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The Tangential Nucleus Controls a Gravito-inertial Vestibulo-ocular Reflex
Whilst adult vertebrates sense changes in head position using two classes of accelerometer, at larval stages zebraïŹsh lack functional semicircular canals and rely exclusively on their otolithic organs to transduce vestibular information. Despite this limitation, they perform an effective vestibulo-ocular reïŹex (VOR) that serves to stabilize gaze in response to pitch and roll tilts. Using single-cell electroporations and targeted laser-ablations, we identiïŹed a speciïŹc class of central vestibular neurons, located in the tangential nucleus, which are essential for the utricle-dependent VOR. Tangential nucleus neurons project contralaterally to extraocular motoneurons, and in addition, to multiple sites within the reticulospinal complex. We propose that tangential neurons function as a broadband inertial accelerometer, processing utricular acceleration signals to control the activity of extraocular and postural neurons, thus completing a fundamental three-neuron circuit responsible for gaze stabilization.Molecular and Cellular Biolog
Additions to Philippine slender skinks of the Brachymeles bonitae complex (Reptilia: Squamata: Scincidae) IV: Resurrection and redescription of Brachymeles burksi
The diversity of Philippine amphibians and reptiles has increased over the last few decades, in part due to re-evaluation of species formerly believed to be widespread. Many of these investigations of widespread species have uncovered multiple closely related cryptic lineages comprising species complexes, each restricted to individual Pleistocene Aggregate Island Complexes (PAICs). One group in particular for which widespread cryptic diversity has been common is the clade of Philippine skinks of the genus Brachymeles. Recent phylogenetic studies of the formerly recognized widespread species Brachymeles bonitae have indicated that this species is actually a complex distributed across several major PAICs and smaller island groups in the central and northern Philippines, with numerous species that exhibit an array of digit loss and limb reduction patterns. Despite the recent revisions to the B. bonitae species complex, studies suggest that unique cryptic lineages still exist within this group. In this paper, we resurrect the species Brachymeles burksi Taylor 1917, for a lineage of non-pentadactyl, semi-fossorial skink from Mindoro and Marinduque islands. First described in 1917, B. burksi was synonymized with B. bonitae in 1956, and has rarely been reconsidered since. Evaluation of genetic and morphological data (qualitative traits, meristic counts, and mensural measurements), and comparison of recently-obtained specimens to Taylorâs original description support this speciesâ recognition, as does its insular distribution on isolated islands in the central portions of the archipelago. Morphologically, B. burksi is differentiated from other members of the genus based on a suite of unique phenotypic characteristics, including a small body size, digitless limbs, a high number of presacral vertebrae, the absence of auricular openings, and discrete (non-overlapping) meristic scale counts. The recognition of this central Philippine species further increases the diversity of non-pentadactyl members of the B. bonitae complex, and reinforces the biogeographic uniqueness of the Mindoro faunal region
Interrogating a Hexokinase-Selected Small-Molecule Library for Inhibitors of Plasmodium falciparum Hexokinase
This is the published version.Parasites in the genus Plasmodium cause disease throughout the tropic and subtropical regions of the world. P. falciparum, one of the deadliest species of the parasite, relies on glycolysis for the generation of ATP while it inhabits the mammalian red blood cell. The first step in glycolysis is catalyzed by hexokinase (HK). While the 55.3-kDa P. falciparum HK (PfHK) shares several biochemical characteristics with mammalian HKs, including being inhibited by its products, it has limited amino acid identity (âŒ26%) to the human HKs, suggesting that enzyme-specific therapeutics could be generated. To that end, interrogation of a selected small-molecule library of HK inhibitors has identified a class of PfHK inhibitors, isobenzothiazolinones, some of which have 50% inhibitory concentrations (IC50s) of <1 ÎŒM. Inhibition was reversible by dilution but not by treatment with a reducing agent, suggesting that the basis for enzyme inactivation was not covalent association with the inhibitor. Lastly, six of these compounds and the related molecule ebselen inhibited P. falciparum growth in vitro (50% effective concentration [EC50] of â„0.6 and <6.8 ÎŒM). These findings suggest that the chemotypes identified here could represent leads for future development of therapeutics against P. falciparum
The Open Cluster Chemical Analysis and Mapping Survey: Local Galactic Metallicity Gradient with APOGEE using SDSS DR10
The Open Cluster Chemical Analysis and Mapping (OCCAM) Survey aims to produce
a comprehensive, uniform, infrared-based dataset for hundreds of open clusters,
and constrain key Galactic dynamical and chemical parameters from this sample.
This first contribution from the OCCAM survey presents analysis of 141 members
stars in 28 open clusters with high-resolution metallicities derived from a
large uniform sample collected as part of the SDSS-III/Apache Point Observatory
Galactic Evolution Experiment (APOGEE). This sample includes the first
high-resolution metallicity measurements for 22 open clusters. With this
largest ever uniformly observed sample of open cluster stars we investigate the
Galactic disk gradients of both [M/H] and [alpha/M]. We find basically no
gradient across this range in [alpha/M], but [M/H] does show a gradient for
R_{GC} < 10 kpc and a significant flattening beyond R_{GC} = 10 kpc. In
particular, whereas fitting a single linear trend yields an [M/H] gradient of
-0.09 +/- 0.03$ dex/kpc --- similar to previously measure gradients inside 13
kpc --- by independently fitting inside and outside 10 kpc separately we find a
significantly steeper gradient near the Sun (7.9 <= R_{GC} <= 10) than
previously found (-0.20 +/- 0.08 dex/kpc) and a nearly flat trend beyond 10 kpc
(-0.02 +/- 0.09 dex/kpc).Comment: 6 pages, 4 figures, ApJ letters, in pres
Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia
SummaryMany human cancers are dramatically accelerated by chronic inflammation. However, the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that KrasG12D induces expression of functional IL-17 receptors on PanIN epithelial cells and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation
Gut Microbiome Metagenomics Analysis Suggests a Functional Model for the Development of Autoimmunity for Type 1 Diabetes
Peer reviewe
Ca. Nitrososphaera and Bradyrhizobium are inversely correlated and related to agricultural practices in long-term field experiments
Agricultural land management, such as fertilization, liming, and tillage affects soil properties, including pH, organic matter content, nitrification rates, and the microbial community. Three different study sites were used to identify microorganisms that correlate with agricultural land use and to determine which factors regulate the relative abundance of the microbial signatures of the agricultural land-use. The three sites included in this study are the Broadbalk Experiment at Rothamsted Research, UK, the Everglades Agricultural Area, Florida, USA, and the Kellogg Biological Station, Michigan, USA. The effects of agricultural management on the abundance and diversity of bacteria and archaea were determined using high throughput, barcoded 16S rRNA sequencing. In addition, the relative abundance of these organisms was correlated with soil features. Two groups of microorganisms involved in nitrogen cycle were highly correlated with land use at all three sites. The ammonia oxidizing-archaea, dominated by Ca. Nitrososphaera, were positively correlated with agriculture while a ubiquitous group of soil bacteria closely related to the diazotrophic symbiont, Bradyrhizobium, was negatively correlated with agricultural management. Analysis of successional plots showed that the abundance of ammonia oxidizing-archaea declined and the abundance of bradyrhizobia increased with time away from agriculture. This observation suggests that the effect of agriculture on the relative abundance of these genera is reversible. Soil pH and NH(3) concentrations were positively correlated with archaeal abundance but negatively correlated with the abundance of Bradyrhizobium. The high correlations of Ca. Nitrososphaera and Bradyrhizobium abundances with agricultural management at three long-term experiments with different edaphoclimatic conditions allowed us to suggest these two genera as signature microorganisms for agricultural land use
The methylome of the gut microbiome : disparate Dam methylation patterns in intestinal Bacteroides dorei
Peer reviewe
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