AMPK Phosphorylates LMX1b to Regulate a Brainstem Neurogenic Network Important for Control of Breathing in Neonatal Mice.

Ventilatory drive is modulated by a variety of neurochemical inputs that converge on spatially oriented clusters of cells within the brainstem. This regulation is required to maintain energy homeostasis and is essential to sustain life across all mammalian organisms. Therefore, the anatomical orientation of these cellular clusters during development must have a defined mechanistic basis with redundant genomic variants.

Mild Hypoxia Accelerates Cerebral Cavernous Malformation Disease Through CX3CR1-CX3CL1 Signaling.

Background: Heterogeneity in the severity of cerebral cavernous malformations (CCMs) disease, including brain bleedings and thrombosis that cause neurological disabilities in patients, suggests that environmental, genetic, or biological factors act as disease modifiers. Still, the underlying mechanisms are not entirely understood. Here, we report that mild hypoxia accelerates CCM disease by promoting angiogenesis, neuroinflammation, and vascular thrombosis in the brains of CCM mouse models.

Bewildering biogeography: Waves of dispersal and diversification across southern Wallacea by bent-toed geckos (genus: Cyrtodactylus).

Bent-toed Geckos, genus Cyrtodactylus, are one of the most diverse terrestrial vertebrate groups, and their range extends from South Asia into Australo-Papua and adjacent Pacific islands. Given the generally high faunal endemism on Wallacean islands, it is rather paradoxical that the diversity in these geckos appears to be so low (21 species in Wallacea, 15 in the Philippines) compared with continental shelf assemblages (>300 species on Sunda + Sahul Shelves + adjacent islands). To determine whether this shortfall was real or an artifact of historical undersampling, we analyzed mitochondrial DNA sequences of hundreds of southern Wallacean samples (Lesser Sundas + southern Maluku).

Inflammation biomarkers in OSA, chronic obstructive pulmonary disease, and chronic obstructive pulmonary disease/OSA overlap syndrome.

Study Objectives: The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in a single individual, also known as overlap syndrome (OVS), is associated with higher cardiovascular risk and mortality than either OSA or COPD alone. However, the underlying mechanisms remain unclear. We hypothesized that patients with OVS have elevated systemic inflammatory biomarkers relative to patients with either disease alone, which could explain greater cardiovascular risk observed in OVS.

Neuroinflammation Plays a Critical Role in Cerebral Cavernous Malformation Disease.

Background: Cerebral cavernous malformations (CCMs) are neurovascular lesions caused by loss of function mutations in 1 of 3 genes, including ), , and ). CCMs affect ≈1 out of 200 children and adults, and no pharmacologic therapy is available. CCM lesion count, size, and aggressiveness vary widely among patients of similar ages with the same mutation or even within members of the same family.

Obstructive Sleep Apnea-induced Endothelial Dysfunction Is Mediated by miR-210.

Obstructive sleep apnea (OSA)-induced endothelial cell (EC) dysfunction contributes to OSA-related cardiovascular sequelae. The mechanistic basis of endothelial impairment by OSA is unclear. The goals of this study were to identify the mechanism of OSA-induced EC dysfunction and explore the potential therapies for OSA-accelerated cardiovascular disease.

Phylogenetic relationships of southern Wallacean ranid frogs (Anura: Ranidae: Hylarana).

Frogs in the family Ranidae are diverse in Asia and are thought to have dispersed to the Sahul Shelf approximately 10 million years ago, where they radiated into more than a dozen species. Ranid species in the intervening oceanic islands of Wallacea, such as Hylarana florensis and H. elberti from the Lesser Sundas and H.

Diverge and Conquer: Phylogenomics of southern Wallacean forest skinks (Genus: Sphenomorphus) and their colonization of the Lesser Sunda Archipelago.

The archipelagos of Wallacea extend between the Sunda and Sahul Shelves, serving as a semipermeable two-way filter influencing faunal exchange between Asia and Australo-Papua. Forest skinks (Genus Sphenomorphus) are widespread throughout southern Wallacea and exhibit complex clinal, ontogenetic, sexual, and seasonal morphological variation, rendering species delimitation difficult. We screened a mitochondrial marker for 245 Sphenomorphus specimens from this area to inform the selection of 104 samples from which we used targeted sequence capture to generate a dataset of 1154 nuclear genes (∼1.

A new species of Stegonotus (Serpentes: Colubridae) from the remnant coastal forests of southern Timor-Leste.

During the first amphibian and reptile survey of Timor-Leste, we discovered a population of groundsnakes, genus Stegonotus, in the last remnant of lowland coastal forest along the countrys southern coast, which represents a new species. This sexually dimorphic species can be differentiated from all other Wallacean Stegonotus by a combination of 17-17-15 dorsals, ventrals (female 206; males 197207), paired subcaudals (female 61; males 7175), the gull wing + condition of the rostral, large squared prefrontals that each are 2.5 times the area of the internasals and two-thirds the size of the frontal, a snout-scale ratio of near 0.

Threes Company: discovery of a third syntype of Stegonotus lividus, a species of colubrid snake from Pulau Semau, Lesser Sunda Islands, Indonesia, with comments on an unpublished 19th Century manuscript by the naturalist Salomon Mller.

We report on the discovery of a third, male specimen of Stegonotus lividus in the collection of the Musum National dHistoire Naturelle in Paris, France, and demonstrate that it is not only a member of the original type series but the only one of the three syntypes, whose morphology was detailed in the original description. We herein identify it as a paralectotype. In their description of S.

An evaluation of the nomina for death adders (Acanthophis Daudin, 1803) proposed by Wells amp; Wellington (1985), and confirmation of A. cryptamydros Maddock et al., 2015 as the valid name for the Kimberley death adder.

We assess the availability of four names proposed by Wells Wellington (1985) for Australian death adders (Acanthophis). In agreement with previous literature, A. hawkei is an available name, whereas A.

Phylogenomic Analysis Reveals Dispersal-Driven Speciation and Divergence with Gene Flow in Lesser Sunda Flying Lizards (Genus Draco).

The Lesser Sunda Archipelago offers exceptional potential as a model system for studying the dynamics of dispersal-driven diversification. The geographic proximity of the islands suggests the possibility for successful dispersal, but this is countered by the permanence of the marine barriers and extreme intervening currents that are expected to hinder gene flow. Phylogenetic and species delimitation analyses of flying lizards (genus Draco) using single mitochondrial genes, complete mitochondrial genomes, and exome-capture data sets identified 9-11 deeply divergent lineages including single-island endemics, lineages that span multiple islands, and parapatrically distributed nonsister lineages on the larger islands.

Roles of KLF4 and AMPK in the inhibition of glycolysis by pulsatile shear stress in endothelial cells.

Vascular endothelial cells (ECs) sense and respond to hemodynamic forces such as pulsatile shear stress (PS) and oscillatory shear stress (OS). Among the metabolic pathways, glycolysis is differentially regulated by atheroprone OS and atheroprotective PS. Studying the molecular mechanisms by which PS suppresses glycolytic flux at the epigenetic, transcriptomic, and kinomic levels, we have demonstrated that glucokinase regulatory protein (GCKR) was markedly induced by PS in vitro and in vivo, although PS down-regulates other glycolysis enzymes such as hexokinase (HK1).

Metformin Use in Diabetes Prior to Hospitalization: Effects on Mortality in Covid-19.

Objective: Although type 2 diabetes mellitus (T2DM) has been reported as a risk factor for coronavirus disease 2019 (COVID-19), the effect of pharmacologic agents used to treat T2DM, such as metformin, on COVID-19 outcomes remains unclear. Metformin increases the expression of angiotensin converting enzyme 2, a known receptor for severe acute respiratory syndrome coronavirus 2. Data from people with T2DM hospitalized for COVID-19 were used to test the hypothesis that metformin use is associated with improved survival in this population.

Endothelial mechanobiology.

Lining the luminal surface of the vasculature, endothelial cells (ECs) are in direct contact with and differentially respond to hemodynamic forces depending on their anatomic location. Pulsatile shear stress (PS) is defined by laminar flow and is predominantly located in straight vascular regions, while disturbed or oscillatory shear stress (OS) is localized to branch points and bifurcations. Such flow patterns have become a central focus of vascular diseases, such as atherosclerosis, because the focal distribution of endothelial dysfunction corresponds to regions exposed to OS, whereas endothelial homeostasis is maintained in regions defined by PS.

Shear stress regulation of miR-93 and miR-484 maturation through nucleolin.

Pulsatile shear (PS) and oscillatory shear (OS) elicit distinct mechanotransduction signals that maintain endothelial homeostasis or induce endothelial dysfunction, respectively. A subset of microRNAs (miRs) in vascular endothelial cells (ECs) are differentially regulated by PS and OS, but the regulation of the miR processing and its implications in EC biology by shear stress are poorly understood. From a systematic in silico analysis for RNA binding proteins that regulate miR processing, we found that nucleolin (NCL) is a major regulator of miR processing in response to OS and essential for the maturation of miR-93 and miR-484 that target mRNAs encoding Krüppel-like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS).

AMPK: An Epigenetic Landscape Modulator.

Activated by AMP-dependent and -independent mechanisms, AMP-activated protein kinase (AMPK) plays a central role in the regulation of cellular bioenergetics and cellular survival. AMPK regulates a diverse set of signaling networks that converge to epigenetically mediate transcriptional events. Reversible histone and DNA modifications, such as acetylation and methylation, result in structural chromatin alterations that influence transcriptional machinery access to genomic regulatory elements.

Historical considerations and comments on the type series of Cyrtodactylus marmoratus Gray, 1831, with an updated comparative table for the bent-toed geckos of the Sunda Islands and Sulawesi.

Cyrtodactylus marmoratus Gray, 1831, a species of bent-toed gecko exhibiting a precloacal groove in males, was described on the basis of specimens collected by Heinrich Kuhl and Johan Conrad van Hasselt in Java, Greater Sunda Islands, Indonesia. Kluge (1985) subsequently designated a lectotype for C. marmoratus from a series of these specimens (i.

A new species of bent-toed gecko, genus Cyrtodactylus Gray, 1827 (Reptilia: Squamata: Gekkonidae), from Jawa Timur Province, Java, Indonesia, with taxonomic remarks on C. fumosus (Müller, 1895).

A new species of the gekkonid lizard genus Cyrtodactylus Gray, 1827 is described from Klakah, Lumajang Regency, Jawa Timur Province, Java, Indonesia. Cyrtodactylus klakahensis sp. nov.

An inconspicuous, conspicuous new species of Asian pipesnake, genus Cylindrophis (Reptilia: Squamata: Cylindrophiidae), from the south coast of Jawa Tengah, Java, Indonesia, and an overview of the tangled taxonomic history of C. ruffus (Laurenti, 1768).

We describe a new species of Cylindrophis currently known only from Grabag, Purworejo Regency, Jawa Tengah Pro-vince (Central Java), Java, Indonesia. Cylindrophis subocularis sp. nov.

Re-examination of Hemidactylus tenkatei van Lidth de Jeude, 1895: Populations from Timor provide insight into the taxonomy of the H. brookii Gray, 1845 complex (Squamata: Gekkonidae).

Recent herpetofaunal investigations in Timor-Leste revealed populations similar to Hemidactylus brookii Gray, 1845 in four of 13 districts. In order to properly identify these populations, we examined their relationships to other H. brookii-complex populations, notably those from nearby Roti Island, Indonesia (to which the name H.