P02-07. High Concentrations of Interleukin-15 and Low Concentrations of CCL5 in Breast Milk are Associated with Protection against Postnatal HIV Transmission

Background: Natural variations in IL-15 concentration have not been investigated for an association with an immune-protection against HIV. Given IL-15's central role in anti-HIV immunity, we hypothesized that higher concentrations of IL-15 in breast milk may protect against postnatal mother-to-child HIV transmission. Methods: In a case-control study nested within a clinical trial in Zambia, we compared IL-15 concentrations in breast milk of 22 HIV-infected women who transmitted HIV to their infants through breastfeeding with those of 72 who did not, as well as 18 HIV-uninfected women. Breast milk HIV RNA quantity, sodium, CXCL12, CCL5, and IL-8 concentrations were measured as well as maternal plasma HIV RNA concentrations and CD4 cell count. We used logistic regression modeling to adjust for potential confounders. Results: Higher concentrations of IL-15 in breast milk (adjusted odds ratio [AOR]: 0.01 per log10 pg/ml increase, 95% confidence interval [CI]: <0.001 to 0.3) were associated with protection against postnatal HIV transmission in univariate analysis and after adjusting for maternal CD4 cell counts, breast milk HIV RNA, CCL5, CXCL12, and IL-8 concentrations. Breast milk IL-15 concentration correlated with breast milk sodium, the other cytokines and HIV RNA concentration. It was inversely correlated with infant birth weight and tended to be higher in 1 week than in 1 month post-partum samples. Breast milk CCL5 concentrations were associated with increased risk of HIV transmission (AOR: 12.7 95% CI: 1.6 to 102.0) in adjusted analysis. Breast milk CXCL12 and IL-8 concentrations were not independently associated with transmission. Conclusion: High concentration of IL-15 were associated with a protection against breastfeeding HIV transmission after adjusting for other pro-inflammatory cytokines, HIV RNA in breast milk, and maternal CD4 cell count. These results corroborate a protective role of IL-15-mediated cellular immunity against HIV transmission during breastfeeding. They are informative for vaccination studies using IL-15 as an adjuvant

First Records of Stelis permaculata Cockerell (Hymenoptera: Megachilidae) in Minnesota, United States of America and Manitoba, Canada

Abstract New records are reported for the cleptoparasitic bee Stelis permaculata Cockerell (Hymenoptera: Megachilidae) from Minnesota, United States of America and Manitoba, Canada. Minnesota records come from trap-nests, which also collected the host, Heriades carinata Cresson

Minnesota State Records for Osmia georgica, Megachile inimica, and Megachile frugalis (Hymenoptera, Megachilidae), Including a New Nest Description for Megachile frugalis Compared with Other Species in the Subgenus Sayapis

In this note, we report the first Minnesota state records of Osmia (Helicosmia) georgica Cresson 1878,Megachile (Sayapis) inimica Cresson 1872, and Megachile (Sayapis) frugalis Cresson 1872, which were collected in 2018. We also provide the first description of the nest structure of M. frugalis. All three species typically have more southern distributions. The nest of M. frugalis shows similar structure to other species in the subgenus Sayapis Titus, such as M. inimica and M. pugnata, particularly in that the longitudinal nest cell walls lack a lining of leaf pieces, and the cell partitions are made from a layer of leaf pieces followed by a layer of masticated vegetation and soil particles

Changes in epithelial proportions and transcriptional state underlie major premenopausal breast cancer risks

The human breast undergoes lifelong remodeling in response to estrogen and progesterone, but hormone exposure also increases breast cancer risk. Here, we use single-cell analysis to identify distinct mechanisms through which breast composition and cell state affect hormone signaling. We show that prior pregnancy reduces the transcriptional response of hormone-responsive (HR+) epithelial cells, whereas high body mass index (BMI) reduces overall HR+ cell proportions. These distinct changes both impact neighboring cells by effectively reducing the magnitude of paracrine signals originating from HR+ cells. Because pregnancy and high BMI are known to protect against hormone-dependent breast cancer in premenopausal women, our findings directly link breast cancer risk with person-to-person heterogeneity in hormone responsiveness. More broadly, our findings illustrate how cell proportions and cell state can collectively impact cell communities through the action of cell-to-cell signaling networks

The Massive Progenitor of the Type II-Linear Supernova 2009kr

We present early-time photometric and spectroscopic observations of supernova (SN) 2009kr in NGC 1832. We find that its properties to date support its classification as Type II-linear (SN II-L), a relatively rare subclass of core-collapse supernovae (SNe). We have also identified a candidate for the SN progenitor star through comparison of pre-explosion, archival images taken with WFPC2 on board the Hubble Space Telescope with SN images obtained using adaptive optics plus NIRC2 on the 10 m Keck-II telescope. Although the host galaxy's substantial distance (similar to 26 Mpc) results in large uncertainties in the relative astrometry, we find that if this candidate is indeed the progenitor, it is a highly luminous (M(V)(0) = -7.8 mag) yellow supergiant with initial mass similar to 18-24 M(circle dot). This would be the first time that an SN II-L progenitor has been directly identified. Its mass may be a bridge between the upper initial mass limit for the more common Type II-plateau SNe and the inferred initial mass estimate for one Type II-narrow SN.Hungarian OTKA K76816NSF AST-0707769, AST-0908886Sylvia & Jim Katzman FoundationTABASGO FoundationNASA through STScI AR-11248, GO-10877Harvard UniversityUC BerkeleyUniversity of VirginiaNASA/Swift NNX09AQ66GDOEAstronom

Differential disruption of genomic integrity and cell cycle regulation in normal human fibroblasts by the HPV oncoproteins.

Genomic integrity is maintained by a network of cellular activities that assess the status of the genome at a given point in time, provide signals to proceed with or halt cell cycle progression, and provide for repair of damaged DNA. Mutations in any part of these pathways can have the ultimate effect of disturbing chromosomal integrity. Recent work suggests that p53 performs this integrator function in mammalian cells. Our present study demonstrates that in mortal cells, the expression of E6 and E7 viral oncoproteins of type 16 human papillomavirus each disrupts the integration of these signals by diverged pathways. Cells expressing E6 protein, which binds and degrades the p53 protein, exhibited alterations in cell cycle control when placed in drug and displayed the ability to amplify the CAD gene. The expression of E7, which binds different cellular proteins important for transformation, including Rb, led to a p53-independent alteration in cell cycle control, a widespread cytocidal response, and polyploidy as a mechanism of drug resistance. These results demonstrate that diverse perturbations of molecular pathways can have different effects on chromosomal integrity

Designing organisational effectiveness in social entrepreneurial enterprises

Background: Fundamental principles that encourage problem solving are included in the intersection between design thinking and systems thinking. In this study, we examined if these principles contribute to the nature of organisational effectiveness (OE) in the context of a social enterprise. Aim: The objective of the study was to explore the nature of OE in social enterprises. Setting: This exploratory qualitative study investigated the OE of social enterprises in South Africa. Methods: A three-phased Delphi method was conducted by a panel of experts. Results: Our findings indicate that the principles for the OE of social enterprises include, in particular, good, just, and useful services and/or products, as well as a satisfying human experience. In the context of a social enterprise, OE is therefore about the mission and resources of the enterprise. The enterprise can be viewed as making an impact when satisfying human (community and/or beneficiary) needs through useful products or services designed for good, and when promoting just relationships among and ethical conduct by all stakeholders. Conclusion: The framework or principles for social enterprises’ OE may be used to guide leadership, governance of resources (such as finances), and training in solving ‘wicked problems’ in such ecosystems. It is recommended that social entrepreneurs also apply the framework. Contribution: This paper offers four principles that are applicable when systems thinking overlaps with design thinking to guide the OE of social enterprises

ESAF: Full Simulation of Space-Based Extensive Air Showers Detectors

Future detection of Extensive Air Showers (EAS) produced by Ultra High Energy Cosmic Particles (UHECP) by means of space based fluorescence telescopes will open a new window on the universe and allow cosmic ray and neutrino astronomy at a level that is virtually impossible for ground based detectors. In this paper we summarize the results obtained in the context of the EUSO project by means of a detailed Monte Carlo simulation of all the physical processes involved in the fluorescence technique, from the Extensive Air Shower development to the instrument response. Particular emphasis is given to modeling the light propagation in the atmosphere and the effect of clouds. Main results on energy threshold and resolution, direction resolution and Xmax determination are reported. Results are based on EUSO telescope design, but are also extended to larger and more sensitive detectors.Comment: 38 pages, 48 figures Corrected typos. Changed content. Added figure

Spinal Cord Ischemia Related to Disc Herniation:Case Report and a Review of the Literature

Symptoms of spinal cord ischemia can mimic myelopathy due to spinal cord compression in the acute phase. Thoracic disc herniation with limited spinal cord compression but rapid progression of neurological symptoms causes a clinical dilemma as to whether emergency decompression should be performed. We report a case of acute progressive myelopathy due to spinal cord ischemia related to thoracic disc herniation initially managed by Th8 laminectomy with reduction of the herniated disc. Repeat imaging showed T2-weighted hyperintensity in the posterior cord. The clinical and radiological course supports posterior spinal artery ischemia. This case illustrates and a review of the literature shows that thoracic disc herniation may be complicated by ischemic myelopathy even in the absence of cord compression