Integer programming for selecting set of informative markers in paternity inference

BACKGROUND: Parentage information is fundamental to various life sciences. Recent advances in sequencing technologies have made it possible to accurately infer parentage even in non-model species. The optimization of sets of genome-wide markers is valuable for cost-effective applications but requires extremely large amounts of computation, which presses for the development of new efficient algorithms. RESULTS: Here, for a closed half-sib population, we generalized the process of marker loci selection as a binary integer programming problem. The proposed systematic formulation considered marker localization and the family structure of the potential parental population, resulting in an accurate assignment with a small set of markers. We also proposed an efficient heuristic approach, which effectively improved the number of markers, localization, and tolerance to missing data of the set. Applying this method to the actual genotypes of apple (Malus × domestica) germplasm, we identified a set of 34 SNP markers that distinguished 300 potential parents crossed to a particular cultivar with a greater than 99% accuracy. CONCLUSIONS: We present a novel approach for selecting informative markers based on binary integer programming. Since the data generated by high-throughput sequencing technology far exceeds the requirement for parentage assignment, a combination of the systematic marker selection with targeted SNP genotyping, such as KASP, allows flexibly enlarging the analysis up to a scale that has been unrealistic in various species. The method developed in this study can be directly applied to unsolved large-scale problems in breeding, reproduction, and ecological research, and is expected to lead to novel knowledge in various biological fields. The implementation is available at https://github.com/SoNishiyama/IP-SIMPAT

Acute effects of difference in glucose intake on arterial stiffness in healthy subjects

Background: Post-prandial hyperglycemia is associated with higher cardiovascular risk, which causes arterial stiffening and impaired function. Although post-prandial increases in blood glucose are proportional to the level of intake, the acute effects of different glucose intakes on arterial stiffness have not been fully characterized. The present study aimed to determine the acute effects of differences in glucose intake on arterial stiffness. Methods: Six healthy middle-aged and elderly individuals (mean age, 60.0 ± 12.1 years) were orally administered 15, 20, and 25 g of glucose on separate days in a randomized, controlled, cross-over fashion. Brachial-ankle pulse wave velocity, heart-brachial pulse wave velocity, cardio-ankle vascular index, brachial and ankle blood pressure, heart rate, and blood glucose and serum insulin concentrations before and 30, 60, and 90 min after glucose ingestion were measured. Results: Compared to baseline, brachial-ankle pulse wave velocity was higher at 30, 60 and 90 min after ingestion of 25 g glucose, and higher at 90 min after ingestion of 20 g glucose, but at no time points after ingestion of 15 g. Cardio-ankle vascular index was higher at 60 min than at baseline after ingestion of 25 g glucose, but not after ingestion of 15 or 20 g. Conclusions: These results suggest that brachial-ankle pulse wave velocity and cardio-ankle vascular index is affected by the quantity of glucose ingested. Proposed presently is that glucose intake should be reduced at each meal to avoid increases in brachial-ankle pulse wave velocity and cardio-ankle vascular index during acute hyperglycemia

A Longitudinal SPECT Study of Different Patterns of Regional Cerebral Blood Flow in Alzheimer's Disease with or without Diabetes

Aims: To determine the effect of diabetes mellitus (DM) on regional cerebral blood flow (rCBF) patterns in patients with Alzheimer’s disease (AD). Methods: We investigated the initial rCBF of 71 AD patients (36 without DM and 35 with DM) and the final rCBF of 23 AD patients (12 without DM and 11 with DM) after an average of 32 months. Single-photon emission computed tomography (SPECT) data were analyzed by statistical brain imaging. Results: The initial SPECT showed that AD patients without DM had lower rCBF in the left and right inferior temporal gyri than AD patients with DM. A follow-up SPECT demonstrated that rCBF decreased in more widespread regions, including the parietal, temporal, frontal, and limbic lobes, in AD patients without than with DM. Conclusion: This study suggests that functional brain abnormalities in AD differ depending on the DM status at baseline and during follow-up, reflecting neuropathologic differences

Yearly variations in Be-7 concentrations in surface air at Iceland and Japan for 15 years from 2003: Solar modulation of cosmogenic nuclide

The Tenth Symposium on Polar Science/Ordinary sessions: [OS] Space and upper atmospheric sciences, Wed. 4 Dec. / Institute of Statistics and Mathematics (ISM) Seminar room 2 (D304) (3rd floor

Endometrial Polyps:MR Imaging Features

The purpose of this study is to evaluate the diagnostic usefulness of magnetic resonance imaging (MRI) characteristics of endometrial polyps in order to differentiate them from other endometrial lesions. MRI was retrospectively reviewed in 40 patients with pathologically proven endometrial polyps. Special attention was paid to the sizes, shapes, margins, internal structures, signal intensities, and post-contrast enhancement patterns. A central fibrous core, intratumoral cysts, and hemorrhage were seen in 30 (75%), 22 (55%), and 14 (35%) patients, respectively. The predominant signal intensity of the lesions showed iso-to slightly low signal intensity relative to the endometrium on T2-weighted images in 36 (90%), low signal intensity on diffusion-weighted images in 32 (80%), and strong or moderate enhancement on enhanced T1-weighted images in 28 patients (70%), respectively. In 32 (80%) patients, the endometrial polyps showed global or partial early enhancement. On dynamic study, rapid enhancement with a persistent strong enhancement pattern was seen in 17 (42.5%) and a gradually increasing enhancement pattern was seen in 17 patients (42.5%). These MRI features can be helpful to distinguish the endometrial polyps from various other endometrial lesions

スタチンはYAP制御を介してゲムシタビンの肝内胆管癌抑制効果を増強させる

Cholangiocarcinoma (CCA) is associated with high mortality rates because of its resistance to conventional gemcitabine-based chemotherapy. Hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors (statins) reportedly exert anti-cancer effects in CCA and lower the risk of CCA; however, the underlying mechanism of these effects remains unclear. The proliferative and oncogenic activities of the transcriptional co-activator Yes-associated protein (YAP) are driven by its association with the TEA domain (TEAD) of transcription factors; thereby, upregulating genes that promote cell growth, inhibit apoptosis, and confer chemoresistance. This study investigated the effects of atorvastatin in combination with gemcitabine on the progression of human CCA associated with YAP oncogenic regulation. Both atorvastatin and gemcitabine concentration-dependently suppressed the proliferation of HuCCT-1 and KKU-M213 human CCA cells. Moreover, both agents induced cellular apoptosis by upregulating the pro-apoptotic marker BAX and downregulating the anti-apoptotic markers MCL1 and BCL2. Atorvastatin also significantly decreased the mRNA expression of the TEAD target genes CTGF, CYR61, ANKRD1, and MFAP5 in both CCA cell lines. A xenograft tumor growth assay indicated that atorvastatin and gemcitabine potently repressed human CCA cell-derived subcutaneous tumor growth by inhibiting YAP nuclear translocation and TEAD transcriptional activation. Notably, the anti-cancer effects of the individual agents were significantly enhanced in combination. These results indicate that gemcitabine plus atorvastatin could serve as a potential novel treatment option for CCA.博士（医学）・甲第778号・令和3年3月15日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Human intestinal spirochetosis accompanied by human immunodeficiency virus infection:a case report

We present a middle-aged, heterosexual Japanese man with mixed infections including human intestinal spirochetosis, which led us to the detection of human immunodeficiency virus (HIV) infection. The patient had syphilis without related physical or neurological findings. An examination for the serum antibody for HIV performed 9 years previously was negative. In a complete medical checkup at the present time, human intestinal spirochetosis and unspecified entamebic cysts were suggested by histological examination of colonic biopsy material and parasitic examination of the intestinal fluid, respectively. Moreover, a serological test for the antibody for HIV was positive. In specimens obtained by colonoscopy, Brachyspira aalborgi was diagnosed by ultrastructural study and the polymerase chain reaction method for bacterial 16S ribosomal deoxyribonucleic acid. Although HIV infection remains at low prevalence in Japan, we recommend examination for HIV infection in patients with human intestinal spirochetosis, especially when other co-infections are apparent.</p

Sarcopenia and Muscle Functions at Various Stages of Alzheimer Disease

Although sarcopenia is closely linked to dementia, particularly Alzheimer disease (AD), there are few studies examining the prevalence and associated factors of sarcopenia in subjects with AD. This study aimed to investigate the prevalence of sarcopenia, factors associated with sarcopenia in elderly subjects with AD, and differences in muscle functions of the upper and lower extremities and gait speed at various stages of AD. We evaluated handgrip and knee extension strength, muscle mass, and gait speed in 285 elderly outpatients with probable AD (mean age 82. 0 ± 5.3 years), including early AD (n = 82), mild AD (n = 90), and moderate AD (n = 113), and 67 elderly outpatients with normal cognition (NC) (mean age 81.1 ± 4.7 years). Sarcopenia was defined according to the consensus of the Asian Working Group for Sarcopenia. The prevalence rate of sarcopenia was significantly higher in early AD, mild AD, and moderate AD than in NC (11% in NC, 36% in early AD, 45% in mild AD, and 60% in moderate AD of the female group, and 13% in NC, 41% in early AD, 47% in mild AD, and 47% in moderate AD of the male group). Age, body mass index, and Mini-mental state examination score were associated with sarcopenia in female or male AD groups. Decreased muscle strength without loss of muscle mass of the upper and lower extremities in the female AD group and those of the lower extremity in the AD male group were found in early and mild stages. Both muscle strength and mass decreased in the moderate AD. Low gait speed was also found in the early female and male AD which progressed with advancing dementia. Subjects with AD, even the early stages of AD, showed a high prevalence rate of sarcopenia. Higher age, lower BMI, and lower MMSE score were associated with sarcopenia in the female or male AD. There were differences in muscle functions and physical performance between the stages of the female and male AD

リポポリサッカライドの外因性投与はコリン欠乏 L-アミノ酸置換食誘発脂肪性肝炎モデルマウスにおいて肝線維化を促進する

Various rodent models have been proposed for basic research; however, the pathogenesis of human nonalcoholic steatohepatitis (NASH) is difficult to closely mimic. Lipopolysaccharide (LPS) has been reported to play a pivotal role in fibrosis development during NASH progression via activation of toll-like receptor 4 (TLR4) signaling. This study aimed to clarify the impact of low-dose LPS challenge on NASH pathological progression and to establish a novel murine NASH model. C57BL/6J mice were fed a choline-deficient l-amino-acid-defined (CDAA) diet to induce NASH, and low-dose LPS (0.5 mg/kg) was intraperitoneally injected thrice a week. CDAA-fed mice showed hepatic CD14 overexpression, and low-dose LPS challenge enhanced TLR4/NF-κB signaling activation in the liver of CDAA-fed mice. LPS challenge potentiated CDAA-diet-mediated insulin resistance, hepatic steatosis with upregulated lipogenic genes, and F4/80-positive macrophage infiltration with increased proinflammatory cytokines. It is noteworthy that LPS administration extensively boosted pericellular fibrosis with the activation of hepatic stellate cells in CDAA-fed mice. Exogenous LPS administration exacerbated pericellular fibrosis in CDAA-mediated steatohepatitis in mice. These findings suggest a key role for LPS/TLR4 signaling in NASH progression, and the authors therefore propose this as a suitable model to mimic human NASH.博士（医学）・甲第738号・令和2年3月16日© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)