Cladribine effects on patient-reported outcomes and their clinical and biometric correlates in highly active relapsing multiple sclerosis at first switch: the observational, multicenter, prospective, phase IV CLADFIT-MS study.

Patient-reported outcomes (PROs) are essential for understanding the effects of MS and its treatments on patients' lives; they play an important role in multiple sclerosis (MS) research and practice. We present the protocol for an observational study to prospectively assess the effect of cladribine tablets on PROs and their correlation to disability and physical activity in adults with highly active relapsing MS switching from a first disease modifying drug (DMD) to cladribine tablets in routine clinical practice at study sites in Italy. The primary objective will be to evaluate changes from baseline in the impact of highly active MS on self-assessed physical functioning 52 weeks after the switch to cladribine tablets using the Multiple Sclerosis Impact Scale-29 (MSIS-29).

Utilizing primary human airway mucociliary tissue cultures to model ramifications of chronic E-cigarette usage.

Electronic cigarettes are battery powered devices that use a vape-liquid to produce a vapor that is inhaled. A consequence of the rise in e-cigarette usage was the 2019 emergence of a vaping-induced respiratory disease denoted as 'e-cigarette or vaping use-associated lung injury' (EVALI). One of the suspected causes of EVALI is Vitamin E Acetate (VEA), which was found to be a diluent in certain illicit vape-pens, whereas nicotine is commonly diluted in equal parts propylene glycol and vegetable glycerin (PG:VG).

What factors do patients consider when choosing a hand surgeon?

This study evaluated what patients consider in choosing a surgeon. A survey was given to 303 patients. Most found their hand surgeon through a medical or family/friend referral ( < .

Got milk? Maternal immune activation during the mid-lactational period affects nutritional milk quality and adolescent offspring sensory processing in male and female rats.

Previous studies have underscored the importance of breastfeeding and parental care on offspring development and behavior. However, their contribution as dynamic variables in animal models of early life stress are often overlooked. In the present study, we investigated how lipopolysaccharide (LPS)-induced maternal immune activation (MIA) on postnatal day (P)10 affects maternal care, milk, and offspring development.

Milking It for All It's Worth: The Effects of Environmental Enrichment on Maternal Nurturance, Lactation Quality, and Offspring Social Behavior.

Breastfeeding confers robust benefits to offspring development in terms of growth, immunity, and neurophysiology. Similarly, improving environmental complexity, i.e.

Corticosterone induces discrete epigenetic signatures in the dorsal and ventral hippocampus that depend upon sex and genotype: focus on methylated Nr3c1 gene.

The genomic effects of circulating glucocorticoids are particularly relevant in cortico-limbic structures, which express a high concentration of steroid hormone receptors. To date, no studies have investigated genomic differences in hippocampal subregions, namely the dorsal (dHPC) and ventral (vHPC) hippocampus, in preclinical models treated with exogenous glucocorticoids. Chronic oral corticosterone (CORT) in mouse is a pharmacological approach that disrupts the activity of the hypothalamic-pituitary-adrenal axis, increases affective behavior, and induces genomic changes after stress in the HPC of wildtype (WT) mice and mice heterozygous for the gene coding for brain-derived neurotrophic factor Val66Met (hMet), a variant associated with genetic susceptibility to stress.

The dynamic nature of the coronavirus receptor, angiotensin-converting enzyme 2 (ACE2) in differentiating airway epithelia.

Once inhaled, SARS-CoV-2 particles enter respiratory ciliated cells by interacting with angiotensin converting enzyme 2 (ACE2). Understanding the nature of ACE2 within airway tissue has become a recent focus particularly in light of the COVID-19 pandemic. Airway mucociliary tissue was generated using primary human nasal epithelial cells and the air-liquid interface (ALI) model of differentiation.

Genomic modules and intramodular network concordance in susceptible and resilient male mice across models of stress.

The multifactorial etiology of stress-related disorders necessitates a constant interrogation of the molecular convergences in preclinical models of stress that use disparate paradigms as stressors spanning from environmental challenges to genetic predisposition to hormonal signaling. Using RNA-sequencing, we investigated the genomic signatures in the ventral hippocampus common to mouse models of stress. Chronic oral corticosterone (CORT) induced increased anxiety- and depression-like behavior in wild-type male mice and male mice heterozygous for the gene coding for brain-derived neurotrophic factor Val66Met, a variant associated with genetic susceptibility to stress.

Isolation, expansion, differentiation, and histological processing of human nasal epithelial cells.

This protocol is intended as a guide for implementing or refining the usage of the air-liquid interface (ALI) model system to generate airway mucociliary tissue . We present a streamlined protocol for isolating the stem cells from inferior nasal turbinates of donors, allowing for a simple and low-cost supply of primary cells for research. We also provide our detailed protocols for ALI tissue processing and immunofluorescence to aid in the standardization of these techniques between research groups.

Combining Non-reducing SDS-PAGE Analysis and Chemical Crosslinking to Detect Multimeric Complexes Stabilized by Disulfide Linkages in Mammalian Cells in Culture.

The structures of many proteins are stabilized through covalent disulfide linkages. In recent work, this bond has also been classified as a post-translational modification. Thus, it is important to be able to study this modification in living cells.

Cysteine residues contribute to the dimerization and enzymatic activity of human nuclear dUTP nucleotidohydrolase (nDut).

dUTPase is an enzyme found in all organisms that have thymine as a constituent of DNA. Through evolution, humans have two major isoforms of dUTPase: a mitochondrial (mDut) and a nuclear (nDut) isoform. The nuclear isoform of dUTPase is a 164-amino-acids-long protein containing three cysteine residues.

Analysis of Nuclear Uracil DNA-Glycosylase (nUDG) Turnover During the Cell Cycle.

Uracil-DNA glycosylases (UDG/UNG) are enzymes that remove uracil from DNA and initiate base-excision repair. These enzymes play a key role in maintaining genomic integrity by reducing the mutagenic events caused by G:C to A:T transition mutations. The recent finding that a family of RNA editing enzymes (AID/APOBECs) can deaminate cytosine in DNA has raised the interest in these base-excision repair enzymes.

Clustering of chronic rhinosinusitis symptomatology reveals novel associations with objective clinical and demographic characteristics.

Background: Chronic rhinosinusitis (CRS) is associated with varied head and neck symptomatology and quality-of-life impairments that are not necessarily correlated with each other or with objective measures of disease.

Objective: To determine how clustering patterns of CRS symptoms associate with objective clinical findings.

Methods: Symptom scores from 193 Sinonasal Outcomes Test-22 (SNOT-22) questionnaires, from 177 consecutive CRS patients, were analyzed by principal component analysis (PCA) to uncover fewer and physiologically understandable latent components.

Intraventricular injection of 6-hydroxydopamine results in an increased number of tyrosine hydroxylase immune-positive cells in the rat cortex.

Previously we have demonstrated that intraventricular injection of 6-hydroxydopamine (6-OHDA) results in increased proliferation and de-differentiation of rat cortical astrocytes into progenitor-like cells 4 days after lesion (Wachter et al., 2010). To find out if these cells express tyrosine hydroxylase (TH), the rate-limiting enzyme in the catecholamine synthesis pathway, we performed immunohistochemistry in the rat cortex following intraventricular injection of 6-OHDA.

Host egg age of Leptoglossus occidentalis (Heteroptera, Coreidae) and parasitism by Gryon pennsylvanicum (Hymenoptera, Platygastridae).

Leptoglossus occidentalis Heidemann (Heteroptera, Coreidae) is native to Western North America and is a serious pest for seed production of conifers. The pest was accidentally introduced into Europe in the 1990s. Since then, seed loss has been recorded in Pinus pinea (L.

Analysis of nuclear uracil-DNA glycosylase (nUDG) turnover during the cell cycle.

Uracil-DNA glycosylases (UDG/UNG) are enzymes that remove uracil from DNA and initiate base-excision repair. These enzymes play a key role in maintaining genomic integrity by reducing the mutagenic events caused by G:C to A:T transition mutations. The recent finding that a family of RNA editing enzymes (AID/APOBECs) can deaminate cytosine in DNA has raised the interest in these base-excision repair enzymes.

X4 and R5 HIV-1 have distinct post-entry requirements for uracil DNA glycosylase during infection of primary cells.

It has been assumed that R5 and X4 HIV utilize similar strategies to support viral cDNA synthesis post viral entry. In this study, we provide evidence to show that R5 and X4 HIV have distinct requirements for host cell uracil DNA glycosylase (UNG2) during the early stage of infection. UNG2 has been previously implicated in HIV infection, but its precise role remains controversial.

Fluorodeoxyuridine modulates cellular expression of the DNA base excision repair enzyme uracil-DNA glycosylase.

The thymidylate synthase inhibitor 5-fluorouracil (5-FU) continues to play a pivotal role in the treatment of cancer. A downstream event of thymidylate synthase inhibition involves the induction of a self-defeating base excision repair process. With the depletion of TTP pools, there is also an increase in dUMP.

Proliferation-dependent expression of nuclear uracil-DNA glycosylase is mediated in part by E2F-4.

There are two isoforms of the prototypical human uracil-DNA glycosylase: one mitochondrial (UDG1) and one nuclear (UDG1A). Results presented here reveal a novel genetic organization of UDG1. Specifically, the UDG1 5' UTR is composed of two non-coding exons and the promoter region is located much farther upstream than previously recognized.

Proteolytic degradation of the nuclear isoform of uracil-DNA glycosylase occurs during the S phase of the cell cycle.

Uracil-DNA glycosylases are enzymes that remove uracil from DNA and initiate base-excision repair. These enzymes play a key role in maintaining genomic integrity by reducing the mutagenic events caused by G:C to A:T transition mutations. The recent finding that a family of RNA editing enzymes (APOBECs) can deaminate cytosine in DNA has raised the interest in these base-excision repair enzymes.

The transcription factor, NFI/CTF plays a positive regulatory role in expression of the hSMUG1 gene.

SMUG1 is a recently discovered uracil-DNA glycosylase with the ability to remove uracil from single-stranded as well as double-stranded DNA. SMUG1 also has the capacity to excise oxidized pyrimidine bases such as 5-hydroxymethyluracil and 5-formyluracil from DNA. Very little is known about the regulation of this enzyme.

hSMUG1 can functionally compensate for Ung1 in the yeast Saccharomyces cerevisiae.

There are at least four distinct families of enzymes that recognize and remove uracil from DNA. Family-3 (SMUG1) enzymes have recently been identified and have a preference for uracil in single-stranded DNA when assayed in vitro. Here we investigate the in vivo function of SMUG1 using the yeast Saccharomyces cerevisiae as a model system.

The nature of enzymes involved in uracil-DNA repair: isoform characteristics of proteins responsible for nuclear and mitochondrial genomic integrity.

The absence of uracil from DNA genomes is a consequence of enzyme functions that eliminate intracellular dUTP pools and that purposefully recognize and remove uracil moieties from DNA. These enzymatic functions are dUTP nucleotidohydrolase (dUTPase) and uracil-DNA glycosylase (UDG), respectively. There are distinct nuclear and mitochondrial isoforms of each of these enzymes in human cells.