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      Sex Matters: Robust Sex Differences in Signal Detection in the HIV-1 Transgenic Rat

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          Abstract

          Sex differences in human immunodeficiency virus type-1 (HIV-1) have been repeatedly suggested. Females, who account for 51% of HIV-1 seropositive individuals, are inadequately represented in clinical and preclinical studies, as well as in the description of HIV-1 associated neurocognitive disorders (HAND). Direct comparisons of neurocognitive decline in women and men must be made to address this underrepresentation. The effect of biological sex (i.e., the biological factors, including chromosomes and hormones, determining male or female characteristics; WHO, 2017) on sustained attention, which is commonly impaired in HIV-1 seropositive individuals, was investigated in intact HIV-1 transgenic (Tg) and control animals using a signal detection operant task. Analyses revealed a robust sex difference in the rate of task acquisition, collapsed across genotype, with female animals meeting criteria in shaping (at least 60 reinforcers for three consecutive or five non-consecutive sessions) and signal detection (70% accuracy for five consecutive or seven non-consecutive sessions) significantly more slowly than male animals. Presence of the HIV-1 transgene also had a significant effect on shaping and signal detection acquisition, with HIV-1 Tg animals displaying significant deficits in the rate of acquisition relative to control animals–deficits that were more prominent in female HIV-1 Tg animals. Once the animals’ reached asymptotic performance in the signal detection task, female animals achieved a lower percent accuracy across test sessions and exhibited a decreased response rate relative to male animals, although there was no compelling evidence for any effect of transgene. Results indicate that the factor of biological sex may be a moderator of the influence of the HIV-1 transgene on signal detection. Understanding the impact of biological sex on neurocognitive deficits in HIV-1 is crucial for the development of sex-based therapeutics and cure strategies.

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          The X-files in immunity: sex-based differences predispose immune responses

          Sex-based differences in immune responses can influence the susceptibility to autoimmune and infectious diseases and the efficacy of therapeutic drugs. In this Perspective, Eleanor Fish discusses factors, such as X-linked genes, hormones and societal context, that underlie disparate immune responses in men and women.
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            A continuous performance test of brain damage.

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              Female rats are not more variable than male rats: a meta-analysis of neuroscience studies

              Background Not including female rats or mice in neuroscience research has been justified due to the variable nature of female data caused by hormonal fluctuations associated with the female reproductive cycle. In this study, we investigated whether female rats are more variable than male rats in scientific reports of neuroscience-related traits. Methods PubMed and Web of Science were searched for the period from August 1, 2010, to July 31, 2014, for articles that included both male and female rats and that measured diverse aspects of brain function. Only empirical articles using both male and female gonad-intact adult rats, written in English, and including the number of subjects (or a range) were included. This resulted in 311 articles for analysis. Data were extracted from digital images from article PDFs and from manuscript tables and text. The mean and standard deviation (SD) were determined for each data point and their quotient provided a coefficient of variation (CV) as a measure of trait-specific variability for each sex. Additionally, the results were coded for the type of research being measured (behavior, electrophysiology, histology, neurochemistry, and non-brain measures) and for the strain of rat. Over 6000 data points were extracted for both males and females. Subsets of the data were coded for whether male and female mean values differed significantly and whether animals were grouped or individually housed. Results Across all traits, there were no sex differences in trait variability, as indicated by the CV, and there were no sex differences in any of the four neuroscience categories, even in instances in which mean values for males and females were significantly different. Female rats were not more variable at any stage of the estrous cycle than male rats. There were no sex differences in the effect of housing conditions on CV. On one of four measures of non-brain function, females were more variable than males. Conclusions We conclude that even when female rats are used in neuroscience experiments without regard to the estrous cycle stage, their data are not more variable than those of male rats. This is true for behavioral, electrophysiological, neurochemical, and histological measures. Thus, when designing neuroscience experiments to include both male and female rats, power analyses based on variance in male measures are sufficient to yield accurate numbers for females as well, even when the estrous cycle is not taken into consideration. Electronic supplementary material The online version of this article (doi:10.1186/s13293-016-0087-5) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                06 November 2017
                2017
                : 11
                : 212
                Affiliations
                [1] 1Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina , Columbia, SC, United States
                [2] 2Department of Psychology, University of South Carolina , Columbia, SC, United States
                Author notes

                Edited by: Francesca Cirulli, Istituto Superiore di Sanità, Italy

                Reviewed by: Akiko Shimamoto, Meharry Medical College, United States; Gordon Alfred Barr, Children’s Hospital of Philadelphia, United States

                *Correspondence: Charles F. Mactutus mactutus@ 123456mailbox.sc.edu
                Article
                10.3389/fnbeh.2017.00212
                5681841
                c4dea6e0-5273-4d9b-9383-c14e0f77696e
                Copyright © 2017 McLaurin, Booze, Mactutus and Fairchild.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 27 July 2017
                : 17 October 2017
                Page count
                Figures: 3, Tables: 0, Equations: 8, References: 80, Pages: 11, Words: 8743
                Funding
                Funded by: National Institute on Drug Abuse 10.13039/100000026
                Award ID: DA013137
                Funded by: Eunice Kennedy Shriver National Institute of Child Health and Human Development 10.13039/100009633
                Award ID: HD043680
                Funded by: National Institute of Mental Health 10.13039/100000025
                Award ID: MH106392
                Funded by: National Institute of Neurological Disorders and Stroke 10.13039/100000065
                Award ID: NS100624
                Categories
                Neuroscience
                Original Research

                Neurosciences
                hiv-1 transgenic rat,biological sex,sustained attention,neuroinflammation
                Neurosciences
                hiv-1 transgenic rat, biological sex, sustained attention, neuroinflammation

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