Group I mGluR5 metabotropic glutamate receptors regulate proliferation of neuronal progenitors in specific forebrain developmental domains

Major classical neurotransmitters including GABA and glutamate play novel morphogenic roles during development of the mammalian CNS. During forebrain neurogenesis, glutamate regulates neuroblast proliferation in different germinal domains using receptor subtype-specific mechanisms. For example, ionotropic N -methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptors mediate distinct proliferative effects in ventral or dorsal forebrain germinal domains, and regulate the correct number of neurons that populate the striatum or cerebral cortex. Recent work suggests metabotropic receptors may also mediate glutamate's proliferative effects. Group I mGluR5 receptor subtypes are highly expressed in forebrain germinal zones. Using in vitro and in vivo methods, we demonstrate mGluR5 receptor activation plays an important role in neuroblast proliferation in the ventral telencephalon, and helps determine the complement of striatum projection neurons. mGluR5 receptor-mediated effects on striatal neuronal progenitors are restricted mainly to early cycling populations in the ventricular zone, with little effect on secondary proliferative populations in the subventricular zone. In contrast to proliferative effects in the ventral telencephalon, mGluR5 receptors do not modulate proliferation of dorsal telencephalon-derived cortical neuroblasts. Heterogeneous domain-specific proliferative effects of glutamate-mediated by specific receptor subtypes provide an important developmental mechanism allowing generation of the correct complement of neuronal subtypes that populate the mammalian forebrain.     

Naturally acquired IgM antibody response to the C-terminal region of the merozoite surface protein 1 of Plasmodium vivax in Korea: use for serodiagnosis of vivax malaria

The antibody levels against the C-terminal region of the merozoite surface protein 1 of Plasmodium vivax (PvMSP1c) were measured in 276 patients with P. vivax malaria (patient group), 320 malaria-na?ve healthy individuals (control group 1), and 70 malaria-na?ve individuals with various disorders (control group 2) using the immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA) and the direct sandwich ELISA. To evaluate the antibody response during relapse, 5 relapsed patients were tested using the IgM capture ELISA. The IgM antibodies were negative in 99.7% of control group 1 and in 100% of control group 2; they were positive in 90.6% of the patient group. The total antibody levels were positive in 88.4% of the patient group with the direct sandwich ELISA. The sera from the second malaria episode, i.e., relapsed patients, were 100% positive on the IgM capture ELISA. The results of this study suggest that the IgM capture ELISA may be a useful diagnostic method for P. vivax malaria for both primary infection and relapse.     

Activation of brain protein phosphatase-1(I) following cardiac arrest and resuscitation involving an interaction with 14-3-3 gamma

The intracellular signaling mechanisms that couple transient cerebral ischemia to cell death and neuroprotective mechanisms provide potential therapeutic targets for cardiac arrest. Protein phosphatase (PP)-1 is a major serine/threonine phosphatase that interacts with and dephosphorylates critical regulators of energy metabolism, ionic balance, and apoptosis. We report here that PP-1_I, a major regulated form of PP-1, is activated in brain by approximately twofold in vivo following cardiac arrest and resuscitation in a clinically relevant pig model of transient global cerebral ischemia and reperfusion. PP-1_I purified to near homogeneity from either control or ischemic pig brain consisted of the PP-1 catalytic subunit, the inhibitor-2 regulatory subunit, as well as the novel constituents 14-3-3γ, Rab GDP dissociation protein β, PFTAIRE kinase, and C-TAK1 kinase. PP-1_I purified from ischemic brain contained significantly less 14-3-3γ than PP-1_I purified from control brain, and purified 14-3-3γ directly inhibited the catalytic subunit of PP-1 and reconstituted PP-1_I. These findings suggest that activation of brain PP-1_I following global cerebral ischemia in vivo involves dissociation of 14-3-3γ, a novel inhibitory modulator of PP-1_I. This identifies modulation of PP-1_I by 14-3-3 in global cerebral ischemia as a potential signaling mechanism-based approach to neuroprotection.     

Population genetics of commercial and feral honey bees in Western Australia

Due to the introduction of exotic honey bee (Apis mellifera L.) diseases in the eastern states, the borders of the state of Western Australia were closed to the import of bees for breeding and other purposes > 25 yr ago. To provide genetically improved stock for the industry, a closed population breeding program was established that now provides stock for the majority of Western Australian beekeepers. Given concerns that inbreeding may have resulted from the closed population breeding structure, we assessed the genetic diversity within and between the breeding lines by using microsatellite and mitochondrial markers. We found that the breeding population still maintains considerable genetic diversity, despite 25 yr of selective breeding. We also investigated the genetic distance of the closed population breeding program to that of beekeepers outside of the program, and the feral Western Australian honey bee population. The feral population is genetically distinct from the closed population, but not from the genetic stock maintained by beekeepers outside of the program. The honey bees of Western Australia show three mitotypes, originating from two subspecies: Apis mellifera ligustica (mitotypes C1 and M7b) and Apis mellifera iberica (mitotype M6). Only mitotypes C1 and M6 are present in the commercial populations. The feral population contains all three mitotypes.     

Host ethnicity and virus genotype shape the hepatitis B virus-specific T-cell repertoire

Repertoire composition, quantity, and qualitative functional ability are the parameters that define virus-specific T-cell responses and are linked with their potential to control infection. We took advantage of the segregation of different hepatitis B virus (HBV) genotypes in geographically and genetically distinct host populations to directly analyze the impact that host and virus variables exert on these virus-specific T-cell parameters. T-cell responses against the entire HBV proteome were analyzed in a total of 109 HBV-infected subjects of distinct ethnicities (47 of Chinese origin and 62 of Caucasian origin). We demonstrate that HBV-specific T-cell quantity is determined by the virological and clinical profiles of the patients, which outweigh any influence of race or viral diversity. In contrast, HBV-specific T-cell repertoires are divergent in the two ethnic groups, with T-cell epitopes frequently found in Caucasian patients seldom detected in Chinese patients. In conclusion, we provide a direct biological evaluation of the impact that host and virus variables exert on virus-specific T-cell responses. The discordance between HBV-specific CD8 T-cell repertoires present in Caucasian and Chinese subjects shows the ability of HLA micropolymorphisms to diversify T-cell responses and has implications for the rational development of therapeutic and prophylactic vaccines for worldwide use.     

The First Outbreak of Chorioptes texanus (Acari: Psoroptidae) Infestation in a Cattle Farm in Korea

Mites in the genus Chorioptes cause a mild form of skin disease in both domestic and wild ruminants. In July 2006, dermatitis characterized by alopecia, marked lichenification, accumulation of crust, and fissuring was recognized in 14 out of 200 Holstein dairy cattle raised in the cattle farm of the National Institute of Animal Science in Cheonan, Republic of Korea. Skin lesions were distributed mainly over the tail base, and sacral and perineal regions. Microscopic examinations of skin scraping samples from severely affected areas revealed numerous mites of all developmental stages. Morphologically, pedicels of the mites were short and unjointed. The tarsal suckers occurred on the pedicels of all the legs in the male worm and on the first, second, and fourth pair of legs in the adult female worm. A single long seta at the tarsus of legs III and the length of legs II being about twice as long as legs IV in adult male mites were observed. Arising anterior to the inner-most spatulate seta was a short seta with an average of 26.4 ± 5.8 µm in length. Also, the length of setae #4 on the opisthosomal lobes was relatively short. Based on these observations, the mites were identified as Choriptes texanus. Although the chorioptic mange may not influence the mortality rate in the affected farm, reports indicate that a decline in milk production can be observed. This is the first report of chorioptic infestation in a cattle farm from Korea.     

Tegumental ultrastructure of adult Gynaecotyla squatarolae (Digenea: Microphallidae)

Gynaecotyla squatarolae (Digenea: Microphallidae) adult flukes were recovered from experimental chicks at day 4-6 post-infection and their tegumental ultrastructure was observed with a scanning electron microscopy. They were pyriform in shape, and their anterior halves were concaved ventrally. The whole body surface was covered with tegumental spines, which were wide and 16-17 digitated between oral and ventral suckers. The density of spines and number of digits decreased posteriorly. The oral sucker was subterminal and the excretory pore was at the posterior end of the worm. Two ventral suckers were similar in appearance and protruded near midline of the worm. The genital atrium was dextral to the small ventral sucker. The dorsal surface was covered with tegumental spines, but the spines were sparser than on the ventral surface. On the middle portion of the dorsal surface, a small opening presumed to be the Laurer's canal was seen. From these findings, it has been confirmed that the adult G. squatarolae has unique characteristics in the surface ultrastructure.     

Tumor hypoxia blocks Wnt processing and secretion through the induction of endoplasmic reticulum stress

Poorly formed tumor blood vessels lead to regions of microenvironmental stress due to depletion of oxygen and glucose and accumulation of waste products (acidosis). These conditions contribute to tumor progression and correlate with poor patient prognosis. Here we show that the microenvironmental stresses found in the solid tumor are able to inhibit the canonical Wnt/β-catenin signaling pathway. However, tumor cells harboring common β-catenin pathway mutations, such as loss of adenomatous polyposis coli, are insensitive to this novel hypoxic effect. The underlying mechanism responsible is hypoxia-induced endoplasmic reticulum (ER) stress that inhibits normal Wnt protein processing and secretion. ER stress causes dissociation between GRP78/BiP and Wnt, an interaction essential for its correct posttranslational processing. Microenvironmental stress can therefore block autocrine and paracrine signaling of the Wnt/β-catenin pathway and negatively affect tumor growth. This study provides a general paradigm relating oxygen status to ER function and growth factor signaling.     

MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression

microRNAs in the miR-106b family are overexpressed in multiple tumor types and are correlated with the expression of genes that regulate the cell cycle. Consistent with these observations, miR-106b family gain of function promotes cell cycle progression, whereas loss of function reverses this phenotype. Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A. We show that p21 is a direct target of miR-106b and that its silencing plays a key role in miR-106b-induced cell cycle phenotypes. We also show that miR-106b overrides a doxorubicin-induced DNA damage checkpoint. Thus, miR-106b family members contribute to tumor cell proliferation in part by regulating cell cycle progression and by modulating checkpoint functions.