Mitofusin 2 controls mitochondrial and synaptic dynamics of suprachiasmatic VIP neurons and related circadian rhythms.

Sustaining the strong rhythmic interactions between cellular adaptations and environmental cues has been posited as essential for preserving the physiological and behavioral alignment of an organism to the proper phase of the daily light/dark (LD) cycle. Here, we demonstrate that mitochondria and synaptic input organization of suprachiasmatic (SCN) vasoactive intestinal peptide-expressing (VIP-expressing) neurons showed circadian rhythmicity. Perturbed mitochondrial dynamics achieved by conditional ablation of the fusogenic protein mitofusin 2 (Mfn2) in VIP neurons caused disrupted circadian oscillation in mitochondria and synapses in SCN VIP neurons, leading to desynchronization of entrainment to the LD cycle in Mfn2-deficient mice that resulted in an advanced phase angle of their locomotor activity onset, alterations in core body temperature, and sleep-wake amount and architecture.

The Expression and Molecular Roles of MAMDC2 in MSS Colorectal Cancer with a High Tumor Stromal Ratio.

Colorectal cancer (CRC) heterogeneity is strongly influenced by molecular subtypes and tumor stroma interactions. The meprin/A5/PTPmu (MAM) domain, a conserved structural motif in transmembrane proteins, remains undercharacterized in CRC pathogenesis. We analyzed RNA-seq data from TCGA-COAD to evaluate MAM domain gene expression.

Mitofusin 2 controls mitochondrial and synaptic dynamics of suprachiasmatic VIP neurons and related circadian rhythms including sleep.

Sustaining the strong rhythmic interactions between cellular adaptations and environmental cues has been posited as essential for preserving the physiological and behavioral alignment of an organism to the proper phase of the daily light/dark cycle. Here, we show that mitochondria and synaptic input organization of suprachiasmatic (SCN) vasoactive intestinal peptide (VIP)-expressing neurons show circadian rhythmicity. Perturbed mitochondrial dynamics achieved by conditional ablation of the fusogenic protein mitofusin 2 (Mfn2) in VIP neurons cause disrupted circadian oscillation in mitochondria and synapses in SCN VIP neurons leading to desynchronization of entrainment to the light/dark cycle in Mfn2 deficient mice that resulted in advanced phase angle of their locomotor activity onset, alterations in core body temperature and sleep-wake amount and architecture.

CRISPR-mediated WNK4 point mutation aggravates tumor progression and weakens chemotherapy sensitivity in gastric cancer.

Objective: Gastric cancer (GC) is the fifth most common malignancy, the molecular targets of which have been increasingly explored in recent years. As a serine/threonine protein kinase, the role of WNK lysine deficient protein kinase 4 (WNK4) in GC was clarified in this study.

Methods: Human GC lines AGS and MKN45 were stably transfected with a WNK4 mutant constructed by the CRISPR/Cas9 method and treated with cis-dichlorodiammine platinum (CDDP, 2 μg/mL) and 5-fluorouracil (5-FU, 5 μg/mL) for 48h.

Neurons for infant social behaviors in the mouse zona incerta.

Understanding the neural basis of infant social behaviors is crucial for elucidating the mechanisms of early social and emotional development. In this work, we report a specific population of somatostatin-expressing neurons in the zona incerta (ZI) of preweaning mice that responds dynamically to social interactions, particularly those with their mother. Bidirectional neural activity manipulations in pups revealed that widespread connectivity of preweaning ZI neurons to sensory, emotional, and cognitive brain centers mediates two key adaptive functions associated with maternal presence: the reduction of behavior distress and the facilitation of learning.

Numerical Simulation and Machine Learning Prediction of the Direct Chill Casting Process of Large-Scale Aluminum Ingots.

The large-scale ingot of the 7xxx-series aluminum alloys fabricated by direct chill (DC) casting often suffers from foundry defects such as cracks and cold shut due to the formidable challenges in the precise controlling of casting parameters. In this manuscript, by using the integrated computational method combining numerical simulations with machine learning, we systematically estimated the evolution of multi-physical fields and grain structures during the solidification processes. The numerical simulation results quantified the influences of key casting parameters including pouring temperature, casting speed, primary cooling intensity, and secondary cooling water flow rate on the shape of the mushy zone, heat transport, residual stress, and grain structure of DC casting ingots.

A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model.

Anorexia nervosa (AN) is a psychiatric illness with the highest mortality. Current treatment options have been limited to psychotherapy and nutritional support, with low efficacy and high relapse rates. Hypothalamic AgRP (agouti-related peptide) neurons that coexpress AGRP and neuropeptide Y (NPY) play a critical role in driving feeding while also modulating other complex behaviors.

Applying lysozyme, alkaline protease, and sodium hypochlorite to reduce bioclogging during managed aquifer recharge: A laboratory study.

Alleviating bacterial-induced clogging is of great importance to improve the efficiency of managed aquifer recharge (MAR). Enzymes (lysozyme and alkaline protease) and sodium hypochlorite (NaClO) are common biological and chemical reagents for inhibiting bacterial growth and activity. To investigate the applicability of these reagents to reduce bioclogging, percolation experiments were performed to simulate a weak alkaline recharge water infiltration through laboratory-scale sand columns, with adding 10 mg/L lysozyme, alkaline protease, and NaClO, respectively.

TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons.

The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide-expressing (AGRP-expressing) neurons play an essential role in driving feeding, while also modulating nonfeeding behaviors. Besides AGRP, these neurons produce neuropeptide Y (NPY) and the neurotransmitter GABA, which act in concert to stimulate food intake and decrease energy expenditure.

Advances of gold nanoclusters for bioimaging.

Gold nanoclusters (AuNCs) have become a promising material for bioimaging detection because of their tunable photoluminescence, large Stokes shift, low photobleaching, and good biocompatibility. Last decade, great efforts have been made to develop AuNCs for enhanced imaging contrast and multimodal imaging. Herein, an updated overview of recent advances in AuNCs was present for visible fluorescence (FL) imaging, near-infrared fluorescence (NIR-FL) imaging, two-photon near-infrared fluorescence (TP-NIR-FL) imaging, computed tomography (CT) imaging, positron emission tomography (PET) imaging, magnetic resonance imaging (MRI), and photoacoustic (PA) imaging.

LINE-1 activation in the cerebellum drives ataxia.

Dysregulation of long interspersed nuclear element 1 (LINE-1, L1), a dominant class of transposable elements in the human genome, has been linked to neurodegenerative diseases, but whether elevated L1 expression is sufficient to cause neurodegeneration has not been directly tested. Here, we show that the cerebellar expression of L1 is significantly elevated in ataxia telangiectasia patients and strongly anti-correlated with the expression of epigenetic silencers. To examine the role of L1 in the disease etiology, we developed an approach for direct targeting of the L1 promoter for overexpression in mice.

AgRP neurons control structure and function of the medial prefrontal cortex.

Hypothalamic agouti-related peptide and neuropeptide Y-expressing (AgRP) neurons have a critical role in both feeding and non-feeding behaviors of newborn, adolescent, and adult mice, suggesting their broad modulatory impact on brain functions. Here we show that constitutive impairment of AgRP neurons or their peripubertal chemogenetic inhibition resulted in both a numerical and functional reduction of neurons in the medial prefrontal cortex (mPFC) of mice. These changes were accompanied by alteration of oscillatory network activity in mPFC, impaired sensorimotor gating, and altered ambulatory behavior that could be reversed by the administration of clozapine, a non-selective dopamine receptor antagonist.

The steroid hormone estriol (E) regulates epigenetic programming of fetal mouse brain and reproductive tract.

Background: Estriol (E) is a steroid hormone formed only during pregnancy in primates including humans. Although E is synthesized at large amounts through a complex pathway involving the fetus and placenta, it is not required for the maintenance of pregnancy and has classically been considered virtually inactive due to associated very weak canonical estrogen signaling. However, estrogen exposure during pregnancy may have an effect on organs both within and outside the reproductive system, and compounds with binding affinity for estrogen receptors weaker than E have been found to impact reproductive organs and the brain.

From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective.

The hypocretin/orexin (Hcrt/Orx) system in the perifornical lateral hypothalamus has been recognized as a critical node in a complex network of neuronal systems controlling both physiology and behavior in vertebrates. Our understanding of the Hcrt/Orx system and its array of functions and actions has grown exponentially in merely 2 decades. This review will examine the latest progress in discerning the roles played by the Hcrt/Orx system in regulating homeostatic functions and in executing instinctive and learned behaviors.

Activation of Hypocretin Neurons in Endometriosis.

Endometriosis is a gynecological disease affecting 6-10% of women of reproductive age. In addition to gynecologic symptoms, endometriosis is associated with various systemic effects, including inflammation, altered body weight, and behavioral changes. Previous murine studies demonstrate that endometriosis is causally inked to increased pain sensitization, behavioral changes, and low body mass index (BMI).

Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior.

Microglia have been implicated in synapse remodeling by phagocytosis of synaptic elements in the adult brain, but the mechanisms involved in the regulation of this process are ill-defined. By examining microglia-neuronal interaction in the ventral hippocampus, we found a significant reduction in spine synapse number during the light phase of the light/dark cycle accompanied by increased microglia-synapse contacts and an elevated amount of microglial phagocytic inclusions. This was followed by a transient rise in microglial production of reactive oxygen species (ROS) and a concurrent increase in expression of uncoupling protein 2 (Ucp2), a regulator of mitochondrial ROS generation.

Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward autoactivation loop in mice.

Hypothalamic feeding circuits have been identified as having innate synaptic plasticity, mediating adaption to the changing metabolic milieu by controlling responses to feeding and obesity. However, less is known about the regulatory principles underlying the dynamic changes in agouti-related protein (AgRP) perikarya, a region crucial for gating of neural excitation and, hence, feeding. Here we show that AgRP neurons activated by food deprivation, ghrelin administration, or chemogenetics decreased their own inhibitory tone while triggering mitochondrial adaptations in neighboring astrocytes.

Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances the learning of cue-reward contingency.

The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found that ACh levels and nucleus basalis of Meynert (NBM) cholinergic terminal activity in the BLA (NBM-BLA) increased sharply in response to reward-related events and shifted as mice learned the cue-reward contingency.

Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice.

The brain has evolved in an environment where food sources are scarce, and foraging for food is one of the major challenges for survival of the individual and species. Basic and clinical studies show that obesity or overnutrition leads to overwhelming changes in the brain in animals and humans. However, the exact mechanisms underlying the consequences of excessive energy intake are not well understood.

Optimal route of gold nanoclusters administration in mice targeting Parkinson's disease.

To explore the optimal route of gold nanoclusters (AuNCs) administration in mice targeting Parkinson's disease. Assessing the pharmacokinetic and bioavailability of AuNCs in mice administrated following intravenous, intraperitoneal, gavage and intranasal injection. Investigating the biodistribution of AuNCs in mice by atomic absorption spectrometry and transmission electron microscope.

A step towards the automation of intracytoplasmic sperm injection: real time confirmation of mouse and human oocyte penetration and viability by electrical resistance measurement.

Objective: To evaluate if oocyte penetration and viability can be confirmed by an electrical resistance increase. Automated (robotic) intracytoplasmic sperm injection (ICSI) requires confirmation of oolemma penetration before sperm injection. Visual assessment using image processing algorithms have been developed but remain unreliable.

Cichoric acid from witloof inhibit misfolding aggregation and fibrillation of hIAPP.

The misfolding, aggregation and fibrillation of human islet amyloid polypeptide (hIAPP) has been acknowledged as a hallmark event in type-II diabetes. Hence, inhibiting the misfolding, aggregation and fibrillation of hIAPP have been accepted as a vital factor to treat the disease. Here cichoric acid was extracted from witloof to explore its inhibition effects on misfolding, aggregation and fibrillation of hIAPP.

Mediation of the Acute Stress Response by the Skeleton.

We hypothesized that bone evolved, in part, to enhance the ability of bony vertebrates to escape danger in the wild. In support of this notion, we show here that a bone-derived signal is necessary to develop an acute stress response (ASR). Indeed, exposure to various types of stressors in mice, rats (rodents), and humans leads to a rapid and selective surge of circulating bioactive osteocalcin because stressors favor the uptake by osteoblasts of glutamate, which prevents inactivation of osteocalcin prior to its secretion.