Colony context and size-dependent compensation mechanisms give rise to variations in nuclear growth trajectories.

To investigate the fundamental question of how cellular variations arise across spatiotemporal scales in a population of identical healthy cells, we focused on nuclear growth in hiPS cell colonies as a model system. We generated a 3D timelapse dataset of thousands of nuclei over multiple days, and developed open-source tools for image and data analysis and an interactive timelapse viewer for exploring quantitative features of nuclear size and shape. We performed a data-driven analysis of nuclear growth variations across timescales.

A comprehensive review of the ten main platelet receptors involved in platelet activity and cardiovascular disease.

Cardiovascular disease (CVD) is a major cause of death worldwide. Although there are many variables that contribute to the development of this disease, it is predominantly the activity of platelets that provides the mechanisms by which this disease prevails. While there are numerous platelet receptors expressed on the surface of platelets, it is largely the consensus that there are 10 main platelet receptors that contribute to a majority of platelet function.

External globus pallidus input to the dorsal striatum regulates habitual seeking behavior in male mice.

The external globus pallidus (GPe) coordinates action-selection through GABAergic projections throughout the basal ganglia. GPe arkypallidal (arky) neurons project exclusively to the dorsal striatum, which regulates goal-directed and habitual seeking. However, the role of GPe arky neurons in reward-seeking remains unknown.

A novel monobactam lacking antimicrobial activity, MC-100093, reduces sex-specific ethanol preference and depressive-like behaviors in mice.

Several β-lactam derivatives upregulate astrocytic glutamate transporter type 1expression and are known to improve measures in models of mood and alcohol use disorders (AUD) through normalizing glutamatergic states. However, long-term, and high doses of β-lactams may cause adverse side effects for treating mood disorders and AUD. Studies suggest that MC-100093, a novel β-lactam lacking antimicrobial activity, rescues GLT1 expression.

Autism Spectrum Disorder in the Dominican Republic: A Mini Review of the Current Situation.

As the recognition of autism spectrum disorder (ASD) increases, and the prevalence estimates of ASD continue to rise throughout the world, it has become apparent that access to diagnostic and treatment services is highly dependent on geography. Even within countries such as the United States, which has received significant interest and investment in understanding, diagnosing, treating, and providing programs for those with ASD over the last 20+ years, access to information and services is uneven. In poorer countries such as the Dominican Republic (DR), where >40% of citizens live below the poverty level and access to quality healthcare overall continues to be a challenge, issues associated with ASD are not yet being adequately addressed.

Small-Fiber Polyneuropathy Is Prevalent in Patients With Interstitial Cystitis/Bladder Pain Syndrome.

Importance: The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is imperfectly understood. Recent studies reported that small-fiber polyneuropathy (SFPN) is common in fibromyalgia, a condition commonly comorbid with IC/BPS.

Objective: The objective of this study was to determine the prevalence of SFPN in a large cohort of IC/BPS patients.

Pulsed Electromagnetic Field Therapy for Pain Management in Interstitial Cystitis/Bladder Pain Syndrome: A Proof-of-Concept Case Series.

Objective: To evaluate the efficacy of pulsed electromagnetic field (PEMF) therapy for symptom and pain management in women with non-bladder centric interstitial cystitis/bladder pain syndrome (IC/BPS).

Methods: Women with non-bladder centric IC/BPS and a numeric rating scale score for pelvic pain ≥6 underwent twice-daily 8-minute full body PEMF therapy sessions for 4 weeks. The primary outcome metric was a reduction in pelvic pain score ≥2 points.

A Comprehensive Review of PCSK9 Inhibitors.

Cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. A major risk factor for this condition is increased serum low-density lipoprotein cholesterol (LDL-C) levels for which statins have been successful in reducing serum LDL-C to healthy concentrations. However, patients who are statin intolerant or those who do not achieve their treatment goals while on high-intensity statin therapy, such as those with familial hypercholesterolemia, remain at risk.

Adenosine receptors: Emerging non-opioids targets for pain medications.

Physical and emotional pain deteriorates the quality of well-being. Also, numerous non-invasive and invasive treatments for diagnosed diseases such as cancer medications and surgical procedures cause various types of pain. Despite the multidisciplinary approaches available to manage pain, the unmet needs for medication with minimal side effects are substantial.

The effects of estrogen and hormone replacement therapy on platelet activity: a review.

Many studies have shown that an increase in cardiovascular disease in women is related to hormonal changes occurring particularly after menopause with increasing age. While the results of large clinical trials reporting no benefit of hormone replacement therapy (HRT) in cardiovascular disease have been known for some time, there is an increasing body of knowledge regarding the various mechanisms by which estrogen modulates platelet function that could in part explain the higher cardiovascular risk occurring in postmenopausal women and potential benefits of HRT on cardiovascular health. Our review summarizes our current knowledge regarding the effect of endogenous and exogenous estrogen on platelet activity, which can help researchers design future studies.

N-substituated adenosine analog J4 attenuates anxiety-like behaviors in mice.

Rationale: Withdrawal from chronic alcohol exposure produces various physical and mental withdrawal symptoms. Activation of adenosine receptors is known to inhibit withdrawal-induced excitation. However, limited studies investigate how adenosine analogs may prove helpful tools to alleviate alcohol withdrawal-related affective behaviors.

Implication of Adult Hippocampal Neurogenesis in Alzheimer's Disease and Potential Therapeutic Approaches.

Alzheimer's disease is the most common neurodegenerative disease, affecting more than 6 million US citizens and representing the most prevalent cause for dementia. Neurogenesis has been repeatedly reported to be impaired in AD mouse models, but the reason for this impairment remains unclear. Several key factors play a crucial role in AD including Aβ accumulation, intracellular neurofibrillary tangles accumulation, and neuronal loss (specifically in the dentate gyrus of the hippocampus).

Design, Synthesis, and and Evaluation of Novel Fluconazole-Based Compounds with Promising Antifungal Activities.

Demand has arisen for developing new azole antifungal agents with the growth of the resistant rate of infective fungal species to current azole antifungals in recent years. Accordingly, the present study reports the synthesis of novel fluconazole (FLC) analogues bearing urea functionality that led to discovering new azole agents with promising antifungal activities. In particular, compounds and displayed broad-spectrum activity and superior antifungal capabilities compared to the standard drug FLC against sensitive and resistant ().

Hippocampal regenerative medicine: neurogenic implications for addiction and mental disorders.

Psychiatric illness is a prevalent and highly debilitating disorder, and more than 50% of the general population in both middle- and high-income countries experience at least one psychiatric disorder at some point in their lives. As we continue to learn how pervasive psychiatric episodes are in society, we must acknowledge that psychiatric disorders are not solely relegated to a small group of predisposed individuals but rather occur in significant portions of all societal groups. Several distinct brain regions have been implicated in neuropsychiatric disease.

Chronic Alcohol Exposure Induces Aberrant Mitochondrial Morphology and Inhibits Respiratory Capacity in the Medial Prefrontal Cortex of Mice.

Alcohol use disorder (AUD) is characterized as a chronic, relapsing disease with a pattern of excessive drinking despite negative consequences to an individual's life. Severe chronic alcohol use impairs the function of the medial prefrontal cortex (mPFC), which contributes to alcohol-induced cognitive and executive dysfunction. The mPFC contains more mitochondria compared to other cortical areas, which suggests mitochondrial damage may occur in AUD and trigger subsequent behavior change.

Astrocytic glutamate transporter 1 (GLT1) deficient mice exhibit repetitive behaviors.

Glutamatergic dysregulation is known to contribute to obsessive-compulsive disorder (OCD). Astrocytic glutamate transporter 1 (GLT1) is responsible for the majority of glutamate clearance. However, the role of GLT1 in OCD-like behavior remains unclear.

History of the development of antifungal azoles: A review on structures, SAR, and mechanism of action.

With the increasing risk of invasive and life threating fungal infections, there is now a great concern regarding the lower discovery rate of antifungal drugs in comparison to antimicrobial agents. Drugs conventionally used in clinics are not adequate enough to combat the increasing fungal infections, especially fungal forms resistant to fluconazole. Among the limited antifungal agents in clinics, azoles have the largest number of drug candidates in clinical trials and are partly marketed due to the particular focus of pharmaceutical companies and medicinal scientific centers.

Activation of Astrocytes in the Dorsomedial Striatum Facilitates Transition From Habitual to Goal-Directed Reward-Seeking Behavior.

Background: Habitual reward-seeking behavior is a hallmark of addictive behavior. The role of the dorsomedial striatum (DMS) in regulating goal-directed reward-seeking behavior has been long appreciated. However, it remains unclear how the astrocytic activities in the DMS differentially affect the behavioral shift.

Astrocytic Glutamate Transporter 1 (GLT1) Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice.

Glutamatergic dysregulation is known to contribute to altered emotional regulation. Astrocytic glutamate transporter 1 (GLT1) is responsible for the majority of glutamate clearance from synapse. However, the role of astrocytic GLT1 in affective processes such as anxiety- and depression-like behavior is not fully understood.

Lipopolysaccharide Increases Cortical Kynurenic Acid and Deficits in Reference Memory in Mice.

Kynurenic acid (KYNA), a glial-derived metabolite of tryptophan metabolism, is an antagonist of the alpha 7 nicotinic acetylcholine receptor and the glycine-binding site of -methyl-d-aspartate (NMDA) receptors. Kynurenic acid levels are increased in both the brain and cerebrospinal fluid of several psychiatric disorders including bipolar disorder, schizophrenia, and Alzheimer disease. In addition, pro-inflammatory cytokines have been found to be elevated in the blood of schizophrenic patients suggesting inflammation may play a role in psychiatric illness.

Novel Adenosine Analog, 6-(4-Hydroxybenzyl)-Adenosine, Dampens Alcohol Drinking and Seeking Behaviors.

Adenosine signaling is associated with ethanol-related behaviors. We previously found that adenosine A receptor (AR) activation dampens ethanol drinking behaviors in equilibrative nucleoside transporter 1 (ENT1) knockout mice, and AR inhibition augments reward-seeking behavior in wild-type mice. The novel adenosine analog 6-(4-hydroxybenzyl)-adenosine (NHBA), which is isolated from the rhizomes of , activates AR and inhibits ENT1.

Proteomic Profile of a Chronic Binge Ethanol Exposure Model.

Chronic binge alcohol drinking is known to increase risky decision through pathological impulsive behaviors. Recently, we established a novel rodent model of ethanol-induced waiting impulsivity using 5-choice serial reaction time task (5-CSRTT) in mice. However, molecular mechanisms underlying the chronic binge ethanol-induced waiting impulsivity is not well characterized.

Type 1 equilibrative nucleoside transporter (ENT1) regulates sex-specific ethanol drinking during disruption of circadian rhythms.

Disruptions in circadian rhythms are risk factors for excessive alcohol drinking. The ethanol-sensitive adenosine equilibrative nucleoside transporter type 1 (ENT1, slc29a1) regulates ethanol-related behaviors, sleep, and entrainment of circadian rhythms. However, the mechanism underlying the increased ethanol consumption in ENT1 knockout (KO) mice in constant light (LL) and whether there are sex differences in ethanol consumption in ENT1 mice are less studied.

Chronic Ethanol Exposure Disrupts Lactate and Glucose Homeostasis and Induces Dysfunction of the Astrocyte-Neuron Lactate Shuttle in the Brain.

Background: Impairment of monocarboxylate transporter (MCT)-dependent astrocyte-neuron lactate transfer disrupts long-term memory and erases drug-associated memories in mice. However, few studies have examined how drugs of abuse alter astrocyte-neuron lactate transfer in neurocircuits related to addiction. This is particularly pertinent for ethanol (EtOH), which has been demonstrated to impair central nervious system (CNS) glucose uptake and significantly alter peripheral levels of glucose, lactate, acetate, and ketones.