CDK-dependent nuclear localization of B-Cyclin Clb1 promotes FEAR activation during meiosis I in budding yeast

Cyclin-dependent kinases (CDK) are master regulators of the cell cycle in eukaryotes. CDK activity is regulated by the presence, post-translational modification and spatial localization of its regulatory subunit cyclin. In budding yeast, the B-cyclin Clb1 is phosphorylated and localizes to the nucleus during meiosis I. However the functional significance of Clb1's phosphorylation and nuclear localization and their mutual dependency is unknown. In this paper, we demonstrate that meiosis-specific phosphorylation of Clb1 requires its import to the nucleus but not vice versa. While Clb1 phosphorylation is dependent on activity of both CDK and polo-like kinase Cdc5, its nuclear localization requires CDK but not Cdc5 activity. Furthermore we show that increased nuclear localization of Clb1 during meiosis enhances activation of FEAR (Cdc Fourteen Early Anaphase Release) pathway. We discuss the significance of our results in relation to regulation of exit from meiosis I

Shared care: a pathway for the rejuvenation of home haemodialysis?

There much evidence for the benefits to patients of being able to manage their own haemodialysis rather following the thrice weekly model of most in-centre dialysis programmes. Numbers of patients dialysing at home remains disappointingly small and there are considerable variations between renal centres. Shared care models have been promoted as a route of encouraging greater take-up of home haemodialysis (HHD). There is currently little available evidence to support this assertion. Barriers have been identified to increasing self-management by haemodialysis patients, many of which apply to both shared care and HHD programmes. Overcoming the barriers, many of which are institutional is key to increasing numbers of patients dialysing at home. The development of shared care initiatives alone will not foster greater HHD engagement rather the cultural and other barriers to both must be overcome if such growth is to be seen

Exploring the negotiation thesis application among ski resort tourists: a segmentation approach

The negotiation thesis offers a framework for understanding the participation decision making of tourists. Unlike previous studies that investigate the causal relationship between constraints and tourists’ revisit intention, this study identified distinct segments of ski tourist based on the relative strength of constraints experienced and then investigated their decision-making process across a sample of 1,348 tourists of ski resorts. Chi-Squared Automated Interaction Detection (CHAID) analysis revealed that the decision making process regarding intention to revisit a ski destination varies between highly versus less constrained ski tourists, indicating different relative strengths of interpersonal, intrapersonal and structural constraints and different interactions among them when predicting revisit intention. On a practical basis, albeit the vast majority of participants were willing to repeat its visit, we offer customized per segment recommendations on increasing frequency of visitation and spending levels

From Biology to Mathematical Models and Back: Teaching Modeling to Biology Students, and Biology to Math and Engineering Students

We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge that they find difficult. To give students a sense of mastery in each area, several complementary approaches are used in the course: 1) a “live” textbook that allows students to explore models and mathematical processes interactively; 2) benchmark problems providing key skills on which students make continuous progress; 3) assignment of students to teams of two throughout the semester; 4) regular one-on-one interactions with instructors throughout the semester; and 5) a term project in which students reconstruct, analyze, extend, and then write in detail about a recently published biological model. Based on student evaluations and comments, an attitude survey, and the quality of the students' term papers, the course has significantly increased the ability and willingness of biology students to use mathematical concepts and modeling tools to understand biological systems, and it has significantly enhanced engineering students' appreciation of biology

Promoting the use of a self-management strategy among novice chiropractors treating individuals with spine pain: A mixed methods pilot clustered-clinical trial

Background The uptake of Self-Management Support (SMS) among clinicians is suboptimal. To date, few studies have tested knowledge translation (KT) interventions to increase the application of SMS in chiropractic teaching clinics. Study objective Evaluate the feasibility of implementing a KT intervention to promote the use of a SMS strategy among chiropractic interns, their supervisors, and individuals with spine pain compared to controls. Methods Mixed methods pilot clustered-clinical trial. Clusters of 16 Patient Management Teams were allocated to a complex KT intervention (online and workshop training). Primary feasibility outcomes for clinicians, interns and patients were rates of recruitment, retention, and adherence to protocol. A nominal group technique and interviews were used to seek end-users' views on the implementation process, and generate possible solutions. Results In total, 16 (84%) clinicians, 65 (26%) interns and 42 patients agreed to participate. All clinicians in the intervention group completed all KT intervention components, 23 interns (85%) completed the online training and 14 interns (51.8%) attended the workshop training. All clinicians in the intervention and seven (78%) in the control group completed all outcome measures at baseline and 6-month follow-up, while 15 (55.6%) and 23 (60.5%) interns in the intervention and control groups completed the questionnaires at baseline and 6-month follow-up, respectively. Among patients, 10 (52.6%) and 12 (52.2%) in the intervention and control groups respectively completed the questionnaires at the end of the study. Based on interview findings, solutions to improve the feasibility of conducting a full trial include: making SMS a part of the internship, changing the time of introducing the study to the interns, and having more training on SMS. Conclusion Recruitment and retention of chiropractic interns and patients for a larger implementation trial in a single outpatient teaching clinic may be challenging. © 2022 Eilayyan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Hyperbaric oxygen treatment improves GFR in rats with ischaemia/reperfusion renal injury: a possible role for the antioxidant/oxidant balance in the ischaemic kidney

Background. Ischaemic kidney injury continues to play a dominant role in the pathogenesis of acute renal failure (ARF) in many surgical and medical settings. A major event in the induction of renal injury is related to the generation of oxygen-free radicals. Hyperbaric oxygen therapy (HBO) is indicated for treatment of many ischaemic events but not for ARF. Therefore, the present study examined the effects of HBO on kidney function and renal haemodynamics in rats with ischaemic ARF

Using behavioural theories to optimise shared haemodialysis care: a qualitative intervention development study of patient and professional experience

Background Patients in control of their own haemodialysis report better outcomes than those receiving professional controlled care in a hospital setting, even though home and hospital haemodialysis are largely equivalent from mechanical and physiological perspectives. Shared Haemodialysis Care (SHC) describes an initiative in which hospital haemodialysis patients are supported by dialysis staff to become as involved as they wish in their own care; and can improve patient safety, satisfaction and may reduce costs. We do not understand why interventions to support self-management in other conditions have variable effects or how to optimise the delivery of SHC. The purpose of this study was to identify perceived patient and professional (nurses and healthcare assistants) barriers to the uptake of SHC, and to use these data to identify intervention components to optimise care. Methods Individual semi-structured interviews with patients and professionals were conducted to identify barriers and facilitators. Data were coded to behavioural theory to identify solutions. A national UK learning event with multiple stakeholders (patients, carers, commissioners and professionals) explored the salience of these barriers and the acceptability of solutions. Results A complex intervention strategy was designed to optimise SHC for patients and professionals. Interviews were conducted with patients (n = 15) and professionals (n = 7) in two hospitals and three satellite units piloting SHC. Data from patient and professional interviews could be coded to behavioural theory. Analyses identified key barriers (knowledge, beliefs about capabilities, skills and environmental context and resources). An intervention strategy that focuses on providing, first, patients with information about the shared nature of care, how to read prescriptions and use machines, and second, providing professionals with skills and protected time to teach both professionals/patients, as well as providing continual review, may improve the implementation of SHC and be acceptable to stakeholders. Conclusions We have developed an intervention strategy to improve the implementation of SHC for patients and professionals. While this intervention strategy has been systematically developed using behavioural theory, it should be rigorously tested in a subsequent effectiveness evaluation study prior to implementation to ensure that shared haemodialysis care can be delivered equitably, efficiently and safely for all patients

Stampidine prevents mortality in an experimental mouse model of viral hemorrhagic fever caused by lassa virus

BACKGROUND: The potential use of microorganisms as agents of biological warfare (BW) is a growing concern. Lassa virus, a member of the Arenavirus class of Hemorrhagic fever (HF) viruses has emerged as a worldwide concern among public health officials. The purpose of the present study was to further elucidate the antiviral activity spectrum of stampidine, a novel nucleoside analog with potent anti-viral activity against the immunodeficiency viruses HIV-1, HIV-2, and FIV, by examining its effects on survival of mice challenged with Lassa virus. METHODS: We examined the therapeutic effect of Stampidine in CBA mice inoculated with intracerebral injections of the Josiah strain of Lassa virus. Mice were treated either with vehicle or nontoxic doses of stampidine administered intraperitoneally 24 hours prior to, 1 hour prior to, and 24 hours, 48 hours, 72 hours, and 96 hours after virus inoculation. RESULTS: The probability of survival following the Lassa challenge was significantly improved for stampidine treated mice (Kaplan Meier, Chi-squared = 11.7, df = 2, Log-Rank p-value = 0.003). CONCLUSION: Therefore, stampidine shows clinical potential as a new agent for treatment of viral hemorrhagic fevers caused by Lassa virus

CNS activity of Pokeweed Anti-viral Protein (PAP) in mice infected with Lymphocytic Choriomeningitis Virus (LCMV)

BACKGROUND: Others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent PAP (Pokeweed antiviral protein) against a wide range of viruses. The purpose of the present study was to further elucidate the anti-viral spectrum of PAP by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (LCMV). METHODS: We examined the therapeutic effect of PAP in CBA mice inoculated with intracerebral injections of the WE54 strain of LCMV at a 1000 PFU dose level that is lethal to 100% of mice within 7–9 days. Mice were treated either with vehicle or PAP administered intraperitoneally 24 hours prior to, 1 hour prior to and 24 hours, 48 hours 72 hours and 96 hours after virus inoculation. RESULTS: PAP exhibits significant in vivo anti- LCMV activity in mice challenged intracerebrally with an otherwise invariably fatal dose of LCMV. At non-toxic dose levels, PAP significantly prolonged survival in the absence of the majority of disease-associated symptoms. The median survival time of PAP-treated mice was >21 days as opposed to 7 days median survival for the control (p = 0.0069). CONCLUSION: Our results presented herein provide unprecedented experimental evidence that PAP exhibits antiviral activity in the CNS of LCMV-infected mice

Microbial Diversity of a Brazilian Coastal Region Influenced by an Upwelling System and Anthropogenic Activity

BACKGROUND: Upwelling systems are characterised by an intense primary biomass production in the surface (warmest) water after the outcrop of the bottom (coldest) water, which is rich in nutrients. Although it is known that the microbial assemblage plays an important role in the food chain of marine systems and that the upwelling systems that occur in southwest Brazil drive the complex dynamics of the food chain, little is known about the microbial composition present in this region. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a molecular survey based on SSU rRNA gene from the three domains of the phylogenetic tree of life present in a tropical upwelling region (Arraial do Cabo, Rio de Janeiro, Brazil). The aim was to analyse the horizontal and vertical variations of the microbial composition in two geographically close areas influenced by anthropogenic activity (sewage disposal/port activity) and upwelling phenomena, respectively. A lower estimated diversity of microorganisms of the three domains of the phylogenetic tree of life was found in the water of the area influenced by anthropogenic activity compared to the area influenced by upwelling phenomena. We observed a heterogenic distribution of the relative abundance of taxonomic groups, especially in the Archaea and Eukarya domains. The bacterial community was dominated by Proteobacteria, Cyanobacteria and Bacteroidetes phyla, whereas the microeukaryotic community was dominated by Metazoa, Fungi, Alveolata and Stramenopile. The estimated archaeal diversity was the lowest of the three domains and was dominated by uncharacterised marine Crenarchaeota that were most closely related to Marine Group I. CONCLUSIONS/SIGNIFICANCE: The variety of conditions and the presence of different microbial assemblages indicated that the area of Arraial do Cabo can be used as a model for detailed studies that contemplate the correlation between pollution-indicating parameters and the depletion of microbial diversity in areas close to anthropogenic activity; functional roles and geochemical processes; phylogeny of the uncharacterised diversity; and seasonal variations of the microbial assemblages