No evidence for a recent genetic bottleneck in the endangered Sheko cattle breed (African Bos taurus) revealed by microsatellite analysis

Sheko is African taurine cattle, valued for its milk yield, adaptation to humid tsetse infested environment and trypanotolerance. We used 30 microsatellite markers in analyzing 30 DNA samples. We found high genetic diversity and no genetic bottlenecks in endangered Sheko cattle. Sheko cattle have not undergone recent genetic bottlenecks, in spite of drastic reduction in its overall demographic population size. The results were supported by three statistical methods: 
(i) detection of heterozygosity excess 
(ii) a mode-shift indicator of allele distribution pattern 
(iii) the ratio of the number of alleles to the range of allele size, M-ratio test. This breed reflects historical and cultural identity of local communities and represents a unique component of the global domestic animal biodiversity that deserve priority for conservation

Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. Muse cells are endogenous reparative pluripotent-like stem cells distributed in various tissues. They can selectively home to damaged sites after intravenous injection by sensing sphingosine-1-phosphate produced by damaged cells, then exert pleiotropic effects, including tissue protection and spontaneous differentiation into tissue-constituent cells. In G93A-transgenic ALS mice, intravenous injection of 5.0x10(4) cells revealed successful homing of human-Muse cells to the lumbar spinal cords, mainly at the pia-mater and underneath white matter, and exhibited glia-like morphology and GFAP expression. In contrast, such homing or differentiation were not recognized in human mesenchymal stem cells but were instead distributed mainly in the lung. Relative to the vehicle groups, the Muse group significantly improved scores in the rotarod, hanging-wire and muscle strength of lower limbs, recovered the number of motor neurons, and alleviated denervation and myofiber atrophy in lower limb muscles. These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death. Muse cells might also be a promising cell source for the treatment of ALS patients

Clinical and Pathological Benefits of Edaravone for Alzheimer's Disease with Chronic Cerebral Hypoperfusion in a Novel Mouse Model

Alzheimer's disease (AD) and chronic cerebral hypoperfusion (CCH) often coexist in dementia patients in aging societies. The hallmarks of AD including amyloid-β (Aβ)/phosphorylated tau (pTau) and pathology-related events such as neural oxidative stress and neuroinflammation play critical roles in pathogenesis of AD with CCH. A large number of lessons from failures of drugs targeting a single target or pathway on this so complicated disease indicate that disease-modifying therapies targeting multiple key pathways hold potent potential in therapy of the disease. In the present study, we used a novel mouse model of AD with CCH to investigate a potential therapeutic effect of a free radical scavenger, Edaravone (EDA) on AD with CCH via examining motor and cognitive capacity, AD hallmarks, neural oxidative stress, and neuroinflammation. Compared with AD with CCH mice at 12 months of age, EDA significantly improved motor and cognitive deficits, attenuated neuronal loss, reduced Aβ/pTau accumulation, and alleviated neural oxidative stress and neuroinflammation. These findings suggest that EDA possesses clinical and pathological benefits for AD with CCH in the present mouse model and has a potential as a therapeutic agent for AD with CCH via targeting multiple key pathways of the disease pathogenesis

A pneumococcal meningoencephalitis with a small spleen

Streptococcus pneumoniae is a major cause of bacterial meningitis usually in children or elder adults. We report a case of a 38-year-old man having pneumococcal meningoencephalitis with a small spleen (35 cm(3)), compared to seven previous patients with pneumococcal meningitis in our department. Among the eight patients, four cases were due to sinusitis, but the origin could not be identified in the other four cases, including the present case who was the youngest patient with the smallest splenic size. Of interest in the present analysis was the negative or positive correlation between splenic size and age, with or without sinusitis. This is the first report on pneumococcal meningoencephalitis that takes into consideration age, splenic size, and the origin of infection

ミトコンドリアDNA D-loopリョウイキ カラ アキラカニ サレタ フィリピン オヨビ ソノ シュウヘン ショコク スイギュウ シュウダン ノ イデンテキ ブンカ ト ケイトウ イデンガク テキ カンケイ

沼沢スイギュウ（Bubalus bubalis）は，小規模な稲作農家の役畜として大変重要であり，乳，肉および皮も活用されている。これまでにフィリピンとその他周辺諸国スイギュウの遺伝的分化や系統遺伝学的関係は明確にされていない。本研究は，フィリピンで飼養されているスイギュウ集団と中国を含むインドシナ半島集団間の遺伝的分化と系統遺伝学的関係を明らかにすることを目的とした。367頭のミトコンドリアDNA D-loop領域の塩基配列を用い解析を行った。その結果，遺伝的分化の程度を示す指数からフィリピンのVisayasおよびMindanao集団は，台湾集団と近いことが推定された。また，系統樹からもフィリピンおよび台湾集団は近い関係を示し，ミャンマーおよび中国集団と同一のクラスターを形成した。これまでに報告された仮説と一致していることから，中国から台湾，フィリピンへスイギュウが伝わってきたことが推察された。本研究は，頭数が減少しつつある東南アジアのスイギュウの多様な遺伝子をフィリピンスイギュウが保有していることから，国内で利活用しながら貴重な遺伝資源として保全・維持する必要があることを示した。The swamp buffalo (Bubalus bubalis) provides a major source of draft power in cultivating rice farms and has great potential for meat, milk, and hide sources, particularly to smallhold farmers. To date, there is limited published information on mtDNA D-loop sequence variation, genetic divergence, and genetic relationship between the Philippine carabao and other swamp buffalo populations in Asia. Thus, the objective of the study is to determine the phylogenetic relationship among the swamp buffalo populations with Asiatic origins. Dataset construction and data analyses were performed from 307-bp of 367 mtDNA D-loop sequences of swamp buffaloes from the Philippines and Asian countries which were retrieved from NCBI GenBank. The research findings highlighted the genetic relationship among the modern Asian swamp buffalo populations and could be explained in two points : First, the Philippine carabao (native swamp buffalo), particularly the Visayas and Mindanao populations, had the closest affinity to Taiwan swamp buffalo population based on the low pair-wise distance (FST), and, second, the Chinese swamp buffalo could be the ancestral population of the modern population of the swamp buffaloes in Asia, as inferred by mtDNA haplotype phylogenetic tree. The results of this research agreed with the hypothesis of Lau et al. 1998 that after the domestication in the China region, the domesticated swamp buffalo spread with rice farming into Taiwan to the Philippines and the eastern islands of Borneo and Sulawesi. This study revealed that native buffaloes in the Philippines have various genes of buffaloes of which numbers are declining in Southeast Asian countries and showed that it is necessary to conserve and maintain them as valuable genetic resources while utilizing them in the Philippines

Body mass index change in adulthood and lung and upper aerodigestive tract cancers

Body mass index (BMI) has been inversely associated with lung and upper aerodigestive tract (UADT) cancers. However, only a few studies have assessed BMI change in adulthood in relation to cancer. To understand the relationship between BMI change and these cancers in both men and women, we analyzed data from a population‐based case–control study conducted in Los Angeles County. Adulthood BMI change was measured as the proportional change in BMI between age 21 and 1 year before interview or diagnosis. Five categories of BMI change were included, and individuals with no more than a 5% loss or gain were defined as having a stable BMI (reference group). Adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using logistic regression models. Potential confounders included age, gender, ethnicity, education, tobacco smoking and energy intake. For UADT cancers, we also adjusted for alcohol drinking status and frequency. A BMI gain of 25% or higher in adulthood was inversely associated with lung cancer (OR 0.53, 95% CI 0.33–0.84) and UADT cancers (OR 0.44, 95% CI 0.27–0.71). In subgroup analyses, a BMI gain of ≥25% was inversely associated with lung and UADT cancers among current and former smokers, as well as among current and former alcohol drinkers. The inverse association persisted among moderate and heavy smokers (≥20 pack‐years). The observed inverse associations between adulthood BMI gain and lung and UADT cancers indicate a potential role for body weight‐related biological pathways in the development of lung and UADT cancers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92436/1/27383_ftp.pd

Stem cell collection in unmanipulated HLA-haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised blood and bone marrow for patients with haematologic malignancies: the impact of donor characteristics and procedural settings

Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients with haematologic malignancies. However, little information is available about the factors predicting the outcome of peripheral blood stem cell (PBSC) collection and bone marrow (BM) harvest in this transplantation. The effects of donor characteristics and procedure factors on CD34+ cell yield were investigated. A total of 104 related healthy donors received granulocyte-colony stimulating factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had significantly higher yields compared with female donors. In multiple regression analysis for peripheral blood collection, age and flow rate were negatively correlated with cell yield, whereas body mass index, pre-aphaeresis white blood cell (WBC) and circulating immature cell (CIC) counts were positively correlated with cell yields. For BM harvest, age was negatively correlated with cell yields, whereas pre-BM collection CIC counts were positively correlated with cell yield. All donors achieved the final product of ≥6 ×106 kg−1 recipient body weight. This transplantation strategy has been shown to be a feasible approach with acceptable outcomes in stem cell collection for patients who received HLA-haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In donors with multiple high-risk characteristics for poor aphaeresis CD34+ cell yield, BM was an alternative source

Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma.

横紋筋肉腫におけるゲノム・エピゲノム異常の全体図を解明 -横紋筋肉腫を4群に分類-. 京都大学プレスリリース. 2015-07-03.Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel the genetic/epigenetic basis of RMS. On the basis of methylation patterns, RMS is clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes and clinical behaviours. A1 and A2 subtypes, especially A1, largely correspond to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes are characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite the better prognosis of embryonal RMS, patients in the E2 are likely to have a poor prognosis. Our results highlight the close relationships of the methylation status and gene mutations with the biological behaviour in RMS

The Role of Disordered Ribosomal Protein Extensions in the Early Steps of Eubacterial 50 S Ribosomal Subunit Assembly

Although during the past decade research has shown the functional importance of disorder in proteins, many of the structural and dynamics properties of intrinsically unstructured proteins (IUPs) remain to be elucidated. This review is focused on the role of the extensions of the ribosomal proteins in the early steps of the assembly of the eubacterial 50 S subunit. The recent crystallographic structures of the ribosomal particles have revealed the picture of a complex assembly pathway that condenses the rRNA and the ribosomal proteins into active ribosomes. However, little is know about the molecular mechanisms of this process. It is thought that the long basic r-protein extensions that penetrate deeply into the subunit cores play a key role through disorder-order transitions and/or co-folding mechanisms. A current view is that such structural transitions may facilitate the proper rRNA folding. In this paper, the structures of the proteins L3, L4, L13, L20, L22 and L24 that have been experimentally found to be essential for the first steps of ribosome assembly have been compared. On the basis of their structural and dynamics properties, three categories of extensions have been identified. Each of them seems to play a distinct function. Among them, only the coil-helix transition that occurs in a phylogenetically conserved cluster of basic residues of the L20 extension appears to be strictly required for the large subunit assembly in eubacteria. The role of α helix-coil transitions in 23 S RNA folding is discussed in the light of the calcium binding protein calmodulin that shares many structural and dynamics properties with L20