PMEL p.L18del associates with beef quality of Kumamoto sub-breed of Japanese Brown cattle.

Japanese Brown cattle is the second most popular breed among Wagyu breeds and raised mainly in Kumamoto and Kochi Prefectures. Typical coat color of the Kumamoto sub-breed is solid brown, but individuals with diluted coat color are sometimes born. We previously detected four SNPs in PMEL gene and identified p.

Patient Satisfaction Survey on Portable Infusion Pumps for Colorectal Cancer Chemotherapy: Hard-Shelled or Soft-Shelled?

Purpose: Elastomeric infusion pumps are widely used in colorectal cancer chemotherapy. However, no studies to date have investigated patient preferences regarding different infusion pump types.

Patients And Methods: Twenty patients with unresectable colorectal cancer undergoing chemotherapy were initially treated with a portable hard-shelled continuous infusion pump, followed by a soft-shelled continuous infusion pump.

Identification and removal of unexpected proliferative off-target cells emerging after iPSC-derived pancreatic islet cell implantation.

Differentiation of pancreatic endocrine cells from human pluripotent stem cells (PSCs) has been thoroughly investigated for application in cell therapy against diabetes. In the context of induced pancreatic endocrine cell implantation, previous studies have reported graft enlargement resulting from off-target pancreatic lineage cells. However, there is currently no documented evidence of proliferative off-target cells beyond the pancreatic lineage in existing studies.

The R436Q missense mutation in WWP1 disrupts autoinhibition of its E3 ubiquitin ligase activity, leading to self-degradation and loss of function.

Muscular dystrophy in the NH-413 chicken is caused by a missense mutation in the WWP1 gene. WWP1 is a HECT-type E3 ubiquitin ligase containing four tandem WW domains that interact with proline-rich peptide motifs of target proteins, and a short region connecting the second and third WW domains is crucial for the E3 ligase to maintain an autoinhibitory state. A mutation of the arginine in the WW2-WW3 linker to glutamine is thought to affect WWP1 function, but there is little information on this mutation to date.

Causative alleles for chondrodysplastic dwarfism, factor XI deficiency, and factor XIII deficiency in the Kumamoto sub-breed of Japanese Brown cattle.

Japanese Brown cattle are the second most popular Wagyu breed, and the Kumamoto sub-breed shows better daily gain and carcass weight. One of the breeding objectives for this sub-breed is to reduce genetic defects. Chondrodysplastic dwarfism and factor VIII deficiency have been identified as genetic diseases in the Kumamoto sub-breed.

CDK8/19 inhibition plays an important role in pancreatic β-cell induction from human iPSCs.

Background: Transplantation of differentiated cells from human-induced pluripotent stem cells (hiPSCs) holds great promise for clinical treatments. Eliminating the risk factor of malignant cell transformation is essential for ensuring the safety of such cells. This study was aimed at assessing and mitigating mutagenicity that may arise during the cell culture process in the protocol of pancreatic islet cell (iPIC) differentiation from hiPSCs.

PMEL p.Leu18del dilutes coat color of Kumamoto sub-breed of Japanese Brown cattle.

Background: Coat color is important for registration and maintenance of livestock. Standard coat color of Kumamoto sub-breed of Japanese Brown cattle is solid brown, but individuals with diluted coat color have been observed recently. In this study, we attempted to identify polymorphism(s) responsible for coat color dilution by whole genome analysis.

Characterization and reduction of non-endocrine cells accompanying islet-like endocrine cells differentiated from human iPSC.

The differentiation of pancreatic endocrine cells from human pluripotent stem cells has been thoroughly investigated for their application in cell therapy against diabetes. Although non-endocrine cells are inevitable contaminating by-products of the differentiation process, a comprehensive profile of such cells is lacking. Therefore, we characterized non-endocrine cells in iPSC-derived pancreatic islet cells (iPIC) using single-cell transcriptomic analysis.

Leptin gene contributes to beef marbling standard, meat brightness, meat firmness, and beef fat standard of the Kumamoto sub-breed of Japanese Brown cattle.

The Kumamoto sub-breed of Japanese Brown cattle has unique characteristics, such as great growth rate, and their contribution as future breeding materials is expected. To develop a DNA marker for their breeding, we investigated the effects of Leptin gene, controlling energy homeostasis, on carcass traits of the Kumamoto sub-breed. Sequence comparison identified five single nucleotide polymorphisms (SNPs): four linked synonymous mutations and one nonsynonymous mutation.

Tethered spinal cord related to caudal spinal dysraphism in a tailless Holstein calf.

A rare dysraphic caudal spinal anomaly, or caudal agenesis, comprising a tethered spinal cord, was found in a tailless Holstein calf that presented ataxia and paresis with analgesia of the hind limbs. The gently and slimly tapered conus medullaris was poorly formed between S2 and S3 which indicated that it was lying more caudally. The caudal end of the filum terminale adhered to the inner periosteum of the vertebral arch at S4, which is compatible with tethering of the spinal cord.

Neuronal degeneration and cognitive impairment can be prevented via the normalization of mitochondrial dynamics.

Neuronal cells possess a certain degree of plasticity to recover from cell damage. When the stress levels are higher than their plasticity capabilities, neuronal degeneration is triggered. However, the factors correlated to the plasticity capabilities need to be investigated.

MC1R c.310G>- and c.871G > A determine the coat color of Kumamoto sub-breed of Japanese Brown cattle.

Coat color is one of the important factors characterizing breeds for domestic animals. Melanocortin 1 receptor (MC1R) is a representative responsible gene for this phenotype. Two single-nucleotide polymorphisms (SNPs) in bovine MC1R gene, c.

Development of a novel murine heart failure model overexpressing human renin and angiotensinogen.

Renin is the rate-limiting enzyme of the renin-angiotensin system cascade, which drives the pathophysiological progression of heart failure. Species differences in the amino acid sequence of the catalytic domain of renin limit evaluations of the potency and efficacy of human renin inhibitors in animal models, and a high dose of inhibitors is usually needed to show its organ-protective effects in rodents. In the present study, we developed a novel murine heart failure model (triple-tg) to enable us to evaluate the cardioprotective effect of renin inhibitors at more relevant doses for humans, by cross-breeding calsequestrin transgenic (CSQ-tg) mice with human renin and human angiotensinogen double-transgenic mice.

Insulin-Deficient Diabetic Condition Upregulates the Insulin-Secreting Capacity of Human Induced Pluripotent Stem Cell-Derived Pancreatic Endocrine Progenitor Cells After Implantation in Mice.

The host environment is a crucial factor for considering the transplant of stem cell-derived immature pancreatic cells in patients with type 1 diabetes. Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell-derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A NK6 homeobox 1 cells and very few INS cells, were used.

The non-synonymous mutation in bovine gene influences carcass weight.

Meat quality in beef cattle is controlled by genetic factors. () gene, coding a multifunctional cytokine with diverse biological functions, is the candidate gene influencing carcass traits. In this study, we tried to discover DNA polymorphisms associated with beef quality in bovine gene, so that two SNPs (single nucleotide polymorphisms) in the promoter region and one SNP in the CDS (coding sequence) region were identified.

Spectroscopic interferometer with a large length range by rotating diffraction grating.

A new method for spectroscopic interferometry using rotating diffraction grating was developed for industrial measurements. Two diffraction gratings increase the spectroscopic resolution, and the effective measuring range can be extended considerably. Instead of calibrating the wavelength, we used the Fabry-Perot Etalon (standard) to calibrate the system and determine the absolute position.

Acquired Expression of Mutant Causes Progressive Neurodegeneration and Abnormal Behavior.

Neurons have high plasticity in developmental and juvenile stages that decreases in adulthood. Mitochondrial dynamics are highly important in neurons to maintain normal function. To compare dependency on mitochondrial dynamics in juvenile and adult stages, we generated a mouse model capable of selective timing of the expression of a mutant of the mitochondrial fusion factor ().

Structure-Activity Relationship of Biakamide, Selective Growth Inhibitors under Nutrient-Starved Condition from Marine Sponge.

The tumor microenvironment is considered as one of the important targets for anticancer drug discovery. In particular, nutrient deficiency may be observed in tumor microenvironment; biakamides A-D (1-4) isolated from marine sponge Petrosaspongia sp. as growth inhibitors against cancer cells adapted to glucose-deprived conditions have potential as new drugs and tools for elucidating adaptation mechanisms to these conditions.

An administration of TAK-683 at a minimally effective dose for luteinizing hormone stimulation under the absence of the ovary induces luteinizing hormone surge in ovary-intact goats.

The present study aimed to evaluate hormonal responses and their association with the TAK-683 blood concentrations in goats administered TAK-683 at a low dose, which had been previously determined as the minimally effective dose for luteinizing hormone (LH) stimulation in ovariectomized goats. In Experiment 1, 5 µg of TAK-683 treatment had no significant stimulatory effect on LH secretion in ovariectomized Shiba goats (n = 4). In Experiment 2, cycling goats received the treatment of prostaglandin F and progesterone-releasing controlled internal drug releasing (CIDR) to induce the follicular phase, then they were treated with 5 µg of TAK-683 (hour 0) intravenously (n = 4, IV) or subcutaneously (n = 3, SC) or with vehicle intravenously (n = 4, control) at 12 h after CIDR removal.

Knockdown of Pathogenic Proteins via pecific and ongenetic nhibitor of Apoptosis Protein (IAP)-dependent rotein asers (SNIPERs).

Many diseases, especially cancers, result from aberrant or overexpression of pathogenic proteins. Specific inhibitors against these proteins have shown remarkable therapeutic effects, but these are limited mainly to enzymes. An alternative approach that may have utility in drug development relies on selective degradation of pathogenic proteins via small chimeric molecules linking an E3 ubiquitin ligase to the targeted protein for proteasomal degradation.

Biakamides A-D, Unique Polyketides from a Marine Sponge, Act as Selective Growth Inhibitors of Tumor Cells Adapted to Nutrient Starvation.

Biakamides A-D, novel unusually unique polyketides, were isolated from an Indonesian marine sponge (Petrosaspongia sp.) with a constructed bioassay using PANC-1 human pancreatic cancer cells. Through detailed analyses of the one- and two-dimensional NMR spectra of biakamides, planar chemical structures possessing a terminal thiazole, two N-methyl amides, a chloromethylene, and a substituted butyryl moiety were obtained.

Phospholamban Ablation Using CRISPR/Cas9 System Improves Mortality in a Murine Heart Failure Model.

Sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) and its inhibitory protein called phospholamban (PLN) are pivotal for Ca2+ handling in cardiomyocyte and are known that their expression level and activity were changed in the heart failure patients. To examine whether PLN inhibition can improve survival rate as well as cardiac function in heart failure, we performed PLN ablation in calsequestrin overexpressing (CSQ-Tg) mice, a severe heart failure model, using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system. According this method, generation rate of PLN wild type mice (PLN copy >0.

N-Methylniphatyne A, a New 3-Alkylpyridine Alkaloid as an Inhibitor of the Cancer Cells Adapted to Nutrient Starvation, from an Indonesian Marine Sponge of Xestospongia sp.

In the course of searching for selective growth inhibitors of the cancer cells adapted to nutrient starvation, a new 3-alkylpyridine alkaloid named N-methylniphatyne A (1) was isolated from an Indonesian marine sponge of Xestospongia sp. The chemical structure of 1 was determined on the basis of the spectroscopic analysis and comparison with the synthesized 1 and its analogues. Compound 1 showed the cytotoxic activity against PANC-1 cells under the condition of glucose starvation with IC50 value of 16 µM, whereas no growth-inhibition was observed up to 100 µM under the general culture conditions.

Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles.

Despite considerable efforts to develop efficient carriers, the major target organ of short-interfering RNAs (siRNAs) remains limited to the liver. Expanding the application outside the liver is required to increase the value of siRNAs. Here we report on a novel platform targeted to muscular organs by conjugation of siRNAs with anti-CD71 Fab' fragment.

Enhanced Expression of miR-199b-5p Promotes Proliferation of Pancreatic β-Cells by Down-Regulation of MLK3.

Background: The initiation of β-cell proliferation to recover reduced β-cell mass is considered as one of the attractive therapeutic approaches for type 1 and 2 diabetes. In this study, we investigated the involvement of miRNAs in β-cell proliferation.

Methods: Global miRNA array analysis of pancreas tissue was carried out using a 60% partial pancreatectomy (PPx) rodent model, which is a well-characterized model for pancreatic regeneration with accelerated proliferation of β-cells.