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Identification of the pathological mechanisms underlying the GBA-associated parkinsonism (GBA + PD) advances our understanding of PD. This review based on current literature aims to elucidate various genetic and clinical characteristics correlated with GBA mutations and to identify the numerous pathological processes underlying GBA + PD. We also delineate the therapeutic strategies to interfere with the mutant GCase function for further improvement of the related α-synuclein-GCase crosstalks. Moreover, the various therapeutic approaches such as gene therapy, chaperone proteins, and histone deacetylase inhibitors for the treatment of GBA + PD are discussed.

Gestational trophoblastic disease (GTD) is a group of pregnancy-related disorders that arise from abnormal proliferation of placental trophoblast. Some patients with GTD develop hyperthyroidism, a rare but potentially life-threatening complication requiring early detection and management. Existing literature on hyperthyroidism in GTD is scant. This review aims to analyse the epidemiology, pathophysiology and management of this phenomenon.

A comprehensive search of MEDLINE, EMBASE and Cochrane Library was performed to obtain articles that explored hyperthyroidism in GTD. A total of 405 articles were screened and 228 articles were considered for full-text review. We selected articles that explored epidemiology, pathophysiology and outcomes/management of hyperthyroidism in GTD.

The pathophysiology of hyperthyroidism in GTD is well-investigated. Placental trophoblastic tissue secretes excessive hCG, which is structurally similar to thyroid stimulating hormone and also has enhanced thyrotropic activity compaons. Hyperthyroidism should be recognised as an important perioperative consideration for women undergoing surgery for GTD, and requires appropriate management. Future studies should explore risk factors for hyperthyroidism in GTD, which may facilitate earlier identification of high-risk women.

The start and end sites of messenger RNAs (TSSs and TESs) are highly regulated, often in a cell-type-specific manner. Yet the contribution of transcript diversity in regulating gene expression remains largely elusive. We perform an integrative analysis of multiple highly synchronized cell-fate transitions and quantitative genomic techniques in Saccharomyces cerevisiae to identify regulatory functions associated with transcribing alternative isoforms.

Cell-fate transitions feature widespread elevated expression of alternative TSS and, to a lesser degree, TES usage. These dynamically regulated alternative TSSs are located mostly upstream of canonical TSSs, but also within gene bodies possibly encoding for protein isoforms. Increased upstream alternative TSS usage is linked to various effects on canonical TSS levels, which range from co-activation to repression. We identified two key features linked to these outcomes an interplay between alternative and canonical promoter strengths, and distance between altearyotic gene expression, particularly during cell-fate changes.

Increasingly, genomics is informing clinical practice, but challenges remain for medical professionals lacking genetics expertise, and in access to and clinical utility of genomic testing for minority and underrepresented populations. The latter is a particularly pernicious problem due to the historical lack of inclusion of racially and ethnically diverse populations in genomic research and genomic medicine. A further challenge is the rapidly changing landscape of genetic tests and considerations of cost, interpretation, and diagnostic yield for emerging modalities like whole-genome sequencing.

The NYCKidSeq project is a randomized controlled trial recruiting 1130 children and young adults predominantly from Harlem and the Bronx with suspected genetic disorders in three disease categories neurologic, cardiovascular, and immunologic. Two clinical genetic tests will be performed for each participant, either proband, duo, or trio whole-genome sequencing (depending on sample availability) and proband targeted

The NYCKidSeq project will contribute to the innovations and best practices in communicating genomic test results to diverse populations. This work will inform strategies for implementing genomic medicine in health systems serving diverse populations using methods that are clinically useful, technologically savvy, culturally sensitive, and ethically sound.

ClinicalTrials.gov NCT03738098 . Registered on November 13, 2018 Trial Sponsor Icahn School of Medicine at Mount Sinai Contact Name Eimear Kenny, PhD (Principal Investigator) Address Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., Box 1003, New York, NY 10029 Email eimear.kenny@mssm.edu.

ClinicalTrials.gov NCT03738098 . click here Registered on November 13, 2018 Trial Sponsor Icahn School of Medicine at Mount Sinai Contact Name Eimear Kenny, PhD (Principal Investigator) Address Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., Box 1003, New York, NY 10029 Email eimear.kenny@mssm.edu.

Dysregulation of both mitochondrial biogenesis and mitophagy is critical to sustain oncogenic signaling pathways. However, the mechanism of mitophagy in promoting hepatocellular carcinoma (HCC) progression remains poorly understood. In this study, we investigated the clinical significance and biological involvement of mitochondrial inner membrane protein STOML2 in HCC.

STOML2 was identified by gene expression profiles of HCC tissues and was measured in tissue microarray and cell lines. Gain/loss-of-function experiment was applied to study the biological function of STOML2 in HCC. Flow cytometry, Western blotting, laser confocalmicroscopy, transmission electron microscopy, and co-immunoprecipitation were used to detect and analyze mitophagy. ChIP and luciferase reporter assay were conducted to evaluate the relationship between STOML2 and HIF-1α. The sensitivity to lenvatinib was assessed in HCC both in vitro and in vivo.

Increased expression of STOML2 was found in HCC compared with paired peritumoral tisesponse of HCC to lenvatinib. Combinations of pharmacologic inhibitors that concurrently block both angiogenesis and mitophagy may serve as an effective treatment for HCC.

Our findings suggested that STOML2 could amplify mitophagy through interacting and stabilizing PINK1, which promote HCC metastasis and modulate the response of HCC to lenvatinib. Combinations of pharmacologic inhibitors that concurrently block both angiogenesis and mitophagy may serve as an effective treatment for HCC.