Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation

Posted on Posted in AMRC Research

Date: 9 May 2018   Highlights Self-condensation culture enables endothelialization of diverse tissue fragments Vascularization facilitates tissue survival after transplantation Vascularized islet transplant enhances therapeutic potential against diabetes Rapid induction of functional vasculatures preserves original islet architecture   Summary Clinical transplantation of tissue fragments, including islets, faces a critical challenge because of a lack of effective […]

De Novo Hotspot Variants in CYFIP2 Cause Early-Onset Epileptic Encephalopathy

Posted on Posted in AMRC Research

Date: 13 Apr 2018   Objective The cytoplasmic fragile X mental retardation 1 interacting proteins 2 (CYFIP2) is a component of the WAVE regulatory complex, which is involved in actin dynamics. An obvious association of CYFIP2 variants with human neurological disorders has never been reported. Here, we identified de novo hotspot CYFIP2 variants in neurodevelopmental disorders […]

CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage

Posted on Posted in AMRC Research

Date: 06 Apr 2018   A small molecule for stroke therapy Better therapies for motor impairments after stroke are greatly needed. In mice and nonhuman primates, Abe et al. found that edonerpic maleate enhanced synaptic plasticity and functional recovery after a traumatic insult to the brain (see the Perspective by Rumpel). This recovery of motor function […]

Transcription Factor IRF8 Governs Enhancer 1 Landscape Dynamics in Mononuclear Phagocyte Progenitors

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Date: 07 Mar 2018   Monocytes and dendritic cells (DCs), mononuclear phagocytes essential for immune responses, develop from hematopoietic stem cells via monocyte–DC progenitors (MDPs). The molecular basis of their development remains unclear. Because promoter-distal enhancers are key to cell-fate decisions, we analyzed enhancer landscapes during mononuclear phagocyte development in vivo. Monocyte- and DC-specific enhancers were […]

Angiotensin II Type 1 Receptor-associated Protein Inhibits Angiotensin II-induced Insulin Resistance with Suppression of Oxidative Stress in Skeletal Muscle Tissue

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Date: 12 Feb 2018   Enhancement of AT1 receptor-associated protein (ATRAP) in adipose tissue improves high fat diet (HFD)-induced visceral obesity and insulin resistance, and suppresses adipose oxidative stress. However, HFD loading is not a direct stimulatory factor for AT1 receptor. In the present study, we investigated the effect of chronic, low-dose angiotensin II (Ang II) […]

Human iPSC Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids

Posted on Posted in AMRC Research

Date: 8 Feb 2018   Early endoderm progenitors naturally possess robust propagating potential to develop majority of meter-long gastrointestinal tracts and are therefore considered as a promising source for therapy. Here, we demonstrated the reproducible generation of human CDX2+ posterior gut endoderm cells (PGECs) from five induced pluripotent stem cell clones by manipulating FGF, TGF and […]

Biallelic Variants in CNPY3, Encoding an Endoplasmic Reticulum Chaperone, Cause Early-Onset Epileptic Encephalopathy

Posted on Posted in AMRC Research

Date: 26 Jan 2018   Early-onset epileptic encephalopathies, includingWest syndrome (WS), are a group of neurological disorders characterized by developmental impairments and intractable seizures from early infancy. We have now identified biallelic CNPY3 variants in three individuals with WS; these include compound-heterozygous missense and frameshift variants in a family with two affected siblings (individuals 1 and […]

Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder

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Date: 16 Jan 2018   Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and […]

Phosphorylation of an intrinsically disordered region of Ets1 shifts a multi-modal interaction ensemble to an auto-inhibitory state

Posted on Posted in AMRC Research

Date: 04 Jan 2018   Multi-modal interactions are frequently observed in intrinsically disordered regions (IDRs) of proteins upon binding to their partners. In many cases, post-translational modifications in IDRs are accompanied by coupled folding and binding. From both molecular simulations and biochemical experiments with mutational studies, we show that the IDR including a Ser rich region […]

Matrix metalloproteinase-7 induces homotypic tumor cell aggregation via proteolytic cleavage of the membrane-bound Kunitz-type inhibitor HAI-1

Posted on Posted in AMRC Research

Date: 15 Dec 2017   Matrix metalloproteinase-7 (MMP-7) plays important roles in tumor progression and metastasis. Our previous studies have demonstrated that MMP-7 binds to colon cancer cells via cell surface-bound cholesterol sulfate and induces significant cell aggregation by cleaving cell-surface protein(s). These aggregated cells exhibit a dramatically enhanced metastatic potential. However, the molecular mechanism inducing […]