenocarcinoma.

Milletdb: a multi-omics database to accelerate the research of functional genomics and molecular breeding of millets.

Millets are a class of nutrient-rich coarse cereals with high resistance to abiotic stress; thus, they guarantee food security for people living in areas with extreme climatic conditions and provide stress-related genetic resources for other crops. However, no platform is available to provide a comprehensive and systematic multi-omics analysis for millets, which seriously hinders the mining of stress-related genes and the molecular breeding of millets. Here, a free, web-accessible, user-friendly millets multi-omics database platform (Milletdb, http://milletdb.novogene.com) has been developed. The Milletdb contains six millets and their one related species genomes, graph-based pan-genomics of pearl millet, and stress-related multi-omics data, which enable Milletdb to be the most complete millets multi-omics database available. We stored GWAS (genome-wide association study) results of 20 yield-related trait data obtained under three environmental conditions [field (no stress), early drought and late drought] for 2 years in the database, allowing users to identify stress-related genes that support yield improvement. Milletdb can simplify the functional genomics analysis of millets by providing users with 20 different tools (e.g., 'Gene mapping', 'Co-expression', 'KEGG/GO Enrichment' analysis, etc.). On the Milletdb platform, a gene PMA1G03779.1 was identified through 'GWAS', which has the potential to modulate yield and respond to different environmental stresses. Using the tools provided by Milletdb, we found that the stress-related PLATZs TFs (transcription factors) family expands in 87.5% of millet accessions and contributes to vegetative growth and abiotic stress responses. Milletdb can effectively serve researchers in the mining of key genes, genome editing and molecular breeding of millets.

Epigenetic malleability at core promoter initiates tobacco PR-1a expression post salicylic acid treatment.

BACKGROUND: Tobacco's PR-1a gene is induced by pathogen attack or exogenous application of salicylic acid (SA). Nucleosome mapping and chromatin immunoprecipitation assay were used to delineate the histone modifications on the PR-1a promoter. However, the epigenetic modifications of the inducible promoter of the PR-1a gene are not fully understood yet. METHODS AND RESULTS: Southern approach was used to scan the promoter of PR-1a to identify presence of nucleosomes, ChIP assays were performed using anti-histones antibodies of repressive chromatin by di- methylated at H3K9 and H4K20 or active chromatin by acetylated H3K9/14 and H4K16 to find epigenetic malleability of nucleosome over core promoter in uninduced or induced state post SA treatment. Class I and II mammalian histone deacetylase (HDAC) inhibitor TSA treatment was used to enhance the expression of PR-1a by facilitating the histone acetylation post SA treatment. Here, we report correlated consequences of the epigenetic modifications correspond to disassembly of the nucleosome (spans from - 102 to + 55 bp, masks TATA and transcription initiation) and repressor complex from core promoter, eventually initiates the transcription of PR-1a gene post SA treatment. While active chromatin marks di and trimethylation of H3K4, acetylation of H3K9 and H4K16 are increased which are associated to the transcription initiation of PR-1a following SA treatment. However, in uninduced state constitutive expression of a negative regulator (SNI1) of AtPR1, suppresses AtPR1 expression by six-fold in Arabidopsis thaliana. Further, we report 50-to-1000-fold increased expression of AtPR1 in uninduced lsd1 mutant plants, up to threefold increased expression of AtPR1 in uninduced histone acetyl transferases (HATs) mutant plants, SNI1 dependent negative regulation of AtPR1, all together our results suggest that inactive state of PR-1a is indeed maintained by a repressive complex. CONCLUSION: The study aimed to reveal the mechanism of transcription initiation of tobacco PR-1a gene in presence or absence of SA. This is the first study that reports nucleosome and repressor complex over core promoter region maintains the inactivation of gene in uninduced state, and upon induction disassembling of both initiates the downstream gene activation process.

Unraveling the ameliorative potentials of native lichen Pyxine cocoes (Sw.) Nyl., during COVID 19 phase.

Due to the rapid increase in the novel coronavirus virulence, the entire world implemented the practice of lockdown along with the constraint of human movement. The obligation of quarantine halted most of the commercial and industrial movement that prominently disturbed the distinct key environmental parameters directly associated with the plant's and animal's health conditions. In this regard, the research aims to study the sudden shut-off of vehicular activity impact on the naturally growing lichen of the genus Pyxine cocoes. The results showed an increase in the pigments, Fv/Fm ratio, and phytohormones during the lockdown and concurrently the decreasing levels in the post-lockdown period. Interestingly, modulations in the phytohormones occur in the lockdown period as compared to the post-lockdown period. The metals Al, Cr, and Fe show the highest increasing trends in the unlocking period, whereas As, Cd, Pb, Cu, Hg, Mn, and Zn show very little variation during the running and post-lockdown phases. The lichen photosynthetic activity justifies further examination as initial biological indicators of the abrupt environmental variations prompted by such types of atmospheric situations and, to a greater extent, for the risk assessment in the near future. In conclusion, stress-phytohormone and amino acids play a significant role as stress reducers. Although lichens are well known for long environmental assessment, the present study will provide qualitative and quantitative variation in physiochemical changes in the short term and sudden environmental fluctuations. HIGHLIGHTS: • Qualitative and quantitative variation in biochemical parameters in lichen during and post-lockdown period was analyzed. • Stress-phytohormone and amino acids play a significant role as stress reducers. • Selectivity sequence reflection in heavy metal accumulation may be used in future studies.

Chronic alcohol exposure induces hepatocyte damage by inducing oxidative stress, SATB2 and stem cell-like characteristics, and activating lipogenesis.

Alcohol is a risk factor for hepatocellular carcinoma (HCC). However, the molecular mechanism by which chronic alcohol consumption contributes to HCC is not well understood. The purpose of the study was to demonstrate the effects of chronic ethanol exposure on the damage of human normal hepatocytes. Our data showed that chronic exposure of hepatocytes with ethanol induced changes similar to transformed hepatocytes that is, exhibited colonies and anchorage-independent growth. These damaged hepatocytes contained high levels of reactive oxygen species (ROS) and showed induction of the SATB2 gene. Furthermore, damaged hepatocytes gained the phenotypes of CSCs which expressed stem cell markers (CD133, CD44, CD90, EpCAM, AFP and LGR5), and pluripotency maintaining factors (Sox-2, POU5F1/Oct4 and KLF-4). Ethanol exposure also induced Nanog, a pluripotency maintaining transcription factor that functions in concert with Oct4 and SOX-2. Furthermore, ethanol induced expression of EMT-related transcription factors (Snail, Slug and Zeb1), N-Cadherin, and inhibited E-cadherin expression in damaged hepatocytes. Ethanol enhanced recruitment of SATB2 to promoters of Bcl-2, Nanog, c-Myc, Klf4 and Oct4. Ethanol also induced activation of the Wnt/TCF-LEF1 pathway and its targets (Bcl-2, Cyclin D1, AXIN2 and Myc). Finally, ethanol induced hepatocellular steatosis, SREBP1 transcription, and modulated the expression of SREBP1c, ACAC, ACLY, FASN, IL-1ß, IL-6, TNF-α, GPC3, FLNB and p53. These data suggest that chronic alcohol consumption may contribute towards the development of HCC by damaging normal hepatocytes with the generation of inflammatory environment, induction of SATB2, stem cell-like characteristics, and cellular steatosis.

Ethanol exposure of human pancreatic normal ductal epithelial cells induces EMT phenotype and enhances pancreatic cancer development in KC (Pdx1-Cre and LSL-KrasG12D ) mice.

Alcohol is a risk factor for pancreatic cancer. However, the molecular mechanism by which chronic alcohol consumption influences pancreatic cancer development is not well understood. We have recently demonstrated that chronic ethanol exposure of pancreatic normal ductal epithelial cells (HPNE) induces cellular transformation by generating cancer stem cells (CSCs). Here, we examined whether chronic ethanol treatment induces epithelial-mesenchymal transition in HPNE cells and promotes pancreatic cancer development in KC (Pdx1-Cre, and LSL-KrasG12D ) mice. Our data demonstrate that chronic ethanol exposure of HPNE cells induces SATB2 gene and those cells became highly motile. Ethanol treatment of HPNE cells results in downregulation of E-Cadherin and upregulation of N-Cadherin, Snail, Slug, Zeb1, Nanog and BMI-1. Suppression of SATB2 expression in ethanol-transformed HPNE cells inhibits EMT phenotypes. KC mice fed with an ethanol-containing diet show enhanced pancreatic cancer growth and development than those fed with a control diet. Pancreas isolated from KC mice fed with an ethanol-containing diet show higher expression of stem cell markers (CD133, CD44, CD24), pluripotency-maintaining factors (cMyc, KLF4, SOX-2, and Oct-4), N-Cadherin, EMT-transcription factors (Snail, Slug, and Zeb1), and lower expression of E-cadherin than those isolated from mice fed with a control diet. Furthermore, pancreas isolated from KC mice fed with an ethanol-containing diet show higher expression of inflammatory cytokines (TNF-α, IL-6, and IL-8) and PTGS-2 (COX-2) gene than those isolated from mice fed with a control diet. These data suggest that chronic alcohol consumption may contribute to pancreatic cancer development by generating inflammatory signals and CSCs.

Functional performance and patient satisfaction comparison between a 3D printed and a standard transradial prosthesis: a case report.

BACKGROUND: The delay between amputation and prosthesis fitting contributes to the high rate of prosthetic abandonment despite advances in technology. Three-dimensional (3D) printing has allowed for the rapid fabrication of prostheses. Allowing individuals with amputations to interact with a prosthesis shortly after their procedure may reduce rejection chances. The purpose of the current investigation is to compare functional outcomes and patient satisfaction between a standard transradial prosthesis fitted in a clinic with a 3D-printed prosthesis fitted remotely. The standard prosthesis featured a hook terminal device, while the 3D printed prosthesis' terminal device was a functional hand. RESULTS: The main finding of this case study was that the use of a 3D printed arm prosthesis fitted remotely resulted in better functional performance, but lower overall patient satisfaction than the standard arm prosthesis. Use of the 3D printed arm resulted in improved gross manual dexterity as measured by the Box and Block test. The 3D printed prosthesis also allowed improved performance in bimanual coordination. However, the standard-hook device scored higher in patient satisfaction survey results. The patient's concerns with the 3D printed prosthesis were the durability and effectiveness of the device. CONCLUSION: While durability and complex grip patterns remain a concern, the positive attributes of 3D printed prostheses include visual appeal, ease of donning, and customization of parameters to improve upper-limb symmetry offers a promising option to familiarize new amputee patients with the use of a prosthesis. Rapid manufacturing and remote fitting allows 3D printed devices to serve as postoperative transitional devices and may function as definitive devices with minimal loss of functionality if standard clinic-based prostheses are not available. METHODS: The patient was a 59-year-old male with a traumatic transradial amputation of the dominant arm. A 3D printed transradial prosthesis was remotely fitted and manufactured using photogrammetry. Assessments were performed initially with the standard-hook prosthesis and then with the 3D printed device after a 5-week familiarization period. Functional outcomes were evaluated using the Box and Block Test and Bimanual Coordination Tray Test. Patient satisfaction was evaluated using two self-reported questionnaires (the QUEST 2.0 and the modified OPUS).

Gender Affirming Laryngeal and Voice Surgery.

Gender affirmation laryngeal and voice surgeries are components of "voice-lift" or cosmetic voice surgeries. Feminization surgery can modify vocal folds (fundamental frequency [Fo]) and vocal tract (resonance frequency). For increased pitch, vocal folds should be shorter, thinner, and tighter. Cricothyroid approximation (CTA) surgery increases tension of the vocal folds. Endoscopic procedures for pitch raising are done by shortening the length and reducing mass of vocal folds. This shortening is achieved by surgically creating anterior glottic web. Comparing the results of various open and endoscopic surgical techniques, fundamental frequency (Fo) is raised maximally and remains stable after GL as compared with CTA.

Transpiration efficiency: insights from comparisons of C4 cereal species.

We have previously reported that there is a tight link between high transpiration efficiency (TE; shoot biomass per unit water transpired) and restriction of transpiration under high vapor pressure deficit (VPD). In this study, we examine other factors affecting TE among major C4 cereals, namely species' differences, soil type, and source-sink relationships. We found that TE in maize (10 genotypes) was higher overall than in pearl millet (10 genotypes), and somewhat higher than in sorghum (16 genotypes). Overall, transpiration efficiency was higher in high-clay than in sandy soil under high VPD, but the effect was species-dependent with maize showing large variations in TE and yield across different soil types whilst pearl millet showed no variation in TE. This suggested that species fitness was specific to soil type. Removal of cobs drastically decreased TE in maize under high VPD, but removal of panicles did not have the same effect in pearl millet, suggesting that source-sink balance also drove variations in TE. We interpret the differences in TE between species as being accounted for by differences in the capacity to restrict transpiration under high VPD, with breeding history possibly having favored the source-sink balance in maize. This suggests that there is also scope to increase TE in pearl millet and sorghum through breeding. With regards to soil conditions, our results indicate that it appears to be critical to consider hydraulic characteristics and the root system together in order to better understand stomatal regulation and restriction of transpiration under high VPD. Finally, our results highlight the importance of sink strength in regulating transpiration/photosynthesis, and hence in influencing TE.

Synthetic Tunability and Biophysical Basis for Fabricating Highly Fluorescent and Stable DNA Copper Nanoclusters.

The real motivation in the present work is to tune the synthesis variables that can result in a highly fluorescent and stable DNA copper nanocluster (CuNC) and also to understand the intricate mechanism behind this process. Here, carefully optimized concentrations of various reactants enabled the creation of a DNA-encapsulated CuNC for AT-DNA, displaying a size of <1.0 nm as confirmed by transmission electron microscopy and dynamic light scattering. The extremely small size of the AT-DNACuNC supports the discrete electronic transitions, also characterized by an exceptionally strong negative circular dichroism (CD) band around 350 nm, whose intensity is well correlated with the observed strong fluorescence emission intensity. This remarkably strong CD can open new applications in the detection and quantification of a specific DNACuNC. Further, time-dependent fluorescence analysis suggested stronger photostabilization of these DNACuNCs. The simulation study, based on Cu ion distribution, explained how AT-DNA is a better candidate for NC formation than GC-DNA. In conclusion, the better-tuned synthesis procedure has resulted in a highly compact, well-defined three-dimensional conformation that promotes a more favorable microenvironment to sequester a DNA-based CuNC with high brightness and outstanding photostability.

Impact of COVID-19 on Patient Trends and Outcome: Results from a Tertiary Care Burn and Plastic Unit in Northern India.

Background Burn and trauma injuries need emergency care and resuscitation, which required uninterrupted delivery of inpatient care services during the coronavirus disease 2019 (COVID-19) pandemic. Burn patients are physiologically immunocompromised, increasing the risk of COVID-19 infection in them. This study analyzes the impact of COVID-19 pandemic on patient trends in a burn and plastic unit and assesses the effect of COVID-19 infection in burns. Methods This single-center, retrospective observational case-control study was conducted in the Department of Burns, Plastic and Maxillofacial Surgery of a tertiary care hospital in New Delhi, India. Patient data was collected from April 1, 2019 to August 10, 2019 and from April 1, 2020 to August 10, 2020. All data of burns and trauma patients collected was analyzed and compared. Results There were total 350 admissions during COVID time period and 562 admissions during non-COVID time period. The admission rate, type of burn injury, and death rate did not vary significantly during the two time periods. Thermal burn was the most common type of burn injury. There were total 18 cases diagnosed to be COVID-19 positive during the pandemic. There were two deaths among COVID-19 positive burn cases. Conclusion This study finds no difference in patient patterns during COVID and non-COVID time period. Amongst burn patients, no increased risk of COVID-19 infection is seen with larger body surface area of burns. No increase in mortality is seen in burn patients infected with COVID-19.

SATB2 is a novel biomarker and therapeutic target for cancer.

Several studies have confirmed the involvement of cancer stem cells (CSC) in tumour progression, metastasis, drug resistance and cancer relapse. SATB2 (special AT-rich binding protein-2) acts as a transcriptional co-factor and modulates chromatin architecture to regulate gene expression. The purpose of this review was to discuss the pathophysiological roles of SATB2 and assess whether it could be used as a therapeutic target for cancer. SATB2 modulated the expression of those genes which regulated pluripotency and self-renewal. Overexpression of SATB2 gene in normal epithelial cells was shown to induce transformation, as a result transformed cells gained CSC's characteristics by expressing stem cell markers and pluripotency maintaining factors, suggesting its role as an oncogene. In addition, SATB2 induced epithelial-mesenchymal transition (EMT) and metastasis. Interestingly, the expression of SATB2 was positively correlated with the activation of ß-catenin/TCF-LEF pathway. Furthermore, SATB2 silencing inhibited EMT and their positive regulators, and tumour growth, and suppressed the expression of stem cell markers, pluripotency maintaining factors, cell cycle and cell survival genes, and TCF/LEF targets. Based on the cancer genome atlas (TCGA) expression data and published papers, SATB2 alone or in combination with other proteins could be used a diagnostic biomarker for cancer. Although there is no pharmacological inhibitor of SATB2, studies using genetic approaches suggest that SATB2 could be a potential target for cancer treatment and prevention.

α-Mangostin-encapsulated PLGA nanoparticles inhibit colorectal cancer growth by inhibiting Notch pathway.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related mortality. Recent studies have stated that Notch signalling is highly activated in cancer stem cells (CSCs) and plays an important role in the development and progression of CRC. Like normal colorectal epithelium, CRCs are organized hierarchically and include populations of CSCs. In order to enhance the biological activity of α-mangostin, we formulated α-mangostin-encapsulated PLGA nanoparticles (Mang-NPs) and examined the molecular mechanisms by which Mang-NPs inhibit CRC cell viability, colony formation, epithelial-mesenchymal transition (EMT) and induce apoptosis. Mang-NPs inhibited cell viability, colony formation and induced apoptosis. Mang-NPs also inhibited EMT by up-regulating E-cadherin and inhibiting N-cadherin and transcription factors Snail, Slug and Zeb1. As dysregulated signalling through the Notch receptors promotes oncogenesis, we measured the effects of Mang-NPs on Notch pathway. Mang-NPs inhibited Notch signalling by suppressing the expression of Notch receptors (Notch1 and Notch2), their ligands (Jagged 1 and DLL4), γ-secretase complex protein (Nicastrin) and downstream target (Hes-1). Notch receptor signalling regulates cell fate determination in stem cell population. Finally, Mang-NPs inhibited the self-renewal capacity of CSCs, stem cell markers (CD133, CD44, Musashi and LGR5) and pluripotency maintaining factors (Oct4, Sox-2, KLF-4, c-Myc and Nanog). Overall, our data suggest that Mang-NPs can inhibit CRC growth, EMT and CSCs' population by suppressing Notch pathway and its target. Therefore, Mang-NPs can be used for the treatment and prevention of CRC.

The Impact of obesity and diabetes mellitus on pancreatic cancer: Molecular mechanisms and clinical perspectives.

The incidence of obesity and type 2 diabetes (T2DM) in the Western world has increased dramatically during the recent decades. According to the American Cancer Society, pancreatic cancer (PC) is the fourth leading cause of cancer-related death in the United States. The relationship among obesity, T2DM and PC is complex. Due to increase in obesity, diabetes, alcohol consumption and sedentary lifestyle, the mortality due to PC is expected to rise significantly by year 2040. The underlying mechanisms by which diabetes and obesity contribute to pancreatic tumorigenesis are not well understood. Furthermore, metabolism and microenvironment within the pancreas can also modulate pancreatic carcinogenesis. The risk of PC on a population level may be reduced by modifiable lifestyle risk factors. In this review, the interactions of diabetes and obesity to PC development were summarized, and novel strategies for the prevention and treatment of diabetes and PC were discussed.

Identification of heterotic groups in South-Asian-bred hybrid parents of pearl millet.

KEY MESSAGE: Pearl millet breeding programs can use this heterotic group information on seed and restorer parents to generate new series of pearl millet hybrids having higher yields than the existing hybrids. Five hundred and eighty hybrid parents, 320 R- and 260 B-lines, derived from 6 pearl millet breeding programs in India, genotyped following RAD-GBS (about 0.9 million SNPs) clustered into 12 R- and 7 B-line groups. With few exceptions, hybrid parents of all the breeding programs were found distributed across all the marker-based groups suggesting good diversity in these programs. Three hundred and twenty hybrids generated using 37 (22 R and 15 B) representative parents, evaluated for grain yield at four locations in India, showed significant differences in yield, heterosis, and combining ability. Across all the hybrids, mean mid- and better-parent heterosis for grain yield was 84.0% and 60.5%, respectively. Groups G12 B × G12 R and G10 B × G12 R had highest heterosis of about 10% over best check hybrid Pioneer 86M86. The parents involved in heterotic hybrids were mainly from the groups G4R, G10B, G12B, G12R, and G13B. Based on the heterotic performance and combining ability of groups, 2 B-line (HGB-1 and HGB-2) and 2 R-line (HGR-1 and HGR-2) heterotic groups were identified. Hybrids from HGB-1 × HGR-1 and HGB-2 × HGR-1 showed grain yield heterosis of 10.6 and 9.3%, respectively, over best hybrid check. Results indicated that parental groups can be formed first by molecular markers, which may not predict the best hybrid combination, but it can reveal a practical value of assigning existing and new hybrid pearl millet parental lines into heterotic groups to develop high-yielding hybrids from the different heterotic groups.

Calculation of salt-dependent free energy of binding of ß-lactoglobulin homodimer formation and mechanism of dimer formation using molecular dynamics simulation and three-dimensional reference interaction site model (3D-RISM): diffuse salt ions and non-polar interactions between the monomers favor the dimer formation.

There are several important phenomena in chemistry, biology, and physics where molecules (or parts of a molecule) having charges of the same sign come closer together and become stable. DNA condensation, RNA folding, colloid-colloid interactions are some of the examples of this kind. In the current work, we have investigated how ß-lactoglobulin, a protein found in milk, in spite of carrying +13 charge, favors the homodimer formation in the presence of salt. We have focussed on calculating the protein-protein binding free energy in the presence of salt and identifying the thermodynamic and microscopic mechanism of the process. Estimation of binding free energy of this salt-dependent process is done by combining molecular dynamics simulation with statistical mechanical theory of three-dimensional reference interaction site model (3D-RISM). Binding free energy is evaluated from the chemical potential of the solutes as opposed to potential of mean force calculation, which gives only a constrained free energy. Our calculated values semi-quantitatively match with the experimental results. By examining the different components of binding free energy, we have found that the role of salt ions (especially of Cl-) is to shift the equilibrium towards the dimer. Non-polar (Lennard-Jones) interactions between the monomers is also favorable to the binding free energy. However, water slightly disfavors the dimer formation. For the microscopic mechanism, heterogeneous of both Na+ and Cl- near the charged residues at the binding interface and change of this charge distribution on dimer formation contribute to the stability. A fine-tuning of enthalpic and entropic effects of salt ions is found to operate at different salt concentrations. Both thermodynamic and microscopic mechanism of dimer formation gives detailed insight into the complex electrostatics of charged protein-protein binding.

Multiple roles of CTDK-I throughout the cell.

The heterotrimeric carboxy-terminal domain kinase I (CTDK-I) in yeast is a cyclin-dependent kinase complex that is evolutionally conserved throughout eukaryotes and phosphorylates the C-terminal domain of the largest subunit of RNA polymerase II (RNApII) on the second-position serine (Ser2) residue of YSPTSPS heptapeptide repeats. CTDK-I plays indispensable roles in transcription elongation and transcription-coupled processing, such as the 3'-end processing of nascent mRNA transcripts. However, recent studies have revealed additional roles of CTDK-I beyond its primary effect on transcription by RNApII. Here, we describe recent advances in the regulation of genomic stability and rDNA integrity by CTDK-I and highlight the previously underappreciated cellular roles of CTDK-I in rRNA synthesis by RNA polymerase I and translational initiation and elongation. These multiple roles of CTDK-I throughout the cell expand our understanding of how this complex functions to coordinate diverse cellular processes through gene expression and how the human orthologue exerts its roles in diseased states such as tumorigenesis.