Intrinsic RNA Targeting Triggers Indiscriminate DNase Activity of CRISPR-Cas12a.

The CRISPR-Cas12a system has emerged as a powerful tool for next-generation nucleic acid-based molecular diagnostics. However, it has long been believed to be effective only on DNA targets. Here, we investigate the intrinsic RNA-enabled trans-cleavage activity of AsCas12a and LbCas12a and discover that they can be directly activated by full-size RNA targets, although LbCas12a exhibits weaker trans-cleavage activity than AsCas12a on both single-stranded DNA and RNA substrates.

IHMCIF: An Extension of the PDBx/mmCIF Data Standard for Integrative Structure Determination Methods.

IHMCIF (github.com/ihmwg/IHMCIF) is a data information framework that supports archiving and disseminating macromolecular structures determined by integrative or hybrid modeling (IHM), and making them Findable, Accessible, Interoperable, and Reusable (FAIR). IHMCIF is an extension of the Protein Data Bank Exchange/macromolecular Crystallographic Information Framework (PDBx/mmCIF) that serves as the framework for the Protein Data Bank (PDB) to archive experimentally determined atomic structures of biological macromolecules and their complexes with one another and small molecule ligands (e.

Prenatal stress and hair cortisol in a sample of Latina women.

Background: Stress during pregnancy adversely impacts maternal and infant health. Dysregulation of the hypothalamic pituitary axis is a mediator of the relationship between stress and health. Evidence supporting an association between prenatal chronic stress and cortisol is limited, and the majority of research published has been conducted amongst White participants, who experience less chronic stress than people of color.

CRISPR-powered quantitative keyword search engine in DNA data storage.

Despite the growing interest of archiving information in synthetic DNA to confront data explosion, quantitatively querying the data stored in DNA is still a challenge. Herein, we present Search Enabled by Enzymatic Keyword Recognition (SEEKER), which utilizes CRISPR-Cas12a to rapidly generate visible fluorescence when a DNA target corresponding to the keyword of interest is present. SEEKER achieves quantitative text searching since the growth rate of fluorescence intensity is proportional to keyword frequency.

Discrimination and perinatal depressive symptoms: The protective role of social support and resilience.

Background: Discrimination is an important social determinant of perinatal depression; however, evidence is limited regarding modifiable social and psychological factors that may moderate this association. We examined whether social support and resilience could protect against the adverse effects of discrimination on perinatal depressive symptoms.

Methods: Pregnant people (N = 589) receiving Expect With Me group prenatal care in Nashville, TN and Detroit, MI completed surveys during third trimester of pregnancy and six months postpartum.

Metformin in Esophageal Carcinoma: Exploring Molecular Mechanisms and Therapeutic Insights.

Esophageal cancer (EC) remains a formidable malignancy with limited treatment options and high mortality rates, necessitating the exploration of innovative therapeutic avenues. Through a systematic analysis of a multitude of studies, we synthesize the diverse findings related to metformin's influence on EC. This review comprehensively elucidates the intricate metabolic pathways and molecular mechanisms through which metformin may exert its anti-cancer effects.

Hybrid representation learning for cognitive diagnosis in late-life depression over 5 years with structural MRI.

Late-life depression (LLD) is a highly prevalent mood disorder occurring in older adults and is frequently accompanied by cognitive impairment (CI). Studies have shown that LLD may increase the risk of Alzheimer's disease (AD). However, the heterogeneity of presentation of geriatric depression suggests that multiple biological mechanisms may underlie it.

Cryo-EM structures reveal how phosphate release from Arp3 weakens actin filament branches formed by Arp2/3 complex.

Arp2/3 complex nucleates branched actin filaments for cell and organelle movements. Here we report a 2.7 Å resolution cryo-EM structure of the mature branch junction formed by S.

Group prenatal care successes, challenges, and frameworks for scaling up: a case study in adopting health care innovations.

Background: Group prenatal care enhances quality of care, improves outcomes, and lowers costs. However, this healthcare innovation is not widely available. Using a case-study approach, our objectives were to (1) examine organizational characteristics that support implementation of Expect With Me group prenatal care and (2) identify key factors influencing adoption and sustainability.

Effects of Xylanase A double mutation on substrate specificity and structural dynamics.

While protein activity is traditionally studied with a major focus on the active site, the activity of enzymes has been hypothesized to be linked to the flexibility of adjacent regions, warranting more exploration into how the dynamics in these regions affects catalytic turnover. One such enzyme is Xylanase A (XylA), which cleaves hemicellulose xylan polymers by hydrolysis at internal β-1,4-xylosidic linkages. It contains a "thumb" region whose flexibility has been suggested to affect the activity.

Antenatal Magnesium Sulfate Benefits Female Preterm Infants but Results in Poor Male Outcomes.

Magnesium sulfate (MagSul) is used clinically to prevent eclamptic seizures during pregnancy and as a tocolytic for preterm labor. More recently, it has been implicated as offering neural protection in utero for at-risk infants. However, evidence is mixed.

A 16-Year Chronicle of Developing a Healthy Workplace Participatory Program for in the Connecticut Department of Correction: The Health Improvement through Employee Control (HITEC) Program.

Health Improvement Through Employee Control (HITEC) is a 16-year program directed toward the health of corrections personnel and developed through the application of the principles of Participatory Action Research (PAR) and participatory ergonomics. Its impetus has always been the adverse health status of the corrections workforce: early mortality, depression, obesity, and hypertension. The HITEC program trained small "Design Teams" (DTs) of front-line personnel in participatory methods for intervention design for health improvement and organizational change in line with the principles.

Nfe2l3 promotes neuroprotection and long-distance axon regeneration after injury in vivo.

Nuclear factor erythroid 2 like (Nfe2l) gene family members 1-3 mediate cellular response to oxidative stress, including in the central nervous system (CNS). However, neuronal functions of Nfe2l3 are unknown. Here, we comparatively evaluated expression of Nfe2l1, Nfe2l2, and Nfe2l3 in singe cell RNA-seq (scRNA-seq)-profiled cortical and retinal ganglion cell (RGC) CNS projection neurons, investigated whether Nfe2l3 regulates neuroprotection and axon regeneration after CNS injury in vivo, and characterized a gene network associated with Nfe2l3 in neurons.

The Exposure Peaks of Traffic-Related Ultrafine Particles Associated with Inflammatory Biomarkers and Blood Lipid Profiles.

In this article, we explored the effects of ultrafine particle (UFP) peak exposure on inflammatory biomarkers and blood lipids using two novel metrics-the intensity of peaks and the frequency of peaks. We used data previously collected by the Community Assessment of Freeway Exposure and Health project from participants in the Greater Boston Area. The UFP exposure data were time-activity-adjusted hourly average concentration, estimated using land use regression models based on mobile-monitored ambient concentrations.

Cilia Provide a Platform for the Generation, Regulated Secretion, and Reception of Peptidergic Signals.

Cilia are microtubule-based cellular projections that act as motile, sensory, and secretory organelles. These structures receive information from the environment and transmit downstream signals to the cell body. Cilia also release vesicular ectosomes that bud from the ciliary membrane and carry an array of bioactive enzymes and peptide products.

A mosquito salivary protein-driven influx of myeloid cells facilitates flavivirus transmission.

Mosquitoes transmit many disease-relevant flaviviruses. Efficient viral transmission to mammalian hosts requires mosquito salivary factors. However, the specific salivary components facilitating viral transmission and their mechanisms of action remain largely unknown.

Phenotype of Parathyroid-targeted Deletion in Mice Is Strain-dependent.

Hyperparathyroidism jaw-tumor syndrome is an autosomal dominant disorder caused by mutations in the tumor suppressor gene, encoding parafibromin, and manifesting benign or malignant parathyroid tumors, ossifying jaw fibromas, uterine tumors, and kidney lesions. Sporadic parathyroid carcinomas also frequently exhibit inactivating mutations and loss of parafibromin. To study the role of in parathyroid cell proliferation in vivo, we generated mice with a parathyroid-specific deletion of Homozygous knockout mice on a mixed B6/129/CD1 background had decreased serum calcium and PTH and smaller parathyroid glands compared with heterozygous or wild-type littermates, whereas homozygous -null mice on other backgrounds exhibited no abnormalities in parathyroid gland function or development.

Stimuli-responsive peptide assemblies: Design, self-assembly, modulation, and biomedical applications.

Peptide molecules have design flexibility, self-assembly ability, high biocompatibility, good biodegradability, and easy functionalization, which promote their applications as versatile biomaterials for tissue engineering and biomedicine. In addition, the functionalization of self-assembled peptide nanomaterials with other additive components enhances their stimuli-responsive functions, promoting function-specific applications that induced by both internal and external stimulations. In this review, we demonstrate recent advance in the peptide molecular design, self-assembly, functional tailoring, and biomedical applications of peptide-based nanomaterials.

NOVEL HIGH-STRENGTH POLYESTER COMPOSITE SCAFFOLDS FOR BONE REGENERATION.

Repair of critical sized bone defects, particularly in load-bearing areas, is a major clinical problem that requires surgical intervention and implantation of biological or engineered grafts. For load-bearing sites, it is essential to use engineered grafts that have both sufficient mechanical strength and appropriate pore properties to support bone repair and tissue regeneration. Unfortunately, the mechanical properties of such grafts are often compromised due to the creation of pores required to facilitate tissue ingrowth following implantation.

Lumbar decompression and fusion for symptomatic spinal stenosis in a patient with chronic thoracic sensory level from prior transverse myelitis: a case report.

Background: Many patients with transverse myelitis suffer from sensory loss below the spinal level of the lesion. This is commonly associated with chronic neuropathic pain. However, the presence of somatic pain below a complete thoracic sensory level after transverse myelitis is exceptionally rare, and it is unclear if surgical decompression is an effective form of treatment for these patients.

Dissolvable Immunomodulatory Microneedles for Treatment of Skin Wounds.

Sustained inflammation can halt or delay wound healing, and macrophages play a central role in wound healing. Inflammatory macrophages are responsible for the removal of pathogens, debris, and neutrophils, while anti-inflammatory macrophages stimulate various regenerative processes. Recombinant human Proteoglycan 4 (rhPRG4) is shown to modulate macrophage polarization and to prevent fibrosis and scarring in ear wound healing.

Effectiveness of romosozumab in primary biliary cholangitis at half the recommended dose in an underweight patient.

Romosozumab (RSB) is a monoclonal antibody to sclerostin that is approved for post-menopausal osteoporosis at high fracture risk. It is administered as a monthly 210 mg subcutaneous injection for 12 months. We report the response to half the standard dose of RSB in an underweight patient with severe osteoporosis and primary biliary cholangitis (PBC).