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Long noncoding RNAs (lncRNAs) are important regulators of transcription; however, their involvement in protein translation is not well known. Here we explored whether the lncRNA GAS5 is associated with translation initiation machinery and regulates translation. GAS5 was enriched with eukaryotic translation initiation factor-4E (eIF4E) in an RNA-immunoprecipitation assay using lymphoma cell lines. We identified two RNA binding motifs within eIF4E protein and the deletion of each motif inhibited the binding of GAS5 with eIF4E. To confirm the role of GAS5 in translation regulation, GAS5 siRNA and in vitro transcribed GAS5 RNA were used to knock down or overexpress GAS5, respectively. GAS5 siRNA had no effect on global protein translation but did specifically increase c-Myc protein level without an effect on c-Myc mRNA. The mechanism of this increase in c-Myc protein was enhanced association of c-Myc mRNA with the polysome without any effect on protein stability. In contrast, overexpression of in vitro transcribed GAS5 RNA suppressed c-Myc protein without affecting c-Myc mRNA. Interestingly, GAS5 was found to be bound with c-Myc mRNA, suggesting that GAS5 regulates c-Myc translation through lncRNA-mRNA interaction. Our findings have uncovered a role of GAS5 lncRNA in translation regulation through its interactions with eIF4E and c-Myc mRNA.

Double/triple-hit lymphomas (DHL/THL) account for 5–10% of diffuse large B cell lymphoma (DLBCL) with rearrangement of MYC and BCL2 and/or BCL6 resulting in MYC overexpression. Despite the poor prognosis of DHL, R-CHOP chemotherapy remains the treatment backbone and new targeted therapy is needed. We performed comprehensive cytogenetic studies/fluorescence in situ hybridization on DLBCL and Burkitt lymphoma cell lines ( n = 11) to identify the DHL/THL DLBCL in vitro model. We identified MYC/IG in Raji and Ramos (single hit); MYC/IG-BCL2 (DHL) in DOHH2, OCI-LY1, SUDHL2, and OCI-LY10; MYC/IG-BCL2/BCL6 (THL) in VAL; and no MYC rearrangement in U2932 and HBL1 (WT-MYC). Targeting MYC in the DHL/THL DLBCLs through bromodomain extra-terminal inhibitors (BETi) (JQ1, I-BET, and OTX015) significantly ( p < 0.05) reduced proliferation, similar to WT-MYC cells, accompanied by decreased MYC but not BCL2 protein. Moreover, BETi suppressed MYC transcription and decreased BRD4 binding to MYC promoter in DHL cells. CD47 and PD-L1 are immunoregulatory molecules often expressed on tumors and regulated by MYC . High levels of surface CD47 but not surface PD-L1 was observed in DHL/THL, which was reduced by JQ1 treatment. BETi in combination with Pan-HDAC inhibitor had a limited effect on survival of DHL/THL, while combination of BETi and BCL2 inhibitor (ABT-199) had a significant ( p < 0.005) inhibitory effect on survival followed by BCL-XL inhibition. Overall, the data suggests that MYC-expressing DLBCLs are probably addicted to the MYC-oncogenic effect regardless of MYC rearrangements. In summary, we identified an in vitro model for DHL/THL DLBCLs and provide evidence for the therapeutic potential of BET inhibitor alone or in combination with BCL2 inhibitor.

Background and aims Stillbirth rate is an indicator reflecting quality of maternal healthcare services available to a pregnant woman in a country. At the community and individual level, it continues to be a public health tragedy. This paper presents the stillbirth rate, its causes and characteristics of women who experienced stillbirth from five years data of hospital-based stillbirth surveillance system. We also attempted to study the association between number of antenatal check-ups and causes of stillbirths, period of gestation and maternal parameters like presence of anaemia at the time of delivery. Methodology A multisite hospital-based sentinel surveillance system for estimating the stillbirth rate and its causes was established across seven tertiary care government hospitals of Delhi, India in 2015. A standardized stillbirth form was used to record information, and data was collected using an online portal from all hospitals. The data from 2016 to 2020 was analysed for calculating the stillbirth rate, its causes and maternal characteristics using STATA version 17. Results Of the 12,569 stillbirths recorded among 416,677 deliveries, the still birth rate over the time period 2016–2020 was 29.3 per 1000 births. Nearly 50% women who experienced stillbirths did not receive any antenatal care. Antepartum stillbirths were more common (75.7%), the remaining were the intrapartum stillbirths (24.3%). Among antepartum causes, the most prevalent maternal cause was preterm labour (25.7%) followed by placental abruption/placenta previa/hemorrhage in 15.2%. Among foetal causes, majority of the still births were due to fetal growth restriction (31.2%) followed by congenital malformations (7%). Uterine rupture and eclampsia were reported as major intrapartum causes leading to still births in 11% and 8.3% cases, respectively. Conclusions The stillbirth rate of 29.3 per 1,000 births from hospital data underscores the need for community-based surveillance. Nearly half of pregnant women lacked antenatal care, and 75% of stillbirths were antepartum, stressing the need to strengthen antenatal care- both coverage and quality. Routine symphysio-fundal height measurements, mandatory third-trimester ultrasounds, and partograph use may help reduce intrapartum stillbirths.

Abiotic stresses profoundly alter plant growth and development, resulting in yield losses. Plants have evolved adaptive mechanisms to combat these challenges, triggering intricate molecular responses to maintain tissue hydration and temperature stability during stress. A pivotal player in this defense is histone modification, governing gene expression in response to diverse environmental cues. Post-translational modifications (PTMs) of histone tails, including acetylation, phosphorylation, methylation, ubiquitination, and sumoylation, regulate transcription, DNA processes, and stress-related traits. This review comprehensively explores the world of PTMs of histones in plants and their vital role in imparting various abiotic stress tolerance in plants. Techniques, like chromatin immune precipitation (ChIP), ChIP-qPCR, mass spectrometry, and Cleavage Under Targets and Tag mentation, have unveiled the dynamic histone modification landscape within plant cells. The significance of PTMs in enhancing the plants’ ability to cope with abiotic stresses has also been discussed. Recent advances in PTM research shed light on the molecular basis of stress tolerance in plants. Understanding the intricate proteome complexity due to various proteoforms/protein variants is a challenging task, but emerging single-cell resolution techniques may help to address such challenges. The review provides the future prospects aimed at harnessing the full potential of PTMs for improved plant responses under changing climate change.

Background Anthocyanins such as cyanidin 3- O -glucoside (C3G) have wide applications in industry as food colorants. Their current production heavily relies on extraction from plant tissues. Development of a sustainable method to produce anthocyanins is of considerable interest for industrial use. Previously, E. coli -based microbial production of anthocyanins has been investigated extensively. However, safety concerns on E. coli call for the adoption of a safe production host. In the present study, a GRAS bacterium, Corynebacterium glutamicum , was introduced as the host strain to synthesize C3G. We adopted stepwise metabolic engineering strategies to improve the production titer of C3G. Results Anthocyanidin synthase (ANS) from Petunia hybrida and 3- O -glucosyltransferase (3GT) from Arabidopsis thaliana were coexpressed in C. glutamicum ATCC 13032 to drive the conversion from catechin to C3G. Optimized expression of ANS and 3GT improved the C3G titer by 1- to 15-fold. Further process optimization and improvement of UDP-glucose availability led to ~ 40 mg/L C3G production, representing a > 100-fold titer increase compared to production in the un-engineered, un-optimized starting strain. Conclusions For the first time, we successfully achieved the production of the specialty anthocyanin C3G from the comparatively inexpensive flavonoid precursor catechin in C. glutamicum . This study opens up more possibility of C. glutamicum as a host microbe for the biosynthesis of useful and value-added natural compounds.

In India, digital divide is evident among rural sections of the society among women. For bridging this gap, the physical access to information and communications technology (ICT) along with training to harness these skills is important. This would empower the girls to gain more control over their health, finances, and safety, and can more freely assert their voice and agency. The project aimed to measure the knowledge and skills about the digital tools and its impact in different spheres of life (status of schooling, uptake of government schemes and mobility) for the adolescent girls before and after the implementation of the digital literacy training programme (DLTP) in rural India. The project was implemented in eight blocks of District Gumla of Jharkhand for three years from 2017-2020. The evaluations were conducted in three terms that is, baseline, midline and endline by using quasi-experimental research design. A quantitative questionnaire was developed to collect data from school dropout girls of 10–19 years. The sample coverage for intervention and comparison arm was 314 and 272 at the baseline, 318 and 260 at the midline, and 402 vs 202 in the endline. A state-of-the-art training curriculum was designed covering various components of digital literacy (hardware, software, applications, internet, emailing, social media, cyber security, education and career opportunities in the digital space). A team of facilitators were provided a laptop and a pico projector to conduct trainings in the intervention blocks. Majority of the participants were unmarried, lived along their parents and had ever attended school in both intervention and comparison arm. There was no significant difference in the proportion of girls having digital literacy score above median between intervention and comparison arm at the baseline. At the midline, the proportion of these girls with above median score was significantly higher in the intervention arm [n=203, 63.8%] as compared to the comparison arm [n=107, 41.2%]. Similarly, at the endline, the proportion of girls with higher median score for digital literacy increased significantly in the intervention arm [n=362, 90%] as compared to comparison arm [n=84, 41.6%]. The proportion of girls continuing education, physical access to ICT devices at home, exposure to mass media and perceived physical security increased in the intervention arm at the midline and endline as compared to comparison arm in the baseline. A significantly higher proportion of girls had knowledge about government schemes in the intervention arm as compared to comparison arm at the endline (p<0.05). We conclude that such tailor-made training programs which are weaved within cultural contexts can effectively bridge the digital gaps in resource scare settings. Along with this, they have the potential to bridge the literacy and economic gaps also within the community.

Maize ( Zea mays ) is the most important coarse cereal utilized as a major energy source for animal feed and humans. However, maize grains are deficient in methionine, an essential amino acid required for proper growth and development. Synthetic methionine has been used in animal feed, which is costlier and leads to adverse health effects on end-users. Bio-fortification of maize for methionine is, therefore, the most sustainable and environmental friendly approach. The zein proteins are responsible for methionine deposition in the form of δ-zein, which are major seed storage proteins of maize kernel. The present review summarizes various aspects of methionine including its importance and requirement for different subjects, its role in animal growth and performance, regulation of methionine content in maize and its utilization in human food. This review gives insight into improvement strategies including the selection of natural high-methionine mutants, molecular modulation of maize seed storage proteins and target key enzymes for sulphur metabolism and its flux towards the methionine synthesis, expression of synthetic genes, modifying gene codon and promoters employing genetic engineering approaches to enhance its expression. The compiled information on methionine and essential amino acids linked Quantitative Trait Loci in maize and orthologs cereals will give insight into the hotspot-linked genomic regions across the diverse range of maize germplasm through meta-QTL studies. The detailed information about candidate genes will provide the opportunity to target specific regions for gene editing to enhance methionine content in maize. Overall, this review will be helpful for researchers to design appropriate strategies to develop high-methionine maize.

BackgroundStillbirth remains a major global health challenge, with India bearing a substantial share of the burden. Despite the availability of evidence-based interventions, stillbirth rates (SBRs) remain high due to gaps in healthcare access, quality and the effective delivery of maternal and neonatal care. This study aims to develop and implement an optimised, context-specific model to reduce SBRs in Sangrur district, Punjab.Methods and analysisThis mixed-methods implementation research will adopt a sequential explanatory design. The study will be conducted over 3 years in four blocks of Sangrur. Data will be collected through baseline and endline surveys, verbal autopsies of stillbirths, direct observations of antenatal and intrapartum care, and qualitative interviews with community members and healthcare providers. The intervention package will focus on preconception and antepartum care, intrapartum care and strengthening health systems. The study will use the plan-do-check-act model for continuous improvement, and real-time data collection through electronic systems will support timely decision-making.The study expects to achieve a 25% reduction in SBRs through the optimised delivery of high-quality antenatal and intrapartum care services. Additionally, the research will provide critical evidence on the barriers and facilitators to optimise service delivery, as well as insights into the health system and community factors influencing stillbirth outcomes. This study aims to create a scalable and adaptable intervention model to reduce SBRs in low-resource settings like Sangrur and Punjab. The findings will inform future maternal and neonatal health policies and provide a framework for the broader implementation of similar interventions in other regions of India.Ethics and disseminationThe study protocol has been approved by the International Institute of Health Management Research, Delhi (IIHMR) Institutional Ethics Committee (IRB/2024-2025/01). The study is funded through a competitive call for proposals on stillbirths by the Indian Council of Medical Research (ICMR) under the National Health Research Priority Projects (5/7BMIPR/2022-RBMCH). The research has been awarded by ICMR (project ID NHRP05586) to IIHMR under grant number 5/7/BMIPR/2022-RCN.

BackgroundReducing adult mortality by 2030 is a key component of the United Nations Sustainable Development Goals (UNSDGs). Monitoring progress towards these goals requires timely and reliable information on deaths by age, sex and cause. To estimate baseline measures for UNSDGs, this study aimed to use several different data sources to estimate subnational measures of premature adult mortality (between 30 and 70 years) for India in 2017.MethodsAge-specific population and mortality data were accessed for India and its 21 larger states from the Civil Registration System and Sample Registration System for 2017, and the most recent National Family and Health Survey. Similar data on population and deaths were also procured from the Global Burden of Disease Study 2016 and the National Burden of Disease Estimates Study for 2017. Life table methods were used to estimate life expectancy and age-specific mortality at national and state level from each source. An additional set of life tables were estimated using an international two-parameter model life table system. Three indicators of premature adult mortality were derived by sex for each location and from each data source, for comparative analysisResultsMarked variations in mortality estimates from different sources were noted for each state. Assuming the highest mortality level from all sources as the potentially true value, premature adult mortality was estimated to cause a national total of 2.6 million male and 1.8 million female deaths in 2017, with Bihar, Maharashtra, Tamil Nadu, Uttar Pradesh and West Bengal accounting for half of these deaths. There was marked heterogeneity in risk of premature adult mortality, ranging from 351 per 1000 in Kerala to 558 per 1000 in Chhattisgarh among men, and from 198 per 1000 in Himachal Pradesh to 409 per 1000 in Assam among women.ConclusionsAvailable data and estimates for mortality measurement in India are riddled with uncertainty. While the findings from this analysis may be useful for initial subnational health policy to address UNSDGs, more reliable empirical data is required for monitoring and evaluation. For this, strengthening death registration, improving methods for cause of death ascertainment and establishment of robust mortality statistics programs are a priority.

Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor with single-agent antitumour activity in patients with mantle cell lymphoma. We therefore tested its efficacy and toxicity in combination with rituximab (an antiCD20 antibody) in patients with relapsed or refractory mantle cell lymphoma. In a phase 2 study, patients (aged ≥18 years) at 35 centres in the USA were given temsirolimus 25 mg/week, and rituximab 375mg/m 2 per week for 4 weeks during the first cycle and thereafter a single dose of rituximab every other 28-day cycle. Both drugs were administered intravenously. Responding patients after six cycles could continue treatment for a total of 12 cycles, and were then observed without additional maintenance treatment. The primary endpoint was the proportion of patients with either rituximab-sensitive or rituximab-refractory disease who had at least a partial response. The analyses were done on all patients who were treated. The study was registered with ClinicalTrials.gov, number NCT00109967. 71 patients with mantle cell lymphoma were enrolled and 69 were assessable and were included in the final analysis. The overall response rate (ORR) was 59% (41 of 69 patients)—13 (19%) patients had complete responses and 28 (41%) had partial responses. The ORR was 63% (30 of 48; 95% CI 47–76) for rituximab-sensitive patients, and 52% (11 of 21; 30–74) for rituximab-refractory patients. The most common treatment-related grade 3 or 4 adverse events in rituximab-sensitive and rituximab-refractory patients were thrombocytopenia (eight [17%] and eight [38%], respectively), neutropenia (ten [21%] and five [24%], respectively), fatigue (eight [17%] and two [10%], respectively), leucopenia (six [13%] and three [14%], respectively), pneumonia (five [10%] and two [10%], respectively), lymphopenia (five [10%] and two [10%], respectively), pneumonitis (four [8%] and none, respectively), oedema (four [8%] and none, respectively), dyspnoea (three [6%] and two [10%], respectively), and hypertriglyceridaemia (three [6%] and two [10%], respectively). mTOR inhibitors in combination with rituximab could have a role in the treatment of patients with relapsed and refractory mantle cell lymphoma. National Institutes of Health and the Predolin Foundation.