Cyclic Peptide [RW] in Improving the Ability of First-Line Antibiotics to Inhibit Inside Human Granulomas.

Tuberculosis (TB) is currently one of the leading causes of global mortality. Medical non-compliance due to the length of the treatment and antibiotic side effects has led to the emergence of multidrug-resistant (MDR) strains of () that are difficult to treat. A current therapeutic strategy attempting to circumvent this issue aims to enhance drug delivery to reduce the duration of the antibiotic regimen or dosage of first-line antibiotics.

Calpain-2 as a therapeutic target in repeated concussion-induced neuropathy and behavioral impairment.

Repeated concussion represents a serious health problem as it can result in various brain pathologies, ranging from minor focal tissue injury to severe chronic traumatic encephalopathy. The calcium-dependent protease, calpain, participates in the development of neurodegeneration following concussion, but there is no information regarding the relative contribution of calpain-1 and calpain-2, the major calpain isoforms in the brain. We used a mouse model of repeated concussions, which reproduces most of the behavioral and neuropathological features of the human condition, to address this issue.

Heat Shock Responsive Gene Expression Modulated by mRNA Poly(A) Tail Length.

Poly(A) tail length (PAL) has been implicated in the regulation of mRNA translation activities. However, the extent of such regulation at the transcriptome level is less understood in plants. Herein, we report the development and optimization of a large-scale sequencing technique called the Assay for PAL-sequencing (APAL-seq).

Insight into Molecular Mechanism for Activin A-Induced Bone Morphogenetic Protein Signaling.

Activins transduce the TGF-β pathway through a heteromeric signaling complex consisting of type I and type II receptors, and activins also inhibit bone morphogenetic protein (BMP) signaling mediated by type I receptor ALK2. Recent studies indicated that activin A cross-activates the BMP pathway through ALK2, a mutation associated with Fibrodysplasia Ossificans Progressiva (FOP). How activin A inhibits ALK2WT-mediated BMP signaling but activates ALK2-mediated BMP signaling is not well understood, and here we offer some insights into its molecular mechanism.

SK2 channel regulation of neuronal excitability, synaptic transmission, and brain rhythmic activity in health and diseases.

Small conductance calcium-activated potassium channels (SKs) are solely activated by intracellular Ca and their activation leads to potassium efflux, thereby repolarizing/hyperpolarizing membrane potential. Thus, these channels play a critical role in synaptic transmission, and consequently in information transmission along the neuronal circuits expressing them. SKs are widely but not homogeneously distributed in the central nervous system (CNS).

Understanding the Relationship between Glutathione, TGF-β, and Vitamin D in Combating Infections.

Tuberculosis (TB) remains a pervasive global health threat. A significant proportion of the world's population that is affected by latent tuberculosis infection (LTBI) is at risk for reactivation and subsequent transmission to close contacts. Despite sustained efforts in eradication, the rise of multidrug-resistant strains of () has rendered traditional antibiotic therapy less effective at mitigating the morbidity and mortality of the disease.

The Role of Dendritic Cells in TB and HIV Infection.

Dendritic cells are the principal antigen-presenting cells (APCs) in the host defense mechanism. An altered dendritic cell response increases the risk of susceptibility of infections, such as (), and the survival of the human immunodeficiency virus (HIV). The altered response of dendritic cells leads to decreased activity of T-helper-1 (Th1), Th2, Regulatory T cells (Tregs), and Th17 cells in tuberculosis (TB) infections due to a diminishment of cytokine release from these APCs, while HIV infection leads to DC maturation, allowing DCs to migrate to lymph nodes and the sub-mucosa where they then transfer HIV to CD4 T cells, although there is controversy around this topic.

MSC-derived exosomes protect against oxidative stress-induced skin injury via adaptive regulation of the NRF2 defense system.

Oxidative stress is a major cause of skin injury induced by damaging stimuli such as UV radiation. Currently, owing to their immunomodulatory properties, mesenchymal stem cell-derived exosomes (MSC-Exo), as a nanotherapeutic agent, have attracted considerable attention. Here, we investigated the therapeutic effects of MSC-Exo on oxidative injury in HO-stimulated epidermal keratinocytes and UV-irradiated wild type and nuclear factor-erythroid 2-related factor-2 (Nrf2) knocked down cell and animal models.

General Overview of Nontuberculous Mycobacteria Opportunistic Pathogens: and .

Nontuberculous mycobacteria (NTM) are emerging human pathogens, causing a wide range of clinical diseases affecting individuals who are immunocompromised and who have underlying health conditions. NTM are ubiquitous in the environment, with certain species causing opportunistic infection in humans, including and . The incidence and prevalence of NTM infections are rising globally, especially in developed countries with declining incidence rates of infection.

HDA6-dependent histone deacetylation regulates mRNA polyadenylation in .

Eukaryotic histone deacetylation, critical for maintaining nucleosome structure and regulating gene expression, is mediated by histone deacetylases (HDACs). Although nucleosomes have been reported to regulate mRNA polyadenylation in humans, the role of HDACs in regulating polyadenylation has not been uncovered. Taking advantage of phenotypic studies on , HDA6 (one of HDACs) was found to be a critical part of many biological processes.

Antimycobacterial Effects of Everolimus in a Human Granuloma Model.

has been historically and is currently a threat to global public health. First-line antibiotics have been effective but proven to be burdensome as they have many potential adverse side effects. There has been a recent increase in the number of active tuberculosis (TB) cases due to a prevalence of multidrug and extensively drug-resistant strains of , and an increasing number of highly susceptible people such as those with Type 2 Diabetes (T2DM) and human immunodeficiency virus (HIV) infection.

PKA and Ube3a regulate SK2 channel trafficking to promote synaptic plasticity in hippocampus: Implications for Angelman Syndrome.

The ubiquitin ligase, Ube3a, plays important roles in brain development and functions, since its deficiency results in Angelman Syndrome (AS) while its over-expression increases the risk for autism. We previously showed that the lack of Ube3a-mediated ubiquitination of the Ca-activated small conductance potassium channel, SK2, contributes to impairment of synaptic plasticity and learning in AS mice. Synaptic SK2 levels are also regulated by protein kinase A (PKA), which phosphorylates SK2 in its C-terminal domain, facilitating its endocytosis.

Draft Genome Sequences of Two Potentially Novel Isolates from Backyard and Commercial Chicken Gastrointestinal Tracts.

Here, we present the draft genome sequences of two strains, HF117_J1_D and USDA818B3_A, isolated in Pomona, California, from the gastrointestinal (GI) tract of backyard and commercial broiler chickens, respectively. The draft genomes of both strains appear to represent novel species.

Draft Genome Sequences of Two Isolates from the Poultry Gastrointestinal Tract.

Here, we announce the draft genome sequences of two strains, C8-1-8 and C2-6-12, isolated from the cecal contents of commercial broiler chickens (in Athens, GA). These strains may represent potentially novel species within the genus , and these draft genomes allow further investigation into potential probiotics for poultry.

Discovery of alternative polyadenylation dynamics from single cell types.

Alternative polyadenylation (APA) occurs in the process of mRNA maturation by adding a poly(A) tail at different locations, resulting increased diversity of mRNA isoforms and contributing to the complexity of gene regulatory network. Benefit from the development of high-throughput sequencing technologies, we could now delineate APA profiles of transcriptomes at an unprecedented pace. Especially the single cell RNA sequencing (scRNA-seq) technologies provide us opportunities to interrogate biological details of diverse and rare cell types.

Pre-clinical models of reward deficiency syndrome: A behavioral octopus.

Individuals with mood disorders or with addiction, impulsivity and some personality disorders can share in common a dysfunction in how the brain perceives reward, where processing of natural endorphins or the response to exogenous dopamine stimulants is impaired. Reward Deficiency Syndrome (RDS) is a polygenic trait with implications that suggest cross-talk between different neurological systems that include the known reward pathway, neuroendocrine systems, and motivational systems. In this review we evaluate well-characterized animal models for their construct validity and as potential models for RDS.

Prevalence of the number of pre-gestational diagnoses and trends in the United States in 2006 and 2016.

Introduction: There is a trend in reproductive-aged women to live with more chronic conditions, likely resulting in pregnancies complicated by one or more pre-gestational diagnoses. The objective of this study is to determine the prevalence of women with pre-gestational diagnoses and pregnancy-related complications, and assess the trends of pre-gestational diagnoses between two time-points, ten-years apart from 2006 to 2016.

Materials And Methods: We abstracted pregnant patients from the Healthcare Cost and Utilization Project's National Inpatient Sample by the Agency for Healthcare Research and Quality in 2006 and 2016.

Deletion of the Gene Results in Alterations in Signaling Pathways Related to Alzheimer's Disease, Protein Quality Control and Synaptic Plasticity in Mouse Brain.

Calpains represent a family of calcium-dependent proteases participating in a multitude of functions under physiological or pathological conditions. Calpain-1 is one of the most studied members of the family, is ubiquitously distributed in organs and tissues, and has been shown to be involved in synaptic plasticity and neuroprotection in mammalian brain. Calpain-1 deletion results in a number of phenotypic alterations.

The efficacy of transcranial alternating current stimulation for treating post-stroke depression: Study Protocol Clinical Trial (SPIRIT Compliant).

Background: The treatment of post-stroke depression (PSD) with anti-depressant drugs is partly practical. Transcranial alternating current stimulation (tACS) offers the potential for a novel treatment modality for adult patients with PSD. In this study, we will assess the efficacy and safety of tACS for treating PSD and explore its effect on gamma and beta-oscillations involving in emotional regulation.

Draft Genome Sequences of Two Isolates from Goose and Chicken Gastrointestinal Material.

Here, we present the draft genome sequences of two strains, An7 and USDA918EY, isolated from goose feces (Bend, OR, USA) and chicken ceca (Pomona, CA, USA), respectively. These data may assist with analyses of microorganisms associated with free-ranging and commercial avian species.

Did Proust predict the existence of episodic memory?

Cognitive psychologists have often discussed the idea that when Proust used in his books the concept of involuntary memories, which could be retrieved by an odor or a taste, he was in fact predating the notion of modern episodic memory. Since the publication of his famous "In Search of Lost Time", considerable progress has been made on our understanding of various types of memory and of the mechanisms involved in different brain circuits and synapses responsible for their long-term storage. This review will focus on the role of hippocampus in episodic memory, including its role in encoding time and various elements of episodes, in particular olfactory information.

Pituitary Adenylate Cyclase-Activating Polypeptide Excites Proopiomelanocortin Neurons: Implications for the Regulation of Energy Homeostasis.

Objective: We examined whether pituitary adenylate cyclase-activating polypeptide (PACAP) excites proopiomelanocortin (POMC) neurons via PAC1 receptor mediation and transient receptor potential cation (TRPC) channel activation.

Methods: Electrophysiological recordings were done in slices from both intact male and ovariectomized (OVX) female PACAP-Cre mice and eGFP-POMC mice.

Results: In recordings from POMC neurons in eGFP-POMC mice, PACAP induced a robust inward current and increase in conductance in voltage clamp, and a depolarization and increase in firing in current clamp.

Investigation of a bone lesion in a gorgonopsian (Synapsida) from the Permian of Zambia and periosteal reactions in fossil non-mammalian tetrapods.

While only distantly related to mammals, the anatomy of Permian gorgonopsians has shed light on the functional biology of non-mammalian synapsids and on the origins of iconic 'mammal-like' anatomical traits. However, little is known of gorgonopsian behaviour or physiology, which would aid in reconstructing the paleobiological context in which familiar mammalian features arose. Using multi-modal imaging, we report a discrete osseous lesion in the forelimb of a late Permian-aged gorgonopsian synapsid, recording reactive periosteal bone deposition and providing insights into the origins and diversity of skeletal healing responses in premammalian synapsids.

Improving natural product research translation: From source to clinical trial.

While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop.