Simultaneous infection of Schistosoma mansoni and S. rodhaini in Biomphalaria glabrata: impact on chronobiology and cercarial behaviour

<p>Abstract</p> <p>Background</p> <p>The chances of a schistosome cercaria encountering a suitable definitive host may be enhanced by emergence from the molluscan intermediate host with maximal glycogen stores and by an appropriate chronobiological rhythm. This study aimed to identify and characterize the effects of potential competitive interactions in the snail host <it>Biomphalaria glabrata</it>, between the closely-related <it>Schistosoma mansoni </it>and <it>S. rodhaini</it>, on phenotypic behavioural traits. It was predicted that inter-specific competition would affect chronobiological emergence rhythms and reduce the activity of schistosome swimming behavioural traits. <it>Biomphalaria glabrata </it>snails (120) were exposed to either <it>S. mansoni </it>or <it>S. rodhaini </it>single infections, or a mixed infection of both species simultaneously and the resulting cercarial phenotypic traits were characterised. Cercariae were identified from co-exposed snails by amplification and sequencing of the mitochondrial cytochrome oxidase subunit 1 (CO1).</p> <p>Results</p> <p><it>S. mansoni </it>and <it>S. rodhaini </it>largely maintained their distinct chronobiological rhythms after mixed exposures and infections. However, inter-specific competition appeared to result in a restriction of the shedding pattern of <it>S. rodhaini </it>and slight shift in the shedding pattern of <it>S. mansoni</it>. Inter-specific competition also significantly lowered hourly cercarial production for both parasite species in comparison to single exposures and infections and reduced cercarial swimming activity.</p> <p>Conclusion</p> <p>Inter-specific competition was shown to influence cercarial production, chronobiology and activity and should therefore be investigated further in field situations to determine the effects of these changes on parasite fitness (incorporating both host finding and infectivity) where these two species overlap. Importantly this competition did not result in a large change in chronobiological emergence of cercariae for either species indicating that it would not have a large influence on the species of hosts available for infection at time of emergence. This study has furthermore demonstrated the potential for phenotypic measures to provide markers for species-specific identification even in conditions of co-infection.</p

Sleep disturbance mediates the link between both self-compassion and self-criticism and psychological distress during prolonged periods of stress

Poor sleep and subsequent decline in mental health often occur during times of prolonged stress, such as a pandemic. Self-compassion is linked with improved sleep and better mental health, while self-criticism is linked with poorer sleep and psychological distress. Given there is little evidence of the interrelationships of these constructs, we examined whether higher self-compassion or lower levels of self-criticism can reduce psychological distress directly and indirectly via sleep during times of prolonged stress. Structural equation modelling was used to analyse two samples (N = 722, Study 1, and N = 622, Replication Study) of university students during different stages of the pandemic. An aggregate psychological distress construct was calculated using depression, anxiety and stress measures. We created models that showed insomnia symptoms mediated the relationship between self-compassion/self-criticism and psychological distress. Sleep partially mediated both relationships, and this was the strongest effect in both samples. This suggests that improving self-compassion and reducing self-criticism will improve sleep, leading to reduced psychological distress. As our findings are robust and held at two time points, future research should investigate broader demographics and differing stress responses

A comprehensive resource for induced pluripotent stem cells from patients with primary tauopathies

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies

BMC Medicine celebrates its 5th anniversary

In November 2008, BMC Medicine passed the landmark of its first 5 years of publishing. When we launched the journal with the aim of publishing high quality research of general interest and special importance, we had no idea what the future would bring. To mark the occasion of our 5th anniversary, we consider the achievements of the last 5 years and discuss our plans for the future

Evaluation of gene-based family-based methods to detect novel genes associated with familial late onset Alzheimer disease

AbstractGene-based tests to study the combined effect of rare variants towards a particular phenotype have been widely developed for case-control studies, but their evolution and adaptation for family-based studies, especially for complex incomplete families, has been slower. In this study, we have performed a practical examination of all the latest gene-based methods available for family-based study designs using both simulated and real datasets. We have examined the performance of several collapsing, variance-component and transmission disequilibrium tests across eight different software and twenty-two models utilizing a cohort of 285 families (N=1,235) with late-onset Alzheimer disease (LOAD). After a thorough examination of each of these tests, we propose a methodological approach to identify, with high confidence, genes associated with the studied phenotype with high confidence and we provide recommendations to select the best software and model for family-based gene-based analyses. Additionally, in our dataset, we identified PTK2B, a GWAS candidate gene for sporadic AD, along with six novel genes (CHRD, CLCN2, HDLBP, CPAMD8, NLRP9, MAS1L) as candidates genes for familial LOAD.</jats:p

Clinically early-stage CSPα mutation carrier exhibits remarkable terminal stage neuronal pathology with minimal evidence of synaptic loss

Autosomal dominant adult-onset neuronal ceroid lipofuscinosis (AD-ANCL) is a multisystem disease caused by mutations in the DNAJC5 gene. DNAJC5 encodes Cysteine String Protein-alpha (CSPα), a putative synaptic protein. AD-ANCL has been traditionally considered a lysosomal storage disease based on the intracellular accumulation of ceroid material. Here, we report for the first time the pathological findings of a patient in a clinically early stage of disease, which exhibits the typical neuronal intracellular ceroid accumulation and incipient neuroinflammation but no signs of brain atrophy, neurodegeneration or massive synaptic loss. Interestingly, we found minimal or no apparent reductions in CSPα or synaptophysin in the neuropil. In contrast, brain homogenates from terminal AD-ANCL patients exhibit significant reductions in SNARE-complex forming presynaptic protein levels, including a significant reduction in CSPα and SNAP-25. Frozen samples for the biochemical analyses of synaptic proteins were not available for the early stage AD-ANLC patient. These results suggest that the degeneration seen in the patients with AD-ANCL reported here might be a consequence of both the early effects of CSPα mutations at the cellular soma, most likely lysosome function, and subsequent neuronal loss and synaptic dysfunction

Factors Associated with Potential Medication-Herb/Natural Product Interactions in a Rural Community

Context—Use of both conventional medicines and herbs/natural products are increasing in the United States (US). Consequently, individuals are more likely to be exposed to potentially harmful interactions between these products. Objective—To examine the use of both herbs/natural products and conventional medications in a rural community; examine the prevalence of potential interactions between herbs/natural products and conventional medications; and identify factors associated with exposure to such interactions. Design—Population-based epidemiological study. Setting—Data for this paper were collected between 1999 and 2004 as part of the Johnston County Osteoarthritis Project. Participants—Limited to civilian, non-institutionalized, Caucasian and African American residents, age 45 years or older, of Johnston County, North Carolina. Data used in this paper are from 2,523 individuals who completed face-to-face interviews. Main Outcome Measures—Prevalence of herb/natural product use and exposure to potential interactions between these products and conventional medications. Results—Nineteen percent (n=488) of participants used at least one herb/natural product. Among those who used both conventional medications and herbs/natural products, more than 1 in 5 (97 [21.9%]) were using a combination of products associated with a potential interaction. Odds of exposure to a potential interaction was lower among people who had health insurance and increased with the number of products used. Conclusions—Many people are exposed to potential interactions between herbs/natural products and conventional medications. Research is needed to better understand the effect such interactions may have on patient care

Exome-Sequencing Confirms DNAJC5 Mutations as Cause of Adult Neuronal Ceroid-Lipofuscinosis

We performed whole-exome sequencing in two autopsy-confirmed cases and an elderly unaffected control from a multigenerational family with autosomal dominant neuronal ceroid lipofuscinosis (ANCL). A novel single-nucleotide variation (c.344T>G) in the DNAJC5 gene was identified. Mutational screening in an independent family with autosomal dominant ANCL found an in-frame single codon deletion (c.346_348 delCTC) resulting in a deletion of p.Leu116del. These variants fulfill all genetic criteria for disease-causing mutations: they are found in unrelated families with the same disease, exhibit complete segregation between the mutation and the disease, and are absent in healthy controls. In addition, the associated amino acid substitutions are located in evolutionarily highly conserved residues and are predicted to functionally affect the encoded protein (CSPα). The mutations are located in a cysteine-string domain, which is required for membrane targeting/binding, palmitoylation, and oligomerization of CSPα. We performed a comprehensive in silico analysis of the functional and structural impact of both mutations on CSPα. We found that these mutations dramatically decrease the affinity of CSPα for the membrane. We did not identify any significant effect on palmitoylation status of CSPα. However, a reduction of CSPα membrane affinity may change its palmitoylation and affect proper intracellular sorting. We confirm that CSPα has a strong intrinsic aggregation propensity; however, it is not modified by the mutations. A complementary disease-network analysis suggests a potential interaction with other NCLs genes/pathways. This is the first replication study of the identification of DNAJC5 as the disease-causing gene for autosomal dominant ANCL. The identification of the novel gene in ANCL will allow us to gain a better understanding of the pathological mechanism of ANCLs and constitutes a great advance toward the development of new molecular diagnostic tests and may lead to the development of potential therapies