New neurons in old brains: A cautionary tale for the analysis of neurogenesis in post-mortem tissue.

Adult neurogenesis has primarily been examined in two key regions in the mammalian brain, the subgranular zone of the hippocampus and the subventricular zone. The proliferation and integration of newly generated neurons has been observed widely in adult mammalian species including the human hippocampus. Recent high-profile studies have suggested however, that this process is considerably reduced in humans, occurring in children but declining rapidly and nearly completely in the adult brain. In comparison, rodent studies also show age-related decline but a greater degree of proliferation of new neurons in adult animals. Here, we examine whether differences in tissue fixation, rather than biological difference in human versus rodent studies might account for the diminished levels of neurogenesis sometimes observed in the human brain. To do so we analyzed neurogenesis in the hippocampus of rats that were either perfusion-fixed or the brains extracted and immersion-fixed at various post-mortem intervals. We observed an interaction between animal age and the time delay between death and tissue fixation. While similar levels of neurogenesis were observed in young rats regardless of fixation, older rats had significantly fewer labeled neurons when fixation was not immediate. Furthermore, the morphological detail of the labeled neurons was significantly reduced in the delayed fixation conditions at all ages. This study highlights critical concerns that must be considered when using post-mortem tissue to quantify adult neurogenesis.

The Power of Blood: The Many Faces of Women's Monthly Menses in Jewish Law and Beyond

Menstruation has many faces. This Essay will discuss competing narratives relating to menstruation as portrayed in Jewish law and culture, and assess the implications of such narratives for modern legal systems. These narratives depict menstruation in all its contradictions — as taboo and power, as health and imperfection, and as reflecting biological difference but not inequality. Each narrative will be discussed from a textual, legal, communal and, occasionally, personal perspective, conveying different meanings that have different cultural impacts, modern applications and reflect different aspects of the quest for equality. Together, these narratives provide a holistic vision of womanhood that resists simplification. Acknowledging that not only women menstruate, in this Essay I refer to women as those who menstruate because this is the category associated with menstruation used in Jewish law and it is the complexity of womanhood revealed by Jewish law and culture that I address. These four faces of menstruation are not characterized as positive or negative in and of themselves; rather, I analyze them each on their own terms, discussing how they may impact women in both negative and positive ways. The variability of these narratives demonstrates the need for women to shape their own narratives around their bodies in order to empower themselves within their communities. Moreover, the multiplicity of faces that menstruation involves, and the different ways that femininity can therefore impact womanhood, counsels promoting menstrual justice in a variety of ways, and from a variety of perspectives, creatively empowering women by recognizing their individual complexity. In Jewish law, menstruation engenders impurity, authority, fertility, and biological difference, and each of these faces of womanhood will be discussed in turn.

Dairy Producers Who Market Their Surplus Progeny as Calves Use Germplasm With Slightly Lighter and Less-Conformed Carcasses Than Producers Who Rear Their Surplus Progeny Beyond Weaning

Understanding dairy producer mindset in service sire selection can provide useful information for different junctures along the commercial and extension animal breeding chain. It can aid the targeted marketing of bulls based on farm production systems but also provide useful information for delivering bespoke extension services. The objective of the present study was to examine if differences exist among dairy producers in their choice of dairy and beef service sires depending on the life stage at which the surplus progeny generated from such matings exit the dairy farm. This was predominantly based on evaluating the breed of beef sires used but also their genetic merit for calving difficulty and carcass traits, namely, carcass weight, conformation, and fat score; differences in genetic merit among dairy sires as well as among the dairy cows themselves were also considered. The objective was accomplished through the cross-sectional analyses of progeny fate data from 1,092,403 progeny born in 4,117 Irish dairy herds. Herd-years were categorized into one of four systems based on when the surplus progeny exited the dairy farm: (1) calves sold <70 days of age, (2) cattle sold as yearlings between 250 and 450 days of age, (3) prime cattle sold for finishing (slaughtered between 8 and 120 days of exiting the dairy farm), or (4) prime cattle sold for immediate slaughter (i.e., slaughtered within 7 days of exiting the dairy farm). The mean genetic merit of both the cows and service sires used across the four different systems was estimated using linear mixed models. Of the beef service sires used in herds that sold their surplus progeny as calves, their mean predicted transmitting ability for carcass weight and carcass conformation score was just 2.00 kg and 0.11 scores [scale of 1 (poor) to 15 (excellent)] inferior to the beef service sires used in herds that sold their surplus progeny as prime cattle for immediate slaughter. Similar trends, albeit of smaller magnitude, were evident when comparing the genetic merit of the dairy service sires used in those systems. Cows in herds that sold their surplus progeny as calves were genetically less likely to incur dystocia as well as to have lighter, less-conformed, and leaner carcasses than cows in herds that sold their surplus progeny post-weaning. Hence, results from the present study suggest that diversity in herd strategy regarding when surplus progeny exit the herd influences service sire selection choices in respect of genetic merit for dystocia and carcass attributes. That said, the biological difference based on the current pool of available service sires is small relative to the dairy producers that sell their surplus progeny as young calves; when expressed on a per standard deviation in genetic merit of the beef service sires used across all herds, the difference between extreme systems was, nonetheless, approximately half a standard deviation for carcass weight and conformation.

Sex, gender, and retinoblastoma: analysis of 4351 patients from 153 countries

Objective To investigate in a large global sample of patients with retinoblastoma whether sex predilection exists for this childhood eye cancer. Methods A cross-sectional analysis including 4351 treatment-naive retinoblastoma patients from 153 countries who presented to 278 treatment centers across the world in 2017. The sex ratio (male/female) in the sample was compared to the sex ratio at birth by means of a two-sided proportions test at global level, country economic grouping, continent, and for selected countries. Results For the entire sample, the mean retinoblastoma sex ratio, 1.20, was higher than the weighted global sex ratio at birth, 1.07 (p < 0.001). Analysis at economic grouping, continent, and country-level demonstrated differences in the sex ratio in the sample compared to the ratio at birth in lower-middle-income countries (n = 1940), 1.23 vs. 1.07 (p = 0.019); Asia (n = 2276), 1.28 vs. 1.06 (p < 0.001); and India (n = 558), 1.52 vs. 1.11 (p = 0.008). Sensitivity analysis, excluding data from India, showed that differences remained significant for the remaining sample (χ2 = 6.925, corrected p = 0.025) and for Asia (χ2 = 5.084, corrected p = 0.036). Excluding data from Asia, differences for the remaining sample were nonsignificant (χ2 = 2.205, p = 0.14). Conclusions No proof of sex predilection in retinoblastoma was found in the present study, which is estimated to include over half of new retinoblastoma patients worldwide in 2017. A high male to female ratio in Asian countries, India in specific, which may have had an impact on global-level analysis, is likely due to gender discrimination in access to care in these countries, rather than a biological difference between sexes.

Office of Management and Budget Racial/Ethnic Categories in Mortality Research: A Framework for Including the Voices of Racialized Communities

Since its founding, the US government has sorted people into racial/ethnic categories for the purpose of allowing or disallowing their access to social services and protections. The current Office of Management and Budget racial/ethnic categories originated in a dominant racial narrative that assumed a binary biological difference between Whites and non-Whites, with a hard-edged separation between them. There is debate about their continued use in researching group differences in mortality profiles and health outcomes: should we use them with modifications, cease using them entirely, or develop a new epistemology of human similarities and differences? This essay offers a research framework for including in these debates the daily lived experiences of the 110 million racialized non-White Americans whose lived experiences are the legacy of historically limited access to society’s services and protections. The experience of Latinos in California is used to illustrate the major elements of this framework that may have an effect on mortality and health outcomes: a subaltern fuzzy-edged multivalent racial narrative, agency, voice, and community and cultural resilience.

Serum Analyte Profiles Associated With Crohn’s Disease and Disease Location

Background Crohn’s disease (CD) can affect any segment of the digestive tract but is most often localized in the ileal, ileocolonic, and colorectal regions of the intestines. It is believed that the chronic inflammation in CD is a result of an imbalance between the epithelial barrier, the immune system, and the intestinal microbiota. The aim of the study was to identify circulating markers associated with CD and/or disease location in CD patients. Methods We tested 49 cytokines, chemokines, and growth factors in serum samples from 300 patients with CD and 300 controls. After quality control, analyte levels were tested for association with CD and disease location. Results We identified 13 analytes that were higher in CD patients relative to healthy controls and that remained significant after conservative Bonferroni correction (P &lt; 0.0015). In particular, CXCL9, CXCL1, and interleukin IL-6 had the greatest effect and were highly significant (P &lt; 5 × 10–7). We also identified 9 analytes that were associated with disease location, with VEGF, IL-12p70, and IL-6 being elevated in patients with colorectal disease (P &lt; 3 × 10–4). Conclusions Multiple serum analytes are elevated in CD. These implicate the involvement of multiple cell types from the immune, epithelial, and endothelial systems, suggesting that circulating analytes reflect the inflammatory processes that are ongoing within the gut. Moreover, the identification of distinct profiles according to disease location supports the existence of a biological difference between ileal and colonic CD, consistent with previous genetic and clinical observations.

Cross Gender Oral Communication from Biological Difference and Socialized Identity to Mutual Understanding

Language is an indispensable instrument whereby we organize and build our social ties in our communities, and society at large. Human language is critically interwoven into the processes whereby human beings communicate, build knowledge, transmit information, and determine the identity of both the addresser and the addressee in any communicational exchange. We could hypothetically assert that if there is unmistakably one thing without which man as a species can hardly live in the social realm, it is language par excellence. In an admittedly multi-layered and inherently complex sociolinguistic configuration, the individual speaker’s linguistic choice, the different roles he or she plays, be they in a position of addresser or addressee, and the various situations where the speech takes place do serve as markers reflecting one’s identity and communication styles. In this respect, factors such as sex, age, level of education, occupation, race, and geographical origin can virtually be reflected via one’s speech. This article sets out to analyze (1) the influential role of speech, (2) gender and identity, (3) dominance/difference, and (4) cross-gender oral communication in the Moroccan context using a homogenous convenience sample of Moroccan participants. This study falls within the scope of gender studies. Its major aim is to demonstrate the roles that mixed-gendered interlocutors can play in order to maintain effective communication. Therefore, their perceptions regarding interruptions, conversation dominance, turn-taking and choice of topics in conversations are analyzed. Different research instruments have been implemented to collect data including recordings of real-life conversational speech, classroom observation, and interviews. The findings indicate that gender-based differences permeate the conversational styles of both men and women across cultures and with divergent degrees of strength and expression. It has also been shown that although communication breakdown is a source of frustration, it remains a common phenomenon in social interactions. Therefore, overcoming difficulties in maintaining effective communication between members of different genders is dependent on the interlocutors’ belief that accepting difference in language and communication styles can make cross-gender communication a satisfactory social experience. This study is expected to raise awareness regarding the socialization processes the two sex groups have gone through which shape in substantial ways the way they speak, behave and interact among each other.

A Novel Method to Identify the Differences Between Two Single Cell Groups at Single Gene, Gene Pair, and Gene Module Levels

Single-cell sequencing technology can not only view the heterogeneity of cells from a molecular perspective, but also discover new cell types. Although there are many effective methods on dropout imputation, cell clustering, and lineage reconstruction based on single cell RNA sequencing (RNA-seq) data, there is no systemic pipeline on how to compare two single cell clusters at the molecular level. In the study, we present a novel pipeline on comparing two single cell clusters, including calling differential gene expression, coexpression network modules, and so on. The pipeline could reveal mechanisms behind the biological difference between cell clusters and cell types, and identify cell type specific molecular mechanisms. We applied the pipeline to two famous single-cell databases, Usoskin from mouse brain and Xin from human pancreas, which contained 622 and 1,600 cells, respectively, both of which were composed of four types of cells. As a result, we identified many significant differential genes, differential gene coexpression and network modules among the cell clusters, which confirmed that different cell clusters might perform different functions.

Plxdc family members are novel receptors for the rhesus monkey rhadinovirus (RRV)

The rhesus monkey rhadinovirus (RRV), a γ2-herpesvirus of rhesus macaques, shares many biological features with the human pathogenic Kaposi’s sarcoma-associated herpesvirus (KSHV). Both viruses, as well as the more distantly related Epstein-Barr virus, engage cellular receptors from the Eph family of receptor tyrosine kinases (Ephs). However, the importance of the Eph interaction for RRV entry varies between cell types suggesting the existence of Eph-independent entry pathways. We therefore aimed to identify additional cellular receptors for RRV by affinity enrichment and mass spectrometry. We identified an additional receptor family, the Plexin domain containing proteins 1 and 2 (Plxdc1/2) that bind the RRV gH/gL glycoprotein complex. Preincubation of RRV with soluble Plxdc2 decoy receptor reduced infection by ~60%, while overexpression of Plxdc1 and 2 dramatically enhanced RRV susceptibility and cell-cell fusion of otherwise marginally permissive Raji cells. While the Plxdc2 interaction is conserved between two RRV strains, 26–95 and 17577, Plxdc1 specifically interacts with RRV 26–95 gH. The Plxdc interaction is mediated by a short motif at the N-terminus of RRV gH that is partially conserved between isolate 26–95 and isolate 17577, but absent in KSHV gH. Mutation of this motif abrogated the interaction with Plxdc1/2 and reduced RRV infection in a cell type-specific manner. Taken together, our findings characterize Plxdc1/2 as novel interaction partners and entry receptors for RRV and support the concept of the N-terminal domain of the gammaherpesviral gH/gL complex as a multifunctional receptor-binding domain. Further, Plxdc1/2 usage defines an important biological difference between KSHV and RRV.