Variation in the herd composition counts of sika deer

Herd composition counts (HCC) are commonly used to assess population status in deer. We evaluated the reliability of HCC of sika deer (Cervus nippon Temminck) using repeated counts and by comparing estimated sex ratios and calf-to-female ratios of marked deer on Nakanoshima Island, Hokkaido, Japan between April 1999 and October 2000. Although both total counts and sex and age ratios fluctuated greatly by month, seasonal changes showed a relatively small variance. This suggested that seasonal changes in behavior within sex and age classes contributed to biased ratio estimates obtained from HCC. Route counts should be used as a relative population abundance index with estimates of detection probability, especially for females. Adult sex ratios and age ratios from HCC were unbiased during the rutting season (October–November), and age ratios in spring could be used if yearlings are counted as adults.     

The Population Reference Sample, POPRES: a resource for population, disease, and pharmacological genetics research

Technological and scientific advances, stemming in large part from the Human Genome and HapMap projects, have made large-scale, genome-wide investigations feasible and cost effective. These advances have the potential to dramatically impact drug discovery and development by identifying genetic factors that contribute to variation in disease risk as well as drug pharmacokinetics, treatment efficacy, and adverse drug reactions. In spite of the technological advancements, successful application in biomedical research would be limited without access to suitable sample collections. To facilitate exploratory genetics research, we have assembled a DNA resource from a large number of subjects participating in multiple studies throughout the world. This growing resource was initially genotyped with a commercially available genome-wide 500,000 single-nucleotide polymorphism panel. This project includes nearly 6,000 subjects of African-American, East Asian, South Asian, Mexican, and European origin. Seven informative axes of variation identified via principal-component analysis (PCA) of these data confirm the overall integrity of the data and highlight important features of the genetic structure of diverse populations. The potential value of such extensively genotyped collections is illustrated by selection of genetically matched population controls in a genome-wide analysis of abacavir-associated hypersensitivity reaction. We find that matching based on country of origin, identity-by-state distance, and multidimensional PCA do similarly well to control the type I error rate. The genotype and demographic data from this reference sample are freely available through the NCBI database of Genotypes and Phenotypes (dbGaP).     

Identification and characterization of the ER/lipid droplet-targeting sequence in 17beta-hydroxysteroid dehydrogenase type 11

17β-Hydroxysteroid dehydrogenase type 11 (17βHSD11) is mostly localized on the endoplasmic reticulum (ER) membrane under normal conditions and redistributes to lipid droplets (LDs) when the formation of LDs is induced. In this study, confocal microscopy analyses of the subcellular localization of the mutated 17βHSD11 proteins in cells with or without LDs revealed that both an N-terminal hydrophobic sequence and an adjacent sequence that has a weak homology with the PAT motif are independently necessary and both parts together (28 amino acid residues in total) are sufficient for the dual localization of 17βHSD11. Mutation analyses suggest that the PAT-like motif in 17βHSD11 will not be functionally similar to the canonical PAT motif. Hsp60 was identified as a possibly interacting protein with the PAT-like motif, and biochemical and microscopic analyses suggest that Hsp60 may be partly, but not necessarily involved in recognition of the PAT-like part of the targeting sequence of 17βHSD11.     

TAK1 kinase switches cell fate from apoptosis to necrosis following TNF stimulation

TNF activates three distinct intracellular signaling cascades leading to cell survival, caspase-8–mediated apoptosis, or receptor interacting protein kinase 3 (RIPK3)–dependent necrosis, also called necroptosis. Depending on the cellular context, one of these pathways is activated upon TNF challenge. When caspase-8 is activated, it drives the apoptosis cascade and blocks RIPK3-dependent necrosis. Here we report the biological event switching to activate necrosis over apoptosis. TAK1 kinase is normally transiently activated upon TNF stimulation. We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation. In addition, we also demonstrated that activation of RIPK1 and RIPK3 promoted TAK1 activation, suggesting a positive feedforward loop of RIPK1, RIPK3, and TAK1. Conversely, ablation of TAK1 caused caspase-dependent apoptosis, in which Ripk3 deletion did not block cell death either in vivo or in vitro. Our results reveal that TAK1 activation drives RIPK3-dependent necrosis and inhibits apoptosis. TAK1 acts as a switch between apoptosis and necrosis.     

Inferred L/M cone opsin polymorphism of ancestral tarsiers sheds dim light on the origin of anthropoid primates

Tarsiers are small nocturnal primates with a long history of fuelling debate on the origin and evolution of anthropoid primates. Recently, the discovery of M and L opsin genes in two sister species, Tarsius bancanus (Bornean tarsier) and Tarsius syrichta (Philippine tarsier), respectively, was interpreted as evidence of an ancestral long-to-middle (L/M) opsin polymorphism, which, in turn, suggested a diurnal or cathemeral (arrhythmic) activity pattern. This view is compatible with the hypothesis that stem tarsiers were diurnal; however, a reversion to nocturnality during the Middle Eocene, as evidenced by hyper-enlarged orbits, predates the divergence of T. bancanus and T. syrichta in the Late Miocene. Taken together, these findings suggest that some nocturnal tarsiers possessed high-acuity trichromatic vision, a concept that challenges prevailing views on the adaptive origins of the anthropoid visual system. It is, therefore, important to explore the plausibility and antiquity of trichromatic vision in the genus Tarsius. Here, we show that Sulawesi tarsiers (Tarsius tarsier), a phylogenetic out-group of Philippine and Bornean tarsiers, have an L opsin gene that is more similar to the L opsin gene of T. syrichta than to the M opsin gene of T. bancanus in non-synonymous nucleotide sequence. This result suggests that an L/M opsin polymorphism is the ancestral character state of crown tarsiers and raises the possibility that many hallmarks of the anthropoid visual system evolved under dim (mesopic) light conditions. This interpretation challenges the persistent nocturnal–diurnal dichotomy that has long informed debate on the origin of anthropoid primates.     

Branched-chain amino acids regulate type I tropocollagen and type III tropocollagen syntheses via modulation of mTOR in the skin

Abstract

Branched-chain amino acids (BCAAs) exhibit many physiological functions. However, the potential link and mechanism between BCAA and skin function are unknown. We examined the effects of deletion of branched-chain α-keto acid dehydrogenase kinase (BDK), a key enzyme in BCAA catabolism, on type I and III tropocollagen syntheses in mice. Leucine and isoleucine levels were significantly lower in the skin of BDK-KO mice compared with wild-type mice. No changes in valine concentrations were observed. The levels of type I and III tropocollagen proteins and mRNAs (COL1A1 and COL3A1) were significantly lower in the skin of BDK-KO mice compared with wild-type mice. The phosphorylation of p70 S6 kinase, which indicates mammalian target of rapamycin (mTOR) activation, was reduced in the skin of BDK-KO mice compared with wild-type mice. These findings suggest that deficiencies of leucine and isoleucine reduce type I and III tropocollagen syntheses in skin by suppressing the action of mTOR.     

Rhegmatogenous retinal detachment in a patient with choroidal melanoma simulating choroidal detachment: a case report

Background

Ophthalmologists and retina specialists may consider choroidal detachment if patients with rhegmatogenous retinal detachment present with choroidal elevation. That misdiagnosis may lead to inappropriate treatments, development of tumor cell dissemination, and eventual promotion of patient death. We report a case of a patient with rhegmatogenous retinal detachment associated with choroidal melanoma simulating choroidal detachment according to fundus findings.

Case presentation

A 78-year-old Japanese woman with blurred vision in her right eye was referred to our hospital because of rhegmatogenous retinal detachment with complicated atypical choroidal detachment. Her intraocular pressure was normal with clear anterior chamber. Retinal detachment involving the inferior and nasal retina was observed, and a retinal hole was noted in the same quadrant. A small yellowish choroidal elevation was located in the inferonasal site. Gadolinium-enhanced magnetic resonance imaging revealed enhancement corresponding to the elevation, leading to the identification of a choroidal tumor. Enucleation of the patient’s right eye was eventually performed. The enucleated eye histologically demonstrated malignant melanoma.

Conclusions

If hypotony or an inflammatory sign is absent, ophthalmologists should pay attention to the differential diagnosis of choroidal elevations observed in such patients.

     

Electron microscope researches on the ultrastructure of nucleoli in animal tissues

Summary On the basis of electron microscopy of nucleoli in various physiological stages of similar and different cells, it is assumed that the nucleolonemata appear for the first time in the pre-mitotic stage and subsequently the nucleolus-associated body makes its appearance.The nucleolonema is composed of helically coiled filaments 50 Å in diameter.The nucleolus-associated body comprises tightly packed filaments about 15–30 Å thick which are helically coiled.     

Aminooxy‐naphthylpropionic acid and its derivatives are inhibitors of auxin biosynthesis targeting l‐tryptophan aminotransferase: structure–activity relationships

We previously reported l ‐α‐aminooxy‐phenylpropionic acid (AOPP) to be an inhibitor of auxin biosynthesis, but its precise molecular target was not identified. In this study we found that AOPP targets TRYPTOPHAN AMINOTRANSFERASE of ARABIDOPSIS 1 (TAA1). We then synthesized 14 novel compounds derived from AOPP to study the structure–activity relationships of TAA1 inhibitors in vitro. The aminooxy and carboxy groups of the compounds were essential for inhibition of TAA1 in vitro. Docking simulation analysis revealed that the inhibitory activity of the compounds was correlated with their binding energy with TAA1. These active compounds reduced the endogenous indole‐3‐acetic acid (IAA) content upon application to Arabidopsis seedlings. Among the compounds, we selected 2‐(aminooxy)‐3‐(naphthalen‐2‐yl)propanoic acid (KOK1169/AONP) and analyzed its activities in vitro and in vivo. Arabidopsis seedlings treated with KOK1169 showed typical auxin‐deficient phenotypes, which were reversed by exogenous IAA. In vitro and in vivo experiments indicated that KOK1169 is more specific for TAA1 than other enzymes, such as phenylalanine ammonia‐lyase. We further tested 41 novel compounds with aminooxy and carboxy groups to which we added protection groups to increase their calculated hydrophobicity. Most of these compounds decreased the endogenous auxin level to a greater degree than the original compounds, and resulted in a maximum reduction of about 90% in the endogenous IAA level in Arabidopsis seedlings. We conclude that the newly developed compounds constitute a class of inhibitors of TAA1. We designated them ‘pyruvamine’.