Comparative genome analysis of the major histocompatibility complex (MHC) class I B/C segments in primates elucidated by genomic sequencing in common marmoset (<Emphasis Type="Italic">Callithrix jacchus</Emphasis>)

Common marmoset monkeys (Callithrix jacchus) have emerged as important animal models for biomedical research, necessitating a more extensive characterization of their major histocompatibility complex (MHC) region. However, the genomic information of the marmoset MHC (Caja) is still lacking. The MHC-B/C segment represents the most diverse MHC region among primates. Therefore, in this paper, to elucidate the detailed gene organization and evolutionary processes of the Caja class I B (Caja-B) segment, we determined two parts of the Caja-B sequences with 1,079 kb in total, ranging from H6orf15 to BAT1 and compared the structure and phylogeny with that of other primates. This segment contains 54 genes in total, nine Caja-B genes (Caja-B1 to Caja-B9), two MIC genes (MIC1 and MIC2), eight non-MHC genes, two non-coding genes, and 33 non-MHC pseudogenes that have not been observed in other primate MHC-B/C segments. Caja-B3, Caja-B4, and Caja-B7 encode proper MHC class I proteins according to amino acid structural characteristics. Phylogenetic relationships based on 48 MHC-I nucleotide sequences in primates suggested (1) species-specific divergence for Caja, Mamu, and HLA/Patr/Gogo lineages, (2) independent generation of the “seven coding exon” type MHC-B genes in Mamu and HLA/Patr/Gogo lineages from an ancestral “eight coding exon” type MHC-I gene, (3) parallel correlation with the long and short segmental duplication unit length in Caja and Mamu lineages. These findings indicate that the MHC-B/C segment has been under permanent selective pressure in the evolution of primates.     

Caenorhabditis elegans Aurora A kinase is required for the formation of spindle microtubules in female meiosis

In many animals, female meiotic spindles are assembled in the absence of centrosomes, the major microtubule (MT)-organizing centers. How MTs are formed and organized into meiotic spindles is poorly understood. Here we report that, in Caenorhabditis elegans, Aurora A kinase/AIR-1 is required for the formation of spindle microtubules during female meiosis. When AIR-1 was depleted or its kinase activity was inhibited in C. elegans oocytes, although MTs were formed around chromosomes at germinal vesicle breakdown (GVBD), they were decreased during meiotic prometaphase and failed to form a bipolar spindle, and chromosomes were not separated into two masses. Whereas AIR-1 protein was detected on and around meiotic spindles, its kinase-active form was concentrated on chromosomes at prometaphase and on interchromosomal MTs during late anaphase and telophase. We also found that AIR-1 is involved in the assembly of short, dynamic MTs in the meiotic cytoplasm, and these short MTs were actively incorporated into meiotic spindles. Collectively our results suggest that, after GVBD, the kinase activity of AIR-1 is continuously required for the assembly and/or stabilization of female meiotic spindle MTs.     

Aquaporins and glycerol metabolism

The discovery of aquaporin (AQP) has made a great impact on life sciences. AQPs are a family of homologous water channels widely distributed in plants, unicellular organisms, invertebrates, and vertebrates. So far, 13 AQPs have been identified in human. AQP3, 7, 9, and 10 are subcategorized as aquaglyceroporins which permeabilize glycerol as well as water. Many investigators have demonstrated that AQPs play a crucial role in maintaining water homeostasis, but the physiological significance of some AQPs as a glycerol channel is not fully understood. Adipose tissue is a major source of glycerol and glycerol is one of substrates for gluconeogenesis. This review focuses on recent studies of glycerol metabolism through aquaglyceroporins, and briefly discusses the importance of glycerol channel in adipose tissues and liver.     

Virus-Infection or 5′ppp-RNA Activates Antiviral Signal through Redistribution of IPS-1 Mediated by MFN1

In virus-infected cells, RIG-I-like receptor (RLR) recognizes cytoplasmic viral RNA and triggers innate immune responses including production of type I and III interferon (IFN) and the subsequent expression of IFN-inducible genes. Interferon-β promoter stimulator 1 (IPS-1, also known as MAVS, VISA and Cardif) is a downstream molecule of RLR and is expressed on the outer membrane of mitochondria. While it is known that the location of IPS-1 is essential to its function, its underlying mechanism is unknown. Our aim in this study was to delineate the function of mitochondria so as to identify more precisely its role in innate immunity. In doing so we discovered that viral infection as well as transfection with 5′ppp-RNA resulted in the redistribution of IPS-1 to form speckle-like aggregates in cells. We further found that Mitofusin 1 (MFN1), a key regulator of mitochondrial fusion and a protein associated with IPS-1 on the outer membrane of mitochondria, positively regulates RLR-mediated innate antiviral responses. Conversely, specific knockdown of MFN1 abrogates both the virus-induced redistribution of IPS-1 and IFN production. Our study suggests that mitochondria participate in the segregation of IPS-1 through their fusion processes.     

A protein–protein interaction of stress-responsive myosin VI endowed to inhibit neural progenitor self-replication with RNA binding protein, TLS, in murine hippocampus

We have shown preferential expression of both mRNA and corresponding protein for myosin VI (Myo6) in the murine hippocampus within 24 h after the extreme traumatic experience, water-immersion restraint stress (WIRS), prior to a drastic decrease in neural progenitor proliferation in the dentate gyrus. Myosin (Myo6) protein levels were significantly increased in hippocampus within 24 h after flashback experience in mice previously exposed to WIRS. Myo6 protein was ubiquitously distributed in discrete mouse brain regions with exceptionally high expression in olfactory bulb, whereas Myo6 protein was expressed in cultured rat astroglia and neurons, in addition to Myo6 mRNA expression by cultured neural progenitors. In mouse embryonal carcinoma P19 cells endowed to proliferate and differentiate, Myo6 protein was expressed in line with astroglial marker protein expression. Transient over-expression of Myo6 induced a significant decrease in the size of clustered aggregates as an index of self-replication in P19 cells. Immunoprecipitation analysis revealed the interaction between Myo6 and the RNA-binding protein, translocated in liposarcoma (TLS), while TLS was predominantly expressed by neurons in the cortex, striatum, cerebellum, and hippocampus. These results suggest that Myo6 may play a pivotal role in the mechanism underlying the suppressed adult neurogenesis after traumatic stress in association with TLS.     

Contribution of non-sensory neurons in visual cortical areas to visually guided decisions in the rat

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Emphysema distribution and annual changes in pulmonary function in male patients with chronic obstructive pulmonary disease

Background

The progression of chronic obstructive pulmonary disease (COPD) considerably varies among patients. Those with emphysema identified by quantitative computed tomography (CT) are associated with the rapid progression assessed by forced expiratory volume in one second (FEV₁). However, whether the rate of the decline in lung function is independently affected by the regional distribution or the severity of emphysema in the whole lung is unclear.

Methods

We followed up 131 male patients with COPD for a median of 3.7 years. We measured wall area percent (WA%) in right apical segmental bronchus, total lung volume, percent low attenuation volume (LAV%), and the standard deviation (SD) of LAV% values from CT images of 10 isovolumetric partitions (SD-LAV) as an index of cranial-caudal emphysema heterogeneity. Annual changes in FEV₁ were then determined using a random coefficient model and relative contribution of baseline clinical parameters, pulmonary function, and CT indexes including LAV%, SD-LAV, and WA% to annual changes in FEV₁ were examined.

Results

The mean (SD) annual change in FEV₁ was −44.4 (10.8) mL. Multivariate random coefficient model showed that higher baseline FEV₁, higher LAV%, current smoking, and lower SD-LAV independently contributed to an excessive decline in FEV₁, whereas ratio of residual volume to total lung capacity, ratio of diffusing capacity to alveolar ventilation, and WA% did not, after adjusting for age, height, weight, and ratio of CT-measured total lung volume to physiologically-measured total lung capacity.

Conclusions

A more homogeneous distribution of emphysema contributed to an accelerated decline in FEV₁ independently of baseline pulmonary function, whole-lung emphysema severity, and smoking status. In addition to whole-lung analysis of emphysema, CT assessment of the cranial-caudal distribution of emphysema might be useful for predicting rapid, progressive disease and for developing a targeted strategy with which to prevent disease progression.     

Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts

The H1N1 influenza A virus of swine-origin caused pandemics throughout the world in 2009 and the highly pathogenic H5N1 avian influenza virus has also caused epidemics in Southeast Asia in recent years. The threat of influenza A thus remains a serious global health issue and novel drugs that target these viruses are highly desirable. Influenza A possesses an endonuclease within its RNA polymerase which comprises PA, PB1 and PB2 subunits. To identify potential new anti-influenza compounds in our current study, we screened 33 different types of phytochemicals using a PA endonuclease inhibition assay in vitro and an anti-influenza A virus assay. The marchantins are macrocyclic bisbibenzyls found in liverworts, and plagiochin A and perrottetin F are marchantin-related phytochemicals. We found from our screen that marchantin A, B, E, plagiochin A and perrottetin F inhibit influenza PA endonuclease activity in vitro. These compounds have a 3,4-dihydroxyphenethyl group in common, indicating the importance of this moiety for the inhibition of PA endonuclease. Docking simulations of marchantin E with PA endonuclease suggest a putative "fitting and chelating model" as the mechanism underlying PA endonuclease inhibition. The docking amino acids are well conserved between influenza A and B. In a cultured cell system, marchantin E was further found to inhibit the growth of both H3N2 and H1N1 influenza A viruses, and marchantin A, E and perrotein F showed inhibitory properties towards the growth of influenza B. These marchantins also decreased the viral infectivity titer, with marchantin E showing the strongest activity in this assay. We additionally identified a chemical group that is conserved among different anti-influenza chemicals including marchantins, green tea catechins and dihydroxy phenethylphenylphthalimides. Our present results indicate that marchantins are candidate anti-influenza drugs and demonstrate the utility of the PA endonuclease assay in the screening of phytochemicals for anti-influenza characteristics.     

Interpopulational egg-size variation of a landlocked Rhinogobius goby related to the risk of larval starvation

Reproductive characteristics of a landlocked goby, Rhinogobius sp. (the orange form), in the Lake Biwa water system were compared between the fluvial-lacustrine and lacustrine populations to show the relationship of the egg size to the risk of larval starvation. The comparison of both oocytes in the ovaries and spawned eggs showed that egg size is larger in the fluvial-lacustrine population than in the lacustrine population. Although females of the two populations spawn eggs of the same number as a function of their body size, those of the fluvial-lacustrine population spawn larger eggs even in relation to their body size by investing more in reproduction than those of the lacustrine population. A positive correlation was experimentally shown between the egg size and larval starvation tolerance. Most larvae of the fluvial-lacustrine population (>2 days old) had exhausted their yolk during their larval drift downstream to the lake, indicating that larvae severely suffer from starvation. Egg-size variation between the two populations seemed to be the result of adaptation to the different life cycles, in which the fluvial-lacustrine population confronts the risk of larval starvation, whereas the lacustrine population seems safe from such risk of starvation.