Micro- and macroparasite species richness in birds:The role of host life history and ecology

Identifying the factors shaping variation in parasite diversity among host species is crucial to understand wildlife diseases. Although micro‐ and macroparasites may exert different selective pressures on their hosts, studies investigating the determinants of parasite species richness in animals have rarely considered this divide. Here, we investigated the role of host life history and ecology in explaining the species richness of helminths (macroparasites) and haemosporidians (microparasites) in birds world‐wide. We collated data from multiple global datasets on diverse bird traits (longevity, body mass, coloniality, migration distance/tendency, geographic range size and dietary and habitat breadths) and the species richness of their helminth and haemosporidian parasites. We tested predictors of helminth and haemosporidian parasite richness using phylogenetic generalized linear mixed models in a Bayesian framework. We found that, after controlling for research effort and host phylogeny, the richness of helminths, but not of haemosporidians, increased with host longevity, range size, migration distance and dietary breadth. Overall, these correlates were also important across different helminth groups (acanthocephalans, cestodes, nematodes and trematodes), and two additional ones (body mass, coloniality) emerged as important for cestodes and acanthocephalans. We propose that long life spans may promote the diversity of helminth parasite assemblages over evolutionary time, thus resulting in richer helminth faunas. Similarly, longer‐distance migrations, larger ranges and broader dietary breadths are likely to lead to greater encounter rates and the accumulation of trophically transmitted helminths. In contrast, vector‐borne haemosporidians may be influenced more by factors related to vector ecology than by the host traits included in the analyses. The lack of strong associations between haemosporidian species richness and host characteristics emphasizes the need to find appropriate traits to model the distribution and diversity of parasites with different environmental preferences in order to anticipate disease emergence risks associated with global change

Connections and dynamical trajectories in generalised Newton-Cartan gravity I. An intrinsic view

The "metric" structure of nonrelativistic spacetimes consists of a one-form (the absolute clock) whose kernel is endowed with a positive-definite metric. Contrarily to the relativistic case, the metric structure and the torsion do not determine a unique Galilean (i.e. compatible) connection. This subtlety is intimately related to the fact that the timelike part of the torsion is proportional to the exterior derivative of the absolute clock. When the latter is not closed, torsionfreeness and metric-compatibility are thus mutually exclusive. We will explore generalisations of Galilean connections along the two corresponding alternative roads in a series of papers. In the present one, we focus on compatible connections and investigate the equivalence problem (i.e. the search for the necessary data allowing to uniquely determine connections) in the torsionfree and torsional cases. More precisely, we characterise the affine structure of the spaces of such connections and display the associated model vector spaces. In contrast with the relativistic case, the metric structure does not single out a privileged origin for the space of metric-compatible connections. In our construction, the role of the Levi-Civita connection is played by a whole class of privileged origins, the so-called torsional Newton-Cartan (TNC) geometries recently investigated in the literature. Finally, we discuss a generalisation of Newtonian connections to the torsional case.Comment: 79 pages, 7 figures; v2: added material on affine structure of connection space, former Section 4 postponed to 3rd paper of the serie

Association of rodent-borne Leptospira spp. with urban environments in Malaysian Borneo

Although leptospirosis is traditionally considered a disease of rural, agricultural and flooded environments, Leptospira spp. are found in a range of habitats and infect numerous host species, with rodents among the most significant reservoirs and vectors. To explore the local ecology of Leptospira spp. in a city experiencing rapid urbanization, we assessed Leptospira prevalence in rodents from three locations in Malaysian Borneo with differing levels of anthropogenic influence: 1) high but stable influence (urban); 2) moderate yet increasing (developing); and 3) low (rural). A total of 116 urban, 122 developing and 78 rural rodents were sampled, with the majority of individuals assigned to either the Rattus rattus lineage R3 (n = 165) or Sundamys muelleri (n = 100). Leptospira spp. DNA was detected in 31.6% of all rodents, with more urban rodents positive (44.8%), than developing (32.0%) or rural rodents (28.1%), and these differences were statistically significant. The majority of positive samples were identified by sequence comparison to belong to known human pathogens L. interrogans (n = 57) and L. borgpetersenii (n = 38). Statistical analyses revealed that both Leptospira species occurred more commonly at sites with higher anthropogenic influence, particularly those with a combination of commercial and residential activity, while L. interrogans infection was also associated with low forest cover, and L. borgpetersenii was more likely to be identified at sites without natural bodies of water. This study suggests that some features associated with urbanization may promote the circulation of Leptospira spp., resulting in a potential public health risk in cities that may be substantially underestimated

Modulation of expression and cellular distribution of p21 by macrophage migration inhibitory factor

<p>Abstract</p> <p>Background</p> <p>The pleiotropic protein MIF, (macrophage migration inhibitory factor), has been demonstrated to modulate several key proteins governing cell cycle control and is considered to contribute to cell growth and differentiation. In this study we investigated the effect of MIF on the expression and cellular distribution of the CDK inhibitor p21.</p> <p>Methods</p> <p>The effect of endogenous MIF on p21 expression and distribution was examined by comparing murine dermal fibroblasts derived from <it>wt </it>and MIF -/- mice. The effect of MIF on cell growth and apoptotic rates was compared using ³H-Thymidine incorporation assays and annexin V/PI assays respectively. Total p21 protein levels were compared using flow cytometry and western blotting. p21 mRNA was assessed by RT-PCR. Intracellular p21 staining was performed to assess cellular distribution of total protein. To further confirm observations siRNA was used to knockdown MIF protein in <it>wt </it>cells. Cell cycle analysis was performed using PI incorporation assays.</p> <p>Results</p> <p>MIF-/- murine dermal fibroblasts exhibited reduced proliferative responses and were more susceptible to apoptosis. This was associated with reduced p21 expression and nuclear distribution. Treatment with recombinant MIF protein was demonstrated to reduce both basal and induced apoptosis and increase nuclear p21 expression. Reduced nuclear p21 expression was also observed in MIF siRNA treated <it>wt </it>cells.</p> <p>Conclusion</p> <p>The results demonstrate that in the absence of MIF p21 expression and nuclear distribution is reduced which is associated with a reduction in cell growth and increased apoptosis. MIF may therefore play a role in maintaining homeostatic control of p21.</p

Internship Experiences Contribute to Confident Career Decision Making for Doctoral Students in the Life Sciences.

The Graduate Student Internships for Career Exploration (GSICE) program at the University of California, San Francisco (UCSF), offers structured training and hands-on experience through internships for a broad range of PhD-level careers. The GSICE program model was successfully replicated at the University of California, Davis (UC Davis). Here, we present outcome data for a total of 217 PhD students participating in the UCSF and UC Davis programs from 2010 to 2015 and 2014 to 2015, respectively. The internship programs at the two sites demonstrated comparable participation, internship completion rates, and overall outcomes. Using survey, focus group, and individual interview data, we find that the programs provide students with career development skills, while increasing students' confidence in career exploration and decision making. Internships, in particular, were perceived by students to increase their ability to discern a career area of choice and to increase confidence in pursuing that career. We present data showing that program participation does not change median time to degree and may help some trainees avoid "default postdocs." Our findings suggest important strategies for institutions developing internship programs for PhD students, namely: including a structured training component, allowing postgraduation internships, and providing a central organization point for internship programs

What Does it Mean to be a British Isles Lupus Assessment Group-Based Composite Lupus Assessment Responder? Post Hoc Analysis of 2 Phase 3 Trials

OBJECTIVE: The British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) is a validated global measure of treatment response in systemic lupus erythematosus (SLE) clinical trials. To understand the relevance of BICLA in clinical practice, we investigated relationships between BICLA response and routine SLE assessments, patient-reported outcomes (PROs), and medical resource utilization. METHODS: This was a post hoc analysis of pooled data from the phase III, randomized, placebo-controlled, 52-week TULIP-1 (ClinicalTrials.gov identifier: NCT02446912; n = 457) and TULIP-2 (ClinicalTrials.gov identifier: NCT02446899; n = 362) trials of intravenous anifrolumab (150/300 mg once every 4 weeks) in patients with moderate-to-severe SLE. Changes from baseline to week 52 in clinical assessments, PROs, and medical resource use were compared in BICLA responders versus nonresponders, regardless of treatment assignment. RESULTS: BICLA responders (n = 318) achieved significantly improved outcomes compared with nonresponders (n = 501), including lower flare rates, higher rates of attainment of sustained oral glucocorticoid taper to ≤7.5 mg/day, greater improvements in PROs (Functional Assessment of Chronic Illness Therapy–Fatigue, Short Form 36 Health Survey), and fewer SLE-related hospitalizations/emergency department visits (all nominal P < 0.001). Compared with nonresponders, BICLA responders had greater improvements in global and organ-specific disease activity (Physician’s Global Assessment, SLE Disease Activity Index 2000, Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity, and joint counts; all nominal P < 0.001). BICLA responders had fewer lupus-related serious adverse events than nonresponders. CONCLUSION: BICLA response is associated with clinical benefit in SLE assessments, PROs, and medical resource utilization, confirming its value as a clinical trial end point that is associated with measures important to patient care

A systematic review and meta-analysis of the effects of flavanol-containing tea, cocoa and apple products on body composition and blood lipids: exploring the factors responsible for variability in their efficacy

Several randomized controlled trials (RCTs) and meta-analyses support the benefits of flavanols on cardiometabolic health, but the factors affecting variability in the responses to these compounds have not been properly assessed. The objectives of this meta-analysis were to systematically collect the RCTs-based-evidence of the effects of flavanol-containing tea, cocoa and apple products on selected biomarkers of cardiometabolic risk and to explore the influence of various factors on the variability in the responses to the consumption of these products. A total of 120 RCTs were selected. Despite a high heterogeneity, the intake of the flavanol-containing products was associated using a random model with changes (reported as standardized difference in means (SDM)) in body mass index (−0.15, p &lt; 0.001), waist circumference (−0.29, p &lt; 0.001), total-cholesterol (−0.21, p &lt; 0.001), LDL-cholesterol (−0.23, p &lt; 0.001), and triacylglycerides (−0.11, p = 0.027), and with an increase of HDL-cholesterol (0.15, p = 0.005). Through subgroup analyses, we showed the influence of baseline-BMI, sex, source/form of administration, medication and country of investigation on some of the outcome measures and suggest that flavanols may be more effective in specific subgroups such as those with a BMI ≥ 25.0 kg/m2, non-medicated individuals or by specifically using tea products. This meta-analysis provides the first robust evidence of the effects induced by the consumption of flavanol-containing tea, cocoa and apple products on weight and lipid biomarkers and shows the influence of various factors that can affect their bioefficacy in humans. Of note, some of these effects are quantitatively comparable to those produced by drugs, life-style changes or other natural products. Further, RCTs in well-characterized populations are required to fully comprehend the factors affecting inter-individual responses to flavanol and thereby improve flavanols efficacy in the prevention of cardiometabolic disorders