Reproductive timing of the Scarlet Shiner (Lythrurus fasciolaris) in Northern Alabama

The Scarlet Shiner (Lythrurus fasciolaris) is a cyprinid species widely distributed in parts of the Ohio, Cumberland and Tennessee river drainages of the United States. The objective of this study was to determine the Scarlet Shiner’s reproductive schedule. Maturation of ovaries and oocytes was determined through the categorization of developmental stages from early maturing to ripe, along with the calculation of monthly gonadosomatic index (GSI) measurements over two reproductive seasons in 2012 and 2015. In both years reproductive competence began in April. Average monthly GSI for females peaked in May, followed by a slow decline through August. Average clutch size was largest both years in April and May, although individual females were found with late developmental stage oocytes as late as August. Compared to other studied sympatric cyprinid species, the Scarlet Shiner was found to be a relatively late spawner with an extended spawning tail well into the summer

Is the current law on Conspiracy to commit Murder effective and fair?

“Conspirators be they that…bind themselves by Oath…or other Alliance, that every of them shall aid and support the Enterprise of each other falsely and maliciously to indite.”Established in the Third Ordinance of Conspirators in 1304; the first definition of conspiracy was to prevent and punish those who would plan to use children to present their false accusations in court on their behalf (as children could not be criminally liable). The aim of the law on conspiracy, although widening the scope, has been clear from the thirteenth century: to prevent and punish the planning of a criminal offence. However, since expanding, the law on conspiracy has been criticised especially in regard to sentencing as “unduly harsh.” This is the result of numerous problems with the current law on conspiracy to murder, which is in urgent need of reform. “On the 10th of October 2007, the law commission proposed many recommendations on reforms of statutory conspiracy” (Law Commission 2018). The focus of this legal research is to explore the current state of law regarding conspiracy to murder and the legislation, case law, scholarly and media articles discussed in this report will evaluate the effectiveness and fairness of the law on conspiracy to murder. Thus, the question to sum up our legal research “Is the current law on conspiracy to commit murder effective and fair?

Physiological and Biomechanical Differences Between Seated and Standing Uphill Cycling

International Journal of Exercise Science 13(2): 996-1011, 2020. Despite differences in economy, cyclists climb in seated and standing positions. Prompted by gaps in research, we compared VO2 and heart rate (HR) (Study 1), muscle activation (Study 2) and breathing and pedaling entrainment (Study 3). METHODS: Subjects rode their bicycles on a treadmill in seated and standing positions. In Study 1, VO2 and HR of four male cyclists (21.3 ± 1.7 yrs; 69.1 ± 6 ml/kg/min) were collected, alternating positions every 5 minutes for 20 minutes (8 mph, 8% grade). In Study 2, muscle activations of eight male cyclists (24 ± 5 yrs, 67.6 ± 5.5 ml/kg/min) were collected on Rectus Femoris (RF), Biceps Femoris, Vastus Medialis (VM) and Gastrocnemius alternating positions every minute (8 mph, 8% grade). In Study 3, flow rate and entrainment of nine male cyclists (28 ± 7 yrs, 62.7 ± 7.7 ml/kg/min) were collected in 2-minute stages at 6, 8 and 10 mph, (8% grade) alternating positions every minute. RESULTS: VO2 and HR increased standing (3.17± 0.43 L/min, 175 ± 4 bpm) compared to seated (3.06 ± 0.37 L/min, 166 ± 5 bpm) (p \u3c 0.05). Normalized EMG for RF and VM increased standing (47 ± 5%, 57 ± 15%) compared to seated (34 ± 3%, 36 ± 8%) (p \u3c 0.05). Peak Inspiratory and Expiratory Flow increased standing (3.44±0.07 and 2.45±0.05 L/sec) compared to seated (3.09 ±0.06 and 2.21±0.04 L/sec) (p \u3c 0.05). CONCLUSION: Uphill cycling while standing results in decreased cycling economy due to physiological and biomechanical variations compared to riding seated

Multi-Polygenic Analysis of Nicotine Dependence in Individuals of European Ancestry

Introduction: Heritability estimates of nicotine dependence (ND) range from 40% to 70%, but discovery GWAS of ND are underpowered and have limited predictive utility. In this work, we leverage genetically correlated traits and diseases to increase the accuracy of polygenic risk prediction. Methods: We employed a multi-trait model using summary statistic-based best linear unbiased predictors (SBLUP) of genetic correlates of DSM-IV diagnosis of ND in 6394 individuals of European Ancestry (prevalence = 45.3%, %female = 46.8%, mu(age) = 40.08 [s.d. = 10.43]) and 3061 individuals from a nationally-representative sample with Fagerstrom Test for Nicotine Dependence symptom count (FTND; 51.32% female, mean age = 28.9 [s.d. = 1.70]). Polygenic predictors were derived from GWASs known to be phenotypically and genetically correlated with ND (i.e., Cigarettes per Day [CPD], the Alcohol Use Disorders Identification Test [AUDIT-Consumption and AUDIT-Problems], Neuroticism, Depression, Schizophrenia, Educational Attainment, Body Mass Index [BMI], and Self-Perceived Risk-Taking); including Height as a negative control. Analyses controlled for age, gender, study site, and the first 10 ancestral principal components. Results: The multi-trait model accounted for 3.6% of the total trait variance in DSM-IV ND. Educational Attainment (beta = -0.125; 95% CI: [-0.149,-0.101]), CPD (0.071 [0.047,0.095]), and Self-Perceived Risk-Taking (0.051 [0.026,0.075]) were the most robust predictors. PGS effects on FTND were limited. Conclusions: Risk for ND is not only polygenic, but also pleiotropic. Polygenic effects on ND that are accessible by these traits are limited in size and act additively to explain risk.Peer reviewe

Integration of evidence across human and model organism studies: A meeting report.

The National Institute on Drug Abuse and Joint Institute for Biological Sciences at the Oak Ridge National Laboratory hosted a meeting attended by a diverse group of scientists with expertise in substance use disorders (SUDs), computational biology, and FAIR (Findability, Accessibility, Interoperability, and Reusability) data sharing. The meeting\u27s objective was to discuss and evaluate better strategies to integrate genetic, epigenetic, and \u27omics data across human and model organisms to achieve deeper mechanistic insight into SUDs. Specific topics were to (a) evaluate the current state of substance use genetics and genomics research and fundamental gaps, (b) identify opportunities and challenges of integration and sharing across species and data types, (c) identify current tools and resources for integration of genetic, epigenetic, and phenotypic data, (d) discuss steps and impediment related to data integration, and (e) outline future steps to support more effective collaboration-particularly between animal model research communities and human genetics and clinical research teams. This review summarizes key facets of this catalytic discussion with a focus on new opportunities and gaps in resources and knowledge on SUDs

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Integration of evidence across human and model organism studies: A meeting report

The National Institute on Drug Abuse and Joint Institute for Biological Sciences at the Oak Ridge National Laboratory hosted a meeting attended by a diverse group of scientists with expertise in substance use disorders (SUDs), computational biology, and FAIR (Findability, Accessibility, Interoperability, and Reusability) data sharing. The meeting's objective was to discuss and evaluate better strategies to integrate genetic, epigenetic, and 'omics data across human and model organisms to achieve deeper mechanistic insight into SUDs. Specific topics were to (a) evaluate the current state of substance use genetics and genomics research and fundamental gaps, (b) identify opportunities and challenges of integration and sharing across species and data types, (c) identify current tools and resources for integration of genetic, epigenetic, and phenotypic data, (d) discuss steps and impediment related to data integration, and (e) outline future steps to support more effective collaboration-particularly between animal model research communities and human genetics and clinical research teams. This review summarizes key facets of this catalytic discussion with a focus on new opportunities and gaps in resources and knowledge on SUDs

DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs

Reproductive timing of the Scarlet Shiner (Lythrurus fasciolaris) in North America.

College of Science ; Biological Sciences Department; Advisor: Dr. Bruce Stallsmith ; Date: December 5, 2016; Pages: 20 p