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Introduction: Meiotic recombination (or crossover, CO) is essential for gamete fertility as well as for alleles and genes reshuffling that is at the heart of plant breeding. However, CO remains a limited event, which strongly hampers the rapid production of original and improved cultivars. RecQ4 is a gene encoding a helicase protein that, when mutated, contributes to improve recombination rate in all species where it has been evaluated so far., Methods: In this study, we developed wheat ( Triticum aestivum L.) triple mutant (TM) for the three homoeologous copies of TaRecQ4 as well as mutants for two copies and heterozygous for the last one (Htz-A, Htz-B, Htz-D)., Results: Phenotypic observation revealed a significant reduction of fertility and pollen viability in TM and Htz-B plants compared to wild type plants suggesting major defects during meiosis. Cytogenetic analyses of these plants showed that complete absence of TaRecQ4 as observed in TM plants, leads to chromosome fragmentation during the pachytene stage, resulting in problems in the segregation of chromosomes during meiosis. Htz-A and Htz-D mutants had an almost normal meiotic progression indicating that both TaRecQ4-A and TaRecQ4-D copies are functional and that there is no dosage effect for TaRecQ4 in bread wheat. On the contrary, the TaRecQ4-B copy seems knocked-out, probably because of a SNP leading to a Threonine>Alanine change at position 539 (T539A) of the protein, that occurs in the crucial helicase ATP bind/DEAD/ResIII domain which unwinds nucleic acids. Occurrence of numerous multivalents in TM plants suggests that TaRecQ4 could also play a role in the control of homoeologous recombination., Discussion: These findings provide a foundation for further molecular investigations into wheat meiosis regulation to fully understand the underlying mechanisms of how TaRecQ4 affects chiasma formation, as well as to identify ways to mitigate these defects and enhance both homologous and homoeologous recombination efficiency in wheat., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bazile, Nadaud, Lasserre-Zuber, Kitt, De Oliveira, Choulet and Sourdille.)

Understanding meiotic crossover (CO) variation in crops like bread wheat ( Triticum aestivum L.) is necessary as COs are essential to create new, original and powerful combinations of genes for traits of agronomical interest. We cytogenetically characterized a set of wheat aneuploid lines missing part or all of chromosome 3B to identify the most influential regions for chiasma formation located on this chromosome. We showed that deletion of the short arm did not change the total number of chiasmata genome-wide, whereas this latter was reduced by ~35% while deleting the long arm. Contrary to what was hypothesized in a previous study, deletion of the long arm does not disturb the initiation of the synaptonemal complex (SC) in early meiotic stages. However, progression of the SC is abnormal, and we never observed its completion when the long arm is deleted. By studying six different deletion lines (missing different parts of the long arm), we revealed that at least two genes located in both the proximal (C-3BL2-0.22) and distal (3BL7-0.63-1.00) deletion bins are involved in the control of chiasmata, each deletion reducing the number of chiasmata by ~15%. We combined sequence analyses of deletion bins with RNA-Seq data derived from meiotic tissues and identified a set of genes for which at least the homoeologous copy on chromosome 3B is expressed and which are involved in DNA processing. Among these genes, eight (CAP-E1/E2, DUO1, MLH1, MPK4, MUS81, RTEL1, SYN4, ZIP4) are known to be involved in the recombination pathway., Competing Interests: The authors declare no conflict of interest.

Ensuring balanced distribution of chromosomes in gametes, meiotic recombination is essential for fertility in most sexually reproducing organisms. The repair of the programmed DNA double strand breaks that initiate meiotic recombination requires two DNA strand-exchange proteins, RAD51 and DMC1, to search for and invade an intact DNA molecule on the homologous chromosome. DMC1 is meiosis-specific, while RAD51 is essential for both mitotic and meiotic homologous recombination. DMC1 is the main catalytically active strand-exchange protein during meiosis, while this activity of RAD51 is downregulated. RAD51 is however an essential cofactor in meiosis, supporting the function of DMC1. This work presents a study of the mechanism(s) involved in this and our results point to DMC1 being, at least, a major actor in the meiotic suppression of the RAD51 strand-exchange activity in plants. Ectopic expression of DMC1 in somatic cells renders plants hypersensitive to DNA damage and specifically impairs RAD51-dependent homologous recombination. DNA damage-induced RAD51 focus formation in somatic cells is not however suppressed by ectopic expression of DMC1. Interestingly, DMC1 also forms damage-induced foci in these cells and we further show that the ability of DMC1 to prevent RAD51-mediated recombination is associated with local assembly of DMC1 at DNA breaks. In support of our hypothesis, expression of a dominant negative DMC1 protein in meiosis impairs RAD51-mediated DSB repair. We propose that DMC1 acts to prevent RAD51-mediated recombination in Arabidopsis and that this down-regulation requires local assembly of DMC1 nucleofilaments., Competing Interests: The authors have declared that no competing interests exist.

The lean-to-fat ratio is a major issue in the beef meat industry from both carcass and meat production perspectives. This industrial perspective has motivated meat physiologists to use transcriptomics technologies to decipher mechanisms behind fat deposition within muscle during the time course of muscle growth. However, synthetic biological information from this volume of data remains to be produced to identify mechanisms found in various breeds and rearing practices. We conducted a meta-analysis on 10 transcriptomic data sets stored in public databases, from the longissimus thoracis of five different bovine breeds divergent by age. We updated gene identifiers on the last version of the bovine genome (UCD1.2), and the 715 genes common to the 10 studies were subjected to the meta-analysis. Of the 238 genes differentially expressed (DEG), we identified a transcriptional signature of the dynamic regulation of glycolytic and oxidative metabolisms that agrees with a known shift between those two pathways from the animal puberty. We proposed some master genes of the myogenesis, namely MYOG and MAPK14, as probable regulators of the glycolytic and oxidative metabolisms. We also identified overexpressed genes related to lipid metabolism (APOE, LDLR, MXRA8, and HSP90AA1) that may contribute to the expected enhanced marbling as age increases. Lastly, we proposed a transcriptional signature related to the induction (YBX1) or repression (MAPK14, YWAH, ERBB2) of the commitment of myogenic progenitors into the adipogenic lineage. The relationships between the abundance of the identified mRNA and marbling values remain to be analyzed in a marbling biomarkers discovery perspectives.

In the human genome, most genes undergo splicing, and patterns of codon usage are splicing dependent: guanine and cytosine (GC) content is the highest within single-exon genes and within first exons of multi-exon genes. However, the effects of codon usage on gene expression are typically characterized in unspliced model genes. Here, we measured the effects of splicing on expression in a panel of synonymous reporter genes that varied in nucleotide composition. We found that high GC content increased protein yield, mRNA yield, cytoplasmic mRNA localization, and translation of unspliced reporters. Splicing did not affect the expression of GC-rich variants. However, splicing promoted the expression of AT-rich variants by increasing their steady-state protein and mRNA levels, in part through promoting cytoplasmic localization of mRNA. We propose that splicing promotes the nuclear export of AU-rich mRNAs and that codon- and splicing-dependent effects on expression are under evolutionary pressure in the human genome., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Adipose tissue (AT) deposits, either intramuscular (i.e., marbling) or at the carcass level, are major economic drivers in the beef industry. To identify biomarkers and unravel mechanisms of AT deposition, we combined gel-based and gel-free methods and we mined the differential proteome of the longissimus thoracis from cows differing by two levels of both carcass and muscular adiposities (CMA). We identified 47 proteins with abundances that varied according to CMA. We listed 26 new candidate biomarkers of marbling and confirmed 21 proteins already proposed in the literature. Seven proteins involved in glycolysis or gluconeogenesis were the least abundant, while 14 proteins related to oxidative metabolism, slow-type muscle or retinoic acid metabolism were the most abundant in the high adiposity group. We highlighted eight proteins as differentially abundant and correlated with both CMA, thereby providing the first list of putative biomarkers of carcass adiposity. These proteins would be targeted in future studies aiming to categorize adiposity in cattle., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Driven by the need to better understand the full and intergenerational toll of maternal mortality (MM), a mixed-methods study was conducted in four countries in sub-Saharan Africa to investigate the impacts of maternal death on families and children. The present analysis identifies gender as a fundamental driver not only of maternal, but also child health, through manifestations of gender inequity in household decision making, labor and caregiving, and social norms dictating the status of women. Focus group discussions were conducted with community members, and in depth qualitative interviews with key-informants and stakeholders, in Tanzania, Ethiopia, Malawi, and South Africa between April 2012 and October 2013. Findings highlight that socially constructed gender roles, which define mothers as caregivers and fathers as wage earners, and which limit women's agency regarding childcare decisions, among other things, create considerable gaps when it comes to meeting child nutrition, education, and health care needs following a maternal death. Additionally, our findings show that maternal deaths have differential effects on boy and girl children, and exacerbate specific risks for girl children, including early marriage, early pregnancy, and school drop-out. To combat both MM, and to mitigate impacts on children, investment in health services interventions should be complemented by broader interventions regarding social protection, as well as aimed at shifting social norms and opportunity structures regarding gendered divisions of labor and power at household, community, and society levels., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: HIV-associated Kaposi sarcoma (HIV-KS) is the most common cancer in Malawi. In 2008, the non-governmental organization, Partners In Health, and the Ministry of Health established the Neno Kaposi Sarcoma Clinic (NKSC) to treat HIV-KS in rural Neno district. We aimed to evaluate 12-month clinical outcomes and retention in care for HIV-KS patients in the NKSC, and to describe our implementation model, which featured protocol-guided chemotherapy, integrated antiretroviral therapy (ART) and psychosocial support delivered by community health workers., Methods: We conducted a retrospective cohort study using routine clinical data from 114 adult HIV-KS patients who received ART and ≥1 chemotherapy cycle in the NKSC between March 2008 and February 2012., Results: At enrolment 97% of patients (n/N=103/106) had advanced HIV-KS (stage T1). Most patients were male (n/N=85/114, 75%) with median age 36 years (interquartile range, IQR: 29-42). Patients started ART a median of 77 days prior to chemotherapy (IQR: 36-252), with 97% (n/N=105/108) receiving nevirapine/lamivudine/stavudine. Following standardized protocols, we treated 20 patients (18%) with first-line paclitaxel and 94 patients (82%) with bleomycin plus vincristine (BV). Of the 94 BV patients, 24 (26%) failed to respond to BV requiring change to second-line paclitaxel. A Division of AIDS grade 3/4 adverse event occurred in 29% of patients (n/N=30/102). Neutropenia was the most common grade 3/4 event (n/N=17/102, 17%). Twelve months after chemotherapy initiation, 83% of patients (95% CI: 74-89%) were alive, including 88 (77%) retained in care. Overall survival (OS) at 12 months did not differ by initial chemotherapy regimen (p=0.6). Among patients with T1 disease, low body mass index (BMI) (adjusted hazard ratio, aHR=4.10, 95% CI: 1.06-15.89) and 1 g/dL decrease in baseline haemoglobin (aHR=1.52, 95% CI: 1.03-2.25) were associated with increased death or loss to follow-up at 12 months., Conclusions: The NKSC model resulted in infrequent adverse events, low loss to follow-up and excellent OS. Our results suggest it is safe, effective and feasible to provide standard-of-care chemotherapy regimens from the developed world, integrated with ART, to treat HIV-KS in rural Malawi. Baseline BMI and haemoglobin may represent important patient characteristics associated with HIV-KS survival in rural sub-Saharan Africa.

Background: Maternal mortality, although largely preventable, remains unacceptably high in developing countries such as Malawi and creates a number of intergenerational impacts. Few studies have investigated the far-reaching impacts of maternal death beyond infant survival. This study demonstrates the short- and long-term impacts of maternal death on children, families, and the community in order to raise awareness of the true costs of maternal mortality and poor maternal health care in Neno, a rural and remote district in Malawi., Methods: Qualitative in-depth interviews were conducted to assess the impact of maternal mortality on child, family, and community well-being. We conducted 20 key informant interviews, 20 stakeholder interviews, and six sex-stratified focus group discussions in the seven health centers that cover the district. Transcripts were translated, coded, and analyzed in NVivo 10., Results: Participants noted a number of far-reaching impacts on orphaned children, their new caretakers, and extended families following a maternal death. Female relatives typically took on caregiving responsibilities for orphaned children, regardless of the accompanying financial hardship and frequent lack of familial or governmental support. Maternal death exacerbated children's vulnerabilities to long-term health and social impacts related to nutrition, education, employment, early partnership, pregnancy, and caretaking. Impacts were particularly salient for female children who were often forced to take on the majority of the household responsibilities. Participants cited a number of barriers to accessing quality child health care or support services, and many were unaware of programming available to assist them in raising orphaned children or how to access these services., Conclusions: In order to both reduce preventable maternal mortality and diminish the impacts on children, extended families, and communities, our findings highlight the importance of financing and implementing universal access to emergency obstetric and neonatal care, and contraception, as well as social protection programs, including among remote populations.

Introduction: Palliative care is rarely accessible in rural sub-Saharan Africa. Partners In Health and the Malawi government established the Neno Palliative Care Program (NPCP) to provide palliative care in rural Neno district. We conducted a situation analysis to evaluate early NPCP outcomes and better understand palliative care needs, knowledge, and preferences., Methods: Employing rapid evaluation methodology, we collected data from 3 sources: 1) chart review of all adult patients from the NPCP's first 9 months; 2) structured interviews with patients and caregivers; 3) semi-structured interviews with key stakeholders., Results: The NPCP enrolled 63 patients in its first 9 months. Frequent diagnoses were cancer (n = 50, 79%) and HIV/AIDS (n = 37 of 61, 61%). Nearly all (n = 31, 84%) patients with HIV/AIDS were on antiretroviral therapy. Providers registered 112 patient encounters, including 22 (20%) home visits. Most (n = 43, 68%) patients had documented pain at baseline, of whom 23 (53%) were treated with morphine. A majority (n = 35, 56%) had ≥1 follow-up encounter. Mean African Palliative Outcome Scale pain score decreased non-significantly between baseline and follow-up (3.0 vs. 2.7, p = 0.5) for patients with baseline pain and complete pain assessment documentation. Providers referred 48 (76%) patients for psychosocial services, including community health worker support, socioeconomic assistance, or both. We interviewed 36 patients referred to the NPCP after the chart review period. Most had cancer (n = 19, 53%) or HIV/AIDS (n = 10, 28%). Patients frequently reported needing income (n = 24, 67%) or food (n = 22, 61%). Stakeholders cited a need to make integrated palliative care widely available., Conclusions: We identified a high prevalence of pain and psychosocial needs among patients with serious chronic illnesses in rural Malawi. Early NPCP results suggest that comprehensive palliative care can be provided in rural Africa by integrating disease-modifying treatment and palliative care, linking hospital, clinic, and home-based services, and providing psychosocial support that includes socioeconomic assistance.

Introduction: Despite decades of experience with community health workers (CHWs) in a wide variety of global health projects, there is no established conceptual framework that structures how implementers and researchers can understand, study and improve their respective programs based on lessons learned by other CHW programs., Objective: To apply an original, non-linear framework and case study method, 5-SPICE, to multiple sister projects of a large, international non-governmental organization (NGO), and other CHW projects., Design: Engaging a large group of implementers, researchers and the best available literature, the 5-SPICE framework was refined and then applied to a selection of CHW programs. Insights gleaned from the case study method were summarized in a tabular format named the '5×5-SPICE charts'. This format graphically lists the ways in which essential CHW program elements interact, both positively and negatively, in the implementation field., Results: The 5×5-SPICE charts reveal a variety of insights that come from a more complex understanding of how essential CHW projects interact and influence each other in their unique context. Some have been well described in the literature previously, while others are exclusive to this article. An analysis of how best to compensate CHWs is also offered as an example of the type of insights that this method may yield., Conclusions: The 5-SPICE framework is a novel instrument that can be used to guide discussions about CHW projects. Insights from this process can help guide quality improvement efforts, or be used as hypothesis that will form the basis of a program's research agenda. Recent experience with research protocols embedded into successfully implemented projects demonstrates how such hypothesis can be rigorously tested.

Tungiasis is a disease endemic to poor communities in Latin America, the Caribbean and Africa. It is caused by the female flea, Tunga penetrans, which burrows into the skin of its host to feed while producing and extruding eggs. Consequent lesions may be painful and even crippling with damage ranging from mild erythema and swelling to necrosis. Superinfection of lesions can be serious and may result in auto-amputation or death from tetanus. We describe an outbreak of tungiasis in rural Haiti and a community-based intervention used to address it. Of 177 patients assessed, 132 (47 female, 85 male, 23 children) had tungiasis lesions. Forty-four patients had clinical signs of superinfection; 15 had ectopic lesions. Community health workers cleaned and disinfected patients' feet and any parts of the body with ectopic lesions, and then extracted fleas from existing lesions. Patients with superinfections were treated with appropriate antibiotics. Over 1000 pairs of shoes were distributed in the villages. Over 400 adults were given tetanus vaccinations during follow-up visits. Patients who had been treated reported feeling better and those who had received shoes indicated they had not developed new lesions. All superinfections were resolved. We concluded that community-based care can treat tungiasis effectively.

The porosity of membranes formed from acrylonitrile-sodium methallylsulfonate copolymer was characterized from the analysis of the depression of the melting point of absorbed water. Membranes were obtained either as a foam or as a hollow fiber; the foam consisted of interconnected macrocavities (mean diameter about equal to 1 mm) while the hollow fiber was a symmetric membrane used for blood ultrafiltration. Differential scanning calorimetry (DSC) of water revealed both the Gaussian distribution of pore sizes and correspondingly, their mean size: 5.2 nm for the pores through the walls separating macrocavities in the foam and 5.6 and 10.6 nm associated with two distributions representing nearly equal amounts of absorbed water, for the hollow fiber. In addition to DSC, the water magnetic relaxation showed that the isothermal dehydration of the foam was due to the deswelling of macrocavities while the increasing amount of absorbed water in pores reflects its strong interaction with the polymer., (Copyright 2002 Elsevier Science Ltd.)

The study is concerned with the nitrosopigments formed during curing time. It concludes that a reductant nitrosohaem is formed, with a breakdown of the bond between haem and histidine, and it gives the accurate sequence of the reactions. This study has been conducted by measurement of the iron-dried material ratio, electrophoresis on acetonic extracts of pigments formed with ascorbate or cystein, measurement, during the photodecomposition of this extract, of photometric spectra, of ionised iron, and characterization of pyrroles functions.

The effects of galacturonic, gallic, acetylneuraminic acid, ascorbate, cysteine, glutathion and imidazole on the formation of dimethylnitrosamine and diethylnitrosamine was studied in a simple aqueous medium with four different nitrite contents (50, 100, 500 and 1 000 ppm) and the two amines, compared with control samples. The nitrosamines were determined by the TELLING method (confirmed by photolysis). The results observed were compared with the laws of fixing nitrite in the form of nitrogen oxide, studied previously. For sarcosin and imidazole, the fixing takes into account the phenomena observed. The other substances lead to a conclusion that there are two stages in the process: 1) fixing of the nitrite to a greater or lesser degree in the form of a nitrogen oxide complex, 2) direct effect on the nitrosation reaction which is catalysed or slowed down. The discussion based on the literature, concludes that the final nitrosation reaction give rise to free radicals, even in an aqueous medium.

Thiamin and riboflavin seem to resist fairly well to the proceedings of meat products studied here (cooked hams, patties, dry sausages). This result is normal enough to riboflavin, it is less for thiamin which sensitive to nitrite and to heating is well established by the literature. The origin of these observed phenomenons of protection is probably due to the complexation of these vitamins by the meat proteins. A similar phenomenon has been seen before by several authors on milk proteins, eggs and specially sulfhydril groups. This complexation is confirmed by the important release of both vitamins we noted during processing. They are determined much more easily on processed meat products than on raw materials. The nutritional repercussion of the observed phenomenon is difficult to estimate accurately. The vitamins release we find out, make them more available for the organism but it would be compared to the enzymatic decomplexation which occurs in vivo, during digestion, that we did not studied. Nevertheless such an approach would be necessary for the estimation of the practical value of the analytical determinations generally used.