Stress rapidly suppresses in vivo LH pulses and increases activation of RFRP-3 neurons in male mice

Restraint stress is a psychosocial stressor that suppresses reproductive status, including LH pulsatile secretion, but the neuroendocrine mechanisms underlying this inhibition remains unclear. Reproductive neural populations upstream of gonadotropin-releasing hormone (GnRH) neurons, such as kisspeptin, neurokinin B and RFRP-3 (GnIH) neurons, are possible targets for psychosocial stress to inhibit LH pulses, but this has not been well examined, especially in mice in which prior technical limitations prevented assessment of in vivo LH pulse secretion dynamics. Here, we examined whether one-time acute restraint stress alters in vivo LH pulsatility and reproductive neural populations in male mice, and what the time-course is for such alterations. We found that endogenous LH pulses in castrated male mice are robustly and rapidly suppressed by one-time, acute restraint stress, with suppression observed as quickly as 12–18 min. This rapid LH suppression parallels with increased in vivo corticosterone levels within 15 min of restraint stress. Although Kiss1, Tac2 and Rfrp gene expression in the hypothalamus did not significantly change after 90 or 180 min restraint stress, arcuate Kiss1 neural activation was significantly decreased after 180 min. Interestingly, hypothalamic Rfrp neuronal activation was strongly increased at early times after restraint stress initiation, but was attenuated to levels lower than controls by 180 min of restraint stress. Thus, the male neuroendocrine reproductive axis is quite sensitive to short-term stress exposure, with significantly decreased pulsatile LH secretion and increased hypothalamic Rfrp neuronal activation occurring rapidly, within minutes, and decreased Kiss1 neuronal activation also occurring after longer stress durations

Student Tributes to Professor Kent Newmyer

The following are the published remarks of the students and former students of Professor Kent Newmyer who spoke at a celebration honoring his work on Friday, November 8, 2019, at the University of Connecticut School of Law

Homogeneous links, Seifert surfaces, digraphs and the reduced Alexander polynomial

We give a geometric proof of the following result of Juhasz. \emph{Let $a_g$ be the leading coefficient of the Alexander polynomial of an alternating knot $K$. If $|a_g|<4$ then $K$ has a unique minimal genus Seifert surface.} In doing so, we are able to generalise the result, replacing `minimal genus' with `incompressible' and `alternating' with `homogeneous'. We also examine the implications of our proof for alternating links in general.Comment: 37 pages, 28 figures; v2 Main results generalised from alternating links to homogeneous links. Title change

Rapid transcriptional and metabolic regulation of the deacclimation process in cold acclimated Arabidopsis thaliana

Background: During low temperature exposure, temperate plant species increase their freezing tolerance in a process termed cold acclimation. This is accompanied by dampened oscillations of circadian clock genes and disrupted oscillations of output genes and metabolites. During deacclimation in response to warm temperatures, cold acclimated plants lose freezing tolerance and resume growth and development. While considerable effort has been directed toward understanding the molecular and metabolic basis of cold acclimation, much less information is available about the regulation of deacclimation.Results: We report metabolic (gas chromatography-mass spectrometry) and transcriptional (microarrays, quantitative RT-PCR) responses underlying deacclimation during the first 24 h after a shift of Arabidopsis thaliana (Columbia-0) plants cold acclimated at 4 °C back to warm temperature (20 °C). The data reveal a faster response of the transcriptome than of the metabolome and provide evidence for tightly regulated temporal responses at both levels. Metabolically, deacclimation is associated with decreasing contents of sugars, amino acids, glycolytic and TCA cycle intermediates, indicating an increased need for carbon sources and respiratory energy production for the activation of growth. The early phase of deacclimation also involves extensive down-regulation of protein synthesis and changes in the metabolism of lipids and cell wall components. Hormonal regulation appears particularly important during deacclimation, with extensive changes in the expression of genes related to auxin, gibberellin, brassinosteroid, jasmonate and ethylene metabolism. Members of several transcription factor families that control fundamental aspects of morphogenesis and development are significantly regulated during deacclimation, emphasizing that loss of freezing tolerance and growth resumption are transcriptionally highly interrelated processes. Expression patterns of some clock oscillator components resembled those under warm conditions, indicating at least partial re-activation of the circadian clock during deacclimation.Conclusions: This study provides the first combined metabolomic and transcriptomic analysis of the regulation of deacclimation in cold acclimated plants. The data indicate cascades of rapidly regulated genes and metabolites that underlie the developmental switch resulting in reduced freezing tolerance and the resumption of growth. They constitute a large-scale dataset of genes, metabolites and pathways that are crucial during the initial phase of deacclimation. The data will be an important reference for further analyses of this and other important but under-researched stress deacclimation processes

Staphylococcus aureus sarA regulates inflammation and colonization during central nervous system biofilm formation

Infection is a frequent and serious complication following the treatment of hydrocephalus with CSF shunts, with limited therapeutic options because of biofilm formation along the catheter surface. Here we evaluated the possibility that the sarA regulatory locus engenders S. aureus more resistant to immune recognition in the central nervous system (CNS) based on its reported ability to regulate biofilm formation. We utilized our established model of CNS catheter-associated infection, similar to CSF shunt infections seen in humans, to compare the kinetics of bacterial titers, cytokine production and inflammatory cell influx elicited by wild type S. aureus versus an isogenic sarA mutant. The sarA mutant was more rapidly cleared from infected catheters compared to its isogenic wild type strain. Consistent with this finding, several pro-inflammatory cytokines and chemokines, including IL-17, CXCL1, and IL-1β were significantly increased in the brain following infection with the sarA mutant versus wild type S. aureus, in agreement with the fact that the sarA mutant displayed impaired biofilm growth and favored a planktonic state. Neutrophil influx into the infected hemisphere was also increased in the animals infected with the sarA mutant compared to wild type bacteria. These changes were not attributable to extracellular protease activity, which is increased in the context of SarA mutation, since similar responses were observed between sarA and a sarA/protease mutant. Overall, these results demonstrate that sarA plays an important role in attenuating the inflammatory response during staphylococcal biofilm infection in the CNS via a mechanism that remains to be determined

Textual analysis of internal medicine residency personal statements: themes and gender differences

Context Applicants to US residency training programmes are required to submit a personal statement, the content of which is flexible but often requires them to describe their career goals and aspirations. Despite their importance, no systematic research has explored common themes and gender differences inherent to these statements. Objectives This study was conducted to analyse US applicants’ Electronic Residency Application Service (ERAS) personal statements using two automated textual analysis programs, and to assess for common themes and gender-associated differences. Methods A retrospective cohort study of 2138 personal statements (containing 1 485 255 words) from candidates from 377 national and international medical schools applying to US internal medicine (IM) residency programmes through ERAS was conducted. A mathematical analysis of text segments using a recursive algorithm was performed; two different specifications of the text segments were used to conduct an internal validation. Results Five statistically significant thematic classes were identified through independent review by the researchers. These were best defined as referring to: the appeal of the residency programme; memorable patients; health care as public policy; research and academia, and family inspiration. Some themes were common to all applications. However, important gender-specific differences were identified. Notably, men were more likely to describe personal attributes and to self-promote, whereas women more frequently expressed the communicative and team-based aspects of doctoring. The results were externally validated using a second software program. Although these data comprise part of the national pool, they represent applicants to a single specialty at a single institution. Conclusions By applying textual analysis to material derived from a national cohort, we identified common narrative themes in the personal statements of future US physicians, noting differences between men and women. Together, these data provide novel insight into the dominant discourse of doctoring in this generation of students applying for further training in US IM residency programmes, and depict a diverse group of applicants with multiple motivations, desires and goals. Furthermore, differences seen between men and women add to the growing understanding of bias in medical education. Training programmes may benefit by adapting curricula to foster such diverse interests

Likelihood-ratio ranking of gravitational-wave candidates in a non-Gaussian background

We describe a general approach to detection of transient gravitational-wave signals in the presence of non-Gaussian background noise. We prove that under quite general conditions, the ratio of the likelihood of observed data to contain a signal to the likelihood of it being a noise fluctuation provides optimal ranking for the candidate events found in an experiment. The likelihood-ratio ranking allows us to combine different kinds of data into a single analysis. We apply the general framework to the problem of unifying the results of independent experiments and the problem of accounting for non-Gaussian artifacts in the searches for gravitational waves from compact binary coalescence in LIGO data. We show analytically and confirm through simulations that in both cases the likelihood ratio statistic results in an improved analysis.Comment: 10 pages, 6 figure