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1.
PeerJ ; 12: e16908, 2024.
Article in English | MEDLINE | ID: mdl-38344294

ABSTRACT

Despite reporting very few mpox cases in early 2023, mainland China observed a surge of over 500 cases during the summer. Amid ambiguous prevention strategies and stigma surrounding mpox transmission, the epidemic silently escalated. This study aims to quantify the scale of the mpox epidemic and assess the transmission dynamics of the virus by estimating the effective reproduction number (Re) during its early phase. Publicly available data were aggregated to obtain daily mpox case counts in mainland China, and the Re value was estimated using an exponential growth model. The mean Re value was found to be 1.57 (95% credible interval [1.38-1.78]), suggesting a case doubling time of approximately 2 weeks. This estimate was compared with Re values from 16 other countries' national outbreaks in 2022 that had cumulative case count exceeding 700 symptomatic cases by the end of that year. The Re estimates for these outbreaks ranged from 1.13 for Portugal to 2.31 for Colombia. The pooled mean Re was 1.49 (95% credible interval [1.32-1.67]), which aligns closely with the Re for mainland China. These findings underscore the need for immediate and effective control measures including targeted vaccination campaigns to mitigate the further spread and impact of the epidemic.


Subject(s)
COVID-19 , Epidemics , Mpox (monkeypox) , Humans , COVID-19/epidemiology , SARS-CoV-2 , China/epidemiology
2.
J Comp Neurol ; 532(2): e25556, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37938923

ABSTRACT

Birds have a comprehensive network of sensorimotor projections extending from the forebrain and midbrain to the cerebellum via the pontine nuclei, but the organization of these circuits in the pons is not thoroughly described. Inputs to the pontine nuclei include two retinorecipient areas, nucleus lentiformis mesencephali (LM) and nucleus of the basal optic root (nBOR), which are important structures for analyzing optic flow. Other crucial regions for visuomotor control include the retinorecipient ventral lateral geniculate nucleus (GLv), and optic tectum (TeO). These visual areas, together with the somatosensory area of the anterior (rostral) Wulst, which is homologous to the primary somatosensory cortex in mammals, project to the medial and lateral pontine nuclei (PM, PL). In this study, we used injections of fluorescent tracers to study the organization of these visual and somatosensory inputs to the pontine nuclei in zebra finches. We found a topographic organization of inputs to PM and PL. The PM has a lateral subdivision that predominantly receives projections from the ipsilateral anterior Wulst. The medial PM receives bands of inputs from the ipsilateral GLv and the nucleus laminaris precommisulis, located medial to LM. We also found that the lateral PL receives a strong ipsilateral projection from TeO, while the medial PL and region between the PM and PL receive less prominent projections from nBOR, bilaterally. We discuss these results in the context of the organization of pontine inputs to the cerebellum and possible functional implications of diverse somato-motor and visuomotor inputs and parcellation in the pontine nuclei.


Subject(s)
Finches , Visual Pathways , Animals , Superior Colliculi , Pons , Cerebellum , Mammals
3.
Nature ; 619(7969): 394-402, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37344600

ABSTRACT

In eukaryotes, small RNA guides, such as small interfering RNAs and microRNAs, direct AGO-clade Argonaute proteins to regulate gene expression and defend the genome against external threats. Only animals make a second clade of Argonaute proteins: PIWI proteins. PIWI proteins use PIWI-interacting RNAs (piRNAs) to repress complementary transposon transcripts1,2. In theory, transposons could evade silencing through target site mutations that reduce piRNA complementarity. Here we report that, unlike AGO proteins, PIWI proteins efficiently cleave transcripts that are only partially paired to their piRNA guides. Examination of target binding and cleavage by mouse and sponge PIWI proteins revealed that PIWI slicing tolerates mismatches to any target nucleotide, including those flanking the scissile phosphate. Even canonical seed pairing is dispensable for PIWI binding or cleavage, unlike plant and animal AGOs, which require uninterrupted target pairing from the seed to the nucleotides past the scissile bond3,4. PIWI proteins are therefore better equipped than AGO proteins to target newly acquired or rapidly diverging endogenous transposons without recourse to new small RNA guides. Conversely, the minimum requirements for PIWI slicing are sufficient to avoid inadvertent silencing of host RNAs. Our results demonstrate the biological advantage of PIWI over AGO proteins in defending the genome against transposons and suggest an explanation for why the piRNA pathway was retained in animal evolution.


Subject(s)
Argonaute Proteins , DNA Transposable Elements , Gene Silencing , Piwi-Interacting RNA , Animals , Mice , Argonaute Proteins/classification , Argonaute Proteins/genetics , Argonaute Proteins/metabolism , DNA Transposable Elements/genetics , Piwi-Interacting RNA/genetics , Piwi-Interacting RNA/metabolism , Evolution, Molecular , Phosphates/metabolism , Substrate Specificity
4.
J Comp Neurol ; 531(6): 640-662, 2023 04.
Article in English | MEDLINE | ID: mdl-36648211

ABSTRACT

In birds, the nucleus of the basal optic root (nBOR) and the nucleus lentiformis mesencephali (LM) are brainstem nuclei involved in the analysis of optic flow. A major projection site of both nBOR and LM is the medial column of the inferior olive (IO), which provides climbing fibers to the vestibulocerebellum. This pathway has been well documented in pigeons, but not other birds. Recent works have highlighted that zebra finches show specializations with respect to optic flow processing, which may be reflected in the organization of optic flow pathways to the IO. In this study, we characterized the organization of these pathways in zebra finches. We found that the medial column consists of at least eight subnuclei (i-viii) visible in Nissl-stained tissue. Using anterograde traces we found that the projections from LM and nBOR to the IO were bilateral, but heavier to the ipsilateral side, and showed a complementary pattern: LM projected to subnucleus i, whereas nBOR projected to subnuclei ii and v. Using retrograde tracers, we found that these subnuclei (i, ii and v) projected to the vestibulocerebellum (folia IXcd and X), whereas the other subnuclei projected to IXab and the lateral margin of VII and VIII. The nBOR also projected ipsilaterally to the caudo-medial dorsal lamella of the IO, which the retrograde experiments showed as projecting to the medial margin of VII and VIII. We compare these results with previous studies in other avian species.


Subject(s)
Finches , Optic Flow , Animals , Visual Pathways , Columbidae , Cerebellum , Olivary Nucleus
5.
Reproduction ; 165(3): R91-R102, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36538648

ABSTRACT

In brief: Mouse PIWI-interacting RNAs (piRNAs) are indispensable for spermatogenesis, but whether these small RNAs serve any function beyond gametogenesis is rarely explored. This review summarizes recent findings that demonstrated a requirement for piRNAs in sperm maturation and discusses a potential intergenerational role for paternal piRNAs. Abstract: Unique to animals, PIWI-interacting RNAs (piRNAs) defend organisms against threats to germline integrity evoked by transposons, retroviruses, and inappropriate expression of protein-coding genes. Characterization of mouse piRNAs and studies of more than a dozen piRNA pathway protein mutants detailed in the past 15 years have firmly established an essential role for piRNAs in male fertility. Despite their vital function in spermatogenesis, mammalian piRNAs were thought to be dispensable beyond gamete formation because all piRNA pathway protein mouse mutants are invariably sterile and do not produce sperm. In contrast to the specialized purpose of piRNAs in gamete formation, tRNA-derived fragments and microRNAs have been the focus of research in RNA-mediated paternal contribution, providing additional examples of the versatility of non-coding RNAs. In recent years, the direct elimination of mouse piRNAs using CRISPR/Cas revealed their extended function in post-testicular sperm maturation. An intergenerational contribution from paternal piRNAs has also been proposed. Together with insights into piRNAs in oocytes and early embryos in mice and other mammals, these newly proposed functions of mammalian piRNAs invite further investigations of piRNA dynamics during sperm maturation and fertilization as well as their roles in reproduction beyond gametogenesis.


Subject(s)
Piwi-Interacting RNA , Semen , Male , Animals , Mice , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Semen/metabolism , Spermatozoa/metabolism , Spermatogenesis/genetics , Mammals/genetics
6.
J Agric Food Chem ; 71(1): 382-397, 2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36562602

ABSTRACT

Hyperuricemic nephropathy (HN) is caused by urate crystals that get deposited in the kidney and contribute to renal fibrosis. Uric acid (UA) has been proven to directly cause renal mesangial cell oxidative stress and fibrosis in the pathogenesis of HN. Some antioxidants can be used as chemopreventive agents of HN. Hibiscus sabdariffa leaf extracts (HLE), rich in polyphenol, have been shown to possess hypoglycemic, antioxidant, hypolipidemic, antiatherosclerotic, and anticancer effects. The aim of the study is to examine the inhibitory effect of HLE and its main component ellagic acid (EA) on renal fibrosis. In vitro, mouse renal glomerular mesangial SV40MES13 cells pretreated with UA were demonstrated to trigger obvious morphological changes and viability loss, as well as affect matrix metalloproteinases (MMPs) activities. Noncytotoxic doses of HLE and EA abolished the UA-induced cell injury and MMP-2/9 secretion. In addition, HLE and EA exhibited antioxidant and anti-inflammatory effects on the UA-treated cells with a reduction in transforming growth factor-beta (TGF-ß) production. Next, the UA-activated pro-fibrotic factors, extracellular matrix (ECM) deposition, and epithelial-mesenchymal-transition (EMT) were inhibited by HLE or EA. Mechanistic assays indicated that antifibrotic effects of HLE might be mediated via TGF-ß/Smad signaling, as confirmed by the transfection of Smad7 siRNA. In vivo, HLE and EA supplementations significantly alleviated HN development, which may result from inhibiting adenine-induced TGF-ß production accompanying oxidative stress and inflammation, as well as fibrogenesis. Our data imply that EA-enriched HLE regulates the TGF-ß/Smad signaling, which in turn led to reduced renal mesangial cell injury and fibrosis in HN and provided a new mechanism for its nephroprotective activity.


Subject(s)
Hibiscus , Hyperuricemia , Kidney Diseases , Animals , Mice , Antioxidants/therapeutic use , Ellagic Acid/pharmacology , Fibrosis , Hibiscus/chemistry , Hyperuricemia/drug therapy , Hyperuricemia/genetics , Kidney Diseases/drug therapy , Kidney Diseases/genetics , Kidney Diseases/prevention & control , Transforming Growth Factor beta , Uric Acid , Plant Leaves/chemistry
7.
Elife ; 112022 12 23.
Article in English | MEDLINE | ID: mdl-36476387

ABSTRACT

Axon degeneration contributes to the disruption of neuronal circuit function in diseased and injured nervous systems. Severed axons degenerate following the activation of an evolutionarily conserved signaling pathway, which culminates in the activation of SARM1 in mammals to execute the pathological depletion of the metabolite NAD+. SARM1 NADase activity is activated by the NAD+ precursor nicotinamide mononucleotide (NMN). In mammals, keeping NMN levels low potently preserves axons after injury. However, it remains unclear whether NMN is also a key mediator of axon degeneration and dSarm activation in flies. Here, we demonstrate that lowering NMN levels in Drosophila through the expression of a newly generated prokaryotic NMN-Deamidase (NMN-D) preserves severed axons for months and keeps them circuit-integrated for weeks. NMN-D alters the NAD+ metabolic flux by lowering NMN, while NAD+ remains unchanged in vivo. Increased NMN synthesis by the expression of mouse nicotinamide phosphoribosyltransferase (mNAMPT) leads to faster axon degeneration after injury. We also show that NMN-induced activation of dSarm mediates axon degeneration in vivo. Finally, NMN-D delays neurodegeneration caused by loss of the sole NMN-consuming and NAD+-synthesizing enzyme dNmnat. Our results reveal a critical role for NMN in neurodegeneration in the fly, which extends beyond axonal injury. The potent neuroprotection by reducing NMN levels is similar to the interference with other essential mediators of axon degeneration in Drosophila.


Subject(s)
Drosophila , Nicotinamide Mononucleotide , Animals , Mice , Drosophila/metabolism , Nicotinamide Mononucleotide/metabolism , NAD/metabolism , Axons/physiology , Neurons/physiology , Mammals/metabolism , Cytoskeletal Proteins/metabolism , Armadillo Domain Proteins/genetics , Armadillo Domain Proteins/metabolism
8.
Front Psychol ; 13: 864416, 2022.
Article in English | MEDLINE | ID: mdl-35693500

ABSTRACT

Visual programming language is a crucial part of learning programming. On this basis, it is essential to use visual programming to lower the learning threshold for students to learn about artificial intelligence (AI) to meet current demands in higher education. Therefore, a 3-h AI course with an RGB-to-HSL learning task was implemented; the results of which were used to analyze university students from two different disciplines. Valid data were collected for 65 students (55 men, 10 women) in the Science (Sci)-student group and 39 students (20 men, 19 women) in the Humanities (Hum)-student group. Independent sample t-tests were conducted to analyze the difference between cognitive styles and computational thinking. No significant differences in either cognitive style or computational thinking ability were found after the AI course, indicating that taking visual AI courses lowers the learning threshold for students and makes it possible for them to take more difficult AI courses, which in turn effectively helping them acquire AI knowledge, which is crucial for cultivating talent in the field of AI.

9.
Clin Otolaryngol ; 47(1): 107-114, 2022 01.
Article in English | MEDLINE | ID: mdl-34547825

ABSTRACT

OBJECTIVE: To evaluate the correlation of neonatal parameters with late-onset sensorineural hearing loss (SNHL) and vestibular dysfunction in individuals with congenital cytomegalovirus (cCMV) infection using the National Health Insurance Research Database (NHIRD) in Taiwan. DESIGN: Retrospective cohort study. SETTING: The whole Taiwanese population. PARTICIPANTS: Patients with related diagnostic codes and examinations in their records were regarded as having cCMV infection. Each subject in that group was matched to 10 control individuals with noncongenital CMV infection on the basis of several neonatal parameters, including low gestational age, low birth weight, low Apgar score, maternal history of CMV infection and prolonged cCMV infection. A total of 5893 and 58 930 participants were enrolled in the study and control groups, respectively. MAIN OUTCOME MEASURES: The main outcomes were the development of SNHL and the development of vestibular dysfunction within one year after birth as reflected by diagnostic codes and specific examinations. Cox proportional hazard regression was used to calculate the adjusted hazard ratio (HR) and 95% confidence interval (CI) of each primary outcome between the two groups. RESULTS: Overall, 109 and 397 episodes of SNHL developed in the study group and the control group, respectively, and the study group demonstrated a significantly higher incidence of SNHL (adjusted HR: 2.56; 95% CI: 2.07-3.18). In addition, similar incidence rates of vestibular dysfunction were found in the study group and the control group, with 7 and 90 events, respectively (adjusted HR: 0.77; 95% CI: 0.36-1.67). In subgroup analyses, a higher incidence of SNHL was correlated with lower gestational age (GA) (adjusted HR: 2.09; 95% CI: 1.29-3.39), lower birth weight (BW) (adjusted HR: 2.05; 95% CI: 1.28-3.30) and prolonged cCMV infection (adjusted HR: 3.92; 95% CI: 1.95-7.88). CONCLUSIONS: Low GA, low BW and a long disease course are significantly correlated with late-onset SNHL in cCMV infection.


Subject(s)
Cytomegalovirus Infections/congenital , Cytomegalovirus Infections/complications , Hearing Loss, Sensorineural/virology , Vestibular Diseases/virology , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Neonatal Screening , Retrospective Studies , Risk Factors
10.
Plant Pathol J ; 37(6): 596-606, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34897251

ABSTRACT

Soil-borne diseases are the major problems in mono cropping. A mixture (designated LTM-m) composed of agricultural wastes and a beneficial microorganism Streptomyces saraceticus SS31 was used as soil amendments to evaluate its efficacy for managing Rhizoctonia solani and root knot nematode (Meloidogyne incognita). In vitro antagonistic assays revealed that SS31 spore suspensions and culture broths effectively suppressed the growth of R. solani, reduced nematode egg hatching, and increased juvenile mortality. Assays using two Petri dishes revealed that LTM-m produced volatile compounds to inhibit the growth of R. solani and cause mortality to the root knot nematode eggs and juveniles. Pot and greenhouse tests showed that application of 0.08% LTM-m could achieve a great reduction of both diseases and significantly increase plant fresh weight. Greenhouse trials revealed that application of LTM-m could change soil properties, including soil pH value, electric conductivity, and soil organic matter. Our results indicate that application of LTM-m bio-organic amendments could effectively manage soil-borne pathogens.

11.
J Pers Med ; 11(5)2021 Apr 26.
Article in English | MEDLINE | ID: mdl-33925911

ABSTRACT

The long noncoding RNA, Growth arrest-specific 5 (GAS5) plays a crucial role in the development of oral cancer. However, potential genetic variants in GAS5 that affect the susceptibility and progression of oral cancer have rarely been explored. In this study, two loci of GAS5 single nucleotide polymorphisms (SNPs) (rs145204276 and rs55829688) were genotyped by using the TaqMan allelic discrimination in 1125 oral cancer patients and 1195 non-oral-cancer individuals. After statistical analyses, the distribution of both the GAS5 SNP rs145204276 and GAS5 SNP rs55829688 frequencies were similar between the study and control groups. However, the patients with GAS5 SNP rs145204276 variants (Ins/Del or Del/Del) showed a higher tendency of moderate to poor cell differentiation of oral cancer (OR: 1.454, 95% CI: 1.041-2.031, p = 0.028). Moreover, the GAS5 SNP rs145204276 variants (Ins/Del or Del/Del) in the non-alcohol-drinking population were associated with significantly advanced tumor stage (OR: 1.500, 95% CI: 1.081-2.081, p = 0.015) and larger tumor size (OR: 1.494, 95% CI: 1.076-2.074, p = 0.016). Furthermore, individuals with the GAS5 SNP rs145204276 variant were associated with a higher expression of GAS5 in the GTEx database (p = 0.002), and the higher GAS5 level was associated with poor cell differentiation, advanced tumor stage and larger tumor size in head and neck squamous cell carcinoma from the TCGA database (all p < 0.05). In conclusion, the GAS5 SNP rs145204276 variant is related to poor-differentiation cell status in oral cancer. Besides, the presence of the GAS5 SNP rs145204276 variant is associated with a worse tumor stage and tumor size in oral cancer patients without alcohol drinking.

12.
Auris Nasus Larynx ; 48(5): 870-877, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33549393

ABSTRACT

OBJECTIVES: Recurrent idiopathic sudden sensorineural hearing loss (ISSNHL) is a rare disease. In this study, we evaluated the correlations between hearing recovery after the first and recurrent episodes of ISSNHL and characterized the clinical features of different episodes of ISSNHL. METHODS: This retrospective study was conducted by reviewing medical records pertaining to the period 2008-2018. A total of 30 patients (16 male, 14 female) who had experienced at least two episodes of ISSNHL were included. All patients were had received steroid therapy (including systemic and IT) and/or hyperbaric oxygen therapy within 2 weeks after the onset of disease. The SDRG's criteria was used for the grading of hearing recovery. RESULTS: The median age at the first and second episode of ISSNHL was 48 and 53.5 years, respectively; a total of 30% of patients presented with vertigo in the first episode and 40% presented with vertigo in the second episode. The hearing outcomes of both episodes showed significant improvement after treatment. The rate of complete recovery after the first and second episodes was 46.67% and 33.33%, respectively. A significant positive correlation was observed between the treatment outcomes of the first and second episodes (r = 0.721, p < 0.001). CONCLUSION: In ISSNHL, hearing recovery after a recurrent episode is significantly correlated with the hearing outcome after the initial episode (p = 0.042). The treatment outcome of the first episode is a prognostic factor for the outcomes of recurrent episodes.


Subject(s)
Hearing Loss, Sensorineural/therapy , Hearing Loss, Sudden/therapy , Vertigo/physiopathology , Administration, Intravenous , Administration, Oral , Adult , Audiometry, Pure-Tone , Female , Glucocorticoids/therapeutic use , Hearing Loss, Sensorineural/physiopathology , Hearing Loss, Sudden/physiopathology , Humans , Hyperbaric Oxygenation , Injection, Intratympanic , Male , Middle Aged , Recurrence , Retrospective Studies , Treatment Outcome
14.
Auris Nasus Larynx ; 48(5): 834-840, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33468353

ABSTRACT

OBJECTIVES: Posterior benign paroxysmal positional vertigo (p-BPPV) is the most common type of BPPV, and canalith-repositioning procedure (CRP) is frequently applied for treatment. Supine to prolonged lateral position (SPLP), a simple home-based maneuver, can be performed for treatment of p-BPPV. The purpose of this study was to investigate whether combination of CRP and SPLP could be more effective in symptom alleviation compared with CRP alone and reduce times of repeated CRP for patients with p-BBPV. METHODS: A retrospective chart review enrolled 96 patients diagnosed with primary p-BPPV. Of these patients, 64 patients were included in the CRP group and 32 patients, in the CRP+SPLP group. The outcome was determined according to days required to reach negative result in Dix-Hallpike test, duration of vertigo and dizziness following the first repositioning procedure, and times of CRP performed to reach resolution of p-BPPV. RESULTS: Of patients in the CRP and CRP+SPLP groups, 38% and 16% received CRP at least twice to reach resolution, respectively (P = 0.034). Patients in the CRP group and CRP+SPLP group spent an average of 9.8 ± 6.1 days and 7.9 ± 3.4 days, respectively reaching a negative result in Dix-Hallpike test (P = 0.050). In terms of duration for relieving vertigo and dizziness, the CRP+SPLP group achieved symptom relief with shorter duration (P = 0.036 and P = 0.025, respectively). CONCLUSION: Compared with CRP alone, combination of CRP and SPLP improved the therapeutic effectiveness and shortened the duration of suffering from vertigo and dizziness in patients with p-BPPV.


Subject(s)
Benign Paroxysmal Positional Vertigo/therapy , Patient Positioning/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Otolithic Membrane
15.
Mol Cell ; 81(2): 223-225, 2021 01 21.
Article in English | MEDLINE | ID: mdl-33482091

ABSTRACT

Han et al. (2020) and Shi et al. (2020) report that the E3 ubiquitin ligase ZSWIM8 senses when an RNA and an Argonaute protein-bound microRNA are extensively base paired and directs Argonaute destruction by the proteasome. The result is degradation of the microRNA.


Subject(s)
MicroRNAs , Ubiquitin , Argonaute Proteins/genetics , Argonaute Proteins/metabolism , MicroRNAs/genetics , Proteasome Endopeptidase Complex/metabolism , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/metabolism
16.
Proc Natl Acad Sci U S A ; 117(49): 31267-31277, 2020 12 08.
Article in English | MEDLINE | ID: mdl-33229585

ABSTRACT

Mushroom-forming fungi in the order Agaricales represent an independent origin of bioluminescence in the tree of life; yet the diversity, evolutionary history, and timing of the origin of fungal luciferases remain elusive. We sequenced the genomes and transcriptomes of five bonnet mushroom species (Mycena spp.), a diverse lineage comprising the majority of bioluminescent fungi. Two species with haploid genome assemblies ∼150 Mb are among the largest in Agaricales, and we found that a variety of repeats between Mycena species were differentially mediated by DNA methylation. We show that bioluminescence evolved in the last common ancestor of mycenoid and the marasmioid clade of Agaricales and was maintained through at least 160 million years of evolution. Analyses of synteny across genomes of bioluminescent species resolved how the luciferase cluster was derived by duplication and translocation, frequently rearranged and lost in most Mycena species, but conserved in the Armillaria lineage. Luciferase cluster members were coexpressed across developmental stages, with the highest expression in fruiting body caps and stipes, suggesting fruiting-related adaptive functions. Our results contribute to understanding a de novo origin of bioluminescence and the corresponding gene cluster in a diverse group of enigmatic fungal species.


Subject(s)
Agaricales/genetics , Evolution, Molecular , Fruiting Bodies, Fungal/genetics , Luminescence , Agaricales/chemistry , Base Sequence , Fruiting Bodies, Fungal/chemistry , Genome, Fungal/genetics , Luciferases/genetics , Phylogeny
17.
Nat Genet ; 52(7): 728-739, 2020 07.
Article in English | MEDLINE | ID: mdl-32601478

ABSTRACT

Pachytene PIWI-interacting RNAs (piRNAs), which comprise >80% of small RNAs in the adult mouse testis, have been proposed to bind and regulate target RNAs like microRNAs, cleave targets like short interfering RNAs or lack biological function altogether. Although piRNA pathway protein mutants are male sterile, no biological function has been identified for any mammalian piRNA-producing locus. Here, we report that males lacking piRNAs from a conserved mouse pachytene piRNA locus on chromosome 6 (pi6) produce sperm with defects in capacitation and egg fertilization. Moreover, heterozygous embryos sired by pi6-/- fathers show reduced viability in utero. Molecular analyses suggest that pi6 piRNAs repress gene expression by cleaving messenger RNAs encoding proteins required for sperm function. pi6 also participates in a network of piRNA-piRNA precursor interactions that initiate piRNA production from a second piRNA locus on chromosome 10, as well as pi6 itself. Our data establish a direct role for pachytene piRNAs in spermiogenesis and embryo viability.


Subject(s)
RNA, Small Interfering/genetics , RNA, Small Interfering/physiology , Spermatogenesis/genetics , Animals , Biological Evolution , Cell Nucleus , Embryonic Development , Female , Fertility , Gene Deletion , Gene Expression Regulation , Male , Mice , Mice, Inbred C57BL , Models, Biological , Pachytene Stage/genetics , Promoter Regions, Genetic , RNA, Messenger/metabolism , Sperm Capacitation/genetics , Sperm Capacitation/physiology , Sperm-Ovum Interactions/physiology
18.
Nat Ecol Evol ; 4(1): 156-168, 2020 01.
Article in English | MEDLINE | ID: mdl-31900453

ABSTRACT

In the fetal mouse testis, PIWI-interacting RNAs (piRNAs) guide PIWI proteins to silence transposons but, after birth, most post-pubertal pachytene piRNAs map to the genome uniquely and are thought to regulate genes required for male fertility. In the human male, the developmental classes, precise genomic origins and transcriptional regulation of postnatal piRNAs remain undefined. Here, we demarcate the genes and transcripts that produce postnatal piRNAs in human juvenile and adult testes. As in the mouse, human A-MYB drives transcription of both pachytene piRNA precursor transcripts and messenger RNAs encoding piRNA biogenesis factors. Although human piRNA genes are syntenic to those in other placental mammals, their sequences are poorly conserved. In fact, pachytene piRNA loci are rapidly diverging even among modern humans. Our findings suggest that, during mammalian evolution, pachytene piRNA genes are under few selective constraints. We speculate that pachytene piRNA diversity may provide a hitherto unrecognized driver of reproductive isolation.


Subject(s)
Genome , Testis , Adolescent , Animals , Female , Gene Expression Regulation , Humans , Male , Mice , Pregnancy , RNA, Messenger , RNA, Small Interfering
19.
Article in English | MEDLINE | ID: mdl-31766214

ABSTRACT

This study investigates the development of glaucoma in subjects with surgery-indicated chronic rhinosinusitis (CRS) by the use of the National Health Insurance Research Database in Taiwan. Individuals that received the functional endoscopic sinus surgery (FESS) with a diagnostic code of CRS were regarded as surgery-indicated CRS and enrolled in the study group. Four non-CRS patients were age- and gender-matched to each patient in the study group. The exclusion criteria included legal blindness, ocular tumor, history of eyeball removal, and previous glaucoma. The outcome was regarded as the development of glaucoma, and conditional logistic regression was used for the statistical analysis, which involved multiple potential risk factors in the multivariate model. A total of 6506 patients with surgery-indicated CRS that received FESS and another 26,024 non-CRS individuals were enrolled after exclusion. The age and gender distributions were identical between the two groups due to matching. There were 108 and 294 glaucoma events in the study group and control group, respectively, during the follow-up period, and the study group had a significantly higher adjusted hazard ratio (1.291, 95% confidential interval: 1.031-1.615). The cumulative probability analysis also revealed a correlation between the occurrence of glaucoma and the CRS disease interval. In the subgroup analysis, the chance of developing open-angle glaucoma and normal-tension glaucoma was significantly higher in the study group than in the control group. In conclusion, the existence of surgery-indicated CRS is a significant risk factor for the development of glaucoma, which correlated with the disease interval.


Subject(s)
Glaucoma/epidemiology , Rhinitis/epidemiology , Sinusitis/epidemiology , Adult , Aged , Aged, 80 and over , Chronic Disease , Female , Humans , Male , Middle Aged , Retrospective Studies , Rhinitis/surgery , Risk Factors , Sinusitis/surgery , Taiwan/epidemiology
20.
PLoS One ; 14(10): e0222919, 2019.
Article in English | MEDLINE | ID: mdl-31644539

ABSTRACT

BACKGROUND: To evaluate the incidence of age-related macular degeneration (AMD) in patients diagnosed with sensorineural hearing loss (SNHL) via the application of the National Health Insurance Research Database in Taiwan. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was conducted. Patients with a diagnosis of SNHL was enrolled in the study group after exclusion and a propensity score matched group without SNHL was served as the control group with a 1:2 ratio. The main outcome was regarded as the emergence of AMD diagnostic codes. Cox proportional hazard regression was applied to analyze the incidence and adjusted hazard ratio (aHR) of AMD in the multivariate model. A total of 15,686 patients with SNHL were included in the study group while another 31,372 non-SNHL patients served as the control group. After a follow-up interval up to 16 years, there were 484 AMD events occurred in the study group and 660 AMD cases in those non-SNHL patients with a significantly higher aHR compared to the control group after adjusting for multiple potential risk factors (aHR: 1.399, 95% CI: 1.244-1.574). Other prominent risk factors for AMD included older age, ischemic heart disease, hyperlipidemia, Alzheimer's disease, liver disease and kidney disease. Besides, a higher cumulative probability of AMD was observed in the study group (log-rank P <0.0001). CONCLUSION: The patients with SNHL demonstrated a higher incidence of developing AMD.


Subject(s)
Hearing Loss, Sensorineural/epidemiology , Macular Degeneration/epidemiology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cohort Studies , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models
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