Shiki Okamoto

Cats are renowned for their air‐righting behavior, effectively reorienting themselves in midair to land on their feet. However, how cats move their bodies during air‐righting remains unclear. Complex motor factors, such as trunk flexion and axial torsion, may be involved; however, to obtain a definitive answer, quantitative data on the flexibility of spinal axial torsion and how this flexibility differs between spine regions are needed. In this study, we measured the mechanical properties of the spine under axial torsion and examined their relationship to air‐righting behavior. Destructive failure testing was conducted on five cat cadavers to assess the maximum torque (strength), range of motion, neutral zone, and stiffness of the thoracic and lumbar spine regions separately. Additionally, trunk motion during air‐righting behavior was analyzed in two live cats. The thoracic and lumbar spine regions exhibited marked differences in torsional mechanical properties. The thoracic region exhibited a larger range of motion, a larger neutral zone, and lower stiffness than the lumbar region, indicating greater torsional flexibility. It also showed lower maximum torque, indicating lower torsional strength. Notably, the thoracic region had a neutral zone of 47°, whereas the lumbar region had no neutral zone. During air‐righting, anterior trunk rotation was completed earlier than posterior trunk rotation. These results suggest that trunk rotation during air‐righting in cats occurs sequentially, with the anterior trunk rotating first followed by the posterior trunk, and that their flexible thoracic spine and rigid lumbar spine in axial torsion are suited for this behavior.

Numerous studies have revealed distinct differences in the profiles of gut microbiota between non-obese and obese individuals. To date, however, little is known if any disparities in the community of gut microbiota exist between metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) subjects. We therefore aimed to comprehensively characterize the gut microbiota and circulating metabolites in serum from both MHO and MUO residing in the remote island, Kumejima, where the prevalence of obesity is one of the highest in Japan, and explored possible correlations between the gut microbiota profile and markers of metabolic syndrome. Results revealed that MUO showed significantly higher levels of genera such as g_Succinivibrio, g_Granulicatella, g_Brachyspira, g_Oribacterium and g_Atopobium in comparison to MHO. Moreover, abundance of g_Succinivibrio, g_Brachyspira and g_Atopobium were positively correlated with value of fasting insulin, HOMA-R, circulating triglycerides, diastolic blood pressure, BMI, body weight, waist circumference and HbA1c. In addition, MUO compared to MHO showed an imbalance of serum metabolites, with a significant elevation in 2-oxoisovaleric acid, pyruvic acid, 2-hydroxybutyric acid, and creatine. Our data highlight unmet needs in precision approaches for the treatment of obesity, targeting the gut microbiota profile and serum metabolites in a distinct population affected by obesity.

Extra-virgin olive oil (EVOO), a popular functional food and major source of fat in the Mediterranean diet, possesses a variety of healthful components, including monounsaturated fatty acids and bioactive phenolic compounds that, individually and collectively, exert beneficial effects on cardiometabolic markers of health and act as neuroprotective agents through their anti-inflammatory and antioxidant activities. The gut microbiota and health of the intestinal environment are now considered important factors in the development of obesity, metabolic disease, and even certain neurodegenerative conditions via the gut-brain axis. Recently, data are emerging which demonstrate that the health-promoting benefits of EVOO may also extend to the gut microbiota. In this review, we aimed to examine findings from recent studies regarding the impact of EVOO on gut microbiota and intestinal health and explore how modulations in composition of gut microbiota, production of microbially produced products, and activity and functioning of the mucosal immune system may lead to favorable outcomes in cardiovascular, metabolic, and cognitive health.

Introduction: Adult T cell leukemia-lymphoma (ATL) is clinically divided into aggressive (acute and lymphoma) and indolent (chronic and smoldering) subtypes. Recent studies revealed that ATL has a wide variety of gene alternations (Nat Genet. 2015; 47:1304, Nature. 2016; 534:402). Consistent with the notion that human leukocyte antigen (HLA) play a critical role for immune response, reduced expression of HLA has been shown to associate with poor prognosis in various types of malignancies (Oncogene. 2008; 27:5869). However, it is extremely difficult to assess the impact of somatic mutations of HLA genes in cancer cells because of its highly polymorphic nature. Taking advantage of computational tools using whole-exome sequencing data, somatic mutations of HLA class I genes were previously reported in about 3% of various types of cancers (Nat Biotechnol. 2015; 33:1152). To date, HLA typing has been performed through partial sequencing data of polymorphic exons, resulting in the loss of critical information on the entire region of HLA genes. In this context, using a next generation sequence (NGS)-based HLA DNA typing method, we analyzed the entire region of HLA genes in ATL cells and its impact on clinical outcomes. Methods: The present study was approved by the Investigational Review Board of University of the Ryukyus and Tokai University. Peripheral blood mononuclear cells collected from 25 ATL patients (Pts) (20 with acute type and 5 with chronic type) were analyzed. Cell adhesion molecular 1 (CADM1)-positive ATL cells and CADM1-negative non-ATL cells were separated by a magnetic-activated cell-sorting protocol, and genomic DNAs in each fraction were distinctively extracted. The PCR products of the eight HLA loci (HLA-A, -B, -C, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1) were obtained using the previously designed long ranged PCR primers (Tissue Antigens. 2012; 80:305) that cover the entire HLA gene sequences from the enhancer-promoter region to the 3'UTR region. The full-length level HLA genotypes were determined by mapping of sequence reads obtained by the Ion Torrent system to HLA allele reference sequences in the international ImMunoGeneTics project (IMGT)-HLA database. Somatic mutations and loss of heterozygosity (LOH) generated in ATL cells were identified by detail comparison of sequence data between the ATL and non-ATL cells. Survival curves were estimated using the Kaplan-Meier method and compared by the log-rank test. Results: We found a total of 20 somatic mutations in ATL cells among 9 Pts, including 15 single nucleotide variations (SNVs) and 5 insertions/deletions (indels) (Table 1). Of the 15 SNVs, 3 were nonsense mutations in exon 2/3 of HLA-A/B, 7 were nonsynonymous mutations in exon 1/4/5 of HLA-A/B/C, and 2 were mutations at splice sites in intron 2 of HLA-B/C. The mutations of splice sites in intron 2 and all the 5 indels caused frameshift generating premature stop codons. In contrast to the exons, there were only 3 mutations found in introns. Of 8 Pts harboring LOH, two Pts showed LOH in HLA-A gene, 4 Pts in HLA-A, -C, and -B genes, one Pt in HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genes, and one Pt in all the HLA-genes from HLA-A to HLA-DPB1. All the somatic mutations altering the structure of the HLA proteins (St-mt) and/or LOH were found in Pts with acute type ATL, while no St-mt or LOH were detected in Pts with chronic type ATL. Pts with St-mt/LOH (n = 9) significantly worsened in 3 years overall survival rate as compared to that in Pts without St-mt/LOH (n = 16) (11 % vs. 32 %, P = 0.016) (Fig. 1A). Among Pts with acute type ATL, Pts with St-mutations/LOH (n = 9) also showed a trend to worsen in the survival rate as compared to those in Pts without St-mutation /LOH (n = 11) (11 % vs. 30 %, P=0.064) (Fig. 1B). Conclusion: NGS-based HLA gene analyses at full-length level revealed that St-mt/LOH were frequently occurred predominantly in HLA class I loci in tumor cells from Pts with aggressive ATL. Importantly, St-mt/LOH in HLA genes were associated with aggressive phenotypes and poor prognosis, suggesting the possibility that ATL cells would develop immune escape mechanisms through a variety of acquired abnormalities in HLA gene. Since allogeneic stem cell transplantation is an essential therapeutic option for aggressive ATL, comprehensive knowledges on HLA gene abnormalities provide considerable advantage to optimize therapeutic modalities. Disclosures: Fukushima: Daiichi-Sankyo: Research Funding.

Purpose: Extra virgin olive oil (EVOO) and flaxseed oil (FO) contain a variety of constituents beneficial for chronic inflammation and cardio-metabolic derangement. However, little is known about the impact of EVOO and FO on dysbiosis of gut microbiota, intestinal immunity, and barrier. We, therefore, aimed to assess the impact of EVOO and FO on gut microbiota, mucosal immunity, barrier integrity, and metabolic health in mice. Methods: C57BL/6 J mice were exposed to a low-fat (LF), lard (HF), high fat-extra virgin olive oil (HF-EVOO), or high fat-flaxseed oil (HF-FO) diet for 10 weeks. Gut microbiota assessment was undertaken using 16S rRNA sequencing. Levels of mRNA for genes involved in intestinal inflammation and barrier maintenance in the intestine and bacterial infiltration in the liver were measured by qPCR. Results: HF-EVOO or HF-FO mice showed greater diversity in gut microbiota as well as a lower abundance of the Firmicutes phylum in comparison with HF mice (P < 0.05). The qPCR analyses revealed that mRNA level of FoxP3, a transcription factor, and IL-10, an inducer of regulatory T cells, was significantly elevated in the intestines of mice-fed HF-EVOO in comparison with mice-fed HF (P < 0.05). The mRNA level of the antimicrobial peptide, RegӀӀӀγ, was markedly elevated in the intestines of HF-EVOO and HF-FO compared with HF group (P < 0.05). Conclusions: Our data suggest that the consumption of EVOO or FO can beneficially impact gut microbiota, enhance gut immunity, and assist in the preservation of metabolic health in mice.

Diabetes mellitus is associated with various disorders of the locomotor system including the decline in mass and function of skeletal muscle. The mechanism underlying this association has remained ambiguous, however. We now show that the abundance of the transcription factor KLF15 as well as the expression of genes related to muscle atrophy are increased in skeletal muscle of diabetic model mice, and that mice with muscle-specific KLF15 deficiency are protected from the diabetes-induced decline of skeletal muscle mass. Hyperglycemia was found to upregulate the KLF15 protein in skeletal muscle of diabetic animals, which is achieved via downregulation of the E3 ubiquitin ligase WWP1 and consequent suppression of the ubiquitin-dependent degradation of KLF15. Our results revealed that hyperglycemia, a central disorder in diabetes, promotes muscle atrophy via a WWP1/KLF15 pathway. This pathway may serve as a therapeutic target for decline in skeletal muscle mass accompanied by diabetes mellitus.