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Group B Streptococcus (GBS) is classified into nine serotypes that vary in capsular polysaccharide (CPS) architecture but share in common the presence of a terminal sialic acid (Sia) residue. This position and linkage of GBS Sia closely resembles that of cell surface glycans found abundantly on human cells. CD33-related Siglecs (CD33rSiglecs) are a family of Sia-binding lectins expressed on host leukocytes that engage host Sia-capped glycans and send signals that dampen inflammatory gene activation. We hypothesized that GBS evolved to display CPS Sia as a form of molecular mimicry limiting the activation of an effective innate immune response. In this study, we applied a panel of immunologic and cell-based assays to demonstrate that GBS of several serotypes interacts in a Sia- and serotype-specific manner with certain human CD33rSiglecs, including hSiglec-9 and hSiglec-5 expressed on neutrophils and monocytes. Modification of GBS CPS Sia by O acetylation has recently been recognized, and we further show that the degree of O acetylation can markedly affect the interaction between GBS and hSiglec-5, -7, and -9. Thus, production of Sia-capped bacterial polysaccharide capsules that mimic human cell surface glycans in order to engage CD33rSiglecs may be an example of a previously unrecognized bacterial mechanism of leukocyte manipulation.

Adolescent girls must contend with several sets of competing expectations at the discursive intersection of sexuality, age, gender, and race. This article examines how a feminist mentorship program for early adolescent girls engaged the issue of sexuality. Despite the program's self described feminist orientation, ethnographic analysis revealed its reliance on moralistic, age-based standards of appropriate sexual interest and behavior; the suppression of sexuality; and girl-as-victim discourse. These data bolster the call for reformed, sex-positive approaches to adolescent sexuality and reveal some of the complexities involved in cross-generational feminist interventions. Keywords: adolescence; feminism; gender; sexuality

Sociologists working in the racial formation tradition have made a clear case for understanding race as a political and social construction and have detailed macroprocesses of production. However, we still do not understand enough about how race is reproduced through microlevel interactions. Drawing on ethnographic data from research in schools, the author examines everyday race-making--the processes through which race and racial categories are reproduced and contested in daily life. As racial identities are assigned to individuals and racial categories are mapped onto groups, these groups and individuals are simultaneously included in or excluded from a variety of social interactions and social institutions. It is through these everyday interactions that racial boundaries are formed and renegotiated. Keywords: race; racialization; reproduction; education

Objective The COVID-19 Exposure and Family Impact Scales (CEFIS) were developed in Spring 2020 to assess effects of the COVID-19 pandemic on families and caregivers. Initial psychometric properties were promising. The current study examined the factor structure and evaluated convergent and criterion validity of the CEFIS in a new sample. Methods In October and November 2020, caregivers (N  = 2,531) of youth (0–21 years) scheduled for an ambulatory care visit at Nemours Children's Hospital, Delaware completed the CEFIS and measures of convergent (PROMIS Global Mental Health Scale, Family Assessment Device) and criterion validity (PTSD Checklist—Civilian). Confirmatory factor analysis was used to examine the factor structure of the CEFIS. Bivariate correlations and logistic regression were used to examine convergent and criterion validity. Results Factor analysis supported the original six- and three-factor structures for the Exposure and Impact scales, respectively. Second-order factor analyses supported the use of Exposure, Impact, and Distress total scores. Higher scores on the CEFIS Exposure, Impact, and Distress scales were associated with increased mental health concerns and poorer family functioning. Higher scores on all CEFIS scales were also associated with greater odds of having clinically significant posttraumatic stress symptoms. Conclusions The CEFIS is a psychometrically sound measure of the impact of the COVID-19 pandemic on family and caregiver functioning and may also be useful in identifying families who would benefit from psychological supports. [ABSTRACT FROM AUTHOR]

White student behaviors at a predominantly white university can often negatively impact minority students as a screen for ethnic or racial stereotyping. Problematic peer relations are best understood within the larger social and organizational contexts that support them.

Morphologically distinct TDP‐43 aggregates occur in clinically different FTLD‐TDP subtypes, yet the mechanism of their emergence and contribution to clinical heterogeneity are poorly understood. Several lines of evidence suggest that pathological TDP‐43 follows a prion‐like cascade, but the molecular determinants of this process remain unknown. We use advanced microscopy techniques to compare the seeding properties of pathological FTLD‐TDP‐A and FTLD‐TDP‐C aggregates. Upon inoculation of patient‐derived aggregates in cells, FTLD‐TDP‐A seeds amplify in a template‐dependent fashion, triggering neoaggregation more efficiently than those extracted from FTLD‐TDP‐C patients, correlating with the respective disease progression rates. Neoaggregates are sequentially phosphorylated with N‐to‐C directionality and with subtype‐specific timelines. The resulting FTLD‐TDP‐A neoaggregates are large and contain densely packed fibrils, reminiscent of the pure compacted fibrils present within cytoplasmic inclusions in postmortem brains. In contrast, FTLD‐TDP‐C dystrophic neurites show less dense fibrils mixed with cellular components, and their respective neoaggregates are small, amorphous protein accumulations. These cellular seeding models replicate aspects of the patient pathological diversity and will be a useful tool in the quest for subtype‐specific therapeutics. Synopsis: Pathological TDP‐43 derived from FTLD patient brains triggers de novo aggregation of physiological TDP‐43 in host cells via a prion‐like cascade. Different subtypes of FTLD‐TDP show distinct organization of TDP‐43 aggregates in patient brains, different seeding potencies, neoaggregate structures and C‐terminal serine phosphorylation timelines. Pathological TDP‐43 triggers template‐dependent aggregation and amplification of neoaggregatesFTLD‐TDP‐A and FTLD‐TDP‐C aggregates have different seeding potency (high vs. low) and follow distinct timelines of C‐terminal serine phosphorylationNeoaggregates triggered by FTLD‐TDP‐A and FTLD‐TDP‐C display different aggregation profiles (fibrillar vs. amorphous) resembling the original aggregates in patient brains (densely vs. loosely packed fibrils) [ABSTRACT FROM AUTHOR]

Recurrent urinary tract infections (rUTI) are a costly clinical problem affecting millions of women worldwide each year. The majority of rUTI cases are caused by uropathogenic Escherichia coli (UPEC). Data from humans and mouse models indicate that some instances of rUTI are caused by UPEC emerging from latent reservoirs in the bladder. Women with vaginal dysbiosis, typically characterized by high levels of Gardnerella and other anaerobes, are at increased risk of UTI. Multiple studies have detected Gardnerella in urine collected by transurethral catheterization (to limit vaginal contamination), suggesting that some women experience routine urinary tract exposures. We recently reported that inoculation of Gardnerella into the bladder triggers rUTI from UPEC bladder reservoirs in a mouse model. Here we performed whole bladder RNA-seq to identify host pathways involved in Gardnerella- induced rUTI. We identified a variety host pathways differentially expressed in whole bladders following Gardnerella exposure, such as pathways involved in inflammation/immunity and epithelial turnover. At the gene level, we identified upregulation of Immediate Early (IE) genes, which are induced in various cell types shortly following stimuli like infection and inflammation. One such upregulated IE gene was the orphan nuclear receptor Nur77 (aka Nr4a1). Pilot experiments in Nur77-/- mice suggest that Nur77 is necessary for Gardnerella exposure to trigger rUTI from UPEC reservoirs. These findings demonstrate that bladder gene expression can be impacted by short-lived exposures to urogenital bacteria and warrant future examination of responses in distinct cell types, such as with single cell transcriptomic technologies. The biological validation studies in Nur77-/- mice lay the groundwork for future studies investigating Nur77 and the Immediate Early response in rUTI. [ABSTRACT FROM AUTHOR]