Engineering Crystal Packing in RNA-Protein Complexes II: A Historical Perspective from the Structural Studies of the Spliceosome.

Cryo-electron microscopy has greatly advanced our understanding of how the spliceosome cycles through different conformational states to conduct the chemical reactions that remove introns from pre-mRNA transcripts. The Cryo-EM structures were built upon decades of crystallographic studies of various spliceosomal RNA-protein complexes. In this review we give an overview of the crystal structures solved in the Nagai group, utilizing many of the strategies to design crystal packing as described in the accompanying paper.

Therapeutically leveraging GABA receptors in cancer.

γ-aminobutyric acid or GABA is an amino acid that functionally acts as a neurotransmitter and is critical to neurotransmission. GABA is also a metabolite in the Krebs cycle. It is therefore unsurprising that GABA and its receptors are also present outside of the central nervous system, including in immune cells.

An interactive single cell web portal identifies gene and cell networks in COVID-19 host responses.

Numerous studies have provided single-cell transcriptome profiles of host responses to SARS-CoV-2 infection. Critically lacking however is a data mine that allows users to compare and explore cell profiles to gain insights and develop new hypotheses. To accomplish this, we harmonized datasets from COVID-19 and other control condition blood, bronchoalveolar lavage, and tissue samples, and derived a compendium of gene signature modules per cell type, subtype, clinical condition, and compartment.

Implicating Gene and Cell Networks Responsible for Differential COVID-19 Host Responses via an Interactive Single Cell Web Portal.

Numerous studies have provided single-cell transcriptome profiles of host responses to SARS-CoV-2 infection. Critically lacking however is a datamine that allows users to compare and explore cell profiles to gain insights and develop new hypotheses. To accomplish this, we harmonized datasets from COVID-19 and other control condition blood, bronchoalveolar lavage, and tissue samples, and derived a compendium of gene signature modules per cell type, subtype, clinical condition, and compartment.

Single-cell analysis reveals effective siRNA delivery in brain tumors with microbubble-enhanced ultrasound and cationic nanoparticles.

RNA-based therapies offer unique advantages for treating brain tumors. However, tumor penetrance and uptake are hampered by RNA therapeutic size, charge, and need to be "packaged" in large carriers to improve bioavailability. Here, we have examined delivery of siRNA, packaged in 50-nm cationic lipid-polymer hybrid nanoparticles (LPHs:siRNA), combined with microbubble-enhanced focused ultrasound (MB-FUS) in pediatric and adult preclinical brain tumor models.

Availability of Food Options and Nutrition Education in Local Food Pantries.

Objective: Explore the availability of food options and nutrition education at food pantries and identify the barriers to offering them to pantry clients.

Design: Cross-sectional, mixed-methods study.

Setting: Food pantry, Cincinnati, OH.

Assessing the Digital Divide Among Low-Income Perinatal Women: Opportunities for Provision of Health Information and Counseling.

Objectives: Technology-based health interventions may provide a means to reach low-income perinatal women and improve outcomes for both mother and infant, yet little is known about technology access and interest among this population. This study explored interest, attitudes, and concerns regarding technology to deliver health information and interventions.

Methods: Between May and October 2014, a cross-sectional study of 161 low-income pregnant and/or postpartum mothers (up to 1 year) was conducted, assessing attitudes and behaviors regarding the current use of devices and receptivity to interventions delivered through devices.

Docosahexaenoic Acid Supplementation in Pregnancy Modulates Placental Cellular Signaling and Nutrient Transport Capacity in Obese Women.

Context: Maternal obesity in pregnancy has profound impacts on maternal metabolism and promotes placental nutrient transport, which may contribute to fetal overgrowth in these pregnancies. The fatty acid docosahexaenoic acid (DHA) has bioactive properties that may improve outcomes in obese pregnant women by modulating placental function.

Objective: To determine the effects of DHA supplementation in obese pregnant women on maternal metabolism and placental function.

First In Vivo Testing of Compounds Targeting Group 3 Medulloblastomas Using an Implantable Microdevice as a New Paradigm for Drug Development.

Medulloblastoma is the most common childhood malignant brain tumor. The most lethal medulloblastoma subtype exhibits a high expression of the GABAA receptor α5 subunit gene and MYC amplification. New benzodiazepines have been synthesized to function as α5-GABAA receptor ligands.

Adiponectin and IGFBP-1 in the development of gestational diabetes in obese mothers.

Objective: Gestational diabetes mellitus (GDM) is more common in pregnancies complicated by obesity and both diseases increase the risk for fetal overgrowth and long-term adverse health consequences for the mother and child. Previous studies have linked low maternal serum adiponectin to GDM in normal and overweight women. We hypothesized that lower adiponectin, in particular the high-molecular-weight form, and insulin-like growth factor I (IGF-I) and its binding protein (IGFBP-1) are associated with GDM in pregnant obese Hispanic women.

Population approaches to improve diet, physical activity, and smoking habits: a scientific statement from the American Heart Association.

Background: Poor lifestyle behaviors, including suboptimal diet, physical inactivity, and tobacco use, are leading causes of preventable diseases globally. Although even modest population shifts in risk substantially alter health outcomes, the optimal population-level approaches to improve lifestyle are not well established.

Methods And Results: For this American Heart Association scientific statement, the writing group systematically reviewed and graded the current scientific evidence for effective population approaches to improve dietary habits, increase physical activity, and reduce tobacco use.

Structure of spliceosomal ribonucleoproteins.

Splicing of the precursors of eukaryotic mRNA and some non-coding RNAs is catalyzed by the 'spliceosome', which comprises five RNA-protein complexes (small nuclear ribonucleoproteins, or snRNPs) that assemble in an ordered manner onto precursor-mRNAs. Much progress has been made in determining the gross morphology of spliceosomal assembly intermediates. Recently, the first crystal structure of a spliceosomal snRNP has provided significant insight into assembly and architecture of spliceosomal snRNPs in general and the structure-function relationship of human U1 snRNP in particular.

Lessons learned from the mothers' overweight management study in 4 West Virginia WIC offices.

A pilot was conducted to test the feasibility and compare the effectiveness of a group approach (facilitated group discussions) to that of a self-guided approach (newsletters) to weight management in postpartum women enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (baseline n = 151; final n = 64). Mean group attendance was 3.6/10 sessions.

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP.

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post-translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle.

Interpreting a low resolution map of human U1 snRNP using anomalous scatterers.

We recently determined the crystal structure of the functional core of human U1 snRNP, consisting of nine proteins and one RNA, based on a 5.5 A resolution electron density map. At 5-7 A resolution, alpha helices and beta sheets appear as rods and slabs, respectively, hence it is not possible to determine protein fold de novo.

Dietary factors affecting iron status of children residing in rural West Virginia.

This cross-sectional study was designed to determine the prevalence of iron deficiency among a group of infants (6 to 11.9 months) and toddlers (12 to 24 months) and to examine the relationship between dietary intake and iron status. Participants were recruited from WIC clinics in counties where the prevalence of anemia was high (>10%).

Environmental perceptions related to physical activity in high- and low-risk counties.

To identify whether perceptions about the physical activity environment were related to the prevalence of sedentary lifestyle, residents from high-risk (n = 153) or low-risk (n = 100) counties were interviewed. County risk status was determined by the prevalence of cardiovascular mortality, overweight, and sedentary lifestyle. Key public officials in the same counties were also interviewed.

Factors related to postpartum depressive symptoms in low-income women.

Objective: This study examined the relationship of depressive symptoms to psychosocial and lifestyle variables in postpartum women.

Design: The Mothers' Overweight Management Study (MOMS) was a randomized, weight-gain prevention trial. Baseline data are presented on the Beck Depression Inventory (BDI), Perceived Stress Scale, Social Support Questionnaire, smoking status, body weight, waist circumference, and step counts.

The prevalence of heart-healthy menu items in West Virginia restaurants.

Objective: To determine the prevalence of heart-healthy choices offered in restaurants.

Methods: Menus (N=273) were obtained from restaurants in the 10 most populated cities in West Virginia. A survey assessed the number of restaurants that provide point-of- purchase nutrition information and the heart-healthy choices offered.

Stages of change for weight management in postpartum women.

Objective: This study examined factors related to stages of change for weight-management behaviors in postpartum women.

Design: Cross-sectional data, collected at baseline, are reported from the Mothers' Overweight Management Study (MOMS), a randomized, controlled trial conducted in postpartum women who participated in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).Subjects/Setting Subjects were a sample of WIC recipients (N=151) older than 18 years of age with a child younger than 2 years.

Dietary intake of children at high risk for cardiovascular disease.

Cardiovascular disease and obesity begin in childhood, and dietary interventions to prevent them should be initiated then. We hypothesized that children who were at high risk for cardiovascular disease based on family history would have diets that were different than those of children from low-risk families. Two hundred ninety-seven children were screened for family history of early cardiovascular disease; had height, weight, and finger-stick total cholesterol measured; and filled out food frequency questionnaires.