Effects of Tectonics and Large Scale Climatic Changes On the Evolutionary History of \u3ci\u3eHyalomma\u3c/i\u3e ticks

Hyalomma Koch, 1844 are ixodid ticks that infest mammals, birds and reptiles, to which 27 recognized species occur across the Afrotropical, Palearctic and Oriental regions. Despite their medical and veterinary importance, the evolutionary history of the group is enigmatic. To investigate various taxonomic hypotheses based on morphology, and also some of the mechanisms involved in the diversification of the genus, we sequenced and analysed data derived from two mtDNA fragments, three nuclear DNA genes and 47 morphological characters. Bayesian and Parsimony analyses based on the combined data (2242 characters for 84 taxa) provided maximum resolution and strongly supported the monophyly of Hyalomma and the subgenus Euhyalomma Filippova, 1984 (including H. punt Hoogstraal, Kaiser and Pedersen, 1969). A predicted close evolutionary association was found between morphologically similar H. dromedarii Koch, 1844, H. somalicum Tonelli Rondelli, 1935, H. impeltatum Schulze and Schlottke, 1929 and H. punt, and together they form a sister lineage to H. asiaticum Schulze and Schlottke, 1929, H. schulzei Olenev, 1931 and H. scupense Schulze, 1919. Congruent with morphological suggestions, H. anatolicum Koch, 1844, H. excavatum Koch, 1844 and H. lusitanicum Koch, 1844 form a clade and so also H. glabrum Delpy, 1949, H. marginatum Koch, 1844, H. turanicum Pomerantzev, 1946 and H. rufipes Koch, 1844. Wide scale continental sampling revealed cryptic divergences within African H. truncatum Koch, 1844 and H. rufipes and suggested that the taxonomy of these lineages is in need of a revision. The most basal lineages in Hyalomma represent taxa currently confined to Eurasia and molecular clock estimates suggest that members of the genus started to diverge approximately 36.25 million years ago (Mya). The early diversification event coincides well with the collision of the Indian and Eurasian Plates, an event that was also characterized by large scale faunal turnover in the region. Using S-Diva, we also propose that the closure of the Tethyan seaway allowed for the genus to first enter Africa approximately 17.73 Mya. In concert, our data supports the notion that tectonic events and large scale global changes in the environment contributed significantly to produce the rich species diversity currently found in the genus Hyalomma

Metabolic Control in Type 1 Diabetes: Is Adjunctive Therapy the Way Forward?

Despite advances in insulin therapies, patients with type 1 diabetes (T1DM) have a shorter life span due to hyperglycaemia-induced vascular disease and hypoglycaemic complications secondary to insulin therapy. Restricting therapy for T1DM to insulin replacement is perhaps an over-simplistic approach, and we focus in this work on reviewing the role of adjuvant therapy in this population. Current data suggest that adding metformin to insulin therapy in T1DM temporarily lowers HbA1c and reduces weight and insulin requirements, but this treatment fails to show a longer-term glycaemic benefit. Agents in the sodium glucose co-transporter-2 inhibitor (SGLT-2) class demonstrate the greatest promise in correcting hyperglycaemia, but there are safety concerns in relation to the risk of diabetic ketoacidosis. Glucagon-like peptide-1 agonists (GLP-1) show a modest effect on glycaemia, if any, but significantly reduce weight, which may make them suitable for use in overweight T1DM patients. Treatment with pramlintide is not widely available worldwide, although there is evidence to indicate that this agent reduces both HbA1c and weight in T1DM. A criticism of adjuvant studies is the heavy reliance on HbA1c as the primary endpoint while generally ignoring other glycaemic parameters. Moreover, vascular risk markers and measures of insulin resistance—important considerations in individuals with a longer T1DM duration—are yet to be fully investigated following adjuvant therapies. Finally, studies to date have made the assumption that T1DM patients are a homogeneous group of individuals who respond similarly to adjuvant therapies, which is unlikely to be the case. Future longer-term adjuvant studies investigating different glycaemic parameters, surrogate vascular markers and harder clinical outcomes will refine our understanding of the roles of such therapies in various subgroups of T1DM patients

A prenylated dsRNA sensor protects against severe COVID-19

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Against the Flow: The Colonisation of the Lesotho Highlands by Freshwater Limpets

To date, limited research has taken place on the evolutionary history of biodiversity in the high-altitude zones of southern Africa, particularly the Lesotho Highlands. The few studies that do exist point to similar high-altitude zones being either prolific museums (i.e., refugia and cradles) for cold-evolved species or sinks for temperate species post the Last Glacial Maximum, yet the role this zone has played for freshwater biodiversity is unknown for almost all freshwater taxa. In this study, we address this lack of knowledge by looking at the phylogeography of the freshwater limpet genus, Burnupia, across its southern and eastern African range, but particularly focusing on the Lesotho Highlands. We used COI data to reconstruct the evolutionary history of the genus, quantify phylogenetic species diversity, test both isolation by distance (IBD) and by elevation (IBE) and model ancestral area estimation “in” and “out” of the Highlands to determine: 1) The diversity and endemicity of Burnupia spp. in the Highlands in comparison to the broader southern African region and 2) when did the colonisation of the Highlands happen. Our results showed that at least two of the nine southern African phylogenetic species delimited occur in the Highlands (which appears average for the geographical extent of this area in comparison to the broader southern African region) and that the genus has been present in the Lesotho Highlands for somewhere between 1.38–0.23 million years. However, we found the endemicity of at least one of the two Highland species, supported by weak but significant IBD and IBE in Burnupia. Therefore we favour the notion that the Highlands are likely an important haven for cold-evolved species. As our results also generated a lot of data useful for Burnupia systematics, we discuss some taxonomic implications of our findings

A revision of the extant species of Theodoxus (Gastropoda, Neritidae) in Asia, with the description of three new species

Asia contains a high species diversity of the freshwater gastropod genus Theodoxus. Recent molecular and morphological reviews of this diversity have uncovered a number of yet undescribed species while suggesting the urgent revision of several others. Moreover, some of these studies have indicated a number of species previously not recorded for this continent. Despite the advancements, a taxonomic revision and an update on the distribution of Theodoxus spp. in Asia is still pending. Here, we construct the most robust phylogeny of Theodoxus up to now and review original descriptions, type material, recent taxonomic revisions, compendia, and species lists to provide a comprehensive checklist of all known extant Asian Theodoxus spp. Our checklist also provides descriptions for three recently discovered and yet undescribed species (Theodoxus gurur Sands & Glöer, sp. nov., Theodoxus wesselinghi Sands & Glöer, sp. nov., and Theodoxus wilkei Sands & Glöer, sp. nov.), as well as shows the need to synonymise several previously described morphospecies. The present revision recognizes 14 extant Theodoxus spp. for Asia. Some of these species are widespread, while others are endemic to just a single location. Based on the revised and new distribution data, we provide updates and new assessments of species conservation statuses

A revision of the extant species of Theodoxus (Gastropoda, Neritidae) in Asia, with the description of three new species

Asia contains a high species diversity of the freshwater gastropod genus Theodoxus. Recent molecular and morphological reviews of this diversity have uncovered a number of yet undescribed species while suggesting the urgent revision of several others. Moreover, some of these studies have indicated a number of species previously not recorded for this continent. Despite the advancements, a taxonomic revision and an update on the distribution of Theodoxus spp. in Asia is still pending. Here, we construct the most robust phylogeny of Theodoxus up to now and review original descriptions, type material, recent taxonomic revisions, compendia, and species lists to provide a comprehensive checklist of all known extant Asian Theodoxus spp. Our checklist also provides descriptions for three recently discovered and yet undescribed species (Theodoxus gurur Sands & Glöer, sp. nov., Theodoxus wesselinghi Sands & Glöer, sp. nov., and Theodoxus wilkei Sands & Glöer, sp. nov.), as well as shows the need to synonymise several previously described morphospecies. The present revision recognizes 14 extant Theodoxus spp. for Asia. Some of these species are widespread, while others are endemic to just a single location. Based on the revised and new distribution data, we provide updates and new assessments of species conservation statuses

De Novo Mutation Rates in Sticklebacks

Mutation rate is a fundamental parameter in population genetics. Apart from being an important scaling parameter for demographic and phylogenetic inference, it allows one to understand at what rate new genetic diversity is generated and what the expected level of genetic diversity is in a population at equilibrium. However, except for well-established model organisms, accurate estimates of de novo mutation rates are available for a very limited number of organisms from the wild. We estimated mutation rates (mu) in two marine populations of the nine-spined stickleback (Pungitius pungitius) with the aid of several 2- and 3-generational family pedigrees, deep (>50x) whole-genome resequences and a high-quality reference genome. After stringent filtering, we discovered 308 germline mutations in 106 offspring translating to mu = 4.83 x 10(-9) and mu = 4.29 x 10(-9) per base per generation in the two populations, respectively. Up to 20% of the mutations were shared by full-sibs showing that the level of parental mosaicism was relatively high. Since the estimated mu was 3.1 times smaller than the commonly used substitution rate, recalibration with mu led to substantial increase in estimated divergence times between different stickleback species. Our estimates of the de novo mutation rate should provide a useful resource for research focused on fish population genetics and that of sticklebacks in particular.Peer reviewe