bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the INSR gene variants on the long-term response to a 31-month childhood obesity intervention
Authors: Chen Jing , Shan Rui , Xiao Wu-Cai , Liu Zheng 
Published: May 2022

ABSTRACTObjectiveTo explore effects of the INSR genotype on the waist circumference reduction after a lifestyle-based obesity intervention.MethodsThis was a nested study in a cluster-randomized controlled trial conducted from September 2018 to June 2019 in Beijing, China. Four schools (200 children) were randomized to the intervention group (diet and physical activity) and 4 schools (193 children) were randomized to the control group (usual practice without a focus on obesity prevention). We followed up children at 9 months (the end of the intervention) and 31 months (22 months after the intervention), and genotyped 7 independent SNPs in the INSR gene. We assessed genetic effects on changes in five waist-related indicators [waist circumference, waist-to-hip ratio (whr), waist-to-height ratio (WHtR), waist circumference adjusted by BMI (WCadjBMI), waist-to-hip ratio adjusted by BMI (WHRadjBMI)] from baseline to 9 months and from 9 months to 31 months in the intervention and control group, respectively, and compared whether genetic effects differed by group (i.e., gene-group interaction).ResultsFrom baseline to 9 months, we found that INSR rs7508679, rs10420008, rs11883325, and rs4804416 modified the intervention effects on changes in all waist-related indicators (all P < 0.05). In the control group, the effect allele was associated with greater increases in waist-related indicators, whereas opposite-directional associations were observed in the intervention group. Such interactions between SNPs and group assignment were almost not observed from 9 months to 31 months.ConclusionOur data suggested that children carrying effect alleles of rs7508679, rs10420008, rs11883325, or rs4804416 may benefit more from a lifestyle intervention for obesity prevention, but the effect appeared to be attenuated in the long term.
Risk factors for adolescent smoking uptake – analysis of prospective data from the UK Millennium Cohort Study
Authors: Vrinten Charlotte , Parnham Jennie C , Filippidis Filippos T , Hopkinson Nicholas S , Laverty Anthony A 
Published: May 2022

ABSTRACTBackgroundMost smokers take up their habit in adolescence. Risk factors for smoking are changing over time as demographics shift, and technologies such as social media create new avenues for the tobacco industry to recruit smokers. We assessed risk factors associated with smoking uptake among a representative cohort of UK adolescents.MethodsData come from 8,944 children followed prospectively as part of the UK Millennium Cohort Study. Smoking uptake was assessed as adolescents who had never smoked tobacco at age 14, but reported smoking ≥1 cigarette per week by age 17 (regular smoking). We used logistic regression to assess associations between smoking uptake and selected socio-demographic factors including household income, caregiver smoking, peer smoking, and social media use. Weighted percentages and Office for National Statistics Data were used to estimate numbers of regular smokers and new smokers in the UK.ResultsAmong the whole sample, 10.6% of adolescents were regular smokers at age 17. Of these, 52% had started smoking between ages 14 and 17. Uptake was more common if caregivers (14.7% vs 5.7%, p<0.001) or friends smoked (13.0% vs. 5.1%, p<0.001), and among those reporting >5hours/day of social media use (10.0% vs 5.2%, p=0.006). Applying these percentages to population data, an estimated 160,000 adolescents in the UK were regular smokers by age 17, of whom more than 100,000 took up the habit between ages 14 and 17.DiscussionSmoking behaviour remains highly transmissible within families and peer groups, reinforcing inequalities. Social media are highlighted as a potential vector.What this paper addsWhat is already known on this subject?Cross sectional data suggest that certain population groups, such as those from more deprived backgrounds, are more likely to take up smoking earlier in life, a factor which is linked to greater health risks.What important gaps in knowledge exist on this topic?There are few prospective studies with nationally representative data that track smoking uptake in adolescence and how this is changing over time in the UK.What this study addsAround one in nine adolescents in the UK were regular smokers by age 17 and around half (52%) had taken up the habit since they were 14 years old.Smoking among peers and caregivers was linked to adolescent smoking uptake and more time spent on social media was associated with greater likelihood of smoking uptake.
A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation
Authors: Hug Nele , Aitken Stuart , Longman Dasa , Raab Michaela , Armes Hannah , Mann Abigail R. , Rio-Machin Ana , Fitzgibbon Jude , Rouault-Pierre Kevin , Cáceres Javier F. 
Published: May 2022

ABSTRACTThe DExD/H-box RNA helicase DHX34 is a Nonsense-mediated decay (NMD) factor that together with core NMD factors co-regulates NMD targets in nematodes and in vertebrates. Here, we show that DHX34 is also associated with the human spliceosomal catalytic C complex. Mapping of DHX34 endogenous binding sites using Cross-Linking Immunoprecipitation (CLIP) revealed that DHX34 is preferentially associated with pre-mRNAs and locates at exon-intron boundaries. Accordingly, we observed that DHX34 regulates a large number of alternative splicing (AS) events in mammalian cells in culture, establishing a dual role for DHX34 in both NMD and pre-mRNA splicing. We previously showed that germline DHX34 mutations associated to familial Myelodysplasia (MDS)/Acute Myeloid Leukemia (AML) predisposition abrogate its activity in NMD. Interestingly, we observe now that DHX34 regulates the splicing of pre-mRNAs that have been linked to AML/MDS predisposition. This is consistent with silencing experiments in hematopoietic stem/progenitor cells (HSPCs) showing that loss of DHX34 results in differentiation blockade of both erythroid and myeloid lineages, which is a hallmark of AML development. Altogether, these data unveil new cellular functions of DHX34 and suggests that alterations in the levels and/or activity of DHX34 could contribute to human disease.
Spatial and lineage dependent processes underpin floristic assembly in the megadiverse Eastern South American mountains
Authors: Barros-Souza Yago , Borges Leonardo M. 
Published: May 2022

AbstractAimThe astonishing diversity of ancient mountains was likely shaped by multiple evolutionary processes. However, there is an ongoing debate on what were the main processes driving the assembly ofcampos rupestres, the mega-diverse flora of Eastern South American mountains. Although the ancient nature of these mountains suggests their flora should be composed by relatively older lineages, they harbour a number of recently diverged clades. To better understand the evolution of ancient mountains’ floras, we tested if thecampos rupestresare mainly composed by relatively old or recent communities and if angiosperm diversity is geographically structured using analyses of diversity and endemism.LocationEastern South America.Time periodOligocene/Miocene to the present.Major taxa studiedFlowering plants.MethodsWe used analyses of diversity and endemism for 10% of thecampos rupestres flora. We obtained distribution data from online databases, and phylogenetic hypotheses from the literature. With these datasets, we estimated alpha and beta metrics of taxonomic and phylogenetic diversity, and conducted categorical analyses of neo- and paleo-endemism.ResultsPhylogenetic overdispersion predominates in thecampos rupestres. However, this general pattern is permeated by both lineage- and site-specific phylogenetic clustering, suggesting that recent diversification events depend on particular regional conditions and on the overall maintenance of old lineages. Although endemism patterns vary among differentcampos rupestressites, paleo-endemism is widespread and particularly prominent where phylogenetic overdispersion is evident. Moreover, phylogenetic composition indicates variable past spatial connections across different sites, taxonomic composition is highly geographically structured and seems to be influenced by the vegetation surrounding thecampos rupestresand/or by abiotic conditions.Main conclusionsOur results reinforce the idiosyncratic nature of diversification patterns in ancient mountains and suggest that old, climatically buffered, infertile montane ecosystems not only include both relatively old and recent lineages, but that recent diversification is lineage and spatially dependent.
FcRγ−NK cell induction by specific CMV and expansion by subclinical viral infections in rhesus macaques
Authors: Lee Jaewon , Chang W. L. William , Scott Jeannine M. , Hong Suyeon , Lee Taehyung , Deere Jesse D. , Park Peter , Sparger Ellen E. , Dandekar Satya , Hartigan-O’Connor Dennis J. , Barry Peter A. , Kim Sungjin 
Published: May 2022

AbstractLong-lived ‘memory-like’ NK cells, characterized by FcRγ-deficiency and enhanced responsiveness to antibody-bound virus-infected cells, have been found in certain human cytomegalovirus (HCMV)-seropositive individuals. Because humans are exposed to numerous microbes and environmental agents, specific relationships between HCMV and FcRγ-deficient NK cells (also known as g-NK cells) have been challenging to define. Here, we show that a subgroup of rhesus cytomegalovirus (RhCMV)-seropositive macaques possesses FcRγ-deficient NK cells that stably persist and display phenotype resembling human FcRγ-deficient NK cells. Moreover, these macaque NK cells resembled human FcRγ-deficient NK cells with respect to functional characteristics, including enhanced responsiveness to RhCMV-infected target in an antibody-dependent manner and hypo-responsiveness to tumor and cytokine stimulation. These cells were not detected in specific-pathogen-free (SPF) macaques free of RhCMV and six other viruses; however, experimental infection of SPF animals with RhCMV strain UCD59, but not RhCMV strain 68-1 or SIV, led to induction of FcRγ-deficient NK cells. In non-SPF macaques, co-infection by RhCMV with other common viruses was associated with higher frequencies of FcRγ-deficient NK cells. These results support a causal role for specific cytomegalovirus strain(s) in the induction of FcRγ-deficient NK cells, and suggest that co-infection by other viruses further expands this memory-like NK cell pool.
Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, and BA.5
Authors: Wang Qian , Guo Yicheng , Iketani Sho , Nair Manoj S. , Li Zhiteng , Mohri Hiroshi , Wang Maple , Yu Jian , Bowen Anthony D. , Chang Jennifer Y. , Shah Jayesh G. , Nguyen Nadia , Chen Zhiwei , Meyers Kathrine , Yin Michael T. , Sobieszczyk Magdalena E. , Sheng Zizhang , Huang Yaoxing , Liu Lihong , Ho David D. 
Published: May 2022

AbstractSARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged dramatically to become dominant in the United States and South Africa, respectively1,2. These novel subvariants carrying additional mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.
IMMUNE PROFILING UNCOVERS POTENT ADJUVANT CAPACITIES OF SARS-COV-2 INFECTION TO VACCINATION LEADING TO MEMORY T CELL RESPONSES WITH A TH17 SIGNATURE IN CANCER PATIENTS
Authors: Echaide Miriam , Labiano Ibone , Delgado Marina , Fernández de Lascoiti Angela , Ochoa Patricia , Garnica Maider , Ramos Pablo , Chocarro Luisa , Fernández Leticia , Arasanz Hugo , Bocanegra Ana , Blanco Ester , Piñeiro Sergio , Vera Ruth , Alsina Maria , Escors David , Kochan Grazyna 
Published: May 2022

AbstractIt is unclear whether cancer patients show impaired responses to COVID-19 and vaccination. Immune profiling was performed in three cohorts of healthy donors and oncologic patients: infected with SARS CoV-2, BNT162b2-vaccinated, and with previous COVID-19 and subsequently vaccinated. Vaccination was a poor inductor of T cell responses compared to infection, which significantly potentiated vaccination in antibody and T cell responses. T cell major targets in natural infection were the M and S protein, but not the N protein. T cell responses quickly decayed after 6 months post-vaccination, and T cell profiling showed that vaccination expanded effector T cells rather than memory T cell subsets unless the subjects had previous COVID-19. Cancer patients with previous COVID-19 and vaccinated exhibited potent IL-17+ CD4 and CD8 responses and increased neutrophils. Concluding, COVID-19 infection had potent adjuvant effects for vaccination leading to memory T cell differentiation, but with enhanced IL-17 inflammation signatures.TeaserAdjuvancy of SARS CoV-2 in cancer patients.
Competition for cysteine acylation by C16:0 and C18:0 derived lipids is a global phenomenon in the proteome
Authors: Nůsková Hana , Garcia-Cortizo Fabiola , Schwenker Lena Sophie , Tiebe Marcel , Schneider Martin , Helm Dominic , Reid Carissa , Kopp-Schneider Annette , Miller Aubry K. , Teleman Aurelio A. 
Published: May 2022

AbstractS-acylation is a reversible posttranslational protein modification consisting of attachment of a fatty acid to a cysteine via a thioester bond. Research over the last few years has shown that a variety of different fatty acids, such as C16:0, C18:0 or C18:1, are used in cells to S-acylate proteins. We recently showed that GNAI proteins can be acylated on a single residue, Cys3, with either C16:0 or C18:1 and that the relative proportion of acylation with these fatty acids depends on the level of the respective fatty acid in the cell’s environment. This has functional consequences for GNAI proteins, with the identity of the acylating fatty acid affecting the subcellular localization of GNAIs. Unclear is whether this competitive acylation is specific to GNAI proteins or a more general phenomenon in the proteome. We perform here a proteome screen to identify proteins acylated with different fatty acids. We identify 218 proteins acylated with C16:0 and 308 proteins acylated with C18-lipids, thereby uncovering novel targets of acylation. We find that most proteins that can be acylated by palmitic acid (C16:0) can also be acylated with C18-fatty acids. For proteins with more than one acylation site, we find that this competitive acylation occurs on each individual cysteine residue. This raises the possibility that the function of many different proteins can be regulated by the lipid environment via differential S-acylation.
Regulation of odd chain fatty acid metabolism in the development of metabolic diseases in mice fed a low protein diet
Authors: Ampong Isaac 
Published: May 2022

AbstractNonalcoholic fatty liver disease (NAFLD) and Metabolic syndrome (MS) have become a global health concern as incidence of these metabolic disorders is growing rapidly in developing countries particularly in the Middle East, South America and Africa. Studies have shown that protein restriction is associated with increased risk of metabolic diseases, possibly through effects on fatty acid (FA) metabolism. In the present study, we investigated whether a low protein diet modulates FA metabolism and whether methyl donor supplementation can ameliorate these effects and improve metabolic health. Male C57BL/6 mice were fed either a low protein diet (LPD, 90 g/kg protein, n=8), a LPD supplemented with methyl donors (MD-LPD; choline chloride, betaine, methionine, folic acid, vitamin B12, n=8) or normal protein diet (NPD, 180 g/kg protein, n=8) for 7 weeks prior to analysis of serum fatty acid profiles by GC FID and MS and liver fatty acid synthesis and uptake gene expression by RT-qPCR. We observed significant depletion of serum C15:0 and C17:0 in LPD-fed males compared to NPD. Serum long chain saturated FAs C18:0 and C24:0 were increased in LPD male mice compared to NPD. Gene expression analysis revealed an upregulation of hepatic cluster of differentiation 36 (CD36) expression in LPD mice compared to NPD suggesting increased fat uptake in the liver. However, when LPD diet was supplemented with methyl donors, we observed either no change in serum C15: 0 and an increased serum C17:0 compared to LPD with no methyl donor supplementation. Again, methyl donor supplementation upregulated fatty acid desaturase 1 (FADS1), thioredoxin-1 (TRX1) and catalase (CAT) expression in the liver of MD-LPD fed mice compared to LPD mice. Altogether, our study revealed that odd chain fatty acids (OCFA)s are key early markers observed in a suboptimal diet-induced metabolic changes and may be potential targets to improve metabolic health outcomes.
Spike mutation resilient scFv76 antibody counteracts SARS-CoV-2 lung damage upon aerosol delivery
Authors: Milazzo Ferdinando M. , Chaves-Sanjuan Antonio , Minenkova Olga , Santapaola Daniela , Anastasi Anna M. , Battistuzzi Gianfranco , Chiapparino Caterina , Rosi Antonio , Pich Emilio Merlo , Albertoni Claudio , Marra Emanuele , Luberto Laura , Viollet Cécile , Spagnoli Luigi G. , Riccio Anna , Rossi Antonio , Santoro M. Gabriella , Ballabio Federico , Paissoni Cristina , Camilloni Carlo , Bolognesi Martino , De Santis Rita 
Published: May 2022

ABSTRACTUneven worldwide vaccination coverage against SARS-CoV-2 and emergence of variants escaping immunity call for broadly-effective and easily-deployable therapeutics. We previously described the human single-chain scFv76 antibody, which recognizes SARS-CoV-2 Alfa, Beta, Gamma and Delta variants. We now show that scFv76 also neutralizes infectivity and fusogenic activity of Omicron BA.1 and BA.2 variants. Cryo-EM analysis reveals that scFv76 binds to a well-conserved SARS-CoV-2 spike epitope, providing the structural basis for its broad-spectrum activity. Moreover, we demonstrate that nebulized scFv76 exhibits therapeutic efficacy in a severe hACE2 transgenic mouse model of COVID-19 pneumonia, as shown by body weight and pulmonary viral load data. Counteraction of infection correlates with the inhibition of lung inflammation observed by histopathology and expression of inflammatory cytokines and chemokines. Biomarkers of pulmonary endothelial damage were also significantly reduced in scFv76-treated mice. Altogether the results support the use of nebulized scFv76 for COVID-19 induced by any SARS-CoV-2 variants emerged so far.
Whole exome-sequencing of vitiligo lesions indicate lower burden of somatic variations: implications in risk for non-melanoma skin cancers
Authors: Gupta Iti , Shankrit Shambhavi , Narta Kiran , Ghazi Madeeha , Grover Ritika , Pandey Rajesh , Kar Hemanta K , Menon Shruti M , Gupta Aayush , Yenamandra Vamsi K , Singh Archana , Mukerji Mitali , Mukhopadhyay Arijit , Rani Rajni , Gokhale Rajesh S , Dash Debasis , Natarajan Vivek T 
Published: May 2022

AbstractMapping of somatic variations has enabled understanding the progression of clonal variations from healthy skin to cutaneous malignancies. Highlighting, the adaptive nature of pigmentation, germline mutations in albinism amplify skin cancer susceptibility. However, lower incidence of non-melanoma skin cancer among subjects with acquired depigmenting skin disorder vitiligo is enigmatic and a matter of longstanding debate. To address this, we performed high-coverage exome sequencing of matched non-lesional and lesional vitiligo skin along with whole blood to account for germline variations. Our analysis suggests lower burden of somatic cancer-associated variations in exposed depigmented lesional skin compared to the non-lesional skin. A detailed investigation of vitiligo skin transcriptome reveals elevation of DNA repair and cell-proliferation pathways. Validation by comet-assay for DNA damage and cell cycle analysis of epidermal cells suggest undamaged DNA in vitiligo lesions that could be attributed to higher proliferation-coupled repair. Endorsing this, UV-signature variations are not prominent, instead SBS5 associated with endogenous mutational processes is conspicuous in both the vitiligo tissues. Our systematic pilot study indicates lower somatic mutation burden in vitiligo skin and supports the earlier demographic observation on lower risk of non-melanoma skin cancer in vitiligo subjects, providing an opportunity to learn strategies for cancer prevention from vitiligo.Brief SummaryVitiligo skin harbors decreased somatic variation burden in cancer-associated genes and a concomitant augmentation in DNA repair response, explaining the lower incidence of cutaneous malignancies.
Developmental evidence for parental conflict in driving Mimulus species barriers
Authors: Sandstedt Gabrielle D. , Sweigart Andrea L. 
Published: May 2022

ABSTRACTThe endosperm, a tissue that nourishes the embryo in the seeds of flowering plants, is often disrupted in inviable hybrid seeds between species presumed to have divergent histories of parental conflict. Despite the potential importance of parental conflict in plant speciation, we lack direct evidence of its action in driving species barriers. Here, we performed reciprocal crosses between pairs of three monkeyflower species (Mimulus caespitosa, M. tilingii, and M. guttatus). The severity of hybrid seed inviability varies among these crosses, which we determined was due to species divergence in effective ploidy. By performing a time series of seed development, we assessed whether regions within the endosperm were potential targets of parental conflict. We found that the chalazal haustorium, a tissue within the endosperm that occurs at the maternal-filial boundary, develops abnormally in hybrid seeds when the paternal parent has the greater effective ploidy. Within these Mimulus species, parental conflict might target the chalazal haustorium to control sucrose movement from the maternal parent into the endosperm. Consequently, conflict may be exposed in crosses between species. Our study suggests that parental conflict in the endosperm may function as a driver of speciation by targeting regions and developmental stages critical for resource allocation.