Alzheimer's vulnerable brain region relies on a distinct retromer core dedicated to endosomal recycling.

Whether and how the pathogenic disruptions in endosomal trafficking observed in Alzheimer's disease (AD) are linked to its anatomical vulnerability remain unknown. Here, we began addressing these questions by showing that neurons are enriched with a second retromer core, organized around VPS26b, differentially dedicated to endosomal recycling. Next, by imaging mouse models, we show that the trans-entorhinal cortex, a region most vulnerable to AD, is most susceptible to VPS26b depletion-a finding validated by electrophysiology, immunocytochemistry, and behavior.

Age-related Effects of Heroin on Gene Expression in the Hippocampus and Striatum of Cynomolgus Monkeys.

Objective: The aim of this study was to investigate differentially expressed genes and their functions in the hippocampus and striatum after heroin administration in cynomolgus macaques of different ages.

Methods: Cynomolgus monkeys were divided by age as follows: 1 year (A1, n = 2); 3 to 4 years (A2, n = 2); 6 to 8 years (A3, n = 2); and older than 11 years (A4, n = 2). After heroin was injected intramuscularly into the monkeys (0.

Novel crosstalk between Vps26a and Nox4 signaling during neurogenesis.

Despite numerous studies on the molecular switches governing the conversion of stemness to differentiation in embryonic stem cells (ESCs), little is known about the involvement of the retromer complex. Under neural differentiation conditions, Vps26a deficiency (Vps26a) or knockdown suppressed the loss of stemness and subsequent neurogenesis from ESCs or embryonic carcinoma cells, respectively, as evidenced by the long-lasting expression of stemness markers and the slow appearance of neuronal differentiation markers. Interestingly, relatively low reactive oxygen species (ROS) levels were generated during differentiation of Vps26a ESCs, and treatment with an antioxidant or inhibitor of NADPH oxidase (Nox), a family of ROS-generating enzymes, led to restoration of stemness in wild-type cells to the level of Vps26a cells during neurogenesis.

The effects of kinase modulation on in vitro maturation according to different cumulus-oocyte complex morphologies.

Successful production of transgenic pigs requires oocytes with a high developmental competence. However, cumulus-oocyte complexes (COCs) obtained from antral follicles have a heterogeneous morphology. COCs can be classified into one of two classes: class I, with five or more layers of cumulus cells; and class II, with one or two layers of cumulus cells.

Characterization of Recombinant Bovine Sperm Hyaluronidase and Identification of an Important Asn-X-Ser/Thr Motif for Its Activity.

Hyaluronidases are a family of enzymes that catalyse the breakdown of hyaluronic acid, which is abundant in the extracellular matrix and cumulus oocyte complex. To investigate the activity of recombinant bovine sperm hyaluronidase 1 (SPAM1) and determine the effect of the Asn-X-Ser/Thr motif on its activity, the bovine SPAM1 open reading frame was cloned into the mammalian expression vector pCXN2 and then transfected to the HEK293 cell line. Expression of recombinant bovine hyaluronidase was estimated using a hyaluronidase activity assay with gel electrophoresis.

Effects of acute and chronic methamphetamine administration on cynomolgus monkey hippocampus structure and cellular transcriptome.

Methamphetamine (MA), a psychostimulant abused worldwide, gives rise to neurotoxicity in the hippocampus, resulting in cognitive impairments and hippocampal volume reduction. The cellular and molecular mechanisms associated with hippocampal impairments due to MA remain unknown. The aim of this study was to investigate the effects of MA on structural alterations and gene expressions in the hippocampus.

Distinct gating mechanism of SOC channel involving STIM-Orai coupling and an intramolecular interaction of Orai in .

Store-operated calcium entry (SOCE), an important mechanism of Ca signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca signaling raises an interesting question about the evolution of SOCE: How did these two proteins existing in different cellular compartments evolve to interact with each other? We investigated the gating mechanism of Orai channels. Our analysis revealed a mechanism of Orai gating by STIM binding to the intracellular 2-3 loop of Orai in that is radically different from Orai gating by STIM binding to the N and C termini of Orai in mammals.

In vivo study of paraspinal muscle weakness using botulinum toxin in one primate model.

Background: It has been generally speculated that paraspinal muscle weakness is related to the spinal degeneration including intervertebral disc failure. The purpose of this study was to investigate the effects of paraspinal muscle weakness induced by the botulinum toxin type-A on the lumbar spine and behavior pattern in an in-vivo primate model which has an upright locomotion similar to that of humans.

Methods: Botox injections into paraspinal muscle of one cynomolgus monkey were conducted biweekly up to 19 weeks at L2-L3, L3-L4 and L4-L5.

Brain structural changes in cynomolgus monkeys administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A longitudinal voxel-based morphometry and diffusion tensor imaging study.

In animal models of Parkinson's disease (PD), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most widely used agents that damages the nigrostriatal dopaminergic pathway. However, brain structural changes in response to MPTP remain unclear. This study aimed to investigate in vivo longitudinal changes in gray matter (GM) volume and white matter (WM) microstructure in primate models administered with MPTP.

Role of melatonin combined with exercise as a switch-like regulator for circadian behavior in advanced osteoarthritic knee.

Here, we show the role of melatonin combined with or without exercise as a determinant of multicellular behavior in osteoarthritis. We address the relationship between the molecular components governing local circadian clock and changes in the osteoarthritic musculoskeletal axis. Melatonin was injected subcutaneously in animals with advanced knee osteoarthritis (OA) for 4 weeks.

Roles of gangliosides in the differentiation of mouse pluripotent stem cells to neural stem cells and neural cells (Review).

Glycosphingolipids are important components of the outer layer of the plasma membrane in the majority of eukaryotic cells. Specifically, gangliosides are sialic acid‑containing glycosphingolipids that participate in cell‑cell recognition, adhesion, proliferation, differentiation and signal transduction, and are integral components of cell surface microdomains and lipid rafts. Stem cells are defined functionally as cells that have the capacity to self‑renewal and differentiate to generate various cell types.

Inhibitory effect of 1‑tetradecanol on Helicobacter pylori‑induced production of interleukin‑8 and vascular endothelial growth factor in gastric epithelial cells.

Helicobacter pylori (H. pylori) infection activates pro‑inflammatory mediators, including interleukin (IL)‑8 and vascular endothelial growth factor (VEGF) in gastric epithelial cells. 1‑Tetradecanol (1‑TD) has been purified from Dendropanax morbifera Leveille; its physiological activities are poorly understood.

Follistatin Rescues Blastocyst Development of Poor Quality Porcine Cumulus-Oocyte Complexes by Delaying Meiotic Resumption With Decreased cGMP.

Mammalian oocytes resume maturation when removed from follicles and cultured in vitro. During folliculogenesis, oocytes are bathed in follicular fluid (FF), which provides an important and specialized microenvironment for oocyte competence. Follistatin (FST) is one component of FF that may play a role in oocyte maturation and embryo development.

Identification and characterization of the tyrosinase gene (TYR) and its transcript variants (TYR_1 and TYR_2) in the crab-eating macaque (Macaca fascicularis).

Tyrosinase is a copper-containing enzyme that regulates melanin biosynthesis and is encoded by the tyrosinase (TYR) gene. Previous studies demonstrated that mutations in TYR could lead to oculocutaneous albinism type 1 (OCA1) owing to the failure of melanin formation. Although a previous study found that albinism in the rhesus monkey was derived from a mutation in TYR, the identification and characterization of this gene in non-human primates has not been achieved thus far.

Withaferin A inhibits the proliferation of gastric cancer cells by inducing G2/M cell cycle arrest and apoptosis.

Human gastric adenocarcinoma (AGS) is one of the most common types of malignant tumor and the third-leading cause of tumor-associated mortality worldwide. Withaferin A (WA), a steroidal lactone derived from , exhibits antitumor activity in a variety of cancer models. However, to the best of our knowledge, the direct effect of WA on AGS cells has not previously been determined.

Early initiation of antiretroviral treatment postSIV infection does not resolve lymphoid tissue activation.

Objective: Germinal center resident follicular helper T (TFH) cells in lymphoid follicles are a potential sanctuary for HIV/simian immunodeficiency virus (SIV) replication. But the dynamics of germinal centers upon early initiation of antiretroviral therapy (ART) and their potential role in the formation of viral sanctuaries post-SIV infection are not fully understood.

Design: Sequential lymph node biopsies (n = 10) were collected from SIVmac239-infected rhesus macaques before infection, at 5 weeks postinfection/pre-ART, 6 and 12 weeks following ART initiation.

Erratum to: Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells.

The BMB Reports would like to correct in the ACKNOWLEDGEMENTS of BMB Rep. 45(12), 713-718 titled "Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells".

Melatonin as a Novel Interventional Candidate for Fragile X Syndrome with Autism Spectrum Disorder in Humans.

Fragile X syndrome (FXS) is the most common monogenic form of autism spectrum disorder (ASD). FXS with ASD results from the loss of fragile X mental retardation () gene products, including fragile X mental retardation protein (FMRP), which triggers a variety of physiological and behavioral abnormalities. This disorder is also correlated with clock components underlying behavioral circadian rhythms and, thus, a mutation of the gene can result in disturbed sleep patterns and altered circadian rhythms.

Tyrphostin A9 improves blastocyst development in porcine embryos through induction of dynamin-related protein 1-dependent mitochondrial fission.

Mitochondrial dynamics are associated with the development of porcine embryos. However, little is known about the effects of mitochondrial dynamics-related genes (Drp1 and pDrp1-Ser616) on early porcine embryo development. Here, we investigated the effect of Drp1-dependent mitochondrial fission signaling on the development of porcine embryos using the mitochondrial fission inducer, tyrphostin A9 (TA9).

Beneficial effect of interventional exercise on autistic Fragile X syndrome.

[Purpose] The purpose of the present review is to discuss recent published articles in the understanding of efficacy of interventional exercise on autistic Fragile X syndrome (FXS) with special emphasis on its significance in clinical application in patients. [Methods] This review article was identified scientifically and/or clinically relevant articles from PubMed that directly/indirectly met the inclusion criteria. [Results] Mutation of fragile X mental retardation 1 () gene on the X chromosome is related with loss of fragile X mental retardation protein (FMRP) that affecting physiological and behavioral abnormalities.

Dual effect of fetal bovine serum on early development depends on stage-specific reactive oxygen species demands in pigs.

Despite the application of numerous supplements to improve in vitro culture (IVC) conditions of mammalian cells, studies regarding the effect of fetal bovine serum (FBS) on mammalian early embryogenesis, particularly in relation to redox homeostasis, are lacking. Herein, we demonstrated that early development of in vitro-produced (IVP) porcine embryos highly depends on the combination of FBS supplementation timing and embryonic reactive oxygen species (ROS) requirements. Interestingly, FBS significantly reduced intracellular ROS levels in parthenogenetically activated (PA) embryos regardless of the developmental stage.

Native plants ( and ) extracts act as antioxidants to support developmental competence of bovine blastocysts.

Objective: () and () are closely involved in anti-oxidative response and increasing antioxidant enzymes activities. However, the effects of their extracts on development of preimplantation bovine embryos have not been investigated. Therefore, we investigated the effects of and extracts on developmental competence and quality of preimplantation bovine embryos.

-Derived Alternative Splicing Events Specific to Lineages in Gene.

Cathepsin F, which is encoded by , is a cysteine proteinase ubiquitously expressed in several tissues. In a previous study, novel transcripts of the gene were identified in the crab-eating monkey deriving from the integration of an element-YRa1. The occurrence of YRa1-derived alternative transcripts and the mechanism of exonization events in the gene of human, rhesus monkey, and crab-eating monkey were investigated using PCR and reverse transcription PCR on the genomic DNA and cDNA isolated from several tissues.

Identification of Alternative Variants and Insertion of the Novel Polymorphic in Gene during Primate Evolution.

encodes a subunit of the tRNA-splicing endonuclease complex, which catalyzes the identification and cleavage of introns from precursor tRNAs. Previously, we identified an -derived alternative transcript in of cynomolgus monkey. Reverse transcription-polymerase chain reaction (RT-PCR) amplification and sequence analysis of primate and human samples identified five novel alternative transcripts, including the exonized transcript.

Superovulatory responses in cynomolgus monkeys (Macaca fascicularis) depend on the interaction between donor status and superovulation method used.

The current study was performed to investigate the effect of oocyte donor status, including age and body weight, on metaphase II (MII) oocyte recovery using two superovulation methods in cynomolgus monkeys. The use of Method A [recombinant gonadotrophin (75 IU/kg, 3 ×, 3-day intervals) and human chorionic gonadotropin (hCG)] led to great increases in ovary size and the mean number of MII oocytes retrieved in age- and body-weight-dependent manner; in contrast, both the parameters were similar in Method B [recombinant gonadotrophin (60 IU, twice daily, 6 days), recombinant gonadotropin and recombinant human luteinizing hormone (rhLH) (60 IU, twice daily, 3 days), and hCG]. Importantly, Method A showed maximal MII oocyte recovery rate in > 60-month-old or 4.