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Summary: The integration of metabolomics with other omics ("multi-omics") offers complementary insights into disease biology. However, this integration remains challenging due to the fragmented landscape of current methodologies, which often require programming experience or bioinformatics expertise. Moreover, existing approaches are limited in their ability to accommodate unidentified metabolites, resulting in the exclusion of a significant portion of data from untargeted metabolomics experiments. Here, we introduce iModMix - Integrative Module Analysis for Multi-omics Data , a novel approach that uses a graphical lasso to construct network modules for integration and analysis of multi-omics data. iModMix uses a horizontal integration strategy, allowing metabolomics data to be analyzed alongside proteomics or transcriptomics to explore complex molecular associations within biological systems. Importantly, it can incorporate both identified and unidentified metabolites, addressing a key limitation of existing methodologies. iModMix is available as a user-friendly R Shiny application that requires no programming experience (https://imodmix.moffitt.org), and it includes example data from several publicly available multi-omic studies for exploration. An R package is available for advanced users (https://github.com/biodatalab/iModMix)., Availability and Implementation: Shiny application: https://imodmix.moffitt.org. The R package and source code: https://github.com/biodatalab/iModMix.

Spatial transcriptomics (ST) is a powerful tool for understanding tissue biology and disease mechanisms. However, the advanced data analysis and programming skills required can hinder researchers from realizing of the full potential of ST. To address this, we developed spatialGE, a web application that simplifies the analysis of ST data. The application spatialGE provided a user-friendly interface that guides users without programming expertise through various analysis pipelines, including quality control, normalization, domain detection, phenotyping, and multiple spatial analyses. It also enabled comparative analysis among samples and supported various ST technologies. The utility of spatialGE was demonstrated through its application in studying the tumor microenvironment of two data sets: 10X Visium samples from a cohort of melanoma metastasis and Nanostring CosMx fields of vision from a cohort of Merkel cell carcinoma samples. These results support the ability of spatialGE to identify spatial gene expression patterns that provide valuable insights into the tumor microenvironment and highlight its utility in democratizing ST data analysis for the wider scientific community.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ∼50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA sequencing (RNA-seq) with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In nonresponders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL1. Responders have increased type I/II interferons and preexisting tissue resident (Trm) CD8 or Vδ1 γδ T cells that functionally converge with overlapping antigen-specific transcriptional programs and clonal expansion of public T-cell receptors. Spatial transcriptomics demonstrated colocalization of T cells with B and dendritic cells, which supply chemokines and costimulation. Lastly, ICB significantly increased clonal expansion or recruitment of Trm and Vδ1 cells in tumors specifically in responders, underscoring their therapeutic importance. These data identify potential clinically actionable biomarkers and therapeutic targets for MCC. Significance: MCC serves as a model of ICB response. We utilized the largest-to-date, multimodal MCC dataset (n = 116 patients) to uncover unique tumor-intrinsic properties and immune circuits that predict response. We identified CD8 Trm and Vδ1 T cells as clinically actionable mediators of ICB response in major histocompatibility complex-high and -low MCCs, respectively., (©2024 American Association for Cancer Research.)

Spatial transcriptomics (ST) is a powerful tool for understanding tissue biology and disease mechanisms. However, its potential is often underutilized due to the advanced data analysis and programming skills required. To address this, we present spatialGE, a web application that simplifies the analysis of ST data. The application spatialGE provides a user-friendly interface that guides users without programming expertise through various analysis pipelines, including quality control, normalization, domain detection, phenotyping, and multiple spatial analyses. It also enables comparative analysis among samples and supports various ST technologies. We demonstrate the utility of spatialGE through its application in studying the tumor microenvironment of melanoma brain metastasis and Merkel cell carcinoma. Our results highlight the ability of spatialGE to identify spatial gene expression patterns and enrichments, providing valuable insights into the tumor microenvironment and its utility in democratizing ST data analysis for the wider scientific community.

Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. Here, we characterize the tumor microenvironment of LMD and patient-matched extra-cranial metastases using spatial transcriptomics in a small number of clinical specimens (nine tissues from two patients) with extensive in vitro and in vivo validation. The spatial landscape of melanoma LMD is characterized by a lack of immune infiltration and instead exhibits a higher level of stromal involvement. The tumor-stroma interactions at the leptomeninges activate tumor-promoting signaling, mediated through upregulation of SERPINA3. The meningeal stroma is required for melanoma cells to survive in the cerebrospinal fluid (CSF) and promotes MAPK inhibitor resistance. Knocking down SERPINA3 or inhibiting the downstream IGR1R/PI3K/AKT axis results in tumor cell death and re-sensitization to MAPK-targeting therapy. Our data provide a spatial atlas of melanoma LMD, identify the tumor-promoting role of meningeal stroma, and demonstrate a mechanism for overcoming microenvironment-mediated drug resistance in LMD., Competing Interests: Declaration of interests P.A.F. would like to disclose consultancy with AbbVie Inc., Bristol-Myers Squibb, Boehringer-Ingelheim, NCI Neuro-Oncology Branch Peer Review, NCRI, NIH, Novellus, Physical Sciences Oncology Network, Tocagen (not active), Ziopharm, and the National Brain Tumor Society. He is also on the advisory board for Bayer, BTG, GlaxoSmithKline (GSK), Inovio, Novocure, AnHeart Therapeutics, and Midatech., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Spatial transcriptomics (ST) assays represent a revolution in how the architecture of tissues is studied by allowing for the exploration of cells in their spatial context. A common element in the analysis is delineating tissue domains or "niches" followed by detecting differentially expressed genes to infer the biological identity of the tissue domains or cell types. However, many studies approach differential expression analysis by using statistical approaches often applied in the analysis of non-spatial scRNA data (e.g., two-sample t-tests, Wilcoxon's rank sum test), hence neglecting the spatial dependency observed in ST data. In this study, we show that applying linear mixed models with spatial correlation structures using spatial random effects effectively accounts for the spatial autocorrelation and reduces inflation of type-I error rate observed in non-spatial based differential expression testing. We also show that spatial linear models with an exponential correlation structure provide a better fit to the ST data as compared to non-spatial models, particularly for spatially resolved technologies that quantify expression at finer scales (i.e., single-cell resolution)., (© 2024. The Author(s).)

The authors have withdrawn their manuscript owing to incorrect handling of multiple measures in the survival analyses. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. The inaccessible nature of the disease site and lack of understanding of the biology of this unique metastatic site are major barriers to developing efficacious therapies for patients with melanoma LMD. Here, we characterize the tumor microenvironment of the leptomeningeal tissues and patient-matched extra-cranial metastatic sites using spatial transcriptomic analyses with in vitro and in vivo validation. We show the spatial landscape of melanoma LMD to be characterized by a lack of immune infiltration and instead exhibit a higher level of stromal involvement. We show that the tumor-stroma interactions at the leptomeninges activate pathways implicated in tumor-promoting signaling, mediated through upregulation of SERPINA3 at the tumor-stroma interface. Our functional experiments establish that the meningeal stroma is required for melanoma cells to survive in the CSF environment and that these interactions lead to a lack of MAPK inhibitor sensitivity in the tumor. We show that knocking down SERPINA3 or inhibiting the downstream IGR1R/PI3K/AKT axis results in re-sensitization of the tumor to MAPK-targeting therapy and tumor cell death in the leptomeningeal environment. Our data provides a spatial atlas of melanoma LMD, identifies the tumor-promoting role of meningeal stroma, and demonstrates a mechanism for overcoming microenvironment-mediated drug resistance unique to this metastatic site., Competing Interests: DECLARATION OF INTEREST: HA, OO, MLK, YR, YP, VL, WDC, RM, KT, BF, and IS declare no relevant conflicts of interest. PAF would like to disclose consultancy with AbbVie Inc., Bristol-Myers Squibb, Boehringer-Ingelheim, NCI Neuro-Oncology Branch Peer Review, NCRI, NIH, Novellus, Physical Sciences Oncology Network, Tocagen (not active), Ziopharm, National Brain Tumor Society. He is also on the advisory board for Bayer, BTG, GlaxoSmithKline (GSK), Inovio, Novocure, AnHeart Therapeutics, and Midatech.

Leptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor survival outcomes. We utilized comprehensive multi-omics analyses of CSF from patients with lymphoma LMD to demonstrate an immunosuppressive cellular microenvironment and identified dysregulations in proteins and lipids indicating neurodegenerative processes. Strikingly, we found a significant accumulation of toxic branched-chain keto acids (BCKA) in the CSF of patients with LMD. The BCKA accumulation was found to be a pan-cancer occurrence, evident in lymphoma, breast cancer, and melanoma LMD patients. Functionally, BCKA disrupted the viability and function of endogenous T lymphocytes, chimeric antigen receptor (CAR) T cells, neurons, and meningeal cells. Treatment of LMD mice with BCKA-reducing sodium phenylbutyrate significantly improved neurological function, survival outcomes, and efficacy of anti-CD19 CAR T cell therapy. This is the first report of BCKA accumulation in LMD and provides preclinical evidence that targeting these toxic metabolites improves outcomes., Competing Interests: IS, MLK, YR, RK, OO, HA, TR, BE, GCW, ZC, YAC, ML, LNFD, SAC, PAS, and VI declare no relevant conflicts of interest. MDJ would like to disclose consultancy for Kite/Gilead and Novartis and research funding from Kite/Gilead, Incyte, and Loxo@Lilly. PAF would like to disclose consultancy with AbbVie Inc., Bristol-Myers Squibb, Boehringer-Ingelheim, NCI Neuro-Oncology Branch Peer Review, NCRI, NIH, Novellus, Physical Sciences Oncology Network, Tocagen (not active), Ziopharm, National Brain Tumor Society. He is also on the advisory board for Bayer, BTG, GlaxoSmithKline (GSK), Inovio, Novocure, AnHeart Therapeutics, and Midatech. MH would like to disclose that Moffitt Cancer Center has licensed Intellectual Property (IP) related to the proliferation and expansion of tumor-infiltrating lymphocytes (TILs) to Iovance Biotherapeutics. MH is a co-inventor on such Intellectual Property. MH reports common stock holdings in AbbVie, Inc., Amgen, Inc., BioHaven Pharmaceuticals, and Bristol Myers Squibb. SPT would like to disclose that Moffitt Cancer Center has licensed Intellectual Property (IP) related to the proliferation and expansion of tumor-infiltrating lymphocytes (TILs) to Iovance Biotherapeutics. Moffitt has also licensed IP to Tuhura Biopharma. Dr. Pilon-Thomas (SPT) is an inventor on such Intellectual Property. SPT is listed as a co-inventor on a patent application with Provectus Biopharmaceuticals. SPT participates in sponsored research agreements with Provectus Biopharmaceuticals, Iovance Biotherapeutics, Intellia Therapeutics, Dyve Biosciences, Turnstone Biologics, and Celgene that are not related to this research. SPT has received research support that is not related to this research from the following entities: NIHNCI, DOD, Swim Across America, the V Foundation, and The Mark Foundation for Cancer Research. SPT has received consulting fees from Seagen Inc., Morphogenesis, Inc., and KSQ Therapeutics. FLL would like to disclose the following: Scientific Advisory Role/Consulting Fees: A2, Allogene, Amgen, Bluebird Bio, BMS, Calibr, Caribou, Cowen, EcoR1, Gerson Lehrman Group (GLG), Iovance, Kite Pharma, Janssen, Legend Biotech, Novartis, Sana, Umoja, Pfizer. Data Safety Monitoring Board: Data and Safety Monitoring Board for the NCI Safety Oversight CAR T-cell Therapies Committee. Research Contracts or Grants to my Institution for Service: Kite Pharma (Institutional), Allogene (Institutional), CERo Therapeutics (Institutional), Novartis (Institutional), BlueBird Bio (Institutional), 2SeventyBio (Institutional), BMS (Institutional), National Cancer Institute (R01CA244328 MPI: Locke; P30CA076292 PI: Cleveland), Leukemia and Lymphoma Society Scholar in Clinical Research (PI: Locke). Patents, Royalties, Other Intellectual Property: Several patents held by the institution in my name (unlicensed) in the field of cellular immunotherapy. Education or Editorial Activity: Aptitude Health, ASH, BioPharma Communications CARE Education, Clinical Care Options Oncology, Imedex, Society for Immunotherapy of Cancer

Summary: Spatially resolved transcriptomics promises to increase our understanding of the tumor microenvironment and improve cancer prognosis and therapies. Nonetheless, analytical methods to explore associations between the spatial heterogeneity of the tumor and clinical data are not available. Hence, we have developed spatialGE, a software that provides visualizations and quantification of the tumor microenvironment heterogeneity through gene expression surfaces, spatial heterogeneity statistics that can be compared against clinical information, spot-level cell deconvolution and spatially informed clustering, all using a new data object to store data and resulting analyses simultaneously., Availability and Implementation: The R package and tutorial/vignette are available at https://github.com/FridleyLab/spatialGE. A script to reproduce the analyses in this manuscript is available in Supplementary information. The Thrane study data included in spatialGE was made available from the public available from the website https://www.spatialresearch.org/resources-published-datasets/doi-10-1158-0008-5472-can-18-0747/., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Summary: Multiplex immunofluorescence (mIF) staining combined with quantitative digital image analysis is a novel and increasingly used technique that allows for the characterization of the tumor immune microenvironment (TIME). Generally, mIF data is used to examine the abundance of immune cells in the TIME; however, this does not capture spatial patterns of immune cells throughout the TIME, a metric increasingly recognized as important for prognosis. To address this gap, we developed an R package spatialTIME that enables spatial analysis of mIF data, as well as the iTIME web application that provides a robust but simplified user interface for describing both abundance and spatial architecture of the TIME. The spatialTIME package calculates univariate and bivariate spatial statistics (e.g. Ripley's K, Besag's L, Macron's M and G or nearest neighbor distance) and creates publication quality plots for spatial organization of the cells in each tissue sample. The iTIME web application allows users to statistically compare the abundance measures with patient clinical features along with visualization of the TIME for one tissue sample at a time., Availability and Implementation: spatialTIME is implemented in R and can be downloaded from GitHub (https://github.com/FridleyLab/spatialTIME) or CRAN. An extensive vignette for using spatialTIME can also be found at https://cran.r-project.org/web/packages/spatialTIME/index.html. iTIME is implemented within a R Shiny application and can be accessed online (http://itime.moffitt.org/), with code available on GitHub (https://github.com/FridleyLab/iTIME)., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Species interactions can promote mating behavior divergence, particularly when these interactions are costly due to maladaptive hybridization. Selection against hybridization can indirectly cause evolution of reproductive isolation within species, a process termed cascade reinforcement. This process can drive incipient speciation by generating divergent selection pressures among populations that interact with different species assemblages. Theoretical and empirical studies indicate that divergent selection on gene expression networks has the potential to increase reproductive isolation among populations. After identifying candidate synaptic transmission genes derived from neurophysiological studies in anurans, we test for divergence of gene expression in a system undergoing cascade reinforcement, the Upland Chorus Frog (Pseudacris feriarum)., Results: Our analyses identified seven candidate synaptic transmission genes that have diverged between ancestral and reinforced populations of P. feriarum, including five that encode synaptic vesicle proteins. Our gene correlation network analyses revealed four genetic modules that have diverged between these populations, two possessing a significant concentration of neurotransmission enrichment terms: one for synaptic membrane components and the other for metabolism of the neurotransmitter nitric oxide. We also ascertained that a greater number of genes have diverged in expression by geography than by sex. Moreover, we found that more genes have diverged within females as compared to males between populations. Conversely, we observed no difference in the number of differentially-expressed genes within the ancestral compared to the reinforced population between the sexes., Conclusions: This work is consistent with the idea that divergent selection on mating behaviors via cascade reinforcement contributed to evolution of gene expression in P. feriarum. Although our study design does not allow us to fully rule out the influence of environment and demography, the fact that more genes diverged in females than males points to a role for cascade reinforcement. Our discoveries of divergent candidate genes and gene networks related to neurotransmission support the idea that neural mechanisms of acoustic mating behaviors have diverged between populations, and agree with previous neurophysiological studies in frogs. Increasing support for this hypothesis, however, will require additional experiments under common garden conditions. Our work points to the importance of future replicated and tissue-specific studies to elucidate the relative contribution of gene expression divergence to the evolution of reproductive isolation during incipient speciation., (© 2021. The Author(s).)

This biographical account summarizes the professional career and scientific contributions of John Paul Richard Thomas, a contemporary leading figure in the systematics of West Indian amphibians and non-avian reptiles, especially of blind snakes of the families Typhlopidae and Leptotyphlopidae. Since his first expedition to the West Indies in 1957, Richard's vast field experience (including three trips to Peru between 1968 and 1974), impressive collecting skills, and remarkable ability to detect phenotypic variation among natural populations have resulted in the description of more than 70 species of snakes (24 typhlopids, 4 leptotyphlopids), lizards, and frogs in 16 genera and 11 taxonomic families. Richard joined the faculty of the Department of Biology, University of Puerto Rico, Río Piedras, in 1976 and ever since his efforts significantly advanced organismal biology research at the institution. Although primarily a systematist, his desire to understand multiple aspects of an organism's biology and contagious passion for becoming intimately familiar with animals in their natural environments provided his students the opportunity to conduct research in fields such as behavioral and evolutionary ecology. Richard's mentoring fostered the scientific interests of his graduate students, who were exposed first-hand to every aspect of research, an invaluable experience that served as a springboard for the development of their professional careers inside and outside academia. This Commentary is a fitting tribute to an influential, unassuming scientist whose passion for turning over rocks has led to the discovery of many interesting species., (© 2021 American Association for Anatomy.)

Liotyphlops is a genus of blindsnakes distributed in Central and South America. We reviewed specimens of Liotyphlops albirostris along its current distribution range and, based on morphological data and ecological niche modeling analyses, we restrict the geographical range of L. albirostris and validate three previously described species. In this revision, we describe the morphological variation in the populations from Panamá, Colombia, Ecuador, and Venezuela, and propose a new taxonomic arrangement. We revalidate three previous synonyms of L. albirostris to full species status, while dividing the populations from Colombia in two subspecies-one attributed to a previously recognized species from the Caribbean region, and a new one from the Andean region. The new species differs from L. albirostris from Panamá in cephalic scale arrangements that effectively reduces the previously reported variability of these scales in L. albirostris. We also explore some osteological differences that are congruent with the variation observed. We hope that the recognition of these new species better represents the diversity within Liotyphlops, helping to bring these new species out of their cryptic status so that they will be considered in future conservation efforts., (© 2021 American Association for Anatomy.)

John Paul Richard Thomas is among the living herpetologists to have described the greatest number of new species of amphibians and reptiles, and his contributions to the herpetology of the West Indies, particularly the Greater Antilles, have been exceptional. His academic career followed an unusual path, having established a strong reputation and described 50 new taxa prior to beginning his doctoral studies. His career was strongly influenced by Albert Schwartz and later was characterized by extensive and fruitful collaboration with S. Blair Hedges. Thomas' contributions to the study of blind snakes have been noteworthy. In addition to describing 28 species of scolecophidians he has been a keen observer of blind snake morphology and his 1976 dissertation remains a valuable source of osteological data. We outline some of the highlights of the career of Richard Thomas and provide a bibliography of his scientific works and a listing of the 108 taxa of amphibians and reptiles described by him., (© 2021 American Association for Anatomy.)

Immune modulation is considered a hallmark of cancer initiation and progression. The recent development of immunotherapies has ushered in a new era of cancer treatment. These therapeutics have led to revolutionary breakthroughs; however, the efficacy of immunotherapy has been modest and is often restricted to a subset of patients. Hence, identification of which cancer patients will benefit from immunotherapy is essential. Multiplex immunofluorescence (mIF) microscopy allows for the assessment and visualization of the tumor immune microenvironment (TIME). The data output following image and machine learning analyses for cell segmenting and phenotyping consists of the following information for each tumor sample: the number of positive cells for each marker and phenotype(s) of interest, number of total cells, percent of positive cells for each marker, and spatial locations for all measured cells. There are many challenges in the analysis of mIF data, including many tissue samples with zero positive cells or "zero-inflated" data, repeated measurements from multiple TMA cores or tissue slides per subject, and spatial analyses to determine the level of clustering and co-localization between the cell types in the TIME. In this review paper, we will discuss the challenges in the statistical analysis of mIF data and opportunities for further research.

Determining the optimal targets of genomic subsampling for phylogenomics, phylogeography, and population genomics remains a challenge for evolutionary biologists. Of the available methods for subsampling the genome, hybrid enrichment (sequence capture) has become one of the primary means of data collection for systematics, due to the flexibility and cost efficiency of this approach. Despite the utility of this method, information is lacking as to what genomic targets are most appropriate for addressing questions at different evolutionary scales. In this study, first, we compare the benefits of target loci developed for deep- and shallow scales by comparing these loci at each of three taxonomic levels: within a genus (phylogenetics), within a species (phylogeography), and within a hybrid zone (population genomics). Specifically, we target evolutionarily conserved loci that are appropriate for deeper phylogenetic scales and more rapidly evolving loci that are informative for phylogeographic and population genomic scales. Second, we assess the efficacy of targeting multiple-locus sets for different taxonomic levels in the same hybrid enrichment reaction, an approach we term hierarchical hybrid enrichment. Third, we apply this approach to the North American chorus frog genus Pseudacris to answer key evolutionary questions across taxonomic and temporal scales. We demonstrate that in this system the type of genomic target that produces the most resolved gene trees differs depending on the taxonomic level, although the potential for error is substantially lower for the deep-scale loci at all levels. We successfully recover data for the two different locus sets with high efficiency. Using hierarchical data targeting deep and shallow levels: we 1) resolve the phylogeny of the genus Pseudacris and introduce a novel visual and hypothesis testing method that uses nodal heat maps to examine the robustness of branch support values to the removal of sites and loci; 2) estimate the phylogeographic history of Pseudacris feriarum, which reveals up to five independent invasions leading to sympatry with congener Pseudacris nigrita to form replicated reinforcement contact zones with ongoing gene flow into sympatry; and 3) quantify with high confidence the frequency of hybridization in one of these zones between P. feriarum and P. nigrita, which is lower than microsatellite-based estimates. We find that the hierarchical hybrid enrichment approach offers an efficient, multitiered data collection method for simultaneously addressing questions spanning multiple evolutionary scales. [Anchored hybrid enrichment; heat map; hybridization; phylogenetics; phylogeography; population genomics; reinforcement; reproductive character displacement.]., (© The Author(s) 2019. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Variation in microbiota of the coffee berry borer (CBB) Hypothenemus hampei was studied. Diversity, structure and function of bacterial communities were compared between eggs vs adults, CBBs from shade coffee vs sun coffee, CBBs from the field vs raised in the laboratory, and CBBs with and without the antibiotic tetracycline., Methods and Results: We sequenced the region V4 of the gene 16 S rRNA. Pseudomonadaceae and Enterobacteriaceae, particularly Pseudomonas and Pantoea, dominated microbiotas of the CBB. Comparative functional inferences with PICRUSt suggested that samples from the field were enriched for genes involved in carbohydrate and protein digestion and absorption, while laboratory-reared samples were higher in genes for melanization and caffeine metabolism., Conclusions: Microbiotas of the CBB were diverse and dominated by the genus Pseudomonas, several species of which have been previously associated with caffeine degradation in this insect. Wolbachia was the only endosymbiont detected with known ability to manipulate host reproduction., Significance and Impact of the Study: This study demonstrates that stage of development and origin of samples affected the structure and function of the CBB's bacterial communities. This is the first attempt to predict functional significance of the CBB microbiota in nutrition, reproduction and defence., (© 2018 The Society for Applied Microbiology.)

Tenuipalpidae comprises mites that transmit viruses to agriculturally important plants. Several tenuipalpid species present parthenogenesis, and in Brevipalpus yothersi , the endosymbiont Cardinium has been associated with female-only colonies. It is unclear what the bacterial composition of B. yothersi is, and how common Cardinium is in those microbiomes. We performed a comparative analysis of the bacteriomes in three populations of B. yothersi and three additional Tetranychoidea species using sequences from V4-fragment of 16S DNA. The bacteriomes were dominated by Bacteroidetes (especially Cardinium ) and Proteobacteria, showing a remarkably low alpha diversity. Cardinium was present in about 22% of all sequences; however, it was not present in R. indica and T. evansi . In B. yothersi , the proportion of Cardinium was higher in adults than eggs, suggesting that proliferation of the bacteria could be the result of selective pressures from the host. This hypothesis was further supported because colonies of B. yothersi from different populations showed different bacterial assemblages, and bacteriomes from different mite species showed similar abundances of Cardinium . A phylogenetic analysis of Cardinium revealed that not only specialization but horizontal transmission has been important for this symbiosis. Together, these results represent a glimpse into the evolution of the Tetranychoidea and Cardinium ., Competing Interests: The authors declare no conflict of interest.

The geology of the northern Andean region has driven the evolutionary history of Neotropical fauna through the creation of barriers and connections that have resulted in speciation and dispersal events, respectively. One of the most conspicuous groups of anuran fauna in the Andes and surrounding areas is the direct-developing species of the genus Pristimantis. We investigated the molecular phylogenetic placement of 12 species from the montane Andes of Colombia in a broader geographical context with a new genus-level phylogeny in order to identify the role of Andean orogeny over the last 40million years and the effect of elevational differences in diversification of Pristimantis. We examined the biogeographic history of the genus using ancestral range reconstruction by biogeographic regions and elevational ranges. We recognized the middle elevational band (between 1000 and 3000m) in the Northwestern Andes region of Colombia and Ecuador as a focal point for the origin and radiation of Pristimantis species. Additionally, we found several Andean migrations toward new habitats in Central Andes and Merida Andes for some species groups. We suggest that the paleogeological changes in the Northwestern Andes were the main promoter of speciation in Pristimantis, and may have served as a corridor for the dispersion of lowland species., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Helicobacter pylori is a bacterium that lives in the human stomach and is a major risk factor for gastric cancer and ulcers. H.pylori is host dependent and has been carried with human populations around the world after their departure from Africa. We wished to investigate how H.pylori has coevolved with its host during that time, focusing on strains from Japanese and European populations, given that gastric cancer incidence is high in Japanese populations, while low in European. A positive selection analysis of eight H.pylori genomes was conducted, using maximum likelihood based pairwise comparisons in order to maximize the number of strain-specific genes included in the study. Using the genic Ka/Ks ratio, comparisons of four Japanese H.pylori genomes suggests 25-34 genes under positive selection, while four European H.pylori genomes suggests 16-21 genes; few of the genes identified were in common between lineages. Of the identified genes which were annotated, 38% possessed homologs associated with pathogenicity and / or host adaptation, consistent with their involvement in a coevolutionary 'arms race' with the host. Given the efficacy of identifying host interaction factors de novo, in the absence of functionally annotated homologs our evolutionary approach may have value in identifying novel genes which H.pylori employs to interact with the human gut environment. In addition, the larger number of genes inferred as being under positive selection in Japanese strains compared to European implies a stronger overall adaptive pressure, potentially resulting from an elevated immune response which may be linked to increased inflammation, an initial stage in the development of gastric cancer., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.)