Investigating the timeless susceptibility of undergraduate college students for contracting and transmitting sexually transmitted infections: A historical analysis

National rates of sexually transmitted infections (STIs) are at an all time high and college aged undergraduate students continue to contract and transmit them at a rate disproportionally higher than any other demographic group. The timeless causes of this health disparity date back to the 1990s, and range from factors as simple as condom usage and number of sexual partners to more complex factors such as levels of sexual self-efficacy and various obstacles to obtaining screening and testing. The effects of these factors are clear and negatively contribute to both the growing STI and HIV/AIDS epidemics. This historical analysis will review literature from the 1990s, early 2000s and present day, to discuss the relevance of critically analyzing the history of eerily similar STI trends over the past decades for devising the necessary innovative solutions required for successful resolution of increased rates of STIs among undergraduate college students

BIOMOLECULAR ENGINEERING FOR THE DESIGN AND CHARACTERIZATION OF IMMUNE MODULATING PROTEINS

Biomolecular engineering can be used both to design new molecules with sophisticated fit-for-purpose properties and/or to manipulate and subsequently characterize molecules in ways that provide insight into the behaviors of the native protein. Here, the use of biomolecular engineering for both the design and characterization of immune-modulating proteins of therapeutic potential is described. In a design example, a novel interleukin-2 (IL-2) immunocytokine (IC) aimed at improving the tolerability and efficacy of an IL-2 therapy in cancer is described. Specifically, an IL-2-based cytokine/antibody fusion protein (immunocytokine) was engineered to augment the ratio of immune effector cells to regulatory T cells by altering affinities of the IL-2/IL-2 receptor interface as well as increase the intratumoral bioavailability of IL-2 by combining molecularly engineered collagen binding domains and intratumoral administration. The bioactivity and bioavailability of the engineered IC was localized to and retained in the tumor, thereby minimizing IL-2 toxicity. Furthermore, the immunocytokine exhibited single-agent therapeutic efficacy, elicited an abscopal response, and was synergistic with immune checkpoint blockade in mouse tumors models. In a characterization example, biomolecular engineering was used to manipulate the native interaction between interleukin-7 (IL-7) and an anti-IL-7 neutralizing antibody in an effort to study the mechanism through which the neutralizing antibody paradoxically potentiates IL-7 activity. Specifically, the creation of a single-chain fusion protein between IL-7 and a neutralizing anti-IL-7 antibody and its subsequent characterization alongside the native cytokine, antibody, and cytokine/antibody complexes in biophysical, functional, and crystallographic studies is described. These studies elucidated a probable mechanism through which the activity of IL-7 is potentiated by the anti-IL-7 neutralizing antibody, and ongoing work evaluating the therapeutic potential of the single-chain fusion protein and cytokine/antibody complex in chimeric antigen receptor T (CAR-T) cell therapy and sepsis-induced lymphopenia is presented. Finally, published collaborative work is appended that describes the design of recombinant class II major histocompatibility complex monomers that were incorporated into an ex vivo nanoparticle-based artificial antigen presenting cell platform to promote the expansion of antigen-specific T cells for use in adoptive cell transfer applications in cancer immunotherapy. Collectively, the work described herein demonstrates the use of biomolecular engineering for the design and characterization of immune-modulating proteins of therapeutic potential

Route of Glucose Uptake in the Group a Streptococcus Impacts SLS-Mediated Hemolysis and Survival in Human Blood

The transport and metabolism of glucose has been shown to have far reaching consequences in the transcriptional profile of many bacteria. As glucose is most often the preferred carbon source for bacteria, its presence in the environment leads to the repression of many alternate carbohydrate pathways, a condition known as carbon catabolite repression (CCR). Additionally, the expression of many virulence factors is also dependent on the presence of glucose. Despite its importance, little is known about the transport routes of glucose in the human pathogen Streptococcus pyogenes. Considering that Streptococcus pyogenes is an important human pathogen responsible for over 500,000 deaths every year, we characterized the routes of glucose transport in an effort to understand its importance in GAS pathogenesis. Using a deletion of glucokinase (ΔnagC) to block utilization of glucose imported by non-PTS pathways, we determined that of the two glucose transport pathways in GAS (PTS and non-PTS), the non-PTS pathway played a more significant role in glucose transport. However, the expression of both pathways is linked by a currently unknown mechanism, as blocking the non-PTS uptake of glucose reduces ptsI (EI) expression. Similar to the effects of the deletion of the PTS pathway, lack of the non-PTS pathway also leads to the early activity of Streptolysin S. However, this early activity did not adversely or favorably affect survival of ΔnagC in whole human blood. In a subcutaneous murine infection model, ΔnagC-infected mice showed increased lesion severity at the local site of infection; although, lesion size and dissemination from the site of infection was similar to wild type. Here, we show that glucose transport in GAS is primarily via a non-PTS pathway. The route of glucose transport differentially affects the survival of GAS in whole human blood, as well as the lesion size at the local site of infection in a murine skin infection model

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<p>The transport and metabolism of glucose has been shown to have far reaching consequences in the transcriptional profile of many bacteria. As glucose is most often the preferred carbon source for bacteria, its presence in the environment leads to the repression of many alternate carbohydrate pathways, a condition known as carbon catabolite repression (CCR). Additionally, the expression of many virulence factors is also dependent on the presence of glucose. Despite its importance, little is known about the transport routes of glucose in the human pathogen Streptococcus pyogenes. Considering that Streptococcus pyogenes is an important human pathogen responsible for over 500,000 deaths every year, we characterized the routes of glucose transport in an effort to understand its importance in GAS pathogenesis. Using a deletion of glucokinase (ΔnagC) to block utilization of glucose imported by non-PTS pathways, we determined that of the two glucose transport pathways in GAS (PTS and non-PTS), the non-PTS pathway played a more significant role in glucose transport. However, the expression of both pathways is linked by a currently unknown mechanism, as blocking the non-PTS uptake of glucose reduces ptsI (EI) expression. Similar to the effects of the deletion of the PTS pathway, lack of the non-PTS pathway also leads to the early activity of Streptolysin S. However, this early activity did not adversely or favorably affect survival of ΔnagC in whole human blood. In a subcutaneous murine infection model, ΔnagC-infected mice showed increased lesion severity at the local site of infection; although, lesion size and dissemination from the site of infection was similar to wild type. Here, we show that glucose transport in GAS is primarily via a non-PTS pathway. The route of glucose transport differentially affects the survival of GAS in whole human blood, as well as the lesion size at the local site of infection in a murine skin infection model.</p

A global metagenomic map of urban microbiomes and antimicrobial resistance

We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.Funding: the Tri-I Program in Computational Biology and Medicine (CBM) funded by NIH grant 1T32GM083937; GitHub; Philip Blood and the Extreme Science and Engineering Discovery Environment (XSEDE), supported by NSF grant number ACI-1548562 and NSF award number ACI-1445606; NASA (NNX14AH50G, NNX17AB26G), the NIH (R01AI151059, R25EB020393, R21AI129851, R35GM138152, U01DA053941); STARR Foundation (I13- 0052); LLS (MCL7001-18, LLS 9238-16, LLS-MCL7001-18); the NSF (1840275); the Bill and Melinda Gates Foundation (OPP1151054); the Alfred P. Sloan Foundation (G-2015-13964); Swiss National Science Foundation grant number 407540_167331; NIH award number UL1TR000457; the US Department of Energy Joint Genome Institute under contract number DE-AC02-05CH11231; the National Energy Research Scientific Computing Center, supported by the Office of Science of the US Department of Energy; Stockholm Health Authority grant SLL 20160933; the Institut Pasteur Korea; an NRF Korea grant (NRF-2014K1A4A7A01074645, 2017M3A9G6068246); the CONICYT Fondecyt Iniciación grants 11140666 and 11160905; Keio University Funds for Individual Research; funds from the Yamagata prefectural government and the city of Tsuruoka; JSPS KAKENHI grant number 20K10436; the bilateral AT-UA collaboration fund (WTZ:UA 02/2019; Ministry of Education and Science of Ukraine, UA:M/84-2019, M/126-2020); Kyiv Academic Univeristy; Ministry of Education and Science of Ukraine project numbers 0118U100290 and 0120U101734; Centro de Excelencia Severo Ochoa 2013–2017; the CERCA Programme / Generalitat de Catalunya; the CRG-Novartis-Africa mobility program 2016; research funds from National Cheng Kung University and the Ministry of Science and Technology; Taiwan (MOST grant number 106-2321-B-006-016); we thank all the volunteers who made sampling NYC possible, Minciencias (project no. 639677758300), CNPq (EDN - 309973/2015-5), the Open Research Fund of Key Laboratory of Advanced Theory and Application in Statistics and Data Science – MOE, ECNU, the Research Grants Council of Hong Kong through project 11215017, National Key RD Project of China (2018YFE0201603), and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01) (L.S.