Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease,with insights into Pink1 knockout models

Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset,pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra(SNpc).In a reciprocal manner,LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation.Pharmacological intervention in these diseasemodifying pathways may facilitate the development of novel PD therapeutics,despite the current lack of an established drug evaluation model.As such,we reviewed the feasibility of employing the versatile global Pink1knockout(KO)rat model as a self-sufficient,spontaneous PD model for investigating both disease etiology and drug pharmacology.These rats retain clinical features encompassing basal mitophagic flux changes with PD progression.We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.

促黄体激素受体突变导致的性器官发育异常(英文)

The Luteinizing hormone/chorionic gonadotropin receptor (LHR) plays a critical role in human male sexual development. Both gain-of-function and loss-of-function mutations of the LHR have been described. Gain-of-function mutations are dominant and cause constitutive activation of the receptor resulting in familial male-limited precocious puberty (FMPP). All activating mutations are single point mutations and are located in the transmembrane domain (TM). TM helix Ⅵ harbors the largest number of activating mutations with the codon of Asp-578 being the hot-spot of mutation. Besides causing abnormal sexual development, constitutively activated LHR may predispose an individual to the development of testicular neoplasia. The anti-thesis of FMPP is Leydig cell hypoplasia (LCH). This is caused by mutations that inactivate the LHR resulting in subnormal male sexual development or male pseudohermaphroditism. Inactivating mutations are recessive. The genetic cause of LCH is variable and there is no mutation hot-spot. Genotype-phenotype correlation can be identified in LCH with the milder form caused by mutated LHR with residual activity and the severe form caused by absence of signal transduction activity of the mutated receptor. Molecular diagnosis of the disorders caused by mutation of the LHR can be achieved by direct sequencing of the LHR gene.

Extracellular vesicles from iPSC-MSCs alleviate chemotherapy-induced mouse ovarian damage via the ILK-PI3K/AKT pathway

Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma,causing endocrine disorder,reproductive dysfunction,and primary ovarian insufficiency(POI).Recent studies have suggested that extracellular vesicles(EVs)secreted from mesenchymal stem cells(MSCs)exert therapeutic effects in various degenerative diseases.In this study,transplantation of EVs from human induced pluripotent stem cell-derived MSCs(iPSC-MSC-EVs)resulted in significant restoration of ovarian follicle numbers,improved granulosa cell proliferation,and inhibition of apoptosis in chemotherapy-damaged granulosa cells,cultured ovaries,and in vivo ovaries in mice.Mechanistically,treatment with i PSC-MSC-EVs resulted in up-regulation of the integrinlinked kinase(ILK)-PI3K/AKT pathway,which is suppressed during chemotherapy,most likely through the transfer of regulatory microRNAs(miRNAs)targeting ILK pathway genes.This work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients.

Jump further,leap higher,and consolidate stronger:A brief review of the long-term partnership between Kunming Institute of Zoology(KIZ)and the Chinese University of Hong Kong(CUHK)in bioresources and molecular research

The molecular etiologies of many prevalent diseases stem from genetic variations that arise during evolution and natural selection,as well as from environmental effects.The study of genetic diversity in human populations and analysis of molecular evolution in primates and other animal species can provide important insights regarding the pathogenesis of common diseases in both human and animal populations.

New Year Address of Zoological Research

The year 2016 was a wonderful and important one for Zoological Research（ZR）.In recognition of its impressive progress and great potential to develop into a leading journal in the field,ZR is now supported by the“Project for Enhancing International Impact of China STM Journals”（PIIJ）（Class B）（2016–2018）.

Pathogenic TDRD12 variants cause defective piRNA pathway and male infertility in humans and mice

Non-obstructive azoospermia(NOA),the lack of sperm in the ejaculate due to failure of spermatogenesis,can result from a variety of diverse factors,with genetic factors accounting for~30%of NOA cases,including chromosomal aberrations,Y-chromosome microdeletions,and monogenic variants(Tang et al.,2022).More than 2000genes are known to participate in spermatogenesis,and>400 genes specifically linked to azoospermia have been identified through studies in mouse models(Krausz and Riera-Escamilla,2018).However,relatively few genes associated with azoospermia in mice have been verified in humans.

Lactate and protein lactylation:the ugly duckling of energy as the sculpture artist of proteins

Metabolites play important roles in numerous cell biology processes,such as cell proliferation,differentiation,stress response,and cell death[1].Recently,lactate and lactate-derived lysine residue lactylation(Kla)have emerged as newly discovered epigenetic modifications that play critical roles in various physiological and pathological processes.In the history of lactate research,we can categorize the studies into three mile stones(Fig.S1 online).

Developmental staging of male murine embryonic gonad by SAGE analysis

Despite the identification of key genes such as Sry integral to embryonic gonadal development, the genomic classification and identification of chromosomal activation of this process is still poorly understood. To better understand the genetic regulation of gonadal development, we performed Serial Analysis of Gene Expression （SAGE） to profile the genes and novel transcripts, and an average of 152,000 tags from male embryonic gonads at E10.5 （embryonic day 10.5）, E11.5, E12.5, E13.5, E15.5 and E17.5 were analyzed. A total of 275,583 non-singleton tags that do not map to any annotated sequence were identified in the six gonad libraries, and 47,255 tags were mapped to 24,975 annotated sequences, among which 987 sequences were uncharacterized. Utilizing an unsupervised pattern identification technique, we established molecular staging of male gonadal development. Rather than providing a static descriptive analysis, we developed algorithms to cluster the SAGE data and assign SAGE tags to a corresponding chromosomal position; these data are displayed in chromosome graphic format. A prominent increase in global genomic activity from E10.5 to E17.5 was observed. Important chromosomal regions related to the developmental processes were identified and validated based on established mouse models with developmental disorders. These regions may represent markers for early diagnosis for disorders of male gonad development as well as potential treatment targets.

RBM46 is essential for gametogenesis and functions in post-transcriptional roles affecting meiotic cohesin subunits

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis,but the targets and molecular functions of RBM46 remain unknown.Here,we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation.Using a recently reported,high-resolution technique known as LACE-seq and working with low-input cells,we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes.We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions.In Rbm46 knockout mice,the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation,resulting in the failed assembly of axial elements,synapsis disruption,and meiotic arrest.Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.

An everlasting role of genetics and genomics in public health: a meeting report of ACGA-HKSMG International Conference on Genetic and Genomic Medicine 2008

The Association of Chinese Geneticists in America （ACGA） and the Hong Kong Society of Medical Genetics （HKSMG） held their first joint Conference on Genetic and Genomic Medicine in Hong Kong from June 9-11 in 2008 at the Cheung Kung Hai Conference Center, William MW Mong Block, Li Ka Shing Faculty of Medicine, the University of Hong Kong. Other co-organizers included the University of Hong Kong and Chinese Society of Medical Genetics. A satellite conference ＂ACGA-WZMC International Symposium of Genetics and Translational Medicine＂, co-organized with Wenzhou Medical College and Chinese Society of Medical Genetics, was held from June 12-14, 2008 at Wenzhou, Zhejiang Province of China.

Stem cell aging in adult progeria

Aging is considered an irreversible biological process and also a major risk factor for a spectrum of geriatricdiseases. Advanced age-related decline in physiological functions, such as neurodegeneration, development ofcardiovascular disease, endocrine and metabolic dysfunction, and neoplastic transformation, has become thefocus in aging research. Natural aging is not regarded as a programmed process. However, accelerated agingdue to inherited genetic defects in patients of progeria is programmed and resembles many aspects ofnatural aging. Among several premature aging syndromes, Werner syndrome (WS) and Hutchinson–Gilfordprogeria syndrome (HGPS) are two broadly investigated diseases. In this review, we discuss how stem cellaging in WS helps us understand the biology of aging. We also discuss briefly how the altered epigeneticlandscape in aged cells can be reversed to a “juvenile” state. Lastly, we explore the potential application ofthe latest genomic editing technique for stem cell-based therapy and regenerative medicine in the context of aging.