Play2Code: A Web Application To Teach Coding Concepts

Computers are used on a daily basis, but children are not taught the concept of programming until high school or sometimes even college. Play to Code will help bridge this gap by providing young students with a fun, interactive way to learn basic coding principles on their own without the presence of an instructor. While there are some other online applications to help users learn how to code, there are very few that cater to elementary school students specifically. Online resources mostly consist of documentation with technical jargon that is difficult for children to understand, or videos that lack the hands-on experience that kids love to have when learning something new. We believe that exposing this demographic of students to computer science will greatly benefit them in the future and develop passions for coding that they may not have discovered for several years. Even if they do not ultimately decide to pursue computer science, the logical and analytical skills gained will help them in whatever field they ultimately choose

Effect of PhoP-PhoQ Activation by Broad Repertoire of Antimicrobial Peptides on Bacterial Resistance

International audiencePathogenic bacteria can resist their microenvironment by changing the expression of virulence genes. In Salmonella typhimurium, some of these genes are controlled by the two-component system PhoP-PhoQ. Studies have shown that activation of the system by cationic antimicrobial peptides (AMPs) results, among other changes, in outer membrane remodeling. However, it is not fully clear what characteristics of AMPs are required to activate the PhoP-PhoQ system and whether activation can induce resistance to the various AMPs. For that purpose, we investigated the ability of a broad repertoire of AMPs to traverse the inner membrane, to activate the PhoP-PhoQ system, and to induce bacterial resistance. The AMPs differ in length, composition, and net positive charge, and the tested bacteria include two wild-type (WT) Salmonella strains and their corresponding PhoP-PhoQ knock-out mutants. A lacZ-reporting system was adapted to follow PhoP-PhoQ activation. The data revealed that: (i) a good correlation exists among the extent of the positive charge, hydrophobicity, and amphipathicity of an AMP and its potency to activate PhoP-PhoQ; (ii) a +1 charged peptide containing histidines was highly potent, suggesting the existence of an additional mechanism independent of the peptide charge; (iii) the WT bacteria are more resistant to AMPs that are potent activators of PhoP-PhoQ; (iv) only a subset of AMPs, independent of their potency to activate the system, is more toxic to the mutated bacteria compared with the WT strains; and (v) short term exposure of WT bacteria to these AMPs does not enhance resistance. Overall, this study advances our understanding of the molecular mechanism by which AMPs activate PhoP-PhoQ and induce bacterial resistance. It also reveals that some AMPs can overcome such a resistance mechanism

Opposing effects of PhoPQ and PmrAB on the properties of Salmonella enterica serovar Typhimurium: implications on resistance to antimicrobial peptides

The increasing number of resistant bacteria is a major threat worldwide, leading to the search for new antibiotic agents. One of the leading strategies is the use of antimicrobial peptides (AMPs), cationic and hydrophobic innate immune defense peptides. A major target of AMPs is the bacterial membrane. Notably, accumulating data suggest that AMPs can activate the two-component systems (TCSs) of Gram-negative bacteria. These include PhoP-PhoQ (PhoPQ) and PmrA-PmrB (PmrAB), responsible for remodeling of the bacterial cell surface. To better understand this mechanism, we utilized bacteria deficient either in one system alone or in both and biophysical tools including fluorescence spectroscopy, single-cell atomic force microscopy, electron microscopy, and mass spectrometry (Moskowitz, S. M.; Antimicrob. Agents Chemother. 2012, 56, 1019-1030; Cheng, H. Y.; J. Biomed. Sci. 2010, 17, 60). Our data suggested that the two systems have opposing effects on the properties of Salmonella enterica. The knockout of PhoPQ made the bacteria more susceptible to AMPs by making the surface less rigid, more polarized, and permeable with a slightly more negatively charged cell wall. In addition, the periplasmic space is thinner. In contrast, the knockout of PmrAB did not affect its susceptibility, while it made the bacterial outer layer very rigid, less polarized, and less permeable than the other two mutants, with a negatively charged cell wall similar to the WT. Overall, the data suggest that the coexistence of systems with opposing effects on the biophysical properties of the bacteria contribute to their membrane flexibility, which, on the one hand, is important to accommodate changing environments and, on the other hand, may inhibit the development of meaningful resistance to AMPs

Mouse Models of Anemia of Cancer

<div><p>Anemia of cancer (AC) may contribute to cancer-related fatigue and impair quality of life. Improved understanding of the pathogenesis of AC could facilitate better treatment, but animal models to study AC are lacking. We characterized four syngeneic C57BL/6 mouse cancers that cause AC. Mice with two different rapidly-growing metastatic lung cancers developed the characteristic findings of anemia of inflammation (AI), with dramatically different degrees of anemia. Mice with rapidly-growing metastatic melanoma also developed a severe anemia by 14 days, with hematologic and inflammatory parameters similar to AI. Mice with a slow-growing peritoneal ovarian cancer developed an iron-deficiency anemia, likely secondary to chronically impaired nutrition and bleeding into the peritoneal cavity. Of the four models, hepcidin mRNA levels were increased only in the milder lung cancer model. Unlike in our model of systemic inflammation induced by heat-killed <i>Brucella abortus</i>, ablation of hepcidin in the ovarian cancer and the milder lung cancer mouse models did not affect the severity of anemia. Hepcidin-independent mechanisms play an important role in these murine models of AC.</p></div

Mice with metastatic lung cancer have iron-restricted erythropoiesis with hypoferremia and increased tissue iron stores.

<p>C57BL/6 mice were injected intraperitoneally with TC-1 or LLC cells and euthanized after 14 days. Both tumor-bearing mouse models show: (A) elevated ZPP levels compared to controls, indicating iron-restricted heme synthesis; (B) hypoferremia; (C) increased liver iron. (D) The LLC-bearing mice have increased spleen iron, and the TC-1-bearing mice have a trend towards increased spleen iron, TC-1 vs. PBS, P = 0.381. N = 8–19 mice per treatment and control group. *P<0.05, **P<0.001; P by Mann-Whitney rank sum test. Bars and error bars are median ±75^th/25^th percentile.</p

Peripheral blood smears from wild-type tumor and control mice show no significant schistocytosis.

<p>(A) PBS control (B) TC-1 (C) LLC (D) ID8.</p

Summary of Mouse Models.

<p>Summary of Mouse Models.</p

TC-1 and LLC tumor-bearing mice show evidence of systemic inflammation but only TC-1 has increased hepcidin mRNA.

<p>By day 14, (A) both tumor models have increased levels of liver SAA-1 mRNA; (B) TC-1-bearing mice have increased liver hepcidin mRNA levels compared to controls, and LLC-bearing mice have decreased hepcidin. N = 8–19 mice per treatment and control group. *P<0.05; P by Mann-Whitney rank sum test. Bars and error bars are median ±75^th/25^th percentile.</p