VTA dopamine neurons are hyperexcitable in 3xTg-AD mice due to casein kinase 2-dependent SK channel dysfunction.

Alzheimer's disease (AD) patients exhibit neuropsychiatric symptoms that extend beyond classical cognitive deficits, suggesting involvement of subcortical areas. Here, we investigated the role of midbrain dopamine (DA) neurons in AD using the amyloid + tau-driven 3xTg-AD mouse model. We found deficits in reward-based operant learning in AD mice, suggesting possible VTA DA neuron dysregulation.

Breeding zebra finches prioritize reproductive bout over self-maintenance under food restriction.

Reproduction requires high amounts of energy, and challenging environments during breeding can force parents to prioritize their current reproductive bout over self-maintenance or vice versa. However, little is known about how common stressors, such as food restriction, can influence these trade-offs during breeding, and the physiological mechanisms for these trade-off decisions. In this study, adult zebra finches (Taeniopygia castanotis) were subjected to a control diet (ad libitum) or a 40% food restriction while raising nestlings and fledglings, and we measured body mass, furculum fat, plasma corticosterone (CORT) and blood glucose levels of the parents at the time of pairing, when their offspring fledged, and when their offspring reached nutritional independence.

Evaluation of Self-collected Saliva Samples Without Viral Transport Media for SARS-CoV-2 Testing via RT-PCR and Comparison of Amplicon Sequences Against Commonly Used Primers in Diagnostic Assays.

Introduction: Mass screening for SARS-CoV-2 using nasopharyngeal swabs (NPS) is costly, uncomfortable for patients, and increases the chance of virus exposure to health care workers. Therefore, this study focused on determining if self-collected unpreserved saliva can be an effective alternative to NPS collection in COVID-19 surveillance.

Materials And Methods: In this study, patients being tested for SARS-CoV-2 using NPS were asked to provide a saliva sample to compare their results.

Flow Cytometry Analysis of Microglial Phenotypes in the Murine Brain During Aging and Disease.

Microglia, the brain's primary resident immune cell, exists in various phenotypic states depending on intrinsic and extrinsic signaling. Distinguishing between these phenotypes can offer valuable biological insights into neurodevelopmental and neurodegenerative processes. Recent advances in single-cell transcriptomic profiling have allowed for increased granularity and better separation of distinct microglial states.

Postoperative Opioid-Prescribing Practice in Limb Preservation Surgery.

Background: Limb preservation surgery affects more than 100,000 Americans annually. Current postoperative pain management prescribing practices of podiatric physicians in the United States are understudied. We examined prescribing practices for limb preservation surgery to identify prescriber characteristics' that may be associated with postoperative opioid-prescribing practices.

Age- and sex- divergent translatomic responses of the mouse retinal pigmented epithelium.

Aging is the main risk factor for age-related macular degeneration (AMD), a retinal neurodegenerative disease that leads to irreversible blindness, particularly in people over 60 years old. Retinal pigmented epithelium (RPE) atrophy is an AMD hallmark. Genome-wide chromatin accessibility, DNA methylation, and gene expression studies of AMD and control RPE demonstrate epigenomic/transcriptomic changes occur during AMD onset and progression.

Specificity and efficiency of tamoxifen-mediated Cre induction is equivalent regardless of age.

Temporally controlling Cre recombination through tamoxifen (Tam) induction has many advantages for biomedical research. Most studies report early post-natal/juvenile (<2 m.o.

Differential usage of DNA modifications in neurons, astrocytes, and microglia.

Background: Cellular identity is determined partly by cell type-specific epigenomic profiles that regulate gene expression. In neuroscience, there is a pressing need to isolate and characterize the epigenomes of specific CNS cell types in health and disease. In this study, we developed an in vivo tagging mouse model (Camk2a-NuTRAP) for paired isolation of neuronal DNA and RNA without cell sorting and then used this model to assess epigenomic regulation, DNA modifications in particular, of gene expression between neurons and glia.

Consistent specificity and efficiency of tamoxifen-mediated cre induction across ages.

Temporally controlling cre recombination through tamoxifen (Tam) induction has many advantages for biomedical research. Most studies report Tam induction at early post-natal/juvenile (<2 m.o.

Real-World Pitfalls of Analyzing Real-World Data: A Cautionary Note and Path Forward.

Purpose: Real-world data (RWD) are pervasive in oncology research and offer insights into clinical trends and patient outcomes. However, RWD have shortcomings, making them prone to pitfalls during survival analyses. The American Society of Clinical Oncology (ASCO) CancerLinQ Discovery (CLQD) multiple myeloma (MM) data set was used to demonstrate some common pitfalls when analyzing survival from RWD: using incorrect surrogate markers for missing data and/or classification errors, ignoring deaths at time zero, and failing to account for guarantee-time bias.

Microglial senescence contributes to female-biased neuroinflammation in the aging mouse hippocampus: implications for Alzheimer's disease.

Background: Microglia, the brain's principal immune cells, have been implicated in the pathogenesis of Alzheimer's disease (AD), a condition shown to affect more females than males. Although sex differences in microglial function and transcriptomic programming have been described across development and in disease models of AD, no studies have comprehensively identified the sex divergences that emerge in the aging mouse hippocampus. Further, existing models of AD generally develop pathology (amyloid plaques and tau tangles) early in life and fail to recapitulate the aged brain environment associated with late-onset AD.

Multiple Myeloma in Adolescent and Young Adults: An ASCO CancerLinQ and SEER Analysis.

Background: Multiple myeloma (MM) is exceedingly rare in adolescents and young adults (AYAs) < 45 years of age.

Methods: Real-world data from ASCO's CancerLinQ Discovery (CLQD) MM dataset and SEER were utilized to characterize demographics and outcomes of AYA MM patients in the United States in the modern treatment era. Frequencies of SPMs, VTEs, and infections were assessed, as were OS and cause of death.

Microglial MHC-I induction with aging and Alzheimer's is conserved in mouse models and humans.

Major histocompatibility complex I (MHC-I) CNS cellular localization and function is still being determined after previously being thought to be absent from the brain. MHC-I expression has been reported to increase with brain aging in mouse, rat, and human whole tissue analyses, but the cellular localization was undetermined. Neuronal MHC-I is proposed to regulate developmental synapse elimination and tau pathology in Alzheimer's disease (AD).

Differential usage of DNA modifications in neurons, astrocytes, and microglia.

Background: Cellular identity is determined partly by cell type-specific epigenomic profiles that regulate gene expression. In neuroscience, there is a pressing need to isolate and characterize the epigenomes of specific CNS cell types in health and disease. This is especially true as for DNA modifications where most data are derived from bisulfite sequencing that cannot differentiate between DNA methylation and hydroxymethylation.

Survival of U.S. Military Service Members With Lymphoma.

Introduction: Cancer is a prominent cause of mortality in today's active duty service members (ADSMs), killing over 700 ADSMs between 2004 and 2015. Hence, more research is needed to better understand the survival of U.S.

Selective Inhibition of ADAR1 Using 8-Azanebularine-Modified RNA Duplexes.

Adenosine deaminases acting on RNA (ADARs) are RNA editing enzymes that catalyze the hydrolytic deamination of adenosine (A) to inosine (I) in dsRNA. In humans, two catalytically active ADARs, ADAR1 and ADAR2, perform this A-to-I editing event. The growing field of nucleotide base editing has highlighted ADARs as promising therapeutic agents while multiple studies have also identified ADAR1's role in cancer progression.

Microglial senescence contributes to female-biased neuroinflammation in the aging mouse hippocampus: implications for Alzheimer's disease.

Background: Microglia, the brain's principal immune cells, have been implicated in the pathogenesis of Alzheimer's disease (AD), a condition shown to affect more females than males. Although sex differences in microglial function and transcriptomic programming have been described across development and in disease models of AD, no studies have comprehensively identified the sex divergences that emerge in the aging mouse hippocampus. Further, existing models of AD generally develop pathology (amyloid plaques and tau tangles) early in life and fail to recapitulate the aged brain environment associated with late-onset AD.

Microglial MHC-I induction with aging and Alzheimer's is conserved in mouse models and humans.

Major Histocompatibility Complex I (MHC-I) CNS cellular localization and function is still being determined after previously being thought to be absent from the brain. MHC-I expression has been reported to increase with brain aging in mouse, rat, and human whole tissue analyses but the cellular localization was undetermined. Neuronal MHC-I is proposed to regulate developmental synapse elimination and tau pathology in Alzheimer's disease (AD).

Cell-Specific Paired Interrogation of the Mouse Ovarian Epigenome and Transcriptome.

Assessing cell-type-specific epigenomic and transcriptomic changes are key to understanding ovarian aging. To this end, the optimization of the translating ribosome affinity purification (TRAP) method and the isolation of nuclei tagged in specific cell types (INTACT) method was performed for the subsequent paired interrogation of the cell-specific ovarian transcriptome and epigenome using a novel transgenic NuTRAP mouse model. The expression of the NuTRAP allele is under the control of a floxed STOP cassette and can be targeted to specific ovarian cell types using promoter-specific Cre lines.

Neurodegeneration in a novel invertebrate model system: Failed microtubule-mediated cell adhesion and unraveling of macroglia.

Neurodegenerative diseases are among the main causes of death in the United States, leading to irreversible disintegration of neurons. Despite intense international research efforts, cellular mechanisms that initiate neurodegeneration remain elusive, thus inhibiting the development of effective preventative and early onset medical treatment. To identify underlying cellular mechanisms that initiate neuron degeneration, it is critical to identify histological and cellular hallmarks that can be linked to underlying biochemical processes.