Effects of social defeat on iK-ba inflammatory signaling in male c57BL/6J

An estimated 30 million people in the United States have been diagnosed with mood and anxiety disorders. Unfortunately, many of these patients do not adequately respond to current pharmacotherapies, so developing new drugs and strategies to treat such disorders is critically important. There are only a few drugs on the market that target neuroinflammation. Thus, it's critical that we identify anti-inflammatory agents that effectively reduce neuroinflammatory responses, hereby expanding or augmenting available options for treating neurological disorders. Previous work has shown that the derivative of naltrexone, B-funaltrexamine (B-FNA), inhibits inflammatory signaling in human astrocytes in reduced expression of proinflammatory chemokines. IKBa is one of the specific signaling proteins in the inflammation pathway

Study of Postmortem Sodium Concentrations in the Brain, Aqueous Humor and Cerebrospinal Fluid of Horses Received at Oklahoma Animal Disease Diagnostic Laboratory

Water deprivation/sodium ion toxicosis is well documented in certain species. A normal sodium range as well as a toxic range has been previously established for cattle, poultry and swine. Diagnostic laboratories often receive requests for brain sodium levels to use in conjunction with histological findings for diagnosis of water deprivation/sodium ion toxicosis. No reference values for equine brain sodium concentrations have been found in the literature. Aqueous humor, cerebrospinal fluid, cerebellum, and frontal lobe specimens were harvested from horses with a history that did not suggest a neurologic problem and that were submitted to Oklahoma Animal Disease Diagnostic Laboratory for necropsy. Testing was done at Oklahoma Animal Disease Diagnostic Laboratory in the toxicology laboratory using atomic absorption spectrometry to determine sodium levels in the frontal lobe, cerebrospinal fluid, aqueous humor, and cerebellum of the horse. Samples were tested and statistically show that the probable range for sodium in the horse is 984 ppm to 1724 ppm in the frontal lobe, 827 ppm to 1963 ppm in the cerebellum, 75-199 mEq/L (1711 ppm to 4583 ppm) in the aqueous humor, and 22-250 mEq/L (1992 ppm to 9697 ppm) in the CSF. The brain values will be very useful to veterinarians and diagnosticians across the country. With the increased public awareness of cruelty/neglect cases, these values will allow for more accurate diagnosis of water deprivation/sodium ion toxicosis in horses.Veterinary Pathobiolog

Inequalities around fashioned bodies, style, and beauty: A seminar examining social injustices related to the apparel industry, discipline, and/or personal aesthetics

The seminar was centered around scholarship related to or addressing social justice or social justice issues in the apparel industry, our discipline, or personal and/or community aesthetics and styles. We focused on work examining underrepresented populations such as: (a) people of color, (b) the LGBTQ+ community, (c) people of a variety of abilities, and/or (d) other groups that have a history of oppression, discrimination, or power and privilege inequalities. The seminar had a non-traditional “arrangement” in the room with “exhibits” of scholarly work and “mini talks” from each presenter. Our goal was to initiate and encourage these discussions to go beyond the seminar session and for the participants to engage in dialogue at their home institutions and programs while building a network of people in the seminar to dialogue about in the future

Ongoing changes in migration phenology and winter residency at Bracken Bat Cave

Bats play an important role in agroecology and are effective bioindicators of environmental conditions, but little is known about their fundamental migration ecology, much less how these systems are responding to global change. Some of the world's largest bat populations occur during the summer in the south-central United States, when millions of pregnant females migrate from lower latitudes to give birth in communal maternity colonies. Despite a relatively large volume of research into these colonies, many fundamental questions regarding their abundance—including their intra- and interseasonal variability—remain unanswered, and even estimating the size of individual populations has been a long-running challenge. Overall, monitoring these bat populations at high temporal resolution (e.g., nightly) and across long time spans (e.g., decades) has been impossible. Here, we show 22 continuous years of nightly population counts at Bracken Cave, a large bat colony in south-central Texas, enabling the first climate-scale phenological analysis. Using quantitative radar monitoring, we found that spring migration and the summer reproductive cycle have advanced by approximately 2 weeks over the study period. Furthermore, we quantify the ongoing growth of a newly—established overwintering population that indicates a system-wide response to changing environmental conditions. Our observations reveal behavioral plasticity in bats’ ability to adapt to changing resource availability, and provide the first long-term quantification of their response to a changing climate. As aerial insectivores, these changes in bat phenology and propensity for overwintering indicate probable shifts in prey availability, with clear implications for pest management across wider regional agrisystems

Protective effects of β-Funaltrexamine against LPS-induced CCL2 expression and behavioral deficits

Background: Inflammation is present in both neurological and peripheral disorders. Specifically, inflammation is one of the common factors in diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), mood disorders which include anxiety and depression, and even inflammatory bowel disease (IBD). Thus, exploring potential treatments geared toward the assessment of inflammation is crucial to the continuation of treatment development. One pharmacological agent researched for its antiinflammatory effects is β-funaltrexamine (β-FNA), a selective mu-opioid receptor antagonist. Preclinical studies using in vitro human astroglial cells showed that β-FNA inhibited inflammatory signaling, NF-κB signaling, and chemokine expression in a mechanism unrelated to MOR. Also, β-funaltrexamines neuroprotective effects were discovered in a preclinical model of lipopolysaccharide (LPS)-induced neuroinflammation and sickness-like behavior when administered before LPS.Methods: This study determines the effects of β-FNA (50 mg/kg, i.p.) on LPS-induced (0.83 mg/kg, i.p.) sickness-like behavior using a 10 min open field test, and anxiety-like behavior, using a 5 min elevated plus maze in male and female C57BL/6J. It also assesses the effects on LPS-induced neuro and peripheral inflammation when β-FNA is administered immediately or 10 h post-LPS. Tissue collected included whole brain, hippocampus, prefrontal cortex, cerebellum/brain stem, spleen, liver, small intestine, large intestine, and plasma.Results and Conclusions: Levels of inflammatory chemokine Monocyte Chemoattractant Protein-1 (MCP1, also known as CCL2) was measured using an enzyme-linked immunosorbent assay (ELISA). Two-way analysis of variance revealed that at 24 hours, LPS increased chemokines, and β-FNA treatment was protective depending on the dosing schedule and had region-specific effects. Also, to our knowledge, this is the first time β-FNAs effect on female mice has been assessed. Differential effects of β-FNA were found between the whole brain vs. brain regions, central vs. peripheral, and sexes. This study provides insight into the inflammatory protection offered by β-FNA in both the central and peripheral systems and further knowledge of the potential therapeutic options for inflammatory disorders

β-Funaltrexamine protects against lipopolysaccharide-induced neuroinflammation and behavioral impairment

Background: One of the commonalities present in a multitude of neurological disorders is inflammation. For this reason, targeting inflammation has emerged as a viable option for the potential treatment of neurological disorders. Previous work indicated that beta-funaltrexamine (β-FNA), a selective mu-opioid receptor (MOR) antagonist, not only inhibited inflammatory signaling in vitro in human astroglial cells but also inhibited lipopolysaccharide (LPS)-induced neuroinflammation and sickness-like behavior in mice when administered post-LPS immediately.Methods: The present study explores the extent to which β-FNA is protective when treatment occurs 10 hours after LPS administration. Male and female C57BL/6J mice were administered LPS (0.83 mg/kg, i.p.) followed by treatment with β-FNA (50 mg/kg, i.p.) immediately or 10h post-LPS. Sickness-like and anxiety-like behavior was assessed using a 10-min open-field test and a 5-min elevated plus-maze test followed by the collection of the whole brain, hippocampus, frontal cortex, cerebellum/brain stem, and plasma. Levels of inflammatory chemokines/cytokines(interferon γ-induced protein, CXCL10; monocyte chemotactic protein 1, CCL2; interleukin-6, IL-6; interleukin-1β, IL-1β, and Tumor Necrosis Factor Alpha, TNF-α) in tissues were measured using an enzyme-linked immunosorbent assay.Results: Two-way analysis of variance revealed that at 24 hours, LPS increased chemokines and cytokines, and β-FNA treatment was protective depending on the dosing schedule and had region-specific effects. β-FNA inhibited levels of CXCL10 in the hippocampus, frontal cortex, cerebellum/brain stem, and plasma, and more so in males. CCL2 had differential effects between males and females in the frontal cortex, cerebellum/brain stem, and plasma. β-FNA treatment also varied in IL-6, IL-1β, and TNF-α in a region-specific and sex-specific manner. Sickness-like behavior and anxiety-like behavior also differentiated between males and females.Conclusions: This study indicates that LPS-induced neuroinflammation was differentially affected by βFNA treatment across different brain regions. This shows that the treatment might have a regional effect more than a global one. Sex differences between males and females showed differential effects in the timing of treatment, tissue, and in some cases, even in their response to the LPS-induced stimulation. Further examination of β-FNA’s anti-inflammatory and neuroprotective actions is still necessary

Regulation of the androgen receptor by SET9-mediated methylation

The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain communication between the N- and C-termini and recruitment to androgen-target genes. We also show that SET9 is pro-proliferative and anti-apoptotic in prostate cancer cells and demonstrates up-regulated nuclear expression in prostate cancer tissue. In all, our date indicate a new mechanism of AR regulation that may be therapeutically exploitable for prostate cancer treatment

Accretion Rate and the Physical Nature of Unobscured Active Galaxies

We show how accretion rate governs the physical properties of a sample of unobscured broad-line, narrow-line, and lineless active galactic nuclei (AGNs). We avoid the systematic errors plaguing previous studies of AGN accretion rate by using accurate accretion luminosities (L_int) from well-sampled multiwavelength SEDs from the Cosmic Evolution Survey (COSMOS), and accurate black hole masses derived from virial scaling relations (for broad-line AGNs) or host-AGN relations (for narrow-line and lineless AGNs). In general, broad emission lines are present only at the highest accretion rates (L_int/L_Edd > 0.01), and these rapidly accreting AGNs are observed as broad-line AGNs or possibly as obscured narrow-line AGNs. Narrow-line and lineless AGNs at lower specific accretion rates (L_int/L_Edd < 0.01) are unobscured and yet lack a broad line region. The disappearance of the broad emission lines is caused by an expanding radiatively inefficient accretion flow (RIAF) at the inner radius of the accretion disk. The presence of the RIAF also drives L_int/L_Edd < 10^-2 narrow-line and lineless AGNs to 10 times higher ratios of radio to optical/UV emission than L_int/L_Edd > 0.01 broad-line AGNs, since the unbound nature of the RIAF means it is easier to form a radio outflow. The IR torus signature also tends to become weaker or disappear from L_int/L_Edd < 0.01 AGNs, although there may be additional mid-IR synchrotron emission associated with the RIAF. Together these results suggest that specific accretion rate is an important physical "axis" of AGN unification, described by a simple model.Comment: Accepted for publication in the Astrophysical Journal. 15 pages, 9 figure