SpeB of Streptococcus pyogenes Differentially Modulates Antibacterial and Receptor Activating Properties of Human Chemokines

BACKGROUND: CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11, are antibacterial for Streptococcus pyogenes. METHODOLOGY/PRINCIPAL FINDINGS: SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/CXCL11, PF4/CXCL4, GROalpha/CXCL1, GRObeta/CXCL2, GROgamma/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3alpha/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3alpha/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity. CONCLUSIONS/SIGNIFICANCE: SpeB destroys most of the signaling and antibacterial properties of chemokines expressed by an inflamed epithelium. The exception is CXCL9 that preserves its antibacterial activity after hydrolysis, emphasizing its role as a major antimicrobial on inflamed epithelium

Childhood obesity: A comparison of health habits of middle-school students from two communities

Elizabeth A Jackson1,3, Taylor Eagle3, Adam Leidal3, Roopa Gurm3,  Joe Smolarski3, Caren Goldberg2, Bruce Rogers3, Kim A Eagle1,31Division of Cardiovascular Medicine, Department of Internal Medicine, 2Division of Pediatric Cardiology, Department of Pediatrics, 3Michigan Cardiovascular Research and Reporting Program, University of Michigan health System, Ann Arbor, MI, USAObjective: To assess whether children’s diet and physical activity patterns differ between neighboring communities with differing resources.Study design and setting: We compared the health behaviors of middle-school students in two Michigan communities; Ann Arbor and Ypsilanti; median household income of US$46,299 and 28,610, respectively. Self-reported diet and physical activity habits were collected. Participants: A total of 733 middle-school students from two neighboring communities (five Ann Arbor and two Ypsilanti middle schools) participated in the study.Measures: Data on age, gender, and racial/ethnic factors were collected as part of the baseline assessment. Students were also measured for height and weight. Body mass index was calculated. Information on diet and physical activity in addition to amounts and types of sedentary activities was assessed via questionnaires.Results: More Ypsilanti schoolchildren were obese compared to the Ann Arbor schoolchildren (22.2% vs 12.6%; P = 0.01). The Ypsilanti schoolchildren reported higher consumption of fried meats (7.5% vs 3.2%; P = 0.02), French fries or chips (14.3% vs 7.9%; P = 0.02), punch or sports drinks (24.1% vs 12.2%; P = 0.001) and soda (18% vs 7.9%; P < 0.001) compared to the Ann Arbor children. School-based activities including physical education classes (58.6% vs 89.7%; P < 0.001) and sports teams (34.6% vs 62.8%; P < 0.001) differed for Ypsilanti schoolchildren vs Ann Arbor children. Sedentary behaviors were higher in the Ypsilanti children.Conclusions: Differences in diet and physical activity habits among children from two neighboring communities with varying resources suggests a need for school-based interventions to promote healthy behaviors among middle-school students. Keywords: childhood obesity, diet, physical activity, community healt

Ribosome profiling reveals a functional role for autophagy in mRNA translational control.

Autophagy promotes protein degradation, and therefore has been proposed to maintain amino acid pools to sustain protein synthesis during metabolic stress. To date, how autophagy influences the protein synthesis landscape in mammalian cells remains unclear. Here, we utilize ribosome profiling to delineate the effects of genetic ablation of the autophagy regulator, ATG12, on translational control. In mammalian cells, genetic loss of autophagy does not impact global rates of cap dependent translation, even under starvation conditions. Instead, autophagy supports the translation of a subset of mRNAs enriched for cell cycle control and DNA damage repair. In particular, we demonstrate that autophagy enables the translation of the DNA damage repair protein BRCA2, which is functionally required to attenuate DNA damage and promote cell survival in response to PARP inhibition. Overall, our findings illuminate that autophagy impacts protein translation and shapes the protein landscape

Increasing Medical Trainees’ Empathy Through Volunteerism and Mentorship

Background: Within medical education, there have been recent calls for increased understanding and exposure to poverty to increase trainees’ empathy toward the underserved. Students participating in Michigan Cardiovascular Outcomes Research and Reporting Program research program volunteered at World Medical Relief (WMR) in Detroit, Michigan, a nonprofit organization which recycles medical equipment for developing countries and within greater Detroit. Participants’ perceptions of the underserved were measured before and after the experience. Methods: Preliminary questionnaires were given to participants prior to and after exposures at WMR. Questionnaires examined participants’ attitudes toward the underserved, knowledge of medical supply reuse, and their perceived ability to impact change. P values of 4× more likely than previously to have knowledge of the variety of recycled medical supplies at WMR. Prior to volunteering, 48.7% of participants gave little thought to how excess medical supplies could be collected versus 0% after exposure. Participants were 1.5× more likely to agree that the experience was enhanced working with their peers and 2.7× more likely to consider starting their own organization/intervention for medical supply donations. Those participants that never previously volunteered were 1.3× more likely to do so with encouragement from a mentor. Conclusions: Encouraging exposure to such service programs resulted in enhanced knowledge of community resources and increased motivation to participate in outreach and belief of individual responsibility to care for the underserved. Incorporating volunteerism into traditional education programs offers the opportunity to build awareness and interest in students reaching out to the underserved

Ribosome profiling reveals a functional role for autophagy in mRNA translational control.

Autophagy promotes protein degradation, and therefore has been proposed to maintain amino acid pools to sustain protein synthesis during metabolic stress. To date, how autophagy influences the protein synthesis landscape in mammalian cells remains unclear. Here, we utilize ribosome profiling to delineate the effects of genetic ablation of the autophagy regulator, ATG12, on translational control. In mammalian cells, genetic loss of autophagy does not impact global rates of cap dependent translation, even under starvation conditions. Instead, autophagy supports the translation of a subset of mRNAs enriched for cell cycle control and DNA damage repair. In particular, we demonstrate that autophagy enables the translation of the DNA damage repair protein BRCA2, which is functionally required to attenuate DNA damage and promote cell survival in response to PARP inhibition. Overall, our findings illuminate that autophagy impacts protein translation and shapes the protein landscape