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91.
92.
Masahiro Ogaki 《Genetica》1966,37(1):391-402
The facet number of heterozygous females of theBar-eye mutant ofDrosophila melanogaster varies from ±154 to ±665 according to the full eye strains combined with the mutant. TheBar character is commonly recognized as a semidominant, but its manifestation varies from nearly complete dominance to recessiveness according to the mode of the heterozygous combination. Virtually the same is true of the mutantLobe
2 which is usually acknowledged as a complete dominant, but may be manifested as an incompletely dominant gene. Thew
e
andb gp strains decrease the eye size of the heterozygotes withBar, but increase the eye size of the heterozygotes withLobe
2.Co-isogenic strains ofBar, bar-3 andeyeless
2 mutants with Oregonisogenic increase the facet number to degrees 1.4–1.8 times of the original strains. However, the co-isogenicLobe
2 strain with the same Oregonisogenic strain reduces the facets completely, and makes virtually all individuals eye-less. These observations indicate that the same genetic background may give an opposite effect to different small-eye mutants. Analysis was carried out for modifying genes ofbar-3. Modifiers were detected on all large chromosomes, besides a recessive major gene located on the 2nd chromosome of Oregon-isogenic strain.A part of this work was performed in the Division of Biology, California Institute of Technology, Pasadena. 相似文献
93.
Catherine Labbé Kotaro Ogaki Oswaldo Lorenzo-Betancor Minerva M. Carrasquillo Michael G. Heckman Allan McCarthy Alexandra I. Soto-Ortolaza Ronald L. Walton Timothy Lynch Joanna Siuda Grzegorz Opala Anna Krygowska-Wajs Maria Barcikowska Krzysztof Czyzewski Dennis W. Dickson Ryan J. Uitti Zbigniew K. Wszolek Owen A. Ross 《PloS one》2015,10(6)
Genome-wide association studies (GWAS) in Parkinson’s disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11–1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD. 相似文献
94.
Naoyoshi Nagata Kayo Sakamoto Tomohiro Arai Ryota Niikura Takuro Shimbo Masafumi Shinozaki Noriko Ihana Katsunori Sekine Hidetaka Okubo Kazuhiro Watanabe Toshiyuki Sakurai Chizu Yokoi Mikio Yanase Junichi Akiyama Naomi Uemura Mitsuhiko Noda 《PloS one》2015,10(4)
Background
This study aims to investigate the association between body mass index (BMI) or intra-abdominal fat measured by computed tomography (CT) and bowel symptoms.Method
A cohort of 958 Japanese adults who underwent colonoscopy and CT and completed questionnaires after excluding colorectal diseases was analyzed. Six symptoms (constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) using a 7-point Likert scale were evaluated between baseline and second questionnaire for test-retest reliability. Associations between BMI, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and symptom score were analyzed by a rank-ordered logistic model, adjusting for age, sex, smoking, and alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia.Results
Some bowel symptom scores were significantly (p<0.05) different between the age groups, sexes, smoking, and alcohol consumption. In multivariate analysis, constipation was associated with low BMI (p<0.01), low VAT area (p = 0.01), and low SAT area (p<0.01). Moreover, hard stools was associated with low BMI (p<0.01) and low SAT area (p<0.01). The remaining symptoms were not significantly associated with BMI or intra-abdominal fat. Test-retest reliability of bowel symptom scores with a mean duration of 7.5 months was good (mean kappa, 0.672).Conclusions
Both low BMI and low abdominal fat accumulation appears to be useful indicators of increased risk for constipation and hard stools. The long-term test-retest reliability of symptom score suggests that bowel symptoms relevant to BMI or visceral fat remain consistent over several months. 相似文献95.
Hussain Md. Shahjalal ;Nobuaki Shiraki ;Daisuke Sakano ;Kazuhide Kikawa ;Soichiro Ogaki ;Hideo Baba ;Kazuhiko Kume ;Shoen Kume 《分子细胞生物学报》2014,(5):394-408
Human induced pluripotent stem (hiPS) cells are considered a potential source for the generation of insulin-producing pancreatic β-ceUs because of their differentiation capacity. In this study, we have developed a five-step xeno-free culture system to efficiently dif- ferentiate hiPS cells into insulin-producing cells in vitro. We found that a high NOGGIN concentration is crucial for specifically inducing the differentiation first into pancreatic and duodenal homeobox-1 (PDX1)-positive pancreatic progenitors and then into neurogenin 3 (NGN3)-expressing pancreatic endocrine progenitors, while suppressing the differentiation into hepatic or intestinal cells. We also found that a combination of 3-isobutyl-l-methylxanthine (IBMX), exendin-4, and nicotinamide was important for the differentiation into insulin single-positive cells that expressed various pancreatic β-cell markers. Most notably, the differentiated cells contained en- dogenous C-peptide pools that were released in response to various insulin secretagogues and high levels of glucose. Therefore, our results demonstrate the feasibility of generating hiPS-derived pancreatic β-ceUs under xeno-free conditions and highlight their poten- tial to treat patients with type I diabetes. 相似文献
96.
Shawna L. Organ Josephine Hai Nikolina Radulovich Christopher B. Marshall Lisa Leung Takehiko Sasazuki Senji Shirasawa Chang-Qi Zhu Roya Navab Mitsuhiko Ikura Ming-Sound Tsao 《PloS one》2014,9(1)
KRAS is mutated in ∼40% of colorectal cancer (CRC), and there are limited effective treatments for advanced KRAS mutant CRC. Therefore, it is crucial that downstream mediators of oncogenic KRAS continue to be studied. We identified p190RhoGAP as being phosphorylated in the DLD1 CRC cell line, which expresses a heterozygous KRAS G13D allele, and not in DKO4 in which the mutant allele has been deleted by somatic recombination. We found that a ubiquitous binding partner of p190RhoGAP, p120RasGAP (RasGAP), is expressed in much lower levels in DKO4 cells compared to DLD1, and this expression is regulated by KRAS. Rescue of RasGAP expression in DKO4 rescued Rho pathway activation and partially rescued tumorigenicity in DKO4 cells, indicating that the combination of mutant KRAS and RasGAP expression is crucial to these phenotypes. We conclude that RasGAP is an important effector of mutant KRAS in CRC. 相似文献
97.
To clarify the feeding habits and major food sources of sandy beach fishes, the gut contents of 55 fish species collected
on a sandy beach at Fukiagehama, South-West Kyushu Island, Japan, were examined. Ontogenetic changes in food preference were
recognized in nine species (Hypoatherina valenciennei, Lateolabrax japonicus, Trachurus japonicus, Sillago japonica, Sphyraena japonica, Paralichthys olivaceus, Heteromycteris japonica, Paraplagusia japonica, and Takifugu niphobles). A cluster analysis based on dietary overlaps showed that the sandy beach fish assemblage comprised six trophic groups (mysid,
amphipod, zooplankton, juvenile fish, terrestrial insect, and mollusk feeders). Of these, the first three groups were the
most abundantly represented, whereas the last two were represented by only a single species. These results indicated that
epibenthic macrofauna, such as mysids and gammaridean amphipods, and zooplankton, were important food resources for the fish
assemblage at the study site, but infaunal macrobenthos, such as polychaetes and bivalves, being relatively unimportant. 相似文献
98.
Soochong Kim Lina Cipolla Gianni Guidetti Mitsuhiko Okigaki Jianguo Jin Mauro Torti Satya P. Kunapuli 《The Journal of biological chemistry》2013,288(25):18194-18203
Proline-rich tyrosine kinase 2 (Pyk2) is activated by various agonists in platelets. We evaluated the signaling mechanism and the functional role of Pyk2 in platelets by using pharmacological inhibitors and Pyk2-deficient platelets. We found that platelet aggregation and secretion in response to 2-methylthio-ADP (2-MeSADP) and AYPGKF were diminished in the presence of Pyk2 inhibitors or in Pyk2-deficient platelets, suggesting that Pyk2 plays a positive regulatory role in platelet functional responses. It has been shown that ADP-, but not thrombin-induced thromboxane (TxA2) generation depends on integrin signaling. Unlike ADP, thrombin activates G12/13 pathways, and G12/13 pathways can substitute for integrin signaling for TxA2 generation. We found that Pyk2 was activated downstream of both G12/13 and integrin-mediated pathways, and both 2-MeSADP- and AYPGKF-induced TxA2 generation was significantly diminished in Pyk2-deficient platelets. In addition, TxA2 generation induced by co-stimulation of Gi and Gz pathways, which is dependent on integrin signaling, was inhibited by blocking Pyk2. Furthermore, inhibition of 2-MeSADP-induced TxA2 generation by fibrinogen receptor antagonist was not rescued by co-stimulation of G12/13 pathways in the presence of Pyk2 inhibitor. We conclude that Pyk2 is a common signaling effector downstream of both G12/13 and integrin αIIbβ3 signaling, which contributes to thromboxane generation. 相似文献
99.
Noboru Ishiyama Nobutoshi Tanaka Kentaro Abe Yoo Jeong Yang Yazan M. Abbas Masataka Umitsu Bhushan Nagar Stephanie A. Bueler John L. Rubinstein Masatoshi Takeichi Mitsuhiko Ikura 《The Journal of biological chemistry》2013,288(22):15913-15925
α-Catenin is an actin- and vinculin-binding protein that regulates cell-cell adhesion by interacting with cadherin adhesion receptors through β-catenin, but the mechanisms by which it anchors the cadherin-catenin complex to the actin cytoskeleton at adherens junctions remain unclear. Here we determined crystal structures of αE-catenin in the autoinhibited state and the actin-binding domain of αN-catenin. Together with the small-angle x-ray scattering analysis of full-length αN-catenin, we deduced an elongated multidomain assembly of monomeric α-catenin that structurally and functionally couples the vinculin- and actin-binding mechanisms. Cellular and biochemical studies of αE- and αN-catenins show that αE-catenin recruits vinculin to adherens junctions more effectively than αN-catenin, partly because of its higher affinity for actin filaments. We propose a molecular switch mechanism involving multistate conformational changes of α-catenin. This would be driven by actomyosin-generated tension to dynamically regulate the vinculin-assisted linkage between adherens junctions and the actin cytoskeleton. 相似文献
100.
Fernando J. Amador Lynn Kimlicka Peter B. Stathopulos Geneviève M.C. Gasmi-Seabrook David H. MacLennan Filip Van Petegem Mitsuhiko Ikura 《Journal of molecular biology》2013
Ryanodine receptors (RyRs) are large tetrameric calcium (Ca2 +) release channels found on the sarcoplasmic reticulum that respond to dihydropyridine receptor activity through a direct conformational interaction and/or indirect Ca2 + sensitivity, propagating sarcoplasmic reticulum luminal Ca2 + release in the process of excitation–contraction coupling. There are three human RyR subtypes, and several debilitating diseases are linked to heritable mutations in RyR1 and RyR2 including malignant hypothermia, central core disease, catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular dysplasia type 2 (ARVD2). Despite the recent appreciation that many disease-associated mutations within the N-terminal RyRABC domains (i.e., residues 1–559) are located in the putative interfaces mediating tetrameric channel assembly, the precise structural and dynamical consequences of the mutations are not well understood. We used solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography to examine the effect of ARVD2-associated (i.e., R176Q) and CPVT-associated [i.e., P164S, R169Q and delta exon 3 (Δ3)] mutations on the structure and dynamics of RyR2A. Our solution NMR data exposed a mobile α-helix, unique to type 2; further, this α2 helix rescues the β-strand lost in RyR2A Δ3 but remains dynamic in the hot-spot loop (HS-loop) P164S, R169Q and R176Q mutant proteins. Docking of our X-ray crystal/NMR hybrid structure into the RyR1 cryo-electron microscopy map revealed that this RyR2A α2 helix is in close proximity to dense “columns” projecting toward the channel pore. This is in contrast to the HS-loop mutations that cause structural changes largely localized to the intersubunit interface between adjacent ABC domains. Taken together, our data suggest that ARVD2 and CPVT mutations have at least two distinct structural consequences linked to channel dysfunction: perturbation of the HS-loop (i.e., domain A):domain B intersubunit interface and disruption of the communication between the N-terminal region and the channel domain. 相似文献