Category: Nevin Manimala

Sci Rep. 2023 Feb 3;13(1):1980. doi: 10.1038/s41598-023-28593-1.

ABSTRACT

Soybean is highly sensitive to flooding and extreme rainfall. The phenotypic variation of flooding tolerance is a complex quantitative trait controlled by many genes and their interaction with environmental factors. We previously constructed a gene-pool relevant to soybean flooding-tolerant responses from integrated multiple omics and non-omics databases, and selected 144 prioritized flooding tolerance genes (FTgenes). In this study, we proposed a comprehensive framework at the systems level, using competitive (hypergeometric test) and self-contained (sum-statistic, sum-square-statistic) pathway-based approaches to identify biologically enriched pathways through evaluating the joint effects of the FTgenes within annotated pathways. These FTgenes were significantly enriched in 36 pathways in the Gene Ontology database. These pathways were related to plant hormones, defense-related, primary metabolic process, and system development pathways, which plays key roles in soybean flooding-induced responses. We further identified nine key FTgenes from important subnetworks extracted from several gene networks of enriched pathways. The nine key FTgenes were significantly expressed in soybean root under flooding stress in a qRT-PCR analysis. We demonstrated that this systems biology framework is promising to uncover important key genes underlying the molecular mechanisms of flooding-tolerant responses in soybean. This result supplied a good foundation for gene function analysis in further work.

PMID:36737640 | DOI:10.1038/s41598-023-28593-1

Sci Rep. 2023 Feb 3;13(1):1991. doi: 10.1038/s41598-023-29039-4.

ABSTRACT

Quinoa is an important Andean crop that can play a strategic role in the development of degraded lands in hot arid regions due to its high nutritional value, genetic diversity and its high adaptability to stressful environments. The aim of this work was to evaluate the agronomic performance (growth development, grain yield and grain quality characteristics) of seven quinoa genotypes (Giza1, Sajama, Santa Maria, Q102, Q29, Q27 and Q18) cultivated under open field conditions in the Sahara Desert of Algeria. Using randomized complete block design (4 blocks), field trials were conducted during two cropping seasons (2017-2018 and 2018-2019) from November to April. The measured parameters included: plant height, number of panicles per plant, 1000-grain weight (TGW), grain yield (GYd), grain protein content (GPt), grain saponin content (GSC), and maturity indicators. The genotype effect was statistically the main source of variation in most parameters investigated as compared to the effect of cropping year. The Q102 genotype produced the highest GYd (2.87 t/ha) and GPt (16.7 g/100 g DM); and it required medium period (149 days) to reach harvest maturity as compared to other genotypes. The genotype Giza1 showed the lowest GYd and also low values for most of traits measured. However, it had the shortest harvest maturity (139 days) and the lowest GSC (0.62 g/100 g DM). The variety Santa Maria recorded the highest TGW (2.68 g), but it took 164 days to reach harvest maturity and it had high GSC (1.92 g/100 g DM). Though the best yield and grain quality characteristics were not reunited in single genotype, our findings showed that quinoa has multi-benefit potentials as a new crop for the arid agriculture in particular in hot-arid regions of North Africa.

PMID:36737632 | DOI:10.1038/s41598-023-29039-4

Transl Psychiatry. 2023 Feb 3;13(1):38. doi: 10.1038/s41398-023-02332-6.

ABSTRACT

Human brain development starts in the embryonic period. Maternal preconception nutrition and nutrient availability to the embryo may influence brain development at this critical period following conception and early cellular differentiation, thereby affecting offspring neurodevelopmental and behavioural disorder risk. However, studying this is challenging due to difficulties in characterizing preconception nutritional status and few studies have objective neurodevelopmental imaging measures in children. We investigated the associations of maternal preconception circulating blood nutrient-related biomarker mixtures (~15 weeks before conception) with child behavioural symptoms (Child Behaviour Checklist (CBCL), aged 3 years) within the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. The CBCL preschool form evaluates child behaviours based on syndrome scales and Diagnostic and Statistical Manual of Mental Disorders (DSM) oriented scales. These scales consist of internalizing problems, externalizing problems, anxiety problems, pervasive developmental problems, oppositional defiant, etc. We applied data-driven clustering and a method for modelling mixtures (Bayesian kernel machine regression, BKMR) to account for complex, non-linear dependencies between 67 biomarkers. We used effect decomposition analyses to explore the potential mediating role of neonatal (week 1) brain microstructure, specifically orientation dispersion indices (ODI) of 49 cortical and subcortical grey matter regions. We found that higher levels of a nutrient cluster including thiamine, thiamine monophosphate (TMP), pyridoxal phosphate, pyridoxic acid, and pyridoxal were associated with a higher CBCL score for internalizing problems (posterior inclusion probability (PIP) = 0.768). Specifically, thiamine independently influenced CBCL (Conditional PIP = 0.775). Higher maternal preconception thiamine level was also associated with a lower right subthalamic nucleus ODI (P-value = 0.01) while a lower right subthalamic nucleus ODI was associated with higher CBCL scores for multiple domains (P-value < 0.05). One potential mechanism is the suboptimal metabolism of free thiamine to active vitamin B1, but additional follow-up and replication studies in other cohorts are needed.

PMID:36737601 | DOI:10.1038/s41398-023-02332-6

Environ Sci Pollut Res Int. 2023 Feb 4. doi: 10.1007/s11356-023-25665-7. Online ahead of print.

ABSTRACT

This study deals with the asymmetric effect of economic policy uncertainty and political stability on carbon dioxide (CO₂) emissions considering also energy consumption and economic growth. In this context, the study investigates G-7 countries, which make up an important part of the world economy. Also, the study uses yearly data between 1997 and 2021 as the most available intersection data for all countries included. Besides, this study applies a novel nonlinear approach as quantile-on-quantile regression (QQR) as the base model, and quantile regression (QR) is used for robustness. The empirical results present that (i) economic policy uncertainty has a decreasing effect on CO₂ emissions in Italy, Japan, and the United States of America (USA), whereas it has a mixed effect in Canada, France, Germany, and the United Kingdom (UK); (ii) political stability also has a mixed effect on CO₂ emissions; (iii) energy consumption has an accelerating effect on CO₂ emissions while the power of effect changes at quantiles; (iv) economic growth has generally an increasing effect on CO₂ emissions, whereas it has a decreasing effect at lower quantiles in Japan, at middle quantiles in France and Germany, and at higher quantiles in Italy; and (v) the QR results support the robustness of QQR findings. Thus, the empirical results highlight that G-7 countries should consider the asymmetric and quantile-based varying effects of the economic policy uncertainty, political stability, and economic growth to reach their carbon neutrality targets.

PMID:36737567 | DOI:10.1007/s11356-023-25665-7

Ann Surg Oncol. 2023 Feb 3. doi: 10.1245/s10434-023-13148-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Receipt of chemotherapy is associated with decreased satisfaction after breast surgery, but whether timing as adjuvant versus neoadjuvant (NAC) affects patient-reported outcomes (PROs) is unclear. We examined associations between chemotherapy timing and PROs after breast-conserving surgery (BCS) and mastectomy with immediate reconstruction (M-IR).

METHODS: In this retrospective cohort study of patients with stage I-III breast cancer undergoing chemotherapy between January 2017 and December 2019, we compared satisfaction with breasts (SABTR) and chest physical well-being (PWB-CHEST) between chemotherapy groups in BCS and M-IR cohorts. Median SABTR and PWB-CHEST scores (scale 0-100) were compared between chemotherapy groups at baseline and for 3 years postoperatively. Factors associated with SABTR and PWB-CHEST at 1 and 2 years were assessed with multivariable linear regression.

RESULTS: Overall, 640 patients had BCS and 602 had M-IR; 210 (33%) BCS patients and 294 (49%) M-IR patients had NAC. Following BCS, SABTR was higher than baseline at all postoperative timepoints, whereas 3-year SABTR remained similar to baseline following M-IR, independent of chemotherapy timing. In both surgical cohorts, PWB-CHEST was lowest after NAC at 6 months compared with baseline but was similar to adjuvant counterparts by 3 years. NAC was not a statistically significant predictor of SABTR or PWB-CHEST in either surgical cohort on multivariable analysis.

CONCLUSIONS: For patients with breast cancer who require chemotherapy, neoadjuvant versus adjuvant timing does not impact long-term PROs in this study. These findings may inform shared decision making regarding the sequence of treatment in patients with operable disease.

PMID:36737530 | DOI:10.1245/s10434-023-13148-5

Commun Biol. 2023 Feb 3;6(1):143. doi: 10.1038/s42003-023-04491-0.

ABSTRACT

Human lifespan is reported to be heritable. Although previous genome-wide association studies (GWASs) have identified several loci, a limited number of studies have assessed the genetic associations with the real survival information on the participants. We conducted a GWAS to identify loci associated with survival time in the Japanese individuals participated in the BioBank Japan Project by carrying out sex-stratified GWASs involving 78,029 males and 59,664 females. Of them, 31,324 (22.7%) died during the mean follow-up period of 7.44 years. We found a novel locus associated with survival (BET1L; P = 5.89 × 10^-9). By integrating with eQTL data, we detected a significant overlap with eQTL of BET1L in skeletal muscle. A gene-set enrichment analysis showed that genes related to the BCAR1 protein-protein interaction subnetwork influence survival time (P = 1.54 × 10^-7). These findings offer the candidate genes and biological mechanisms associated with human lifespan.

PMID:36737517 | DOI:10.1038/s42003-023-04491-0

Pharmacoecon Open. 2023 Feb 3. doi: 10.1007/s41669-023-00392-4. Online ahead of print.

ABSTRACT

OBJECTIVES: The treatments for high-grade non-muscle invasive bladder cancer (NMIBC) vary between bladder preserving intravesical approaches and radical cystectomy. The impact of these treatments on health-related quality of life may vary widely. The purpose of this study was to elicit the general public’s perspective on quality of life, measured as utility scores associated with treatment for Bacillus Calmette-Guerin (BCG)-unresponsive NMIBC and disease progression, for supporting economic evaluation of newly developed treatments for NMIBC.

MATERIALS AND METHODS: Part I involved the development and testing of health states describing NMIBC, which was informed by a rapid review, expert input and a patient advisor. Part II involved elicitation of societal utility values for the different health states. Time trade-off (TTO) interviews were conducted with members of the UK general public. Five health states described different NMIBC scenarios including disease recurrence and progression. Participants ranked each health state, followed by the TTO valuation exercise. Descriptors included NMIBC symptom severity, impact and treatment characteristics.

RESULTS: In total, 202 members of the general public participated. The mean age was 46 (standard deviation [SD] 14.6) years. Sample mean (SD) EQ-5D-5L visual analogue scale (VAS) and index scores were 83.2 (12.3) and 0.89 (0.18), respectively. Mean utilities were 0.781 for No High-Grade Recurrence, 0.586 for High-Grade Recurrence, 0.572 for > 1-Year Post-cystectomy and 0.283 for metastatic disease. The First Year Post-cystectomy path health state had a mean utility of 0.288. Pairwise comparisons found statistically significant differences between utilities (p < 0.001), except between High-Grade Recurrence and > 1-Year Post-cystectomy (p = 0.524). There were significant differences in utility scores by age and employment status.

CONCLUSION: This study provides utility scores for health states describing living with NMIBC, which is associated with a significant health-related quality-of-life burden. These values address an existing gap in available data and have the potential to be used in models evaluating the cost-effectiveness of both current and newly developed treatments for bladder cancer.

PMID:36737511 | DOI:10.1007/s41669-023-00392-4

Hepatol Int. 2023 Feb 3. doi: 10.1007/s12072-022-10469-7. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks.

APPROACH AND RESULTS: We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10^-3).

CONCLUSIONS: We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.

PMID:36737504 | DOI:10.1007/s12072-022-10469-7

Sci Rep. 2023 Feb 3;13(1):1989. doi: 10.1038/s41598-023-28966-6.

ABSTRACT

The objective of this study was to investigate the impact of lactation stage and parity number on fatty acid and non-volatile polar metabolite profiles in sow colostrum and milk using a metabolomics approach. A total number of 63 colostrum, transient and mature milk were collected from primiparous and multiparous Landrace × Yorkshire crossbred sows. Macrochemical, fatty acid and non-volatile polar metabolite compositions of samples were analyzed using infrared spectrometry, gas chromatography coupled with mass-spectrometry and proton nuclear magnetic resonance spectroscopy, respectively. Univariate and multivariate statistical analysis demonstrated significant impacts of lactation stage and parity number on colostrum and milk compositions. Chemometric analysis revealed significant influences of sow parity on the distinction in fatty acid profiles of mature milk while the distinction in non-volatile polar metabolite profiles was more evident in colostrum. Alterations in the concentration of linoleic (C18:2n6), lignoceric (C24:0), behenic (C22:0), caprylic (C8:0) and myristoleic (C14:1) acid together with those of creatine, creatinine phosphate, glutamate and glycolate were statistically suggested to be mainly affected by sow parity number. Variations in the concentration of these compounds reflected the physiological function of sow mammary gland influenced. This information could be applied for feed and feeding strategies in lactating sows and improving lactating performances.

PMID:36737492 | DOI:10.1038/s41598-023-28966-6

Sci Rep. 2023 Feb 3;13(1):2017. doi: 10.1038/s41598-023-28944-y.

ABSTRACT

Genome-wide association studies (GWAS) have dissected numerous genetic factors underlying refractive errors (RE) such as myopia. Despite significant insights into understanding the genetic architecture of RE, few studies have validated and explored the functional role of candidate genes within these loci. To functionally follow-up on GWAS and characterize the potential role of candidate genes on the development of RE, we prioritized nine genes (TJP2, PDE11A, SHISA6, LAMA2, LRRC4C, KCNQ5, GNB3, RBFOX1, and GRIA4) based on biological and statistical evidence; and used CRISPR/cas9 to generate knock-out zebrafish mutants. These mutant fish were screened for abnormalities in axial length by spectral-domain optical coherence tomography and refractive status by eccentric photorefraction at the juvenile (2 months) and adult (4 months) developmental stage. We found a significantly increased axial length and myopic shift in refractive status in three of our studied mutants, indicating a potential involvement of the human orthologs (LAMA2, LRRC4C, and KCNQ5) in myopia development. Further, in-situ hybridization studies showed that all three genes are expressed throughout the zebrafish retina. Our zebrafish models provide evidence of a functional role of these three genes in refractive error development and offer opportunities to elucidate pathways driving the retina-to-sclera signaling cascade that leads to myopia.

PMID:36737489 | DOI:10.1038/s41598-023-28944-y