ResearchPad - 200 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Interrupting the trajectory of frailty in dementia with Lewy bodies with anabolic exercise, dietary intervention and deprescribing of hazardous medications]]> https://www.researchpad.co/article/elastic_article_9077 An 87-year-old man with dementia with Lewy bodies, living in residential aged care, exhibited rapid functional decline and weight loss associated with injurious falls over 9 months. Independent clinicians (geriatrician and exercise physiologist) assessed him during an extended wait-list period prior to his commencement of a pilot exercise trial. The highly significant role of treatable factors including polypharmacy, sarcopenia and malnutrition as contributors to frailty and rapid functional decline in this patient are described. The results of a targeted intervention of deprescribing, robust exercise and increased caloric intake on his physical and neuropsychological health status are presented. This case highlights the need to aggressively identify and robustly treat reversible contributors to frailty, irrespective of advanced age, progressive ‘untreatable’ neurodegenerative disease and rapidly deteriorating health in such individuals. Frailty is not a contraindication to robust exercise; it is, in fact, one of the most important reasons to prescribe it.

]]>
<![CDATA[Intestinal microbes: an axis of functional diversity among large marine consumers]]> https://www.researchpad.co/article/N11c9ff5b-6314-46a5-963a-c9aec1a1f5de Microbes are ubiquitous throughout the world's oceans, yet the manner and extent of their influence on the ecology and evolution of large, mobile fauna remains poorly understood. Here, we establish the intestinal microbiome as a hidden, and potentially important, ‘functional trait’ of tropical herbivorous fishes—a group of large consumers critical to coral reef resilience. Using field observations, we demonstrate that five common Caribbean fish species display marked differences in where they feed and what they feed on. However, in addition to space use and feeding behaviour—two commonly measured functional traits—we find that interspecific trait differences are even more pronounced when considering the herbivore intestinal microbiome. Microbiome composition was highly species specific. Phylogenetic comparison of the dominant microbiome members to all known microbial taxa suggest that microbiomes are comprised of putative environmental generalists, animal-associates and fish specialists (resident symbionts), the latter of which mapped onto host phylogeny. These putative symbionts are most similar to—among all known microbes—those that occupy the intestines of ecologically and evolutionarily related herbivorous fishes in more distant ocean basins. Our findings therefore suggest that the intestinal microbiome may be an important functional trait among these large-bodied consumers.

]]>
<![CDATA[Spatial heterogeneity of the shorebird gastrointestinal microbiome]]> https://www.researchpad.co/article/N8a8feae3-4d3d-4f89-a789-641d12d54567

The gastrointestinal tract (GIT) consists of connected structures that vary in function and physiology, and different GIT sections potentially provide different habitats for microorganisms. Birds possess unique GIT structures, including the oesophagus, proventriculus, gizzard, small intestine, caeca and large intestine. To understand birds as hosts of microbial ecosystems, we characterized the microbial communities in six sections of the GIT of two shorebird species, the Dunlin and Semipalmated Sandpiper, identified potential host species effects on the GIT microbiome and used microbial source tracking to determine microbial origin throughout the GIT. The upper three GIT sections had higher alpha diversity and genus richness compared to the lower sections, and microbial communities in the upper GIT showed no clustering. The proventriculus and gizzard microbiomes primarily originated from upstream sections, while the majority of the large intestine microbiome originated from the caeca. The heterogeneity of the GIT sections shown in our study urges caution in equating data from faeces or a single GIT component to the entire GIT microbiome but confirms that ecologically similar species may share many attributes in GIT microbiomes.

]]>
<![CDATA[Onward transmission of viruses: how do viruses emerge to cause epidemics after spillover?]]> https://www.researchpad.co/article/N8ac65fd4-3f92-4221-b69b-ec897ae260bb

The critical step in the emergence of a new epidemic or pandemic viral pathogen occurs after it infects the initial spillover host and then is successfully transmitted onwards, causing an outbreak chain of transmission within that new host population. Crossing these choke points sets a pathogen on the pathway to epidemic emergence. While many viruses spill over to infect new or alternative hosts, only a few accomplish this transition—and the reasons for the success of those pathogens are still unclear. Here, we consider this issue related to the emergence of animal viruses, where factors involved likely include the ability to efficiently infect the new animal host, the demographic features of the initial population that favour onward transmission, the level of shedding and degree of susceptibility of individuals of that population, along with pathogen evolution favouring increased replication and more efficient transmission among the new host individuals. A related form of emergence involves mutations that increased spread or virulence of an already-known virus within its usual host. In all of these cases, emergence may be due to altered viral properties, changes in the size or structure of the host populations, ease of transport, climate change or, in the case of arboviruses, to the expansion of the arthropod vectors. Here, we focus on three examples of viruses that have gained efficient onward transmission after spillover: influenza A viruses that are respiratory transmitted, HIV, a retrovirus, that is mostly blood or mucosal transmitted, and canine parvovirus that is faecal:oral transmitted. We describe our current understanding of the changes in the viruses that allowed them to overcome the barriers that prevented efficient replication and spread in their new hosts. We also briefly outline how we could gain a better understanding of the mechanisms and variability in order to better anticipate these events in the future.

This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.

]]>
<![CDATA[Revisiting the hypothesis of an energetic barrier to genome complexity between eukaryotes and prokaryotes]]> https://www.researchpad.co/article/N0bd3f347-f06c-4152-b53d-fbf3e5c05574

The absence of genome complexity in prokaryotes, being the evolutionary precursors to eukaryotic cells comprising all complex life (the prokaryote–eukaryote divide), is a long-standing question in evolutionary biology. A previous study hypothesized that the divide exists because prokaryotic genome size is constrained by bioenergetics (prokaryotic power per gene or genome being significantly lower than eukaryotic ones). However, this hypothesis was evaluated using a relatively small dataset due to lack of data availability at the time, and is therefore controversial. Accordingly, we constructed a larger dataset of genomes, metabolic rates, cell sizes and ploidy levels to investigate whether an energetic barrier to genome complexity exists between eukaryotes and prokaryotes while statistically controlling for the confounding effects of cell size and phylogenetic signals. Notably, we showed that the differences in bioenergetics between prokaryotes and eukaryotes were less significant than those previously reported. More importantly, we found a limited contribution of power per genome and power per gene to the prokaryote–eukaryote dichotomy. Our findings indicate that the prokaryote–eukaryote divide is hard to explain from the energetic perspective. However, our findings may not entirely discount the traditional hypothesis; in contrast, they indicate the need for more careful examination.

]]>
<![CDATA[Evaluation of host effects on ectomycorrhizal fungal community compositions in a forested landscape in northern Japan]]> https://www.researchpad.co/article/Nbee2fa54-010b-4d8d-8fea-6a5ee43e1a1d

Community compositions of ectomycorrhizal (ECM) fungi are similar within the same host taxa. However, careful interpretation is required to determine whether the combination of ECM fungi and plants is explained by the host preference for ECM fungi, or by the influence of neighbouring heterospecific hosts. In the present study, we aimed to evaluate the effects of host species on the ECM community compositions in a forested landscape (approx. 10 km) where monodominant forest stands of six ECM host species belonging to three families were patchily distributed. A total of 180 ECM operational taxonomic units (OTUs) were detected with DNA metabarcoding. Quantitative multivariate analyses revealed that the ECM community compositions were primarily structured by host species and families, regardless of the soil environments and spatial arrangements of the sampling plots. In addition, 38 ECM OTUs were only detected from particular host tree species. Furthermore, the neighbouring plots harboured similar fungal compositions, although the host species were different. The relative effect of the spatial factors on the ECM compositions was weaker than that of host species. Our results suggest that the host preference for ECM fungi is the primary determinant of ECM fungal compositions in the forested landscape.

]]>
<![CDATA[Escaping the immune system by DNA repair and recombination in African trypanosomes]]> https://www.researchpad.co/article/N2fd1a74e-11da-4538-a682-c5c6da2d40d9

African trypanosomes escape the mammalian immune response by antigenic variation—the periodic exchange of one surface coat protein, in Trypanosoma brucei the variant surface glycoprotein (VSG), for an immunologically distinct one. VSG transcription is monoallelic, with only one VSG being expressed at a time from a specialized locus, known as an expression site. VSG switching is a predominantly recombination-driven process that allows VSG sequences to be recombined into the active expression site either replacing the currently active VSG or generating a ‘new’ VSG by segmental gene conversion. In this review, we describe what is known about the factors that influence this process, focusing specifically on DNA repair and recombination.

]]>
<![CDATA[The origins and evolution of macropinocytosis]]> https://www.researchpad.co/article/5c4b8f67d5eed0c48487068a

In macropinocytosis, cells take up micrometre-sized droplets of medium into internal vesicles. These vesicles are acidified and fused to lysosomes, their contents digested and useful compounds extracted. Indigestible contents can be exocytosed. Macropinocytosis has been known for approaching 100 years and is described in both metazoa and amoebae, but not in plants or fungi. Its evolutionary origin goes back to at least the common ancestor of the amoebozoa and opisthokonts, with apparent secondary loss from fungi. The primary function of macropinocytosis in amoebae and some cancer cells is feeding, but the conserved processing pathway for macropinosomes, which involves shrinkage and the retrieval of membrane to the cell surface, has been adapted in immune cells for antigen presentation. Macropinocytic cups are large actin-driven processes, closely related to phagocytic cups and pseudopods and appear to be organized around a conserved signalling patch of PIP3, active Ras and active Rac that directs actin polymerization to its periphery. Patches can form spontaneously and must be sustained by excitable kinetics with strong cooperation from the actin cytoskeleton. Growth-factor signalling shares core components with macropinocytosis, based around phosphatidylinositol 3-kinase (PI3-kinase), and we suggest that it evolved to take control of ancient feeding structures through a coupled growth factor receptor.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.

]]>
<![CDATA[Study rationale and protocol of the BARICO study: a longitudinal, prospective, observational study to evaluate the effects of weight loss on brain function and structure after bariatric surgery]]> https://www.researchpad.co/article/5c644658d5eed0c484c2bb4f

Introduction

Weight loss after bariatric surgery (BS) is often associated with improved cognition and structural brain recovery. However, improved cognition after BS is not always exhibited by patients, in fact, in some cases there is even a decline in cognition. Long-term consequences of BS weight loss, in terms of obesity and related diseases, can be hard to determine due to studies having short follow-up periods and small sample sizes.

The aim of the BARICO study (BAriatric surgery Rijnstate and Radboudumc neuroImaging and Cognition in Obesity) is to determine the long-term effect of weight loss after BS on brain function and structure, using sensitive neuropsychological tests and (functional) MRI ((f)MRI). Secondary study endpoints are associated with changes in metabolic and inflammation status of adipose tissue, liver and gut, in relation to brain structure and function. Also, the possible correlation between weight loss, gut microbiota composition change and neuropsychological outcomes will be investigated.

Methods and analysis

Data from 150 Dutch BS patients (ages between 35 and 55, men and women) will be collected at various time points between 2 months before and up to 10 years after surgery. Neuropsychological tests, questionnaires, blood, faeces and tissue samples will be collected before, during and after surgery to measure changes in cognition, microbiota, metabolic activity and inflammation over time. A subgroup of 75 participants will undergo (f)MRI in relation to executive functioning (determined by the Stroop task), grey and white matter volumes and cerebral blood flow. Regression analyses will be used to explore associations between weight loss and outcome measures.

Ethics and dissemination

This study has been approved by the medical review ethics committee CMO Region Arnhem and Nijmegen (NL63493.091.17). Research findings will be published in peer-reviewed journals and at conferences.

Trial registration number

NTR7288.

]]>
<![CDATA[Cytokine responses in birds challenged with the human food-borne pathogen Campylobacter jejuni implies a Th17 response]]> https://www.researchpad.co/article/5afb2f62463d7e35b7faec9e

Development of process orientated understanding of cytokine interactions within the gastrointestinal tract during an immune response to pathogens requires experimentation and statistical modelling. The immune response against pathogen challenge depends on the specific threat to the host. Here, we show that broiler chickens mount a breed-dependent immune response to Campylobacter jejuni infection in the caeca by analysing experimental data using frequentist and Bayesian structural equation models (SEM). SEM provides a framework by which cytokine interdependencies, based on prior knowledge, can be tested. In both breeds important cytokines including pro-inflammatory interleukin (IL)-1β, , IL-4, IL-17A, interferon (IFN)-γ and anti-inflammatory IL-10 and transforming growth factor (TGF)-β4 were expressed post-challenge. The SEM revealed a putative regulatory pathway illustrating a T helper (Th)17 response and regulation of IL-10, which is breed-dependent. The prominence of the Th17 pathway indicates the cytokine response aims to limit the invasion or colonization of an extracellular bacterial pathogen but the time-dependent nature of the response differs between breeds.

]]>
<![CDATA[The DyP-type peroxidase DtpA is a Tat-substrate required for GlxA maturation and morphogenesis in Streptomyces]]> https://www.researchpad.co/article/5af8f7c2463d7e10e036cf1e

The filamentous bacterium Streptomyces lividans depends on the radical copper oxidase GlxA for the formation of reproductive aerial structures and, in liquid environments, for the formation of pellets. Incorporation of copper into the active site is essential for the formation of a cross-linked tyrosyl-cysteine cofactor, which is needed for enzymatic activity. In this study, we show a crucial link between GlxA maturation and a group of copper-related proteins including the chaperone Sco and a novel DyP-type peroxidase hereinafter called DtpA. Under copper-limiting conditions, the sco and dtpA deletion mutants are blocked in aerial growth and pellet formation, similarly to a glxA mutant. Western blot analysis showed that GlxA maturation is perturbed in the sco and dtpA mutants, but both maturation and morphology can by rescued by increasing the bioavailability of copper. DtpA acts as a peroxidase in the presence of GlxA and is a substrate for the twin-arginine translocation (Tat) translocation pathway. In agreement, the maturation status of GlxA is also perturbed in tat mutants, which can be compensated for by the addition of copper, thereby partially restoring their morphological defects. Our data support a model wherein a copper-trafficking pathway and Tat-dependent secretion of DtpA link to the GlxA-dependent morphogenesis pathway.

]]>
<![CDATA[Host species, pathogens and disease associated with divergent nasal microbial communities in tortoises]]> https://www.researchpad.co/article/5c1522f7d5eed0c4840bd7a4

Diverse bacterial communities are found on every surface of macro-organisms, and they play important roles in maintaining normal physiological functions in their hosts. While the study of microbiomes has expanded with the influx of data enabled by recent technological advances, microbiome research in reptiles lags behind other organisms. We sequenced the nasal microbiomes in a sample of four North American tortoise species, and we found differing community compositions among tortoise species and sampling sites, with higher richness and diversity in Texas and Sonoran desert tortoises. Using these data, we investigated the prevalence and operational taxonomic unit (OTU) diversity of the potential pathogen Pasteurella testudinis and found it to be common, abundant and highly diverse. However, the presence of this bacterium was not associated with differences in bacterial community composition within host species. We also found that the presence of nasal discharge from tortoises at the time of sampling was associated with a decline in diversity and a change in microbiome composition, which we posit is due to the harsh epithelial environment associated with immune responses. Repeated sampling across seasons, and at different points of pathogen colonization, should contribute to our understanding of the causes and consequences of different bacterial communities in these long-lived hosts.

]]>
<![CDATA[Efficacy of an interventional educational programme in mitigating post-traumatic stress in parents who have witnessed a febrile seizure: a pilot before-and-after study]]> https://www.researchpad.co/article/5b585f0d463d7e2a26fc33dd

Objectives

To measure post-traumatic stress in parents who have witnessed their child’s first simple febrile seizure and to assess the impact of workshops where information is dispensed, proper reactions are demonstrated and dialogue is encouraged on the mitigation of parental stress.

Design

A pilot before-and-after study, with control group, using self-reported measures from the Impact of Event Scale-Revised.

Setting

Data from two French participating centres.

Participants

A total of 50 parents who witnessed their child’s first simple febrile seizure.

Intervention

Parents selected themselves into either group 1: attending a workshop (intervention group), or group 2: no further management (control group).

Primary and secondary outcome measures

(1) Parental post-traumatic stress was assessed by the Impact of Event Scale-Revised a minimum of 4 weeks after the seizure (before any workshop if applicable). A high risk of developing post-traumatic stress disorder was indicated by a score ≥33. (2) To assess the efficacy of workshops on the mitigation of parental stress, all parents self-completed the Impact of Event Scale-Revised a second time at a minimum of 10 weeks after the seizure (after any workshop if applicable).

Results

Four weeks after the seizure, 76% of the total parents presented an Impact of Event Scale-Revised score ≥33. At 10 weeks after the seizure, the scores were 18.1 points lower (95% CI 11.66 to 24.61, P<0.0001) in group 1 versus only 5.51 points lower (95% CI 2.76 to 8.27, P=0.0003) in group 2 (intragroup comparison), and were significantly lower in group 1 compared with group 2 (intergroup comparison), P=0.02.

Conclusions

Parents who have witnessed their child’s first simple febrile seizure are at high risk of developing post-traumatic stress disorder 4 weeks after the seizure. Our innovative workshops are associated with a significant mitigation of the parental post-traumatic stress.

]]>
<![CDATA[Efficacy and safety of different drug monotherapies for tension-type headache in adults: study protocol for a Bayesian network meta-analysis]]> https://www.researchpad.co/article/5c6446a9d5eed0c484c2c2c4

Introduction

Tension-type headache (TTH) is the most prevalent neurological disease, with an estimated 1.5 billion cases worldwide. Pharmacotherapy should be considered by patients with TTH who have a limited response to non-pharmacological treatment. However, recommendations for the vast array of therapeutic drugs for TTH partially overlap, with conflicting recommendations for strength in different guidelines; these may confuse the decision-making process of clinicians. Hence, the aims of this study are to analyse the available direct and indirect evidence on different drug monotherapies for TTH in adults, and to generate a treatment ranking according to their efficacy and safety outcomes by using a Bayesian network meta-analysis (NMA).

Methods and analysis

We will systematically search the Cochrane Library, PubMed, Web of Science, Embase, China Biomedical Literature Database, International Clinical Trials Registry Platform and other resources for eligible studies. Randomised controlled trials on different drug monotherapies for TTH will be included. Two review authors (RX and YW) will independently search and select the studies, extract the data and assess the risk of bias. A Bayesian NMA will afterwards be conducted to pool the effect measures across all types of monotherapy drugs. The ranking probabilities of the efficacy and safety of different drug monotherapies will be estimated. Heterogeneity will be quantified using the Q statistic and the I² index. Inconsistency between direct and indirect evidence will be assessed by the node-splitting model. In addition, the overall quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethics and dissemination

No ethical issues are foreseen. The results will be published in a peer-reviewed journal, which will be disseminated electronically and in print.

PROSPERO registration number

CRD42018090554.

]]>