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Low capture rates are a persistent problem in field studies of small rodents in Central Africa. This study aims to improve trapping efficacy by comparing the effectiveness of three types of bait placed in Sherman live traps: the traditionally used fresh manioc, palm nut and bait composed of peanut butter mixed with corn flakes. Trapping sites were located in the buffer zones of a total of five forest national parks in Gabon and Cameroon. Traps lines were placed in a variety of forest and savanna habitats and were alternately baited with the three different bait types. Statistical analyses were performed using the R software. A total of 212 individuals were trapped (during 3000 trap/night) from five species: Nannomys minutoides, Lemniscomys striatus, Hylomyscus alleni, Hylomyscus walterverheyeni and Praomys misonnei. Traps baited with peanut butter-corn flakes (PbCf) captured significantly more rodents (n=125, Trap success Ts=12.25%) than either manioc (n=31, Ts=3.23%; P

The Dobzhansky-Muller model provides a widely accepted mechanism for the evolution of reproductive isolation: incompatible substitutions disrupt interactions between genes. To date, few candidate incompatibility genes have been identified, leaving the genes driving speciation mostly uncharacterized. The importance of interactions in the Dobzhansky-Muller model suggests that gene coexpression networks provide a powerful framework to understand disrupted pathways associated with postzygotic isolation. Here, we perform Weighted Gene Coexpression Network Analysis (WGCNA) to infer gene interactions in hybrids of two recently diverged European house mouse subspecies, Mus mus domesticus and M. m. musculus, which commonly show hybrid male sterility or subfertility. We use genome-wide testis expression data from 467 hybrid mice from two mapping populations: F2s from a laboratory cross between wild-derived pure subspecies strains and offspring of natural hybrids captured in the Central Europe hybrid zone. This large data set enabled us to build a robust consensus network using hybrid males with fertile phenotypes. We identify several expression modules, or groups of coexpressed genes, that are disrupted in subfertile hybrids, including modules functionally enriched for spermatogenesis, cilium and sperm flagellum organization, chromosome organization and DNA repair, and including genes expressed in spermatogonia, spermatocytes and spermatids. Our network-based approach enabled us to hone in on specific hub genes likely to be influencing module-wide gene expression and hence potentially driving Dobzhansky-Muller incompatibilities. A total of 69 (24.6%) of these genes lie in sterility loci identified previously in these mapping populations, and represent promising candidate barrier genes and targets for future functional analysis.

Through the rise of global commodity chains, consumer demand in China and the USA has given rise to the extraction of natural resources in the Congo Basin. The Chinese market for high-valued animal products such as elephant ivory and pangolin scales has encouraged poaching, exploitation and trafficking of these goods in Africa. Chinese demand for other African commodities, however, remains less well known. Using data across a 15-year period (2001–2015), we analysed the relationship between Chinese timber imports and tree-cover loss in the Congo Basin. Tree-cover loss was measured via remote sensing and the value of imports was obtained from official trade statistics. Results indicate that the total accumulated export of wood from Congo Basin countries to China doubled between 2001 and 2015, with 50% of exports originating from Cameroon and the Republic of Congo. We found a positive relationship between measures of Chinese logging and the loss of tree cover in the Congo Basin. Further investigation of the timber products market showed that US demand for Chinese-made furniture was positively correlated with Chinese timber imports from the Congo Basin. These findings suggest that US demand for furniture encourages Chinese economic actors to harvest timber from Congo Basin forests. Our results help to illuminate the complex environmental and economic drivers surrounding trade and deforestation and can help inform consumers about more sustainable ways to purchase wood products from one of the world's preeminent biodiversity hotspots.

Dung beetles are important for the healthy functioning of tropical forest ecosystems, performing essential roles, including nutrient recycling and secondary seed dispersal. Sensitive to changes in both habitat quality and vertebrate diversity, dung beetles are ideal taxa for monitoring ecosystem health. The current study provides the first documentation of dung beetle diversity on the Central African island of Bioko, Equatorial Guinea, which lies off of mainland Cameroon and is characterised by a rugged topology and an elevation of more than 3 000 m. Dung beetles were sampled from three elevations (at ~102 m, 623 m and 1 000 m) along an elevational transect, using pitfall traps baited with human dung. A total of 32 species were captured and identified. Species diversity and composition were similar to that recorded on the mainland site of Mount Cameroon, which is part of the same volcanic chain as Bioko Island. Species richness and abundance declined with increasing elevation, consistent with the inverse relationship between diversity and elevation commonly observed in other systems. Elevational preferences were apparent in several species, suggesting ecological segregation between species along the elevational gradient. The current study also provides valuable baseline data that can be used to monitor changes in ecosystem functioning and community structure, important given the potential long-term impacts of excessive bushmeat hunting on ecosystem health of Bioko Island.Keywords: bush meat hunting, elevational gradient, diversity, species richness, west-central Africa

Objectives The Consolidated Standards of Reporting Trials extension for the stepped-wedge cluster randomized trial (SW-CRT) is a recently published reporting guideline for SW-CRTs. We assess the quality of reporting of a recent sample of SW-CRTs. Study Design and Setting Quality of reporting was asssessed according to the 26 items in the new guideline using a novel crowd sourcing methodology conducted independently and in duplicate, with random assignment, by 50 reviewers. We assessed reliability of the quality assessments, proposing this as a novel way to assess robustness of items in reporting guidelines. Results Several items were well reported. Some items were very poorly reported, including several items that have unique requirements for the SW-CRT, such as the rationale for use of the design, description of the design, identification and recruitment of participants within clusters, and concealment of cluster allocation (not reported in more than 50% of the reports). Agreement across items was moderate (median percentage agreement was 76% [IQR 64 to 86]). Agreement was low for several items including the description of the trial design and why trial ended or stopped for example. Conclusions When reporting SW-CRTs, authors should pay particular attention to ensure clear reporting on the exact format of the design with justification, as well as how clusters and individuals were identified for inclusion in the study, and whether this was done before or after randomization of the clusters, which are crucial for risk of bias assessments. Some items, including why the trial ended, might either not be relevant to SW-CRTs or might be unclearly described in the statement.

Predicting species' capacity to respond to climate change is an essential first step in developing effective conservation strategies. However, conservation prioritization schemes rarely take evolutionary potential into account. Ecotones provide important opportunities for diversifying selection and may thus constitute reservoirs of standing variation, increasing the capacity for future adaptation. Here, we map patterns of environmentally associated genomic and craniometric variation in the central African rodent Praomys misonnei to identify areas with the greatest turnover in genomic composition. We also project patterns of environmentally associated genomic variation under future climate change scenarios to determine where populations may be under the greatest pressure to adapt. While precipitation gradients influence both genomic and craniometric variation, vegetation structure is also an important determinant of craniometric variation. Areas of elevated environmentally associated genomic and craniometric variation overlap with zones of rapid ecological transition underlining their importance as reservoirs of evolutionary potential. We also find that populations in the Sanaga river basin, central Cameroon and coastal Gabon are likely to be under the greatest pressure from climate change. Lastly, we make specific conservation recommendations on how to protect zones of high evolutionary potential and identify areas where populations may be the most susceptible to climate change.

BACKGROUND: One of the major barriers to the dissemination and implementation of psychological treatments is the scarcity of suitably trained therapists. A highly scalable form of Web-centered therapist training, undertaken without external support, has recently been shown to have promise in promoting therapist competence. OBJECTIVE: The aim of this study was to conduct an evaluation of the acceptability and effectiveness of a scalable independent form of Web-centered training in a multinational sample of therapists and investigate the characteristics of those most likely to benefit. METHODS: A cohort of eligible therapists was recruited internationally and offered access to Web-centered training in enhanced cognitive behavioral therapy, a multicomponent, evidence-based, psychological treatment for any form of eating disorder. No external support was provided during training. Therapist competence was assessed using a validated competence measure before training and after 20 weeks. RESULTS: A total of 806 therapists from 33 different countries expressed interest in the study, and 765 (94.9%) completed a pretraining assessment. The median number of training modules completed was 15 out of a possible 18 (interquartile range, IQR: 4-18), and 87.9% (531/604) reported that they treated at least one patient during training as recommended. Median pretraining competence score was 7 (IQR: 5-10, range: 0-19; N=765), and following training, it was 12 (IQR: 9-15, range: 0-20; N=577). The expected change in competence scores from pretraining to posttraining was 3.5 (95% CI 3.1-3.8; P

Although a number of recent studies suggest that climate associated shifts in agriculture are affecting social and economic systems, there have been relatively few studies of these effects in Africa. Such studies would be particularly useful in Central Africa, where the impacts of climate warming are predicted to be high but coincide with an area with low adaptive capacity. Focusing on plantain (Musa paradisiaca), we assess whether recent climate change has led to reduced yields. Analysis of annual temperature between 1950 and 2013 indicated a 0.8°C temperature increase over this 63-year period - a trend that is also observed in monthly temperatures in the last twenty years. From 1991 to 2011, there was a 43% decrease in plantain productivity in Central Africa, which was explained by shifts in temperature (R2=0.68). This decline may have reduced rural household wealth and decreased parental investment in education. Over the past two decades, there was a six month decrease in the duration of school attendance, and the decline was tightly linked to plantain yield (R2=0.82). By 2080, mean annual temperature is expected to increase at least 2°C in Central Africa, and our models predict a concomitant decrease of 39% in plantain yields and 51% in education outcomes, relative to the 1991 baseline. These predictions should be seen as a call-to-action for policy interventions such as farmer training programs to enhance the adaptive capacity of food production systems to mitigate impacts on rural income and education.

Background This study aims to assess the role that Pleistocene refugia, rivers and local habitat conditions may have played in the evolutionary diversification of three central African duiker species (Cephalophus dorsalis, C. callipygus and Philantomba monticola). Genetic data from geo-referenced feces were collected from a wide range of sites across Central Africa. Historical patterns of population genetic structure were assessed using a ~ 650 bp fragment of the mitochondrial control region and contemporary patterns of genetic differentiation were evaluated using 12 polymorphic microsatellite loci. Results Mitochondrial analyses revealed that populations of C. callipygus and P. monticola in the Gulf of Guinea refugium are distinct from other populations in west central Africa. All three species exhibit signatures of past population expansion across much of the study area consistent with a history of postglacial expansion. There was no strong evidence for a riverine barrier effect in any of the three species, suggesting that duikers can readily cross major rivers. Generalized dissimilarity models (GDM) showed that environmental variation explains most of the nuclear genetic differentiation in both C. callipygus and P. monticola. The forest-savanna transition across central Cameroon and the Plateaux Batéké region in southeastern Gabon show the highest environmentally-associated turnover in genetic variability. A pattern of genetic differentiation was also evident between the coast and forest interior that may reflect differences in precipitation and/or vegetation. Conclusions Findings from this study highlight the historical impact of Pleistocene fragmentation and current influence of environmental variation on genetic structure in duikers. Conservation efforts should therefore target areas that harbor as much environmentally-associated genetic variation as possible in order to maximize species’ capacity to adapt to environmental change. Electronic supplementary material The online version of this article (10.1186/s12862-017-1054-4) contains supplementary material, which is available to authorized users.

The tropical forests of the Congo Basin and Gulf of Guinea harbor some of the greatest terrestrial and aquatic biological diversity in the world. However, our knowledge of the rich biological diversity of this region and the evolutionary processes that have shaped it remains limited, as is our understanding of the capacity for species to adapt or otherwise respond to current and projected environmental change. In this regard, research efforts are needed to increase current scientific knowledge of this region's biodiversity, identify the drivers of past diversification, evaluate the potential for species to adapt to environmental change and identify key populations for future conservation. Moreover, when evolutionary research is combined with ongoing environmental monitoring efforts, it can also provide an important set of tools for assessing and mitigating the impacts of development activities. Building on a set of recommendations developed at an international workshop held in Gabon in 2011, we highlight major areas for future evolutionary research that could be directly tied to conservation priorities for the region. These research priorities are centered around five disciplinary themes: (1) documenting and discovering biodiversity; (2) identifying drivers of evolutionary diversification; (3) monitoring environmental change; (4) understanding community and ecosystem level processes; (5) investigating the ecology and epidemiology of disease from an evolutionary perspective (evolutionary epidemiology). Furthermore, we also provide an overview of the needs and priorities for biodiversity education and training in Central Africa. Resume Les forets tropicales du bassin du Congo et du Golfe de Guinee abritent une grande partie de la diversite terrestre et aquatique dans le monde. Pourtant, notre connaissance de la riche diversite biologique de cette region et les processus evolutifs qui l'ont faconnee demeurent encore peu compris, tout comme notre comprehension de la capacite des especes a s'adapter ou a repondre aux changements environnementaux actuels et a venir. De ce fait, des efforts de recherche sont necessaires pour ameliorer les connaissances scientifiques actuelles sur la biodiversite de cette region, determiner les causes des processus de diversifications passees, evaluer le potentiel des especes a repondre aux changements environnementaux et identifier les populations cles pour la conservation dans le futur. Par ailleurs, lorsque la recherche dans le domaine de l'evolution est combinee aux efforts de suivi continu de l'environnement, elle peut aussi fournir un ensemble d'outils importants pour l'evaluation et l'attenuation des impacts des activites de developpement. S'appuyant sur une serie de recommandations elaborees lors de l'atelier international qui s'est tenu au Gabon en 2011, nous soulignons les axes majeurs pour la recherche future dans le domaine de l'evolution qui pourraient etre lies directement aux priorites de la conservation dans la region. Ces priorites de recherche s'articulent autour de cinq thematiques: (1) l'inventaire et la decouverte de la biodiversite; (2) l'identification des causes de la diversification; (3) le suivi des changements environnementaux; (4) la comprehension des processus au niveau des communautes et des ecosystemes; (5) l'etude ecologique et epidemiologique des maladies d'un point de vue evolutif (epidemiologie evolutive). Toutefois, nous donnons egalement un apercu des besoins et des priorites en matiere d'education et de formation dans le domaine de la biodiversite en Afrique centrale.

Despite the biological importance and diversity of nematodes, little is known of the factors influencing their dispersal and shaping their evolutionary history. Populations of the cosmopolitan species Pristionchus pacificus are characterized by high genetic diversity and strong spatial structure, which contrasts with patterns detected in nematode species such as Caenorhabditis elegans. The environmentally heterogeneous volcanic Mascarene Islands provide an ideal setting for investigating fine-scale patterns of nematode migration and gene flow. Based on the analysis of data from 19 nuclear microsatellites and one mitochondrial marker, we infer support for the colonization of both La Reunion Island and Mauritius from similar multiple geographical sources. Although the long-term persistence of populations on both islands is well supported, the historical colonization of one island from the other cannot be discounted. In fact, periodic, bi-directional migration between the islands following their initial colonization is strongly supported in isolation with migration analyses, supporting the occurrence of rare trans-oceanic dispersal events in P. pacificus. Through a combination of population and landscape genetic analyses we also infer non-uniform dispersal across the landscape on the island of La Reunion, probably mediated by the movements of beetle hosts. Collectively, we show that gene flow in P. pacificus is limited by environmental and oceanic barriers, and shaped by the intricacies of the nematode–beetle host interaction. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 112, 1–15.

The hermaphroditic nematode Pristionchus pacificus is a model organism with a range of fully developed genetic tools. The species is globally widespread and highly diverse genetically, consisting of four major independent lineages (lineages A, B, C, and D). Despite its young age (~2.1 Ma), volcanic La Réunion Island harbors all four lineages. Ecological and population genetic research studies suggest that this diversity is due to repeated independent island colonizations by P. pacificus. Here, we use model‐based statistical methods to rigorously test hypotheses regarding the evolutionary history of P. pacificus. First, we employ divergence analyses to date diversification events among the four “world” lineages. Next, we examine demographic properties of a subset of four populations (“a”, “b”, “c”, and “d”), present on La Réunion Island. Finally, we use the results of the divergence and demographic analyses to inform a modeling‐based approximate Bayesian computation (ABC) approach, where we test hypotheses about the order and timing of establishment of the Réunion populations. Our dating estimates place the recent common ancestor of P. pacificus lineages at nearly 500,000 generations past. Our demographic analysis supports recent (a>b>d as the most likely colonization order of the island populations. Collectively, our study comprehensively improves previous inferences about the evolutionary history of P. pacificus.

Understanding how new species form requires investigation of evolutionary forces that cause phenotypic and genotypic changes among populations. However, the mechanisms underlying speciation vary and little is known about whether genomes diversify in the same ways in parallel at the incipient scale. We address this using the nematode, Pristionchus pacificus, which resides at an interesting point on the speciation continuum (distinct evolutionary lineages without reproductive isolation), and inhabits heterogeneous environments subject to divergent environmental pressures. Using whole genome re-sequencing of 264 strains, we estimate FST to identify outlier regions of extraordinary differentiation (∼1.725 Mb of the 172.5 Mb genome). We find evidence for shared divergent genomic regions occurring at a higher frequency than expected by chance among populations of the same evolutionary lineage. We use allele frequency spectra to find that, among lineages, 53% of divergent regions are consistent with adaptive selection, whereas 24% and 23% of such regions suggest background selection and restricted gene flow, respectively. In contrast, among populations from the same lineage, similar proportions (34-48%) of divergent regions correspond to adaptive selection and restricted gene flow, whereas 13-22% suggest background selection. Because speciation often involves phenotypic and genomic divergence, we also evaluate phenotypic variation, focusing on pH tolerance, which we find is diverging in a manner corresponding to environmental differences among populations. Taking a genome-wide association approach, we functionally validate a significant genotype-phenotype association for this trait. Our results are consistent with P. pacificus undergoing heterogeneous genotypic and phenotypic diversification related to both evolutionary and environmental processes.

Pristionchus pacificus, recently established as a model organism in evolutionary biology, is a cosmopolitan nematode that has a necromenic association with scarab beetles. The diverse array of host beetle species and habitat types occupied by P. pacificus make it a good model for investigating local adaptation to novel environments. Presence of P. pacificus on La Reunion Island, a young volcanic island with a dynamic geological history and a wide variety of ecozones, facilitates such investigation in an island biogeographic setting. Microsatellite data from 20 markers and 223 strains and mitochondrial sequence data from 272 strains reveal rich genetic diversity among La Reunion P. pacificus isolates, shaped by differentially timed introductions from diverse sources and in association with different beetle species. Distinctions between volcanic zones and between arid western and wet eastern climatic zones have likely limited westward dispersal of recently colonized lineages and maintained a genetic distinction between eastern and western clades. The highly selfing lifestyle of P. pacificus contributes to the strong fine-scale population structure detected, with each beetle host harbouring strongly differentiated assemblages of strains. Periodic out-crossing generates admixture between genetically diverse lineages, creating a diverse array of allelic combinations likely to increase the evolutionary potential of the species and facilitate adaptation to local environments and beetle hosts.

South-East Asia is one of the world's richest regions in terms of biodiversity. An understanding of the distribution of diversity and the factors shaping it is lacking, yet essential for identifying conservation priorities for the region's highly threatened biodiversity. Here, we take a large-scale comparative approach, combining data from nine forest-associated Anopheles mosquito species and using statistical phylogeographical methods to disentangle the effects of environmental history, species-specific ecology and random coalescent effects. Spatially explicit modelling of Pleistocene demographic history supports a common influence of environmental events in shaping the genetic diversity of all species examined, despite differences in species' mtDNA gene trees. Populations were periodically restricted to allopatric northeastern and northwestern refugia, most likely due to Pleistocene forest fragmentation. Subsequent southwards post-glacial recolonization is supported by a north-south gradient of decreasing genetic diversity. Repeated allopatric fragmentation and recolonization have led to the formation of deeply divergent geographical lineages within four species and a suture zone where these intraspecific lineages meet along the Thai-Myanmar border. A common environmental influence for this divergence was further indicated by strong support for simultaneous divergence within the same four species, dating to approximately 900 thousand years ago (kya). Differences in the geographical structuring of genetic diversity between species are probably the result of varying species' biology. The findings have important implications for conservation planning; if the refugial regions and suture zone identified here are shared by other forest taxa, the unique and high levels of genetic diversity they house will make these areas conservation priorities.

Tropical forests have undergone repeated fragmentation and expansion during Pleistocene glacial and interglacial periods, respectively. The effects of this repeated forest fragmentation in driving vicariance in tropical taxa have been well studied. However, relatively little is known about how often this process results in allopatric speciation, since it may be inhibited by recurrent gene flow during repeated secondary contact, or to what extent Pleistocene-dated speciation results from ecological specialization in the face of gene flow. Here, divergence times and gene flow between three closely-related mosquito species of the Anopheles dirus species complex endemic to the forests of Southeast Asia, are inferred using coalescent based Bayesian analysis. An Isolation with Migration model is applied to sequences of two mitochondrial and three nuclear genes, and 11 microsatellites. The divergence of An. scanloni has occurred despite unidirectional nuclear gene flow from this species into An. dirus. The inferred asymmetric gene flow may result from the unique evolutionary adaptation of An. scanloni to limestone karst habitat, and therefore the fitness advantage of this species over An. dirus in regions of sympatry. Mitochondrial introgression has led to the complete replacement of An. dirus haplotypes with those of An. baimaii through a recent (approximately 62 kya) selective sweep. Speciation of An. baimaii and An. dirus is inferred to have involved allopatric divergence throughout much of the Pleistocene. Secondary contact and bidirectional gene flow has occurred only within the last 100 000 years, by which time the process of allopatric speciation seems to have been largely completed.

Molecular studies of population divergence and speciation across the Oriental Region are sparse, despite the region's high biodiversity and extensive Pliocene and Pleistocene environmental change. A molecular phylogenetic study of the Neocellia Series of Anopheles mosquitoes was undertaken to identify patterns of diversification across the Oriental Region and to infer the role of Pleistocene and Pliocene climatic change. A robust phylogeny was constructed using CO2 and ND5 mitochondrial genes and ITS2 and D3 nuclear ribosomal markers. Bayesian analysis of mitochondrial genes was used to date divergence events. The repeated contraction and expansion of forest habitat resulting from Pleistocene climatic fluctuations appears to have had a substantial impact on intraspecific diversification, but has not driven speciation within this group. Primarily early to mid Pliocene speciation was detected within the Annularis Group, whereas speciation within the Maculatus and Jamesii Groups occurred during the mid and late Pliocene. Both allopatric divergence driven by late Pliocene environmental changes and ecological adaptation, involving altitudinal replacement and seasonality, are likely to have influenced speciation in the Maculatus Group.

There are 3 recognized chromosomal forms (B, E, K) in the taxon of Anopheles maculatus, 1 of the 8 members of the Anopheles maculatus group. Previous studies suggested that forms B and E are cytotypes of the species, but genetic characteristics of form K are unknown. The present study used crossing experiments, and polytene chromosomes of the ovarian nurse cell in F1 hybrids to show that form K is genetically distinct from forms B and E. In addition, postzygotic genetic incompatibility between form K and An. sawadwongporni, An. dravidicus, and An. pseudowillmori are demonstrated. In all crosses, hybrid males were sterile, with atrophied testes and accessory glands, or partially sterile with abnormal spermatozoa. The hybrid females showed varying degrees of atrophied ovaries. The ovarian nurse cell polytene chromosomes of the F1 hybrid females displayed approximately 70% to almost complete asynapsis. The results provide clear evidence that form K should no longer be regarded as a cytotype of An. maculatus. The present study supports previous suggestions that form K represents another species of the Maculatus group.

All organisms must interact with their environment, responding in behavioral, chemical, and other ways to various stimuli throughout their life cycles. Characterizing traits that directly represent an organism's ability to sense and react to their environment provides useful insight into the evolution of life-history strategies. One such trait for the nematode Pristionchus pacificus, chemosensation, is involved in navigation to beetle hosts. Essential for the survival of the nematode, chemosensory behavior may be subject to variation as nematodes discriminate among chemical cues to complete their life cycle. We examine this hypothesis using natural isolates of P. pacificus from La Réunion Island. We select strains from a variety of La Réunion beetle hosts and geographic locations and examine their chemoattraction response toward organic compounds, beetle washes, and live beetles. We find that nematodes show significant differences in their response to various chemicals and are able to chemotax to live beetles in a novel assay. Further, strains can discriminate among different cues, showing more similar responses toward beetle washes than to organic compounds in cluster analyses. However, we find that variance in chemoattraction response is not significantly associated with temperature, location, or beetle host. Rather, strains show a more concerted response toward compounds they most likely directly encounter in the wild. We suggest that divergence in odor-guided behavior in P. pacificus may therefore have an important ecological component.

Author(s): Roach, Katy M; Duffy, Stephen Mark; Coward, William; Feghali-Bostwick, Carol; Wulff, Heike; Bradding, Peter | Abstract: BackgroundIdiopathic pulmonary fibrosis (IPF) is a common, progressive and invariably lethal interstitial lung disease with no effective therapy. We hypothesised that K(Ca)3.1 K(+) channel-dependent cell processes contribute to IPF pathophysiology.MethodsK(Ca)3.1 expression in primary human lung myofibroblasts was examined using RT-PCR, western blot, immunofluorescence and patch-clamp electrophysiology. The role of K(Ca)3.1 channels in myofibroblast proliferation, wound healing, collagen secretion and contraction was examined using two specific and distinct K(Ca)3.1 blockers (TRAM-34 and ICA-17043 [Senicapoc]).ResultsBoth healthy non fibrotic control and IPF-derived human lung myofibroblasts expressed K(Ca)3.1 channel mRNA and protein. K(Ca)3.1 ion currents were elicited more frequently and were larger in IPF-derived myofibroblasts compared to controls. K(Ca)3.1 currents were increased in myofibroblasts by TGFβ1 and basic FGF. K(Ca)3.1 was expressed strongly in IPF tissue. K(Ca)3.1 pharmacological blockade attenuated human myofibroblast proliferation, wound healing, collagen secretion and contractility in vitro, and this was associated with inhibition of TGFβ1-dependent increases in intracellular free Ca(2+).ConclusionsK(Ca)3.1 activity promotes pro-fibrotic human lung myofibroblast function. Blocking K(Ca)3.1 may offer a novel approach to treating IPF with the potential for rapid translation to the clinic.

South-East Asia is one of the world's richest regions in terms of biodiversity. An understanding of the distribution of diversity and the factors shaping it is lacking, yet essential for identifying conservation priorities for the region's highly threatened biodiversity. Here, we take a large-scale comparative approach, combining data from nine forest-associated Anopheles mosquito species and using statistical phylogeographical methods to disentangle the effects of environmental history, species-specific ecology and random coalescent effects. Spatially explicit modelling of Pleistocene demographic history supports a common influence of environmental events in shaping the genetic diversity of all species examined, despite differences in species' mtDNA gene trees. Populations were periodically restricted to allopatric northeastern and northwestern refugia, most likely due to Pleistocene forest fragmentation. Subsequent southwards post-glacial recolonization is supported by a north-south gradient of decreasing genetic diversity. Repeated allopatric fragmentation and recolonization have led to the formation of deeply divergent geographical lineages within four species and a suture zone where these intraspecific lineages meet along the Thai-Myanmar border. A common environmental influence for this divergence was further indicated by strong support for simultaneous divergence within the same four species, dating to approximately 900 thousand years ago (kya). Differences in the geographical structuring of genetic diversity between species are probably the result of varying species' biology. The findings have important implications for conservation planning; if the refugial regions and suture zone identified here are shared by other forest taxa, the unique and high levels of genetic diversity they house will make these areas conservation priorities.

Tropical forests have undergone repeated fragmentation and expansion during Pleistocene glacial and interglacial periods, respectively. The effects of this repeated forest fragmentation in driving vicariance in tropical taxa have been well studied. However, relatively little is known about how often this process results in allopatric speciation, since it may be inhibited by recurrent gene flow during repeated secondary contact, or to what extent Pleistocene-dated speciation results from ecological specialization in the face of gene flow. Here, divergence times and gene flow between three closely-related mosquito species of the Anopheles dirus species complex endemic to the forests of Southeast Asia, are inferred using coalescent based Bayesian analysis. An Isolation with Migration model is applied to sequences of two mitochondrial and three nuclear genes, and 11 microsatellites. The divergence of An. scanloni has occurred despite unidirectional nuclear gene flow from this species into An. dirus. The inferred asymmetric gene flow may result from the unique evolutionary adaptation of An. scanloni to limestone karst habitat, and therefore the fitness advantage of this species over An. dirus in regions of sympatry. Mitochondrial introgression has led to the complete replacement of An. dirus haplotypes with those of An. baimaii through a recent (approximately 62 kya) selective sweep. Speciation of An. baimaii and An. dirus is inferred to have involved allopatric divergence throughout much of the Pleistocene. Secondary contact and bidirectional gene flow has occurred only within the last 100 000 years, by which time the process of allopatric speciation seems to have been largely completed.

We recently reported crossing experiments between Anopheles maculatus form K and five members of the Maculatus group to support the specific status of form K. In the present study, we performed further crosses between form K and a sixth species of the Maculatus group, Anopheles willmori (James). Low viability was observed in hybrid males and females. All hybrid males were sterile with atrophied testes, or partially sterile with abnormal spermatozoa. The hybrid females showed normal ovaries. The ovarian nurse cell polytene chromosomes of the F1 hybrid females displayed complete asynapsis. Backcrossing showed low viability. All males were sterile with atrophied testes or partially sterile with abnormal spermatozoa, and the females showed varying degrees of atrophied ovaries. The results provide clear evidence that form K is not conspecific to A. willmori supporting previous studies that form K represents another species of the Maculatus group.

Background The nematode species Pristionchus pacificus has an androdioecious mating system in which populations consist of self-fertilizing hermaphrodites and relatively few males. The prevalence of males in such a system is likely to depend on the relative pros and cons of outcrossing. While outcrossing generates novel allelic combinations and can therefore increase adaptive potential, it may also disrupt the potentially beneficial consequences of repeated generations of selfing. These include purging of deleterious alleles, inheritance of co-adapted allele complexes, improved hermaphrodite fitness and increased population growth. Here we use experimental and population genetic approaches to test hypotheses relating to male production and outcrossing in laboratory and natural populations of P. pacificus sampled from the volcanic island of La Réunion. Results We find a significant interaction between sampling locality and temperature treatment influencing rates of spontaneous male production in the laboratory. While strains isolated at higher altitude, cooler localities produce a higher proportion of male offspring at 25 °C relative to 20 or 15 °C, the reverse pattern is seen in strains isolated from warmer, low altitude localities. Linkage disequilibrium extends across long physical distances, but fails to approach levels reported for the partially selfing nematode species Caenorhabditis elegans. Finally, we find evidence for admixture between divergent genetic lineages. Conclusions Elevated rates of laboratory male generation appear to occur under environmental conditions which differ from those experienced by populations in nature. Such elevated male generation may result in higher outcrossing rates, hence driving increased effective recombination and the creation of potentially adaptive novel allelic combinations. Patterns of linkage disequilibrium decay support selfing as the predominant reproductive strategy in P. pacificus. Finally, despite the potential for outcrossing depression, our results suggest admixture has occurred between distinct genetic lineages since their independent colonization of the island, suggesting outcrossing depression may not be uniform in this species. Electronic supplementary material The online version of this article (doi:10.1186/s12862-017-0873-7) contains supplementary material, which is available to authorized users.