Mechanisms and regulation of spliceosome-mediated pre-mRNA splicing in Saccharomyces cerevisiae.

Pre-mRNA splicing, the removal of introns and ligation of flanking exons, is a crucial step in eukaryotic gene expression. The spliceosome, a macromolecular complex made up of five small nuclear RNAs (snRNAs) and dozens of proteins, assembles on introns via a complex pathway before catalyzing the two transesterification reactions necessary for splicing. All of these steps have the potential to be highly regulated to ensure correct mRNA isoform production for proper cellular function.

Control of 3' splice site selection by the yeast splicing factor Fyv6.

Pre-mRNA splicing is catalyzed in two steps: 5' splice site (SS) cleavage and exon ligation. A number of proteins transiently associate with spliceosomes to specifically impact these steps (1 and 2 step factors). We recently identified Fyv6 (FAM192A in humans) as a 2 step factor in ; however, we did not determine how widespread Fyv6's impact is on the transcriptome.

The small protein MntS evolved from a signal peptide and acquired a novel function regulating manganese homeostasis in Escherichia coli.

Small proteins (<50 amino acids) are emerging as ubiquitous and important regulators in organisms ranging from bacteria to humans, where they commonly bind to and regulate larger proteins during stress responses. However, fundamental aspects of small proteins, such as their molecular mechanism of action, downregulation after they are no longer needed, and their evolutionary provenance, are poorly understood. Here, we show that the MntS small protein involved in manganese (Mn) homeostasis binds and inhibits the MntP Mn transporter.

Cost of illness in inclusion body myositis: results from a cross-sectional study in Germany.

Background: Inclusion body myositis (IBM) is the most frequent type of myositis in elder patients with a slow chronic progression and refractory to treatment. Previous cost of illness (COI) studies in IBM used claims data to estimate direct costs in the US. No evidence exists globally on both direct and indirect costs in IBM from a societal perspective.

Inclusion body myositis-health-related quality of life and care situation during phases of the "patience journey" in Germany: results from a qualitative study.

Background: To understand the health-related quality of life (HRQoL) in inclusion body myositis (IBM) from a holistic perspective on the background of a complex care situation. The focus was on how the patient journey may be structured over the course of this rare disease.

Methods: An exploratory qualitative study was performed via in-depth semi-structured interviews.

Biochemical and genetic evidence supports Fyv6 as a second-step splicing factor in .

Precursor mRNA (pre-mRNA) splicing is an essential process for gene expression in eukaryotes catalyzed by the spliceosome in two transesterification steps. The spliceosome is a large, highly dynamic complex composed of five small nuclear RNAs and dozens of proteins, some of which are needed throughout the splicing reaction while others only act during specific stages. The human protein FAM192A was recently proposed to be a splicing factor that functions during the second transesterification step, exon ligation, based on analysis of cryo-electron microscopy (cryo-EM) density.

Patient-Reported Health-Related Quality of Life, Anxiety and Depression in Patients with Inclusion Body Myositis: A Register-Based Cross-Sectional Study in Germany.

Inclusion body myositis (IBM) is a rare neuromuscular disease and the most prevalent idiopathic inflammatory myopathy (IIM) in patients aged older than 50 years. A systematic review has shown that no clear-cut conclusions can be drawn about the health-related quality of life (HRQoL) and mental health in IBM. We aimed to assess the HRQoL and mental health, to explore associated disease-related and socioeconomic factors as well as the utilization of psychological support in German IBM patients.

The small protein MntS evolved from a signal peptide and acquired a novel function regulating manganese homeostasis in .

Unlabelled: Small proteins (< 50 amino acids) are emerging as ubiquitous and important regulators in organisms ranging from bacteria to humans, where they commonly bind to and regulate larger proteins during stress responses. However, fundamental aspects of small proteins, such as their molecular mechanism of action, downregulation after they are no longer needed, and their evolutionary provenance are poorly understood. Here we show that the MntS small protein involved in manganese (Mn) homeostasis binds and inhibits the MntP Mn transporter.

Age-related differences in the social associative learning of trust information.

Trust is a key component of social interaction. Older adults, however, often exhibit excessive trust relative to younger adults. One explanation is that older adults may learn to trust differently than younger adults.

Biochemical and Genetic Evidence Supports Fyv6 as a Second-Step Splicing Factor in .

Precursor mRNA (pre-mRNA) splicing is an essential process for gene expression in eukaryotes catalyzed by the spliceosome in two transesterification steps. The spliceosome is a large, highly dynamic complex composed of 5 small nuclear RNAs and dozens of proteins, some of which are needed throughout the splicing reaction while others only act during specific stages. The human protein FAM192A was recently proposed to be a splicing factor that functions during the second transesterification step, exon ligation, based on analysis of cryo-electron microscopy (cryo-EM) density.

The health-related quality of life, mental health and mental illnesses of patients with inclusion body myositis (IBM): results of a mixed methods systematic review.

Background: Inclusion body myositis (IBM) is a rare neuromuscular disease (NMD) and effective therapies are not available. Thus, it is relevant to determine the health-related quality of life (HRQoL) in IBM patients including aspects of mental health and illnesses.

Objectives: To identify and summarize the assessment of HRQoL, mental health and illnesses in IBM, the major factors that determine and influence them as well as the respective influence of IBM in general and compared to other NMD as a systematic review.

Health-related Quality of Life and Satisfaction with German Health Care Services in Patients with Charcot-Marie-Tooth Neuropathy.

BackgroundCharcot-Marie-Tooth (CMT) neuropathies entail a large group of diseases with different gene mutation patterns, which produce heterogeneous phenotypes. Although health-related quality of life (HRQOL) is significantly impaired, a comprehensive assessment of HRQOL in CMT patients in Germany considering phenotypical heterogeneity represented a research gap.ObjectiveThe aim was to assess HRQOL and the satisfaction with health care in CMT patients in Germany.

Characterizing the chemical and sensory profiles of traditional American meads.

The compositional and sensorial profiles of traditional American meads were determined using standard enological, volatile, and descriptive analyses. Forty-one commercial meads produced by 35 meaderies across 20 states were selected to encompass a broad product range. The meads were analyzed for ethanol content, residual sugar, pH, titratable acidity, acetic acid, and free and total sulfur dioxide.

Evaluating the Chemical Components and Flavor Characteristics Responsible for Triggering the Perception of "Beer Flavor" in Non-Alcoholic Beer.

Forty-two commercial non-alcoholic beer (NAB) brands were analyzed using sensory and chemical techniques to understand which analytes and/or flavors were most responsible for invoking the perception of "beer flavor" (for Northern Californian consumers). The aroma and taste profiles of the commercial NABs, a commercial soda, and a carbonated seltzer water (n = 44) were characterized using replicated descriptive and CATA analyses performed by a trained sensory panel (i.e.

Alternative Splicing and Cleavage of GLUT8.

The GLUT () family of membrane-associated transporters are described as glucose transporters. However, this family is divided into three classes and, though the regulated transporter activity of class I proteins is becoming better understood, class III protein functions continue to be obscure. We have cataloged the relative expression and splicing of mRNA isomers in tumors and normal tissues, with a focus on breast tumors and cell lines.

Characterizing Volatile and Nonvolatile Factors Influencing Flavor and American Consumer Preference toward Nonalcoholic Beer.

In this study, the chemical and sensory profiles of 42 different nonalcoholic beer (NAB) brands/styles already on the global market and produced through several different brewing techniques were evaluated. A trained panel (i.e.

[Quality of life in patients with implantable cardioverter-defibrillator from a salutogenic perspective : A qualitative study in cardiologic health service research].

Background: Evidence on disease-related quality of life (DRQoL) of patients with implantable cardioverter-defibrillators (ICDs) has been described heterogeneously. Disease-specific measures of DRQoL in ICD patients are lacking.

Objectives: The aim of this study was to gain a broader understanding of long-term DRQoL in ICD patients.

Experimental Evolution of Extreme Resistance to Ionizing Radiation in after 50 Cycles of Selection.

In previous work (D. R. Harris et al.

Structure-function analysis of manganese exporter proteins across bacteria.

Manganese (Mn) is an essential trace nutrient for organisms because of its role in cofactoring enzymes and providing protection against reactive oxygen species (ROS). Many bacteria require manganese to form pathogenic or symbiotic interactions with eukaryotic host cells. However, excess manganese is toxic, requiring cells to have manganese export mechanisms.

The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses.

Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as damage-associated molecular patterns or alarmins, remains ill defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8(+) T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a CTL-intrinsic fashion, determined plurifunctional effector cell differentiation, and was necessary for virus control.

Development and implementation of a curriculum on cancer screening for small groups of Latino women.

Background: Health programs tailored to serve Latino communities with limited access to health care are necessary. The methods used to develop breast and cervical cancer educational programs and to evaluate their implementation are presented.

Methods: A 12-session curriculum was developed to guide weekly group sessions led by trained community health advisors (ie, consejeras).

Effect of inhibition of dynein function and microtubule-altering drugs on AAV2 transduction.

Over the past decade, adeno-associated (AAV) virus has emerged as an important vector for gene therapy. As a result, understanding its basic biology, including intracellular trafficking, has become increasingly important. Here, we describe the effect of inhibiting dynein function or altering the state of microtubule polymerization on rAAV2 transduction.

Longitudinal study of babies born to mothers enrolled in a preconception prospective pregnancy study: study design and methodology, New York State Angler cohort study.

Persistent environmental chemicals such as organochlorine pesticides and polychlorinated biphenyls (PCBs) have been associated with alterations in fetal development and child health including subtle differences in developmental status. Previous prospective studies have ascertained prenatal or postnatal exposures but none have been designed to assess exposures at critical windows including preconception. To address this gap, we followed infants born to mothers recruited prior to conception in the New York State Prospective Pregnancy Study to assess feasibility issues including acceptability of a relatively invasive study protocol during the child's first 2 years of life.

Expression of Semliki Forest virus E1 protein in Escherichia coli. Low pH-induced pore formation.

Exposure of Semliki Forest virus 1 to mildly acidic conditions results in conformational changes of the viral spike proteins, which in turn leads to a pore formation across its membrane. The ability to form a pore has been ascribed to the ectodomain of the Semliki Forest virus (SFV) E1 spike protein. To elucidate whether the E1 protein per se is sufficient for low pH-dependent pore formation, we expressed E1 in Escherichia coli in an inducible manner using the pET11c expression system.