Development and characterization of microsatellite loci for lotus (Nelumbo nucifera)

This paper reports the development of microsatellite primers for Nelumbo nucifera Gaerten. By screening genomic libraries enriched with 10 kinds of probes, Seventeen polymorphic loci were isolated and primers were designed. Polymorphism of these 17 loci was assessed in 24 individuals. All the 17 loci are polymorphic and the number of alleles ranged from two to seven. Observed heterozygosity and expected heterozygosity ranged from 0.0000 to 0.9176 and from 0.2837 to 0.7917 respectively. These microsatellite loci should be useful for studying the genetic diversity of N. nucifera.     

Purinergic signalling in the subretinal space: a role in the communication between the retina and the RPE

The retinal pigment epithelium (RPE) is separated from the photoreceptor outer segments by the subretinal space. While the actual volume of this space is minimal, the communication that occurs across this microenvironment is important to the visual process, and accumulating evidence suggests the purines ATP and adenosine contribute to this communication. P1 and P2 receptors are localized to membranes on both the photoreceptor outer segments and on the apical membrane of the RPE which border subretinal space. ATP is released across the apical membrane of the RPE into this space in response to various triggers including glutamate and chemical ischemia. This ATP is dephosphorylated into adenosine by a series of ectoenzymes on the RPE apical membrane. Regulation of release and ectoenzyme activity in response to light-sensitive signals can alter the balance of purines in subretinal space, and thus coordinate communication across subretinal space with the visual process.     

Does the pain-protective GTP cyclohydrolase haplotype significantly alter the pattern or severity of pain in humans with chronic pancreatitis?

Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.     

The carotid rete and artiodactyl success

Since the Eocene, the diversity of artiodactyls has increased while that of perissodactyls has decreased. Reasons given for this contrasting pattern are that the evolution of a ruminant digestive tract and improved locomotion in artiodactyls were adaptively advantageous in the highly seasonal post-Eocene climate. We suggest that evolution of a carotid rete, a structure highly developed in artiodactyls but absent in perissodactyls, was at least as important. The rete confers an ability to regulate brain temperature independently of body temperature. The net effect is that in hot ambient conditions artiodactyls are able to conserve energy and water, and in cold ambient conditions they are able to conserve body temperature. In perissodactyls, brain and body temperature change in parallel and thermoregulation requires abundant food and water to warm/cool the body. Consequently, perissodactyls occupy habitats of low seasonality and rich in food and water, such as tropical forests. Conversely, the increased thermoregulatory flexibility of artiodactyls has facilitated invasion of new adaptive zones ranging from the Arctic Circle to deserts and tropical savannahs.     

Sperm contamination in archived and contemporary herring samples

Studies using archived scales and otoliths to examine ancient fish populations have become increasingly common, despite many methodological challenges in ancient DNA research. Here, we describe a case of DNA contamination in both modern and historical samples of Pacific herring (Clupea pallasii), where the source of the contamination is likely from milt spillage during collection. We describe a series of experiments to remove contamination using pre-extraction wash treatments. Though contamination was easily removed from contemporary fin clippings, no method was successful at removing contamination from historical scales. We discuss the implications of our findings to the genetic analysis of archived samples.     

Activation of p38MAPK contributes to expanded polyglutamine-induced cytotoxicity

Background

The signaling pathways that may modulate the pathogenesis of diseases induced by expanded polyglutamine proteins are not well understood.

Methodologies/Principal Findings

Herein we demonstrate that expanded polyglutamine protein cytotoxicity is mediated primarily through activation of p38MAPK and that the atypical PKC iota (PKCι) enzyme antagonizes polyglutamine-induced cell death through induction of the ERK signaling pathway. We show that pharmacological blockade of p38MAPK rescues cells from polyglutamine-induced cell death whereas inhibition of ERK recapitulates the sensitivity observed in cells depleted of PKCι by RNA interference. We provide evidence that two unrelated proteins with expanded polyglutamine repeats induce p38MAPK in cultured cells, and demonstrate induction of p38MAPK in an in vivo model of neurodegeneration (spinocerebellar ataxia 1, or SCA-1).

Conclusions/Significance

Taken together, our data implicate activated p38MAPK in disease progression and suggest that its inhibition may represent a rational strategy for therapeutic intervention in the polyglutamine disorders.     

The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1

WAVE2 regulates T cell receptor (TCR)–stimulated actin cytoskeletal dynamics leading to both integrin clustering and affinity maturation. Although WAVE2 mediates integrin affinity maturation by recruiting vinculin and talin to the immunological synapse in an Arp2/3-dependent manner, the mechanism by which it regulates integrin clustering is unclear. We show that the Abl tyrosine kinase associates with the WAVE2 complex and TCR ligation induces WAVE2-dependent membrane recruitment of Abl. Furthermore, we show that WAVE2 regulates TCR-mediated activation of the integrin regulatory guanosine triphosphatase Rap1 via the recruitment and activation of the CrkL–C3G exchange complex. Moreover, we demonstrate that although Abl does not regulate the recruitment of CrkL–C3G into the membrane, it does affect the tyrosine phosphorylation of C3G, which is required for its guanine nucleotide exchange factor activity toward Rap1. This signaling node regulates not only TCR-stimulated integrin clustering but also affinity maturation. These findings identify a previously unknown mechanism by which the WAVE2 complex regulates TCR signaling to Rap1 and integrin activation.     

Should I Stay or Should I Go? Eukaryotic Translation Initiation Factors 1 and 1A Control Start Codon Recognition

Start codon selection is a key step in translation initiation as it sets the reading frame for decoding. Two eukaryotic initiation factors, eIF1 and eIF1A, are key actors in this process. Recent work has elucidated many details of the mechanisms these factors use to control start site selection. eIF1 prevents the irreversible GTP hydrolysis that commits the ribosome to initiation at a particular codon. eIF1A both promotes and inhibits commitment through the competing influences of its two unstructured termini. Both factors perform their tasks through a variety of interactions with other components of the initiation machinery, in many cases mediated by the unstructured regions of the two proteins.