Automated rendering of multi-stranded DNA complexes with pseudoknots

We present a general method for rendering representations of multi-stranded DNA complexes from textual descriptions into 2D diagrams. The complexes can be arbitrarily pseudoknotted, and if a planar rendering is possible, the method will determine one in time which is essentially linear in the size of the textual description. (That is, except for a final stochastic fine-tuning step.) If a planar rendering is not possible, the method will compute a visually pleasing approximate rendering in quadratic time. Examples of diagrams produced by the method are presented in the paper.Comment: 12 pages, 7 figure

Comparison of diagnostic accuracy of APRI and Transient Elastography for prediction of esophageal variceal bleed in liver cirrhosis

Background: Liver Cirrhosis is the end-stage for chronic liver disease. Repeated course of endoscopy is recommended, as this intervention is expensive and often poorly accepted by patients, there is a need for non-invasive methods to predicts the progression of portal hypertension as well as the presence and size of esophageal varices. This study was aimed to assess the APRI and Transient Elastography for predicting esophageal variceal bleed in cirrhotic patients. Objectives of the study were to study Diagnostic accuracy of APRI for Prediction of esophageal variceal bleed in liver cirrhosis, diagnostic accuracy of Transient Elastography for Prediction of esophageal variceal bleed in liver cirrhosis, comparison of diagnostic accuracy of APRI and Transient Elastography for Prediction of esophageal variceal bleed in liver cirrhosis. Methods: It was a Single centre, observational study in 35 patients of chronic liver disease. Patients were included in the study after fulfilling inclusion and exclusion criteria. CBC, LFT, KFT, SE, viral marker, USG whole abdomen, UGIE, Transient Elastography was done. APRI was calculated for every patient. Results: The APRI and Transient Elastography showed moderate diagnostic accuracy in predicting the presence of esophageal variceal bleed. Transient Elastography performed better for prediction of esophageal variceal bleed. Conclusions: The APRI and Transient Elastography showed moderate diagnostic accuracy in predicting the presence of esophageal variceal bleed. They help in starting prophylactic therapy earlier to prevent the bleeding and other complications of varices. These non-invasive parameters can also play an effective role in conjunction with endoscopy in predicting the presence of esophageal varices

A prospective randomized controlled trial to study the effect of prenatal yoga on maternal weight gain and psychological stress in pregnancy and its association with pregnancy outcomes

Background: Objective of study was to evaluate the effect of prenatal yoga on maternal gestational weight gain (GWG) and psychological stress in pregnancy (PSS) and to evaluate the effect of prenatal yoga on labour outcomes. Methods: Prospective randomized controlled trial conducted at AIIMS, New Delhi between May 2020-December 2021. Sixty women each were recruited in the yoga and control group. Women in the yoga group attended 60 minutes supervised yoga sessions followed by self-sessions. Women in the control group received routine antenatal care along with 30 minutes per day of walking and dietary counselling. The assessment was done for the weight(WT), dietary intake (D) and perceived stress score (PSS) at the time of recruitment (WT1, D1, PSS1), 28 weeks (WT2, D2, PSS2) and 36 weeks (WT3, D3, PSS3) and the results were then compared. Results: At recruitment all the parameters in both groups were comparable. The difference in mean and difference in percentage in terms of gestational weight gain (GWG) at recruitment and at 36 weeks was statistically significant (p-value=0.027). The per cent weight gain in the Yoga group was significantly low (p value=0.048). The control group experienced more amount of stress both at 28 weeks (p-value = 0.021) and 36 weeks (p-value <0.0001). The difference in mean and difference in percentage in terms of PSS1 and PSS2 (p-value=0.011), PSS2 and PSS3 (p-value=0.0001) PSS1 and PSS 3 (p-value=0.0001). Labour outcomes were comparable between both groups. Conclusions: Yoga helps in controlling excessive GWG and helps prevent many adverse feto-maternal outcomes associated with obesity

SSR marker-based DNA fingerprinting of Sub1 introgressed lines in the background of traditional rice varieties of Assam India

350-356Rice varieties are usually characterized by agro-morphological descriptors used for seed certification and seed characterization by following distinctiveness, uniformity, and stability (DUS) test. But in fact, these primary distinguishing morphological descriptors among rice varieties are very limited and hence face problems to distinguish germplasm accessions. Germplasm certification in NBPGR requires a DNA fingerprinting profile to explain germplasm uniqueness compared to existing varieties. Varietal identification has gained a key role worldwide, particularly in plant variety protection. Sixty-two morphological descriptors studies have shown the Sub1 introgressed advanced lines E-6, C-210, C-196, 1189-1 and 1160-1 are distinct from the other varieties for more than 15morphological traits, based on these variations the lines were selected for DNA fingerprinting. About68 SSRs markers were used for DNA fingerprinting in seven genotypes, two of which were parents (Ranjit, Bahadur) and three Sub1 introgressed advanced lines (E6, C210, C196) in Ranjit background, and two Sub1 introgressed advanced lines (1189-1, 1160-1) in Bahadur background. DNA fingerprinting was done on these genotypes of rice using SSR markers. Among the 68 SSR markers, total 65 markers were amplified and three were found not amplified. Out of 65 markersfour of them viz. RM 152, RM 172, RM 251, and RM 346 showed better polymorphism with amplicon size ranges from 155-163 bp, 150-159 bp, 137-147 bp, and 166-175 bp, respectively, and remaining 61 showed monomorphic amplification. Therefore, SSR (Simple-sequence repeats) based DNA fingerprinting helped to differentiate Ranjit, Bahadur, E-6, C-210, C-196, 1189-1, and 1160-1. Hence, the research reveals that newly developed high-yielding Sub1 introgressed advanced lines in the background of traditional Assam rice varieties (Ranjit and Bahadur) are unique in their identity

Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms.

FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity.This work was supported in part by The Leukemia & Lymphoma Society Beat AML Program, the V Foundation for Cancer Research, the Gabrielle’s Angel Foundation for Cancer Research and the National Cancer Institute (1R01CA183947–01; 1U01CA217862–01; 1U54CA224019-01; 3P30CA069533-18S5). H.Z. received a Collins Medical Trust research grant. S.D.B. was supported by the National Cancer Institute (5R01CA138744-08)

Multifaceted link between cancer and inflammation

10.1042/BSR20100136Bioscience Reports3211-15BRPT

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

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Not AvailableConcurrent heat and moisture stress often favours root diseases caused by Macrophomina phaseolina in arid legumes. Molecular analysis revealed 92 % variation within M. phaseolina populations as compared to 8 % among populations. The first three principle coordinates of PCA analysis accounted for a 69.61 % of total variance and Eigen vectors revealed 22.89 % of total variability. The mean values of all the four populations together for Nei’s gene diversity (h) was 0.1990 and Shannon’s information index (i) was 0.3113. The result showed that the genetic diversity of M. phaseolina isolates of population 2 (cowpea) was richest among all the four populations. Analysis of molecular variance indicated that main proportion of genetic variation was within the host than among different hosts. Out of 13 representative isolates seven were molecularly identified as Rhizoctonia bataticola and six as M. phaseolina upon sequencing of 5.8S RNA region. Besides length variation in ITS-1, 5.8S rRNA gene, ITS-2 and total length, the authors report insertion/deletions at a number of places in 13 isolates sequenced. This study underlines that M. phaseolina distribution is independent of host and/or geography and validates the utility of ITS rDNA region as a reliable indicator of phylogenetic interrelationships as an additional approach for identification of the genus Macrophomina and assessing its genetic diversity.Not Availabl