Animals exhibit sex-specific behaviors that are governed by sexually dimorphic circuits. One such behavior in male , courtship, is regulated by various sensory modalities, including olfaction. Here, we reveal how sexually dimorphic olfactory pathways in male flies converge at the third-order, onto lateral horn output neurons, to regulate courtship.
View Article and Find Full Text PDFBackground: Acute liver injury (ALI) that progresses into acute liver failure (ALF) is a life-threatening condition with an increasing incidence and associated costs. Acetaminophen (N-acetyl-p-aminophenol, APAP) overdosing is among the leading causes of ALI and ALF in the Northern Hemisphere. Brain dysfunction defined as is one of the main diagnostic criteria for ALF.
View Article and Find Full Text PDFLittle is known about how insecure attachment affects aggressive behavior and well-being among Vietnamese youth. Using structural equation modeling, we investigate the mediating role of subjective social status (SSS) on the paths from insecure attachment to overt aggressive behavior (OAB) and psychological well-being (PW) in a sample of 1753 Vietnamese adolescents (M = 16.136, SD = 0.
View Article and Find Full Text PDFIsolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal syndrome for Parkinson's disease (PD) and related -synucleinopathies. We conducted a longitudinal imaging study of network changes in iRBD and their relationship to phenoconversion. Expression levels for the PD-related motor and cognitive networks (PDRP and PDCP) were measured at baseline, 2 and 4 years, along with dopamine transporter (DAT) binding.
View Article and Find Full Text PDFmolting offers a powerful entry point to understanding developmentally programmed apical extracellular matrix remodeling. However, the gene regulatory network controlling this process remains poorly understood. Focusing on targets of NHR-23, a key transcription factor that drives molting, we confirmed the Kunitz family protease inhibitor gene as an NHR-23 target.
View Article and Find Full Text PDFSubthalamic nucleus deep brain stimulation (STN-DBS) alleviates motor symptoms of Parkinson's disease (PD), thereby improving quality of life. However, quantitative brain markers to evaluate DBS responses and select suitable patients for surgery are lacking. Here, we used metabolic brain imaging to identify a reproducible STN-DBS network for which individual expression levels increased with stimulation in proportion to motor benefit.
View Article and Find Full Text PDFThe auxin-inducible degron (AID) system is a widely-used system for conditional protein depletion. During the course of an experiment, we depleted the nuclear hormone receptor transcription factor NHR-23 to study molting, and we recovered a spontaneous suppressor allele that bypassed the L1 larval arrest caused by NHR-23 depletion. These mutants also failed to deplete a BFP::AID reporter in the strain background, suggesting a broader defect in the AID system.
View Article and Find Full Text PDFPsychosis that occurs over the course of Alzheimer's disease (AD) is associated with increased caregiver burden and a more rapid cognitive and functional decline. To find new treatment targets, studies modeling psychotic conditions traditionally employ agents known to induce psychosis, utilizing outcomes with cross-species relevance, such as locomotive activity and sensorimotor gating, in rodents. In AD, increased burdens of tau pathology (a diagnostic hallmark of the disease) and treatment with anticholinergic medications have, separately, been reported to increase the risk of psychosis.
View Article and Find Full Text PDFObjective: The purpose of this study was to characterize a metabolic brain network associated with X-linked dystonia-parkinsonism (XDP).
Methods: Thirty right-handed Filipino men with XDP (age = 44.4 ± 8.
In reducing greenhouse gas (GHG) emissions, there is a recognition triggered by the pandemic of the role that walking and cycling (active travel) can make to substitute motorized travel, particularly on short trips. However, there is a lack of evidence at the micro level on the realistic, empirically derived, potential of these options. Here, we used reliable tracing data to examine the potential of these mitigation options for reducing GHG emissions in Vietnam.
View Article and Find Full Text PDFConditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons.
View Article and Find Full Text PDFNematode molting is a remarkable process where animals must repeatedly build a new apical extracellular matrix (aECM) beneath a previously built aECM that is subsequently shed. The nuclear hormone receptor NHR-23 (also known as NR1F1) is an important regulator of C. elegans molting.
View Article and Find Full Text PDFPrimary dystonia is thought to emerge through abnormal functional relationships between basal ganglia and cerebellar motor circuits. These interactions may differ across disease subtypes and provide a novel biomarker for diagnosis and treatment. Using a network mapping algorithm based on resting-state functional MRI (rs-fMRI), a method that is readily implemented on conventional MRI scanners, we identified similar disease topographies in hereditary dystonia associated with the DYT1 or DYT6 mutations and in sporadic patients lacking these mutations.
View Article and Find Full Text PDFLysosomes are an important organelle required for the degradation of a range of cellular components. Lysosome function is critical for development and homeostasis as dysfunction can lead to inherited genetic disorders, cancer, and neurodegenerative and metabolic diseases. The acidic and protease-rich environment of lysosomes poses experimental challenges.
View Article and Find Full Text PDFBackground And Purpose: Although sporadic Creutzfeldt-Jakob disease (sCJD) is a rare cause of dementia, it is critical to understand its functional networks as the prion protein spread throughout the brain may share similar mechanisms with other more common neurodegenerative disorders. In this study, the metabolic brain network associated with sCJD was investigated and its internal network organization was explored.
Methods: We explored 2-[ F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) brain scans of 29 sCJD patients, 56 normal controls (NCs) and 46 other dementia patients from two independent centers.
Background: Brain metabolic alterations and neuroinflammation have been reported in several peripheral inflammatory conditions and present significant potential for targeting with new diagnostic approaches and treatments. However, non-invasive evaluation of these alterations remains a challenge.
Methods: Here, we studied the utility of a micro positron emission tomography (microPET) dual tracer ([C]PBR28 - for microglial activation and [F]FDG for energy metabolism) approach to assess brain dysfunction, including neuroinflammation in murine endotoxemia.
Front Aging Neurosci
November 2022
Background: Metabolic brain imaging with 2-[F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is a supportive diagnostic and differential diagnostic tool for neurodegenerative dementias. In the clinic, scans are usually visually interpreted. However, computer-aided approaches can improve diagnostic accuracy.
View Article and Find Full Text PDFBehavioral variant of frontotemporal dementia (bvFTD) is common among young-onset dementia patients. While bvFTD-specific multivariate metabolic brain pattern (bFDRP) has been identified previously, little is known about its temporal evolution, internal structure, effect of atrophy, and its relationship with nonspecific resting-state networks such as default mode network (DMN). In this multicenter study, we explored FDG-PET brain scans of 111 bvFTD, 26 Alzheimer's disease, 16 Creutzfeldt-Jakob's disease, 24 semantic variant primary progressive aphasia (PPA), 18 nonfluent variant PPA and 77 healthy control subjects (HC) from Slovenia, USA, and Germany.
View Article and Find Full Text PDFSpermatogenesis is the process through which mature male gametes are formed and is necessary for the transmission of genetic information. While much work has established how sperm fate is promoted and maintained, less is known about how the sperm morphogenesis program is executed. We previously identified a novel role for the nuclear hormone receptor transcription factor, NHR-23, in promoting Caenorhabditis elegans spermatogenesis.
View Article and Find Full Text PDFBackground: Idiopathic Parkinson's disease (iPD) is associated with two distinct brain networks, PD-related pattern (PDRP) and PD-related cognitive pattern (PDCP), which correlate respectively with motor and cognitive symptoms. The relationship between the two networks in individual patients is unclear.
Objective: To determine whether a consistent relationship exists between these networks, we measured the difference between PDRP and PDCP expression, termed delta, on an individual basis in independent populations of patients with iPD (n = 356), patients with idiopathic REM sleep behavioral disorder (iRBD) (n = 21), patients with genotypic PD (gPD) carrying GBA1 variants (n = 12) or the LRRK2-G2019S mutation (n = 14), patients with atypical parkinsonian syndromes (n = 238), and healthy control subjects (n = 95) from the United States, Slovenia, India, and South Korea.
Auxin-inducible degradation is a powerful tool for the targeted degradation of proteins with spatiotemporal control. One limitation of the auxin-inducible degradation system is that not all proteins are degraded efficiently. Here, we demonstrate that an alternative degron sequence, termed mIAA7, improves the efficiency of degradation in Caenorhabditiselegans, as previously reported in human cells.
View Article and Find Full Text PDFThe neuroglial extracellular matrix (ECM) provides critical support and physiological cues for the proper growth, differentiation, and function of neuronal cells in the brain. However, in most in vitro settings that study neural physiology, cells are grown as monolayers on stiff surfaces that maximize adhesion and proliferation, and, therefore, they lack the physiological cues that ECM in native neuronal tissues provides. Macromolecular crowding (MMC) is a biophysical phenomenon based on the principle of excluded volume that can be harnessed to induce native ECM deposition by cells in culture.
View Article and Find Full Text PDFThe fetal brain is constantly exposed to maternal IgG before the formation of an effective blood-brain barrier (BBB). Here, we studied the consequences of fetal brain exposure to an antibody to the astrocytic protein aquaporin-4 (AQP4-IgG) in mice. AQP4-IgG was cloned from a patient with neuromyelitis optica spectrum disorder (NMOSD), an autoimmune disease that can affect women of childbearing age.
View Article and Find Full Text PDF