The biogenesis and regulation of animal microRNAs.

MicroRNAs (miRNAs) are small, yet profoundly influential, non-coding RNAs that base-pair with mRNAs to induce RNA silencing. Although the basic principles of miRNA biogenesis and function have been established, recent breakthroughs have yielded important new insights into the molecular mechanisms of miRNA biogenesis. In this Review, we discuss the metazoan miRNA biogenesis pathway step-by-step, focusing on the key biogenesis machinery, including the Drosha-DGCR8 complex (Microprocessor), exportin-5, Dicer and Argonaute.

Symbolic recording of signalling and cis-regulatory element activity to DNA.

Measurements of gene expression or signal transduction activity are conventionally performed using methods that require either the destruction or live imaging of a biological sample within the timeframe of interest. Here we demonstrate an alternative paradigm in which such biological activities are stably recorded to the genome. Enhancer-driven genomic recording of transcriptional activity in multiplex (ENGRAM) is based on the signal-dependent production of prime editing guide RNAs that mediate the insertion of signal-specific barcodes (symbols) into a genomically encoded recording unit.

Chromatin context-dependent regulation and epigenetic manipulation of prime editing.

We set out to exhaustively characterize the impact of the cis-chromatin environment on prime editing, a precise genome engineering tool. Using a highly sensitive method for mapping the genomic locations of randomly integrated reporters, we discover massive position effects, exemplified by editing efficiencies ranging from ∼0% to 94% for an identical target site and edit. Position effects on prime editing efficiency are well predicted by chromatin marks, e.

Different perceptual worlds: Parent and youth perspectives on parenting outcome trajectories from a Latino family-based program.

Discrepancies between parent and youth perceptions of their relationship are a common aspect of generational acculturation gaps influencing immigrant families. Programs designed to strengthen parenting practices among immigrant Latino families commonly address immigration stresses, including differences between parent and youth perceptions, but little is known about discrepancies in their appraisals of program effects on parenting behavior. A randomized trial was conducted examining effects on parent behavior of a program for immigrant families with youth aged 10-14, developed through community-based participatory research principles.

Chromatin context-dependent regulation and epigenetic manipulation of prime editing.

Prime editing is a powerful means of introducing precise changes to specific locations in mammalian genomes. However, the widely varying efficiency of prime editing across target sites of interest has limited its adoption in the context of both basic research and clinical settings. Here, we set out to exhaustively characterize the impact of the chromatin environment on prime editing efficiency.

Structure of the human DICER-pre-miRNA complex in a dicing state.

Dicer has a key role in small RNA biogenesis, processing double-stranded RNAs (dsRNAs). Human DICER (hDICER, also known as DICER1) is specialized for cleaving small hairpin structures such as precursor microRNAs (pre-miRNAs) and has limited activity towards long dsRNAs-unlike its homologues in lower eukaryotes and plants, which cleave long dsRNAs. Although the mechanism by which long dsRNAs are cleaved has been well documented, our understanding of pre-miRNA processing is incomplete because structures of hDICER in a catalytic state are lacking.

Sequence determinant of small RNA production by DICER.

RNA silencing relies on specific and efficient processing of double-stranded RNA by Dicer, which yields microRNAs (miRNAs) and small interfering RNAs (siRNAs). However, our current knowledge of the specificity of Dicer is limited to the secondary structures of its substrates: a double-stranded RNA of approximately 22 base pairs with a 2-nucleotide 3' overhang and a terminal loop. Here we found evidence pointing to an additional sequence-dependent determinant beyond these structural properties.

Systemic Lupus Erythematosus and Lung Involvement: A Comprehensive Review.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiorgan manifestations, including pleuropulmonary involvement (20-90%). The precise mechanism of pleuropulmonary involvement in SLE is not well-understood; however, systemic type 1 interferons, circulating immune complexes, and neutrophils seem to play essential roles. There are eight types of pleuropulmonary involvement: lupus pleuritis, pleural effusion, acute lupus pneumonitis, shrinking lung syndrome, interstitial lung disease, diffuse alveolar hemorrhage (DAH), pulmonary arterial hypertension, and pulmonary embolism.

Simulation Modeling of Reduced Glycosylation Effects on Potassium Channels of Mouse Cardiomyocytes.

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure and the primary reason for heart transplantation; upward of 70% of DCM cases are considered idiopathic. Our experiments showed that reduced hybrid/complex N-glycosylation in mouse cardiomyocytes is linked with DCM. Further, we observed direct effects of reduced N-glycosylation on K gating.

"Race was something we didn't talk about": Racial Socialization in Asian American Families.

Objective: Our goal was to explore racial socialization practices in Asian American families during a time of heightened racial tension.

Background: Asian Americans hold a complex racial position in the United States, made even more complicated by an increase in public protests regarding socioracial injustices in the United States experienced by racial minority groups. Discussions about race and ethnicity occur within Asian American families but often focus on cultural heritage rather than awareness of discrimination and the historical roots of racism.

A quantitative map of human primary microRNA processing sites.

Maturation of canonical microRNA (miRNA) is initiated by DROSHA that cleaves the primary transcript (pri-miRNA). More than 1,800 miRNA loci are annotated in humans, but it remains largely unknown whether and at which sites pri-miRNAs are cleaved by DROSHA. Here, we performed in vitro processing on a full set of human pri-miRNAs (miRBase version 21) followed by sequencing.

A Double-Edged Sword: Dual-Identity Centrality and the Health of Asian American Sexual Minority Individuals.

Asian American sexual minority individuals (AASMI) face the challenge of navigating two identities as both a sexual minority and a racial minority. However, the research base examining AASMI dual-identities remains underdeveloped. In the current study, we investigated the link between AASMI dual-identity centrality and their health and wellbeing using a subsample of 303 AASMI drawn from the Social Justice Sexuality Project dataset (n = 4,953).

Design of Anticancer 2,4-Diaminopyrimidines as Novel Anoctamin 1 (ANO1) Ion Channel Blockers.

Pyrimidine is a privileged scaffold in many synthetic compounds exhibiting diverse pharmacological activities, and is used for therapeutic applications in a broad spectrum of human diseases. In this study, we prepared a small set of pyrimidine libraries based on the structure of two hit compounds that were identified through the screening of an in-house library in order to identify an inhibitor of anoctamin 1 (ANO1). ANO1 is amplified in various types of human malignant tumors, such as head and neck, parathyroid, and gastrointestinal stromal tumors, as well as in breast, lung, and prostate cancers.

Statistical Analysis of County-Level Contributing Factors to Opioid-Related Overdose Deaths in the United States.

This paper examines county-level characteristic factors contributing to opioid-related overdose deaths in the United States. We categorized factors into three groups: demographic, socio-economic, and health care environmental group. These features were used as predictors to model the overdose deaths from all types of opioids including prescription (e.

Racism, stress and health in Asian Americans: A structural equation analysis of mediation and social support group differences.

The buffering effect of social support on the negative effects of racism exposure on health outcomes has been mixed in prior studies regarding Asian Americans. Based on the stress-coping framework and using structural equation modelling (SEM) methods, we tested a theoretical model portraying simultaneous mediational paths from racism exposure to general physical and mental health through racism-related stress. Bootstrap analysis was used to test the indirect effects present in the model.

Micro-bubble flow simulation of dissolved air flotation process for water treatment using computational fluid dynamics technique.

A dissolved air flotation (DAF) system is one of the water treatment processes that purifies contaminants through a buoyancy effect by attaching the moiety of micro-bubbles on their free surface. Since the DAF system was first used in the drinking water treatment in the 1960s, it has been recognized as an effective treatment for the water purification process. Most previous works laid great emphasis on the internal flow behaviors of fluid to improve the purification efficiency of the DAF system.

Stress-activated miR-204 governs senescent phenotypes of chondrocytes to promote osteoarthritis development.

A progressive loss of cartilage matrix leads to the development of osteoarthritis (OA). Matrix homeostasis is disturbed in OA cartilage as the result of reduced production of cartilage-specific matrix and increased secretion of catabolic mediators by chondrocytes. Chondrocyte senescence is a crucial cellular event contributing to such imbalance in matrix metabolism during OA development.

Differential impact of circulating tumor cells on disease recurrence and survivals in patients with head and neck squamous cell carcinomas: An updated meta-analysis.

Purpose: The prognostic impact of circulating tumor cells (CTC) on disease recurrence, progression and survivals in patients with head and neck squamous cell carcinoma (HNSCC) has not been adequately described. The objective of this study was to determine the impacts of the presence of CTC on loco-regional recurrence and survival of HNSCC patients by conducting a systematic review and meta-analysis.

Methods: A comprehensive search for articles published between 1990 and 2016 was conducted and data from these studies were extracted, using the MEDLINE, Cochrane Library, and EMBASE databases.

Functional roles of glutamic acid E143 and E705 residues in the N-terminus and transmembrane domain 7 of Anoctamin 1 in calcium and noxious heat sensing.

Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic Ca2＋ concentration and noxious heat. Although the critical roles of ANO1 have been elucidated in various cell types, the control of its gating mechanisms by Ca2＋ and heat remain more elusive. To investigate critical amino acid residues for modulation of Ca2＋ and heat sensing, we constructed a randomized mutant library for ANO1.

Oscillation control algorithms for resonant sensors with applications to vibratory gyroscopes.

We present two oscillation control algorithms for resonant sensors such as vibratory gyroscopes. One control algorithm tracks the resonant frequency of the resonator and the other algorithm tunes it to the specified resonant frequency by altering the resonator dynamics. Both algorithms maintain the specified amplitude of oscillations.