Miniature rotating transmissive optical drum scanner

A miniature rotating transmissive optical scanner system employs a drum of small size having an interior defined by a circumferential wall rotatable on a drum axis, an optical element positioned within the interior of the drum, and a light-transmissive lens aperture provided at an angular position in the circumferential wall of the drum for scanning a light beam to or from the optical element in the drum along a beam azimuth angle as the drum is rotated. The miniature optical drum scanner configuration obtains a wide scanning field-of-view (FOV) and large effective aperture is achieved within a physically small size

THE EFFECT OF A GAME-SPECIFIC SHORT TERM FATIGUE PROTOCOL ONKICKING IN AUSTRALIAN FOOTBALL

The purpose of this study was to three dimentionally evaluate the effects of a short term game specific fatigue protocol on the kinetics of elite and sub-elite Australian Footballers (AF) during a drop punt kick. Five AF players performed kicks pre and post fatigue protocol. Three dimensional data of the pelvis and kick leg was obtained using a three tower optotrak Certus system (200Hz) and joint torques and moments were calculated in Visual 3D from kick foot toe off until ball contact. Sprint time indicated the protocol induced fatigue. Hip flexion torque significantly increased following fatigue indicating a change in movement strategy similar to that found for jump landing. This greater hip reliant post-fatigue kicking strategy has implications for both skill enhancement and injury prevention

TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a molecule capable of initiating the release of intracellular Ca2+ required for many essential cellular processes. Recent evidence links two-pore channels (TPCs) with NAADP-induced release of Ca2+ from lysosome-like acidic organelles; however, there has been no direct demonstration that TPCs can act as NAADP-sensitive Ca2+-release channels. Controversial evidence also proposes ryanodine receptors as the primary target of NAADP. We show that TPC2, the major lysosomal targeted isoform, is a cation channel with selectivity for Ca2+ that will enable it to act as a Ca2+ release channel in the cellular environment. NAADP opens TPC2 channels in a concentration-dependent manner, binding to high affinity activation and low affinity inhibition sites. At the core of this process is the luminal environment of the channel. The sensitivity of TPC2 to NAADP is steeply dependent on the luminal [Ca2+] allowing extremely low levels of NAADP to open the channel. In parallel, luminal pH controls NAADP affinity for TPC2 by switching from reversible activation of TPC2 at low pH to irreversible activation at neutral pH. Further evidence earmarking TPCs as the likely pathway for NAADP-induced intracellular Ca2+ release is obtained from the use of Ned-19, the selective blocker of cellular NAADP-induced Ca2+ release. Ned-19 antagonizes NAADP-activation of TPC2 in a non-competitive manner at 1 μM but potentiates NAADP activation at nanomolar concentrations. This single-channel study provides a long awaited molecular basis for the peculiar mechanistic features of NAADP signaling and a framework for understanding how NAADP can mediate key physiological events.Publisher PDFPeer reviewe

An emerging role for NAADP-mediated Ca2+ signaling in the pancreatic beta-cell

Several recent reports, including one in this journal, have reignited the debate about whether the calcium-mobilizing messenger, nicotinic adenine nucleotide diphosphate (NAADP) plays a central role in the regulation of calcium signalling in pancreatic β-cell. These studies have highlighted a role for NAADP-induced Ca(2+) mobilization not only in mediating the effects of the incretin, GLP-1 and the autocrine proliferative effects of insulin, but also possibly a fundamental role in glucose-mediated insulin secretion in the pancreatic β-cell

Identification of a Novel Gene for Diabetic Traits in Rats, Mice, and Humans

The genetic basis of type 2 diabetes remains incompletely defined despite the use of multiple genetic strategies. Multiparental populations such as heterogeneous stocks (HS) facilitate gene discovery by allowing fine mapping to only a few megabases, significantly decreasing the number of potential candidate genes compared to traditional mapping strategies. In the present work, we employed expression and sequence analysis in HS rats (Rattus norvegicus) to identify Tpcn2 as a likely causal gene underlying a 3.1-Mb locus for glucose and insulin levels. Global gene expression analysis on liver identified Tpcn2 as the only gene in the region that is differentially expressed between HS rats with glucose intolerance and those with normal glucose regulation. Tpcn2 also maps as a cis-regulating expression QTL and is negatively correlated with fasting glucose levels. We used founder sequence to identify variants within this region and assessed association between 18 variants and diabetic traits by conducting a mixed-model analysis, accounting for the complex family structure of the HS. We found that two variants were significantly associated with fasting glucose levels, including a nonsynonymous coding variant within Tpcn2. Studies in Tpcn2 knockout mice demonstrated a significant decrease in fasting glucose levels and insulin response to a glucose challenge relative to those in wild-type mice. Finally, we identified variants within Tpcn2 that are associated with fasting insulin in humans. These studies indicate that Tpcn2 is a likely causal gene that may play a role in human diabetes and demonstrate the utility of multiparental populations for positionally cloning genes within complex loci

Genetic diversity and distribution of Peromyscus-borne hantaviruses in North America.

The 1993 outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States was associated with Sin Nombre virus, a rodent-borne hantavirus; The virus' primary reservoir is the deer mouse (Peromyscus maniculatus). Hantavirus-infected rodents were identified in various regions of North America. An extensive nucleotide sequence database of an 139 bp fragment amplified from virus M genomic segments was generated. Phylogenetic analysis confirmed that SNV-like hantaviruses are widely distributed in Peromyscus species rodents throughout North America. Classic SNV is the major cause of HPS in North America, but other Peromyscine-borne hantaviruses, e.g., New York and Monongahela viruses, are also associated with HPS cases. Although genetically diverse, SNV-like viruses have slowly coevolved with their rodent hosts. We show that the genetic relationships of hantaviruses in the Americas are complex, most likely as a result of the rapid radiation and speciation of New World sigmodontine rodents and occasional virus-host switching events

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

TPCs: Endolysosomal channels for Ca2+ mobilization from acidic organelles triggered by NAADP

Two-pore channels (TPCs or TPCNs) are novel members of the large superfamily of voltage-gated cation channels with slightly higher sequence homology to the pore-forming subunits of voltage-gated Ca(2+) and Na(+) channels than most other members. Recent studies demonstrate that TPCs locate to endosomes and lysosomes and form Ca(2+) release channels that respond to activation by the Ca(2+) mobilizing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). With multiple endolysosomal targeted NAADP receptors now identified, important new insights into the regulation of endolysosomal function in health and disease will therefore be unveiled

The acid test: the discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca2+ release channels

In this review, we describe the background and implications of our recent discovery that two-pore channels (TPCs) comprise a novel class of calcium release channels gated by the intracellular messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Their localisation to the endolysosomal system highlights a new function for these organelles as targets for NAADP-mediated Ca(2+) mobilisation. In addition, we describe how TPCs may also trigger further Ca(2+) release by coupling to the endoplasmic reticular stores through activation of IP(3) receptors and ryanodine receptors