bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Antiretroviral Therapy on Treatment Outcomes in a Prospective Study of Extensively Drug-Resistant Tuberculosis (XDR-TB) HIV Coinfection Treatment in KwaZulu-Natal, South Africa
Authors: Yuengling Katharine A. , Padayatchi Nesri , Wolf Allison , Mathema Barun , Brown Tyler , Horsburgh C. Robert , O'Donnell Max R.
Published: September 2018

Background:

Extensively drug-resistant tuberculosis (XDR-TB)/HIV coinfection has been associated with high mortality and poor TB outcomes. We performed a prospective study to comprehensively characterize a cohort of patients with XDR-TB.

Methods:

Adult patients with XDR-TB were enrolled at treatment initiation at a TB referral hospital in KwaZulu-Natal Province, South Africa, and followed through the end of treatment. Clinical data, questionnaires, adherence data, and sputum were collected monthly. Whole genome sequencing was performed on baseline Mycobacterium tuberculosis (MTB) isolates. Treatment outcomes were defined using standard definitions.

Results:

One hundred five patients with XDR-TB (76.1% HIV-infected) were enrolled from August 2009 to July 2011. Among HIV-coinfected patients, 82.5% were on antiretroviral therapy initially and 93.8% cumulatively over the study period. At 24 months, 31.4% had a successful outcome and 68.6% had an unsuccessful outcome with 41% mortality. Antiretroviral therapy was associated with improved mortality in HIV-coinfected patients (P = 0.05), as was TB culture conversion (P < 0.0001). On whole genome sequencing, most strains were LAM4/KZN lineage (68%), with few single nucleotide polymorphism differences.

Conclusions:

Despite improved HIV care, treatment outcomes and mortality were only modestly improved compared with previous South African XDR-TB/HIV treatment cohorts. Of note, this study was completed before the introduction of new antimycobacterial agents (eg, bedaquiline and delamanid). As new TB drugs and regimens become available, it is important to monitor treatment to ensure that benefits seen in clinical trials are reproduced in high-burden, low-resource settings.
Identification of a Syndemic of Blood-Borne Disease Transmission and Injection Drug Use Initiation at the US–Mexico Border
Authors: Rafful Claudia , Jain Sonia , Sun Xiaoying , Strathdee Steffanie A. , Garfein Richard S. , Cuevas-Mota Jazmine , Magis-Rodríguez Carlos , Smith Laramie R. , Werb Dan
Published: September 2018

Background:

Efforts to prevent injection drug use (IDU) are increasingly focused on the role that people who inject drugs (PWID) play in the assistance with injection initiation. We studied the association between recent (ie, past 6 months) injection-related HIV risk behaviors and injection initiation assistance into IDU among PWID in the US–Mexico border region.

Setting:

Preventing Injecting by Modifying Existing Responses (PRIMER) is a multicohort study assessing social and structural factors related to injection initiation assistance. This analysis included data collected since 2014 from 2 participating cohorts in San Diego and Tijuana.

Methods:

Participants were 18 years and older and reported IDU within the month before study enrollment. Logistic regression analyses were conducted to assess the association between recent injection-related HIV risk behaviors (eg, distributive/receptive syringe sharing, dividing drugs in a syringe, and paraphernalia sharing) and recent injection initiation assistance.

Results:

Among 892 participants, 41 (4.6%) reported recently providing injection initiation assistance. In multivariable analysis adjusting for potential confounders, reporting a higher number of injection-related risk behaviors was associated with an increased odds of recently assisting others with injection initiation (adjusted odds ratio per risk behavior: 1.3; 95% confidence interval: 1.0 to 1.6, P = 0.04).

Conclusions:

PWID who recently engaged in one or more injection-related HIV risk behavior were more likely to assist others in injection initiation. These results stress the syndemic of injection initiation and risk behaviors, which indicates that prevention of injection-related HIV risk behaviors might also reduce the incidence of injection initiation.
Nerve Ultrasound, Electrophysiological, and Clinical Changes in Treatment-Naive Chronic Inflammatory Demyelinating Polyneuropathy: A Case Report
Authors: Sato Takeo , Terasawa Yuka , Higa Hitomi , Matsuno Hiromasa , Arai Ayumi , Omoto Shusaku , Mitsumura Hidetaka , Toyoda Chizuko , Koike Haruki , Iguchi Yasuyuki
Published: September 2018

We report the case of a 74-year-old woman with treatment-naive chronic inflammatory demyelinating polyneuropathy evaluated by both nerve conduction studies and nerve ultrasound (NUS) before and after initial treatment. Performing both nerve conduction study and NUS before and after initial treatment seems rare for treatment-naive chronic inflammatory demyelinating polyneuropathy. This case yielded two major findings. First, improvement of nerve swelling as evaluated by NUS correlated well with the improvement of neurological symptoms. Second, NUS improvements were seen right after treatment, whereas electrophysiological improvements were not. Nerve ultrasound might thus allow for judgment of curative effects much more immediately and sensitively than nerve conduction study in treatment-naive chronic inflammatory demyelinating polyneuropathy.
ICTV Virus Taxonomy Profile: Quadriviridae
Authors: Chiba Sotaro , Castón José R. , Ghabrial Said A. , Suzuki Nobuhiro ,   ICTV Report Consortium
Published: September 2018

The Quadriviridae is a monogeneric family of non-enveloped spherical viruses with quadripartite dsRNA genomes, each segment of 3.5–5.0 kbp, comprising 16.8–17.1 kbp in total. The family includes the single species Rosellinia necatrix quadrivirus 1. All quadriviruses infect filamentous fungi, and have unique virion structures compared with other known dsRNA viruses. Pathogenicity has not been reported for these viruses. This is a summary of the ICTV Report on the taxonomy of family Quadriviridae, which is available at http://www.ictv.global/report/quadriviridae.
YAP activity is necessary and sufficient for basal progenitor abundance and proliferation in the developing neocortex
Authors: Kostic Milos , Paridaen Judith T.M.L. , Long Katherine , Kalebic Nereo , Langen Barbara , Wimberger Pauline , Kawasaki Hiroshi , Namba Takashi , Huttner Wieland B.
Published: September 2018

The expansion of the neocortex during mammalian evolution has been linked to an enlargement of the subventricular zone during cortical development and an increase in the proliferation of the basal progenitors residing therein. Here, we explored a potential role of YAP, the major downstream effector of the Hippo signaling pathway, in proliferation of basal progenitors. We show that YAP expression and activity are high in ferret and human basal progenitors, which are known to exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. To induce YAP activity in mouse basal progenitors, we expressed a constitutively active YAP (CA-YAP). This resulted in an increase in proliferation of basal progenitor. In addition, CA-YAP expressing mouse basal progenitors promoted the production of upper-layer neurons. To investigate if YAP is required for the proliferation of basal progenitors, we pharmacologically interfered with the function of YAP in the developing ferret and human neocortex. This resulted in a decrease of cycling basal progenitors. In concert, genetical interference with the function of YAP in ferret developing neocortex resulted in decreased abundance of basal progenitors. Together, our data indicate that YAP promotes the proliferation of basal progenitors and suggest that changes in YAP activity levels contributed to the evolutionary expansion of the neocortex.
Discovery of novel thrips vector proteins that bind to the viral attachment protein of the plant bunyavirus, tomato spotted wilt virus
Authors: Badillo-Vargas Ismael E. , Chen Yuting , Martin Kathleen M. , Rotenberg Dorith , Whitfield Anna E.
Published: September 2018

The plant-pathogenic virus, tomato spotted wilt virus (TSWV), encodes a structural glycoprotein (GN) that, like with other bunyavirus/vector interactions, serves a role in viral attachment and possibly entry into arthropod vector host cells. It is well documented thatFrankliniella occidentalisis one of seven competent thrips vectors of TSWV transmission to plant hosts, however, the insect molecules that interact with viral proteins, such as GN, during infection and dissemination in thrips vector tissues are unknown. The goals of this project were to identify TSWV-interacting proteins (TIPs) that interact directly with TSWV GNand to localize expression of these proteins in relation to virus in thrips tissues of principle importance along the route of dissemination. We report here the identification of six TIPs from first instar larvae (L1), the most acquisition-efficient developmental stage of the thrips vector. Sequence analyses of these TIPs revealed homology to proteins associated with the infection cycle of other vector-borne viruses. Immunolocalization of the TIPs in L1s revealed robust expression in the midgut and salivary glands ofF. occidentalis, the tissues most important during virus infection, replication and plant-inoculation. The TIPs and GNinteractions were validated using protein-protein interaction assays. Two of the thrips proteins, endocuticle structural glycoprotein and cyclophilin, were found to be consistent interactors with GN. These newly discovered thrips protein-GNinteractions are essential towards better understanding of transmission of persistent propagative plant viruses by their vectors, as well as for developing new strategies of insect pest management and virus resistance in plants.

Importance Statement

Thrips-transmitted viruses cause devastating losses to numerous food crops worldwide. For negative-sense RNA viruses that infect plants, the arthropod serves as a host as well by supporting virus replication in specific tissues and organs of the vector. The goal of this work was to identify vector/host proteins that bind directly to the viral attachment protein and thus may play a role in the infection cycle in the insect. Using the model plant bunyavirus, tomato spotted wilt virus (TSWV), and the most efficient thrips vector, we identified and validated six TSWV-interacting proteins fromFrankliniella occidentalisfirst instar larvae. Two proteins, an endocuticle structural glycoprotein and cyclophilin, were able to interact directly with the TSWV attachment protein, GN, in insect cells. The TSWV GN-interacting proteins provide new targets for disrupting the virus-vector interaction and could be putative determinants of vector competence.
Influence of prior beliefs on perception in early psychosis: effects of illness stage and hierarchical level of belief
Authors: Haarsma J. , Knolle F. , Griffin J.D. , Taverne H. , Mada M. , Goodyer I.M. ,   the NSPN Consortium, Fletcher P.C. , Murray G.K.
Published: September 2018

Alterations in the balance between prior expectations and sensory evidence may account for faulty perceptions and inferences leading to psychosis. However, uncertainties remain about the nature of altered prior expectations and the degree to which they vary with the emergence of psychosis. We explored how expectations arising at two different levels – cognitive and perceptual – influenced processing of sensory information and whether relative influences of higher and lower level priors differed across people with prodromal symptoms and those with psychotic illness. In two complementary auditory perception experiments, 91 participants (30 with first episode psychosis, 29 at clinical risk for psychosis, and 32 controls) were required to decipher a phoneme within ambiguous auditory input. Expectations were generated in two ways: an accompanying visual input of lip movements observed during auditory presentation, or through written presentation of a phoneme provided prior to auditory presentation. We determined how these different types of information shaped auditory perceptual experience, how this was altered across the prodromal and established phases of psychosis, and how this relates to cingulate glutamate levels assessed by magnetic resonance spectroscopy. The psychosis group relied more on high level cognitive priors compared to both healthy controls and those at clinical risk for psychosis, and more on low level perceptual priors than the clinical risk group. The risk group were marginally less reliant on low level perceptual priors than controls. The results are consistent with previous theory that influences of prior expectations in psychosis in perception differ according to level of prior and illness phase.

General scientific summary

What we perceive and believe on any given moment will allow us to form expectations about what we will experience in the next. In psychosis, it is believed that the influence of these so-called perceptual and cognitive ‘prior’ expectations on perception is altered, thereby giving rise to the symptoms seen in psychosis. However, research thus far has found mixed evidence, some suggesting an increase in the influence of priors and some finding a decrease. Here we test the hypothesis that perceptual and cognitive priors are differentially affected in individuals at-risk for psychosis and individuals with a first episode of psychosis, thereby partially explaining the mixed findings in the literature. We indeed found evidence in favour of this hypothesis, finding weaker perceptual priors in individuals at-risk, but stronger cognitive priors in individuals with first episode psychosis.
Species activity promote the stability of fruit-frugivore interactions across a five-year multilayer network
Authors: Costa José M. , Ramos Jaime A. , Timóteo Sérgio , da Silva Luís P. , Ceia Ricardo S. , Heleno Ruben H.
Published: September 2018

Although biological communities are intrinsically dynamic, with both, species and interactions changing over time, interaction networks analyses to date are still largely static. We implemented a temporal multilayer network approach to explore the changes on species roles and on the emergent structure of a seed-dispersal network over five years. Network topology was relatively constant, with four well defined interaction modules spanning across all years. Importantly, species that were present on more years, were also disproportionally important on each year, thus forming a core of temporally reliable species that are critical to the cohesiveness of the multilayer network structure. We propose a new descriptor termed species activity that reflects the number of temporal, spatial or functional layers (e.g., different years, habitats, or functions) that each species integrates, providing a simple and powerful index of species importance for multilayer network cohesion.
Identification of SMARCD1 as a syndromic intellectual disability gene that is required for memory and context-dependent regulation of neuronal genes in Drosophila
Authors: Nixon Kevin C.J. , Rousseau Justine , Stone Max H. , Sarikahya Mohammed , Ehresmann Sophie , Mizuno Seiji , Matsumoto Naomichi , Miyake Noriko ,   DDD study
Published: September 2018

Mutations in several genes encoding components of the SWI/SNF chromatin remodeling complex cause syndromic intellectual disability (ID). Here, we report on 5 individuals with mutations in the SMARCD1 gene, presenting with ID, developmental delay, hypotonia, feeding difficulties, and small extremities. The mutations were proven to be de novo in 4 of the 5 individuals. Mutations in other SWI/SNF components cause Coffin-Siris, Nicolaides-Baraitser, or other syndromic ID disorders. Although the individuals presented here have some clinical overlap with these disorders, they lack the typical facial dysmorphisms. To gain insight into the function of SMARCD1 in neurons, we investigated the Drosophila ortholog, Bap60, in postmitotic memory-forming neurons of the adult Drosophila mushroom body (MB). Targeted knockdown of Bap60 in the MB of adult flies causes defects in long-term memory. Mushroom body specific transcriptome analysis revealed that Bap60 is required for context-dependent expression of genes involved in neuron function and development in juvenile flies when synaptic connections are actively being formed in response to experience. Taken together, we identify SMARCD1 mutations as a novel cause of ID, and establish a role for the SMARCD1 ortholog Bap60 in regulation of neurodevelopmental genes during a critical time window of juvenile adult brain development that is essential in establishing neuronal circuits that are required for learning and memory.
Mind the Gap: Identifying What Is Missed When Searching Only the Broad Scope with PubMed Clinical Queries
Authors: Sperr Edwin V.
Published: September 2018

Objective

PubMed Clinical Queries are subdivided into “Broad” and “Narrow” versions. These versions are tuned to maximize either retrieval or sensitivity using two different sets of keywords and MeSH headings. While a searcher might assume that all items retrieved by Filter name/Narrow would also be found in the set Filter name/Broad, this is not explicitly guaranteed. It is the purpose of this study to quantify the overlap between these two sets and confirm whether Filter/Narrow is always a subset of Filter/Broad.

Methods

For each of the five PubMed Clinical Queries, PubMed was searched for citations matching the query Filter/Narrow NOT Filter/Broad. This number was compared with that for Filter/Broad to compute a “degree of discordance” between the two sets. This process was then repeated for the MeSH headings for “Medicine” and “Diseases” as well as for a set of test searches.

Results

Four of the five Clinical Queries returned citations using Filter/Narrow that were not found with Filter/Broad. Discordances between the sets Broad and Narrow were generally modest for “Etiology”, “Diagnosis” and “Clinical prediction guides”. “Prognosis” was notably more discordant – a searcher could easily miss one Prognosis/Narrow citation for every ten citations she retrieves when using Prognosis/Broad alone for a given search.

Conclusions

Users of the Clinical Queries apart from “Therapy” who are interested in retrieving as many relevant citations as possible should consider combining Filter/Narrow together with Filter/Broad in their search strategy. This is particularly true for “Prognosis”, as otherwise the risk of missing relevant citations is substantial.
Skin microbiome modulation induced by probiotic solutions
Authors: Paetzold Bernhard , Willis Jesse R. , Lima Joao , Knodlseder Nastassia , Quist Sven R. , Gabaldón Toni , Güell Marc
Published: September 2018

Background

The skin is colonized by a large number of microorganisms, of which most are beneficial or harmless. However, disease states of skin have specific microbiome compositions that are different from those of healthy skin. Gut microbiome modulation through fecal transplant has proven as a valid therapeutic strategy in diseases such as Clostridium difficile infections. Therefore, techniques to modulate the skin microbiome composition may become an interesting therapeutic option in diseases affecting the skin such as psoriasis or acnes vulgaris.

Here we have used mixtures of different skin microbiome components to alter the composition of a recipient skin microbiome.

Results

We show that after sequential applications of a donor microbiome, the recipient microbiome becomes similar to that of the donor. After intervention, an initial, week-long phase is characterized by dominance of donor strains. The level of engraftment depends on the composition of the recipient and donor microbiomes, and the applied bacterial load. We observed higher engraftment using a multi-strain donor solution with recipient skin rich in Cutibacterium acnes subtype H1 and Leifsonia.

Conclusions

We have demonstrated the use of living bacteria to modulate skin microbiome composition.
Defining the transcriptional and post-transcriptional landscapes ofMycobacterium smegmatisin aerobic growth and oxygen limitation
Authors: Martini M. Carla , Zhou Ying , Sun Huaming , Shell Scarlet S.
Published: September 2018

The ability ofMycobacterium tuberculosisto infect, proliferate, and survive during long periods in the human lungs largely depends on the rigorous control of gene expression. Transcriptome-wide analyses are key to understanding gene regulation on a global scale. Here, we combine 5’-end-directed libraries with RNAseq expression libraries to gain insight into the transcriptome organization and post-transcriptional mRNA cleavage landscape in mycobacteria during log phase growth and under hypoxia, a physiologically relevant stress condition. Using the model organismMycobacterium smegmatis, we identified 6,090 transcription start sites (TSSs) with high confidence during log phase growth, of which 67% were categorized as primary TSSs for annotated genes, and the remaining were classified as internal, antisense or orphan, according to their genomic context. Interestingly, over 25% of the RNA transcripts lack a leader sequence, and of the coding sequences that do have leaders, 53% lack a strong consensus Shine-Dalgarno site. This indicates that likeM. tuberculosis,M. smegmatiscan initiate translation through multiple mechanisms. Our approach also allowed us to identify over 3,000 RNA cleavage sites, which occur at a novel sequence motif. The cleavage sites show a positional bias toward mRNA regulatory regions, highlighting the importance of post-transcriptional regulation in gene expression. We show that in low oxygen, a condition associated with the host environment during infection, mycobacteria change their transcriptomic profiles and endonucleolytic RNA cleavage is markedly reduced, suggesting a mechanistic explanation for previous reports of increased mRNA half-lives in response to stress. In addition, a number of TSSs were triggered in hypoxia, 56 of which contain the binding motif for the sigma factor SigF in their promoter regions. This suggests that SigF makes direct contributions to transcriptomic remodeling in hypoxia-challenged mycobacteria. Our results show thatM. smegmatisandM. tuberculosisshare a large number of similarities at the transcriptomic level, suggesting that similar regulatory mechanisms govern both species.
Disruptions in White Matter Maturation and Mediation of Cognitive Development in Youth on the Psychosis Spectrum
Authors: Hegarty Catherine E. , Jolles Dietsje D. , Mennigen Eva , Jalbrzikowski Maria , Bearden Carrie E. , Karlsgodt Katherine H.
Published: September 2018

Background:

Psychosis onset typically occurs in adolescence, and subclinical psychotic experiences peak in adolescence as well. Adolescence is also a time of critical neural and cognitive maturation. Using cross-sectional data from the Philadelphia Neurodevelopmental Cohort, we examine whether regional white matter (WM) development is disrupted in psychosis spectrum (PS) youth whether WM maturation mediates the relationship between age and cognition in typically developing (TD) and PS youth. A third group with intermediate symptom severity (limited PS [LPS]) was included in follow-up analyses to determine whether age-related disruptions in WM scaled with symptom severity.

Methods:

We examined WM microstructure, as assessed via diffusion tensor imaging, in 707 individuals (aged 10–22 years; 499 TD, 171 PS, 37 LPS) by using Tract-Based Spatial Statistics. Multiple regressions were used to evaluate age x group interactions on regional WM indices. Mediation analyses were conducted using a bootstrapping approach.

Results:

There were age x group interactions on fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and retrolenticular internal capsule (RLIC). SLF FA mediated the relationship between age and Complex Cognition in TD, but not PS. Further, inclusion of LPS youth showed that the relationship between age and SLF FA decreased with increasing symptom severity

Conclusions:

Our results show aberrant age-related changes in SLF and RLIC FA in PS youth. SLF development supports emergence of specific higher-order cognitive functions in TD youth, but not in PS. Future mechanistic explanations for these relationships could facilitate development of earlier and refined targets for therapeutic interventions.
Calculating the Mutual Information Between Two Spike Trains
Authors: Houghton Conor
Published: September 2018

It is difficulty to estimate the mutual information between spike trains because established methods require more data than is usually available. Kozachenko-Leonenko estimators promise to solve this problem, but include a smoothing parameter which must be set. It is proposed here that the smoothing parameter can be selected by maximizing the estimated unbiased mutual information. This is tested on fictive data and shown to work very well.
Cell and tissue type independent age-associated DNA methylation changes are not rare but common
Authors: Zhu Tianyu , Zheng Shijie C , Paul Dirk S. , Horvath S. , Teschendorff Andrew E.
Published: September 2018

Age-associated DNA methylation changes have been widely reported across many different tissue and cell types. Epigenetic ‘clocks’ that can predict chronological age with a surprisingly high degree of accuracy appear to do so independently of tissue and cell-type, suggesting that a component of epigenetic drift is cell-type independent. However, the relative amount of age-associated DNAm changes that are specific to a cell or tissue type versus the amount that occurs independently of cell or tissue type is unclear and a matter of debate, with a recent study concluding that most epigenetic drift is tissue-specific. Here, we perform a novel comprehensive statistical analysis, including matched multi cell-type and multi-tissue DNA methylation profiles from the same individuals and adjusting for cell-type heterogeneity, demonstrating that a substantial amount of epigenetic drift, possibly over 70%, is shared between significant numbers of different tissue/cell types. We further show that ELOVL2 is not unique and that many other CpG sites, some mapping to genes in the Wnt and glutamate receptor signaling pathways, are altered with age across at least 10 different cell/tissue types. We propose that while most age-associated DNAm changes are shared between cell-types that the putative functional effect is likely to be tissue-specific.
Complex interactions between local adaptation, plasticity, and sex affect vulnerability to warming in a widespread marine copepod
Authors: Sasaki Matthew , Hedberg Sydney , Richardson Kailin , Dam Hans G.
Published: September 2018

Predicting the response of populations to climate change requires knowledge of thermal performance. Genetic differentiation and phenotypic plasticity affect thermal performance, but the effects of sex and developmental temperatures often go uncharacterized. We used common garden experiments to test for effects of local adaptation, developmental phenotypic plasticity, and individual sex on thermal performance of the ubiquitous copepod,Acartia tonsa. Females had higher thermal tolerance than males in both populations, while the Florida population had higher thermal tolerance compared to the Connecticut population. An effect of developmental phenotypic plasticity on thermal tolerance was observed only in the Connecticut population. Ignoring sex-specific differences may result in a severe underestimation of population-level impacts of warming (i.e. - population decline due to sperm limitation). Further, despite having a higher thermal tolerance, southern populations may be more vulnerable to warming as they lack the ability to respond to increases in temperature through phenotypic plasticity.
Revealing multi-scale population structure in large cohorts
Authors: Diaz-Papkovich Alex , Anderson-Trocmé Luke , Gravel Simon
Published: September 2018

Genetic structure in large cohorts results from technical, sampling and demographic variation. Visualisation is therefore a first step in most genomic analyses. However, existing data exploration methods struggle with unbalanced sampling and the many scales of population structure. We investigate an approach to dimension reduction of genomic data that combines principal components analysis (PCA) with uniform manifold approximation and projection (UMAP) to succinctly illustrate population structure in large cohorts and capture their relationships on local and global scales. Using data from large-scale genomic datasets, we demonstrate that PCA-UMAP effectively clusters closely related individuals while placing them in a global continuum of genetic variation. This approach reveals previously overlooked subpopulations within the American Hispanic population and fine-scale relationships between geography, genotypes, and phenotypes in the UK population. This opens new lines of investigation for demographic research and statistical genetics. Given its small computational cost, PCA-UMAP also provides a general-purpose approach to exploratory analysis in population-scale datasets.

Author summary

Because of geographic isolation, individuals tend to be more genetically related to people living nearby than to people living far. This is an example of population structure, a situation where a large population contains subgroups that share more than the average amount of DNA. This structure can tell us about human history, and it can also have a large effect on medical studies. We use a newly developed method (UMAP) to visualize population structure from three genomic datasets. Using genotype data alone, we reveal numerous subgroups related to ancestry and correlated with traits such as white blood cell count, height, and FEV1, a measure used to detect airway obstruction. We demonstrate that UMAP reveals previously unobserved patterns and fine-scale structure. We show that visualizations work especially well in large datasets containing populations with diverse backgrounds, which are rapidly becoming more common, and that unlike other visualization methods, we can preserve intuitive connections between populations that reflect their shared ancestries. The combination of these results and the effectiveness of the strategy on large and diverse datasets make this an important approach for exploratory analysis for geneticists studying ancestral events and phenotype distributions.
A comprehensive reference transcriptome resource for the Iberian ribbed newtPleurodeles waltl, an emerging model for developmental and regeneration biology
Authors: Matsunami Masatoshi , Suzuki Miyuki , Haramoto Yoshikazu , Fukui Akimasa , Inoue Takeshi , Yamaguchi Katsushi , Uchiyama Ikuo , Mori Kazuki , Tashiro Kosuke , Ito Yuzuru , Takeuchi Takashi , Suzuki Ken-ichi T , Agata Kiyokazu , Shigenobu Shuji , Hayashi Toshinori
Published: September 2018

Urodele amphibian newts have unique biological properties, notably including prominent regeneration ability. Iberian ribbed newt,Pleurodeles waltl, is a promising model newt along with the successful development of the easy breeding system and efficient transgenic and genome editing methods. However, genetic information ofP. waltlwas limited. In the present study, we conducted an intensive transcriptome analysis ofP. waltlusing RNA-sequencing to build gene models and annotate them. We generated 1.2 billion Illumina reads from a wide variety of samples across 11 different tissues and 9 time points during embryogenesis. They were assembled into 202,788 non-redundant contigs that appear to cover nearly complete (~98%)P. waltlprotein-coding genes. Using the gene set as a reference, our gene network analysis identified regeneration-, developmental-stage-, and tissue-specific co-expressed gene modules. Ortholog analyses with other vertebrates revealed the gene repertoire evolution of amphibians which includes urodele-specific loss ofbmp4and duplications ofwnt11b. Our transcriptome resource will enhance future research employing this emerging model animal for regeneration research as well as other areas such as developmental biology, stem cell biology, cancer research, ethology and toxico-genomics. These data are available via our portal website, iNewt (http://www.nibb.ac.jp/imori/main/).
A divergent hepatitis D-like agent in birds
Authors: Wille Michelle , Netter Hans J. , Littlejohn Margaret , Yuen Lilly , Shi Mang , Eden John-Sebastian , Klaassen Marcel , Holmes Edward C. , Hurt Aeron C.
Published: September 2018

Hepatitis delta virus (HDV) is currently only found in humans, and is a satellite virus that depends on hepatitis B virus (HBV) envelope proteins for assembly, release and entry. Using meta-transcriptomics, we identified the genome of a novel HDV-like agent in ducks. Sequence analysis revealed secondary structures that were shared with HDV, including self-complementarity and ribozyme features. The predicted viral protein shares 32% amino acid similarity to the small delta antigen of HDV and comprises a divergent phylogenetic lineage. The discovery of an avian HDV-like agent has important implications for the understanding of the origins of HDV and subviral agents.

Importance

Hepatitis delta virus (HDV) is currently only found in humans, and coinfections of HDV and Hepatitis B virus (HBV) in humans result in severe liver disease. There are a number of hypotheses for the origin of HDV, although a key component of all is that HDV only exists in humans. Here, we describe a novel deltavirus-like agent identified in wild birds. Although this agent is genetically divergent, it exhibits important similarities to HDV, such as the presence of ribosymes and self-complementarity. The discovery of an avian HDV-like agent challenges our understanding of both the origin and the co-evolutionary relationships of subviral agents with helper viruses.
Coculturing bacteria leads to reduced phenotypic heterogeneities
Authors: Heyse Jasmine , Buysschaert Benjamin , Props Ruben , Rubbens Peter , Skirtach Andre G. , Waegeman Willem , Boon Nico
Published: September 2018

Isogenic bacterial populations are known to exhibit phenotypic heterogeneity at the single cell level. Because of difficulties in assessing the phenotypic heterogeneity of a single taxon in a mixed community, the importance of this deeper level of organisation remains relatively unknown for natural communities. In this study, we have used membrane-based microcosms that allow the probing of the phenotypic heterogeneity of a single taxon while interacting with a synthetic or natural community. Individual taxa were studied under axenic conditions, as members of a coculture with physical separation, and as a mixed culture. Phenotypic heterogeneity was assessed through both flow cytometry and Raman spectroscopy. Using this setup, we investigated the effect of microbial interactions on the individual phenotypic heterogeneities of two interacting drinking water isolates. We have demonstrated that interactions between these bacteria lead to an adjustment of their individual phenotypic diversities, and that this adjustment is conditional on the bacterial taxon.

Importance

Laboratory studies have shown the impact of phenotypic heterogeneity on the survival and functionality of isogenic populations. As phenotypic heterogeneity is known to play an important role in pathogenicity and virulence, antibiotics resistance, biotechnological applications and ecosystem properties, it is crucial to understand its influencing factors. An unanswered question is whether bacteria in mixed communities influence the phenotypic heterogeneity of their community partners. We found that coculturing bacteria leads to a reduction in their individual phenotypic heterogeneities, which led us to the hypothesis that the individual phenotypic diversity of a taxon is dependent on the community composition.
Synergistic antifungal effect of amphotericin B-loaded PLGA nanoparticles based ultrasound against C. albicans biofilms
Authors: Yang Min , Du Kaiyue , Hou Yuru , Xie Shuang , Dong Yu , Li Dairong , Du Yonghong
Published: September 2018

C. albicans is human opportunistic pathogens that cause superficial and life-threatening infections. An important reason for the failure of current antifungal drugs is related to biofilm formation mostly associated with implanted medical device. The present study aims to investigate the synergistic antifungal efficacy of low-frequency and low-intensity ultrasound combined with amphotericin B-loaded PLGA nanoparticles (AmB-NPs) on C.albicans biofilms. AmB-NPs were prepared by a double emulsion method and demonstrated the lower toxicity than free AmB, after which biofilms were established and treated with ultrasound and AmB-NPs separately or jointly in vitro and in vivo. The results demonstrated the activity, biomass, and proteinase and phospholipase activities of biofilms were decreased significantly after the combination treatment of AmB-NPs with 42 KHz ultrasound irradiation at an intensity of 0.30 W/cm2 for 15 min compared to the control, the AmB alone or the ultrasound alone treatment (P < 0.01), and the morphology of biofilms was altered remarkably after jointly treatment under CLSM observation and detection, especially thickness thinning and structure loosing. Furthermore, the same synergistic effects were proved in a subcutaneous catheter biofilm rat model. The result of colony forming units of catheter fungus loading exhibited a significant reduction after AmB-NPs and ultrasound jointly treatment for 7 days continuous therapy, and the CLSM images revealed that the biofilm on the catheter surface was substantially eliminated. Our study may provide a new noninvasive, safe and effective application to C.albicans biofilm infection therapy.
Bioprospecting the solar panel microbiome: high-throughput screening for antioxidant bacteria in aCaenorhabditis elegansmodel
Authors: Tanner Kristie , Martorell Patricia , Genovés Salvador , Ramón Daniel , Zacarías Lorenzo , Rodrigo María Jesús , Peretó Juli , Porcar Manuel
Published: September 2018

Microbial communities that are exposed to sunlight typically share a series of adaptations to deal with the radiation they are exposed to, including efficient DNA repair systems, pigment production and protection against oxidative stress, which makes these environments good candidates for the search of novel antioxidant microorganisms. In this research project, we isolated potential antioxidant pigmented bacteria from a dry and highly-irradiated extreme environment: solar panels. High-throughputin vivoassays usingCaenorhabiditis elegansas an experimental model demonstrated the high antioxidant and ultraviolet-protection properties of these bacterial isolates that proved to be rich in carotenoids. Our results suggest that solar panels harbor a microbial community that includes strains with potential applications as antioxidants.
Effects of individuation and grouping on face representations in the visual cortex
Authors: Kim Hyehyeon , Kim Gayoung , Lee Sue-Hyun
Published: September 2018

Top-down signals can influence our visual perception by providing guidance on information processing. Especially, top-down control between two basic frameworks, “Individuation” and “grouping”, is critical for information processing during face perception. Individuation of faces supports identity recognition while grouping subserves higher category level face perception such as race or gender. However, it still remains elusive how top-down dependent control between individuation and grouping affects cortical representations during face perception. Here we performed an fMRI experiment to investigate whether representations across early and high-level visual areas can be altered by top-down control between individuation and grouping process during face perception. Focusing on neural response patterns across the early visual cortex (EVC) and the face-selective area (the fusiform face area (FFA)), we found that the discriminability of individual faces from the response patterns was strong in the FFA but weak in the EVC during the individuation task whereas the EVC but not the FFA showed significant face discrimination during the grouping tasks. Thus, these findings suggest that the representation of face information across the early and high-level visual cortex is flexible depending on the top-down control of the perceptual framework between individuation and grouping.
The Evolution of Early-Life Effects on Social Behaviour – Why Should Social Adversity Carry Over to the Future?
Authors: Kuijper Bram , Johnstone Rufus A.
Published: September 2018

Numerous studies have shown that social adversity in early life can have long-lasting negative consequences for social behaviour in adulthood, consequences that may in turn be propagated to future generations. Given these intergenerational effects, it is puzzling why natural selection might favour such sensitivity to an individual’s early social environment. To address this question, we model the evolution of social sensitivity in the development of in helping behaviours, showing that natural selection indeed favours individuals whose tendency to help others is dependent on early-life social experience. We find that natural selection typically favours positive social feedbacks, in which individuals who received more help in early life are also more likely to help others in adulthood, while individuals who received no early-life help develop low tendencies to helping others later in life. This positive social sensitivity is favoured because of an intergenerational relatedness feedback: patches with many helpers tend to be more productive, leading to higher relatedness within the local group, which in turn favours higher levels of help in the next generation.
Effects of zooplankton carcasses degradation on freshwater bacterial community composition and implications for carbon cycling
Authors: Kolmakova Olesya V. , Gladyshev Michail I. , Fonvielle Jérémy André , Ganzert Lars , Hornick Thomas , Grossart Hans-Peter
Published: September 2018

Non-predatory mortality of zooplankton provides an abundant, yet, little studied source of high quality labile organic matter (LOM) in aquatic ecosystems. Using laboratory microcosms, we followed the decomposition of organic carbon of fresh 13C-labelled Daphnia carcasses by natural bacterioplankton. The experimental setup comprised blank microcosms i.e. artificial lake water without any organic matter additions (B), and microcosms either amended with natural humic matter (H), fresh Daphnia carcasses (D) or both, i.e. humic matter and Daphnia carcasses (HD). Most of the carcass carbon was consumed and respired by the bacterial community within 15 days of incubation. A shift in the bacterial community composition shaped by labile carcass carbon and by humic matter was observed. Nevertheless, we did not observe a quantitative change in humic matter degradation by heterotrophic bacteria in the presence of LOM derived from carcasses. However, carcasses were the main factor driving the bacterial community composition suggesting that the presence of large quantities of dead zooplankton might affect the carbon cycling in aquatic ecosystems. Our results imply that organic matter derived from zooplankton carcasses is efficiently remineralized by a highly specific bacterial community, but doesn’t interfere with the bacterial turnover of more refractory humic matter.
The R package divDyn for quantifying diversity dynamics using fossil sampling data
Authors: Á. T. Kocsis , C. J. Reddin , J. Alroy , W. Kiessling
Published: September 2018

Unbiased time series of diversity dynamics are vital for quantifying the grand history of life. Applications include identifying ancient mass extinctions and inferring both biotic and abiotic controls on diversification rates.

We introduce divDyn, a new R package that facilitates the calculation of taxonomic richness, extinction and origination rates from time-binned fossil sampling data. State-of-the-art sampling completeness metrics, counting protocols, and sampling standardisation functions permit the reconstruction of biologically meaningful time series. Additional functions permit the partitioning of turnover rates by trait and environmental affinity.

We display Phanerozoic-scale diversity dynamics of marine invertebrates using the divDyn package. Using the core function and standard subsampling options, we revisit earlier assessments of declining extinction and origination rates over time and of equilibrial diversity dynamics to assess their methodological dependency.

The modular and fast implementation of published methods ensures traceability, reproducibility, and comparability of future studies.
Single-cell RNA-seq analysis maps the development of human fetal retina
Authors: Lu Yufeng , Yi Wenyang , Wu Qian , Zhong Suijuan , Zuo Zhentao , Zhao Fangqi , Zhang Mei , Tsai Nicole , Zhuo Yan , He Sheng , Zhang Jun , Duan Xin , Wang Xiaoqun , Xue Tian
Published: September 2018

Vision starts with image formation at the retina, which contains diverse neuronal cell types that extract, process, and relay visual information to higher order processing centers in the brain. Though there has been steady progress in defining retinal cell types, very little is known about retinal development in humans, which starts well before birth. In this study, we performed transcriptomic profiling of developing human fetal retina from gestational weeks 12 to 27 using single-cell RNA-seq (scRNA-seq) and used pseudotime analysis to reconstruct the developmental trajectories of retinogenesis. Our analysis reveals transcriptional programs driving differentiation down four different cell types and suggests that Müller glia (MG) can serve as embryonic progenitors in early retinal development. In addition, we also show that transcriptional differences separate retinal progenitor cells (RPCs) into distinct subtypes and use this information to reconstruct RPC developmental trajectories and cell fate. Our results support a hierarchical program of differentiation governing cell-type diversity in the developing human retina. In summary, our work details comprehensive molecular classification of retinal cells, reconstructs their relationships, and paves the way for future mechanistic studies on the impact of gene regulation upon human retinogenesis.
Structural sequence evolution and Computational Modeling Approaches of the Complement System in Leishmaniasis
Authors: Ingale Prajakta , Kabra Ritika , Singh Shailza
Published: September 2018

The complement system acts as central arm of innate immunity that is critical to host defense as well as the development of adaptive immunity. The origins of the complement system have so far been traced, which correlates to near to the beginnings of multi-cellular animal life. Owing to the difficulty in obtaining crystal structures of GPCRs in either inactive or active state, accurate structural modeling is still highly desirable for the majority of GPCRs. In an attempt to dissect the conformational changes associated with GPCR activation, computational modeling approaches is being pursued in this paper along with the evolutionary divergence to deal with the structural variability.