Cold Exposure Exacerbates the Development of Diabetic Polyneuropathy in the Rat

Diabetic polyneuropathy (DPN) and cold-induced nerve injury share several pathogenic mechanisms. This study explores whether cold exposure contributes to the development of DPN. Streptozotocin-induced diabetic rats and controls were exposed to a room temperature (23°C) or cold environment (10°C). H-reflex, tail and sciatic motor, and sensory nerve conduction studies were performed. Analyses of sural nerve, intraepidermal nerve fibers, and skin and nerve nitrotyrosine ELISAs were performed. Diabetic animals exposed to a cold environment had an increased H-reflex four weeks earlier than diabetic room temperature animals (P = .03). Cold-exposed diabetic animals also had greater reduction in motor conduction velocities at 20 weeks (P = .017), decreased skin nerve fiber density (P = .037), and increased skin nitrotyrosine levels (P = .047). Cold exposure appears to hasten the development of DPN in the rat STZ model of diabetes. These findings support that further study into the relationship between ambient temperature and DPN is warranted

Honey bee neurogenomic responses to affiliative and agonistic social interactions

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147835/1/gbb12509-sup-0003-FigureS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147835/2/gbb12509-sup-0002-FigureS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147835/3/gbb12509-sup-0001-FigureS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147835/4/gbb12509.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147835/5/gbb12509_am.pd

Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice

Agonistic encounters are powerful effectors of future behavior, and the ability to learn from this type of social challenge is an essential adaptive trait. We recently identified a conserved transcriptional program defining the response to social challenge across animal species, highly enriched in transcription factor (TF), energy metabolism, and developmental signaling genes. To understand the trajectory of this program and to uncover the most important regulatory influences controlling this response, we integrated gene expression data with the chromatin landscape in the hypothalamus, frontal cortex, and amygdala of socially challenged mice over time. The expression data revealed a complex spatiotemporal patterning of events starting with neural signaling molecules in the frontal cortex and ending in the modulation of developmental factors in the amygdala and hypothalamus, underpinned by a systems-wide shift in expression of energy metabolism-related genes. The transcriptional signals were correlated with significant shifts in chromatin accessibility and a network of challenge-associated TFs. Among these, the conserved metabolic and developmental regulator ESRRA was highlighted for an especially early and important regulatory role. Cell-type deconvolution analysis attributed the differential metabolic and developmental signals in this social context primarily to oligodendrocytes and neurons, respectively, and we show that ESRRA is expressed in both cell types. Localizing ESRRA binding sites in cortical chromatin, we show that this nuclear receptor binds both differentially expressed energy-related and neurodevelopmental TF genes. These data link metabolic and neurodevelopmental signali ng to social challenge, and identify key regulatory drivers of this process with unprecedented tissue and temporal resolution

Cross‐species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147855/1/gbb12502.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147855/2/gbb12502-sup-0002-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147855/3/gbb12502_am.pd

Hydrothermal Synthesis of Delafossite-Type Oxides

The syntheses of copper and silver delafossite-type oxides from their constituent binary metal oxides, oxide hydroxides and hydroxides, by low temperature (<210 °C) and low pressure (<20 atm) hydrothermal reactions are described. Particular emphasis is placed on how the acid-base character of a constituent oxide determines its solubility and therefore whether a particular delafossite-type oxide can be synthesized, a strategy utilized by geologists and mineralogists to understand the conditions necessary for the synthesis of various minerals. Thus, the geochemical and corrosion science literature are shown to be useful in understanding the reaction conditions required for the syntheses of delafossite-type oxides and the relationship between reactant metal oxide acid-base character, solubility, aqueous speciation, and product formation. Manipulation of the key parameters, temperature, pressure, pH, and reactant solubility, results in broad families of phase-pure delafossite-type oxides in moderate to high yields for copper, CuBO2 (B) Al, Sc, Cr, Mn, Fe, Co, Ga, and Rh), and silver, AgBO2 (B ) Al, Sc, Fe, Co, Ni, Ga, Rh, In, and Tl)

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

An emerging role for tcf7l2 at the nexus between metabolic regulation and social behavior

Most animals utilize social behaviors that are preprogrammed at birth, for example, to avoid predators or defend territory. But these programs are also certainly modified by emotional learning and subsequent events. Indeed, failure to modify and master these instinctive responses underlie many behavioral disorders, including schizophrenia, autism, post-traumatic stress disorder, and depression. Interestingly, many of these disorders also have a major metabolic component and several lines of data suggest an integral link between stress, brain metabolism, and plasticity of the adult brain. Our goal is to investigate the molecular basis of that link, focused on the gene regulatory factors with common metabolic and neurodevelopmental function. To investigate this connection, we have turned to gene expression and chromatin analysis, investigating shared genomic actions that guide social behavior across species. In a large collaborative study, we have performed comparable behavioral challenges in three model social species: mice, honeybees, and stickleback fish. We then collected brain RNA and chromatin over a time course to quantify molecular events occurring in these animals’ brains as they adapt to the social challenge. Using this information, we identified shared and unique genes and pathways that respond to social stress across socially responsive regions of the brain. Several of these pathways connected metabolic signaling to plasticity across the brain in all three model species, indicating the evolutionary importance of these links. One particular pathway called out for deeply conserved mechanistic importance was the WNT pathway, which is known to control neurogenesis and plasticity in a wide variety of species. We hypothesize that the link between metabolism and plasticity is channeled through WNT signaling in the animal brain. These experiments also revealed that the conserved pathways are orchestrated by specific transcription factors in each species. In mice, the nuclear receptor ESRRA activates early metabolic signals in the hypothalamus, and these signals, in turn, lead to up-regulation of developmental transcription factors (TFs), most notably the WNT regulator, TCF7L2. Tcf7l2 has been linked to neurodevelopmental disorders, but importantly, is also the single gene that is most highly associated with human metabolic disorders as well. These data focused my attention on understanding the role of TCF7L2 in social challenge response and behavior, with experiments conducted at the whole animal, cellular and molecular levels. Because hypothalamus is central to the regulation of both metabolism and social behavior, I used immunohistochemistry (IHC) to identify TCF7L2-expressing cells in the hypothalamus, and examined the targets of Tcf7l2 molecular actions inside one specific hypothalamic cell type with key roles in both metabolic signaling and hypothalamic plasticity: the tanycytes. Examining TCF7L2 chromatin binding and gene expression in cultured tanycytes derived from wild type and Tcf7l2 mutant mice, I present data suggesting a direct role modulating canonical WNT, BMP and glutamate signaling, and genes involved in differentiation and development of those radial glia-like cells. The data suggest a critical role for Tcf7l2 in maintaining tanycyte pluripotency and the ability of those cells to differentiate into POMC-expressing neurons, a mechanism that permits plasticity of metabolism and behavior in adults. Further Investigations of the role of Tcf7l2 in adult brain may lead to a greater understanding of social disorders and the evolution of sociality itself.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste

An epigenomic shift in amygdala marks the transition to maternal behaviors in alloparenting virgin female mice.

Adults of many species will care for young offspring that are not their own, a phenomenon called alloparenting. However, in many cases, nonparental adults must be sensitized by repeated or extended exposures to newborns before they will robustly display parental-like behaviors. To capture neurogenomic events underlying the transition to active parental caring behaviors, we analyzed brain gene expression and chromatin profiles of virgin female mice co-housed with pregnant dams during pregnancy and after birth. After an initial display of antagonistic behaviors and a surge of defense-related gene expression, we observed a dramatic shift in the chromatin landscape specifically in amygdala of the pup-exposed virgin females compared to females co-housed with mother before birth, accompanied by a dampening of anxiety-related gene expression. This epigenetic shift coincided with hypothalamic expression of the oxytocin gene and the emergence of behaviors and gene expression patterns classically associated with maternal care. The results outline a neurogenomic program associated with dramatic behavioral changes and suggest molecular networks relevant to human postpartum mental health