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Aim: It is well-known that enterococci are abundant in the environment; however, the role of surface water as a reservoir of antimicrobial-resistant enterococci remains largely undefined. In this study, surface water samples were collected over a 2-year period from the Upper Oconee watershed, Athens, GA to examine enterococci and their antimicrobial resistance., Methods and Results: Approximately 97% (445/458) of the samples were positive for enterococci and a total of 637 enterococci were isolated. The predominant species were Enterococcus casseliflavus (33·6%) followed by Enterococcus faecalis (26·5%) and Enterococcus hirae (13·2%). Regardless of species, the highest levels of resistance were to lincomycin (88·5%) and tetracycline (13%); isolates also exhibited resistance to newer antimicrobials, daptomycin (8·9%) and tigecycline (6·4%). Multidrug resistance (resistance ≥3 antimicrobial classes) was observed to as many as five classes of antimicrobials. Resistant enterococci appeared to be randomly dispersed over the seasons rather than clustered by species or antimicrobial resistance., Conclusions: This study demonstrated that surface waters contain a large population of diverse species of antimicrobial-resistant enterococci, including resistance to new antimicrobials., Significance and Impact of the Study: These results may indicate the potential of human intestinal illness and/or colonization of the human gut with resistant enterococci as enterococci correlate with increased disease risk to humans during recreational exposure to water., (© 2019 The Society for Applied Microbiology.)

Motivation: Novel approaches are needed for discovery of targeted therapies for non-small-cell lung cancer (NSCLC) that are specific to certain patients. Whole genome RNAi screening of lung cancer cell lines provides an ideal source for determining candidate drug targets., Results: Unsupervised learning algorithms uncovered patterns of differential vulnerability across lung cancer cell lines to loss of functionally related genes. Such genetic vulnerabilities represent candidate targets for therapy and are found to be involved in splicing, translation and protein folding. In particular, many NSCLC cell lines were especially sensitive to the loss of components of the LSm2-8 protein complex or the CCT/TRiC chaperonin. Different vulnerabilities were also found for different cell line subgroups. Furthermore, the predicted vulnerability of a single adenocarcinoma cell line to loss of the Wnt pathway was experimentally validated with screening of small-molecule Wnt inhibitors against an extensive cell line panel., Availability and Implementation: The clustering algorithm is implemented in Python and is freely available at https://bitbucket.org/youngjh/nsclc_paper, Contact: marcotte@icmb.utexas.edu or jon.young@utexas.edu, Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author 2016. Published by Oxford University Press.)

The Nicotine Dependence in Teens (NDIT) study is a prospective cohort investigation of 1294 students recruited in 1999-2000 from all grade 7 classes in a convenience sample of 10 high schools in Montreal, Canada. Its primary objectives were to study the natural course and determinants of cigarette smoking and nicotine dependence in novice smokers. The main source of data was self-report questionnaires administered in class at school every 3 months from grade 7 to grade 11 (1999-2005), for a total of 20 survey cycles during high school education. Questionnaires were also completed after graduation from high school in 2007-08 and 2011-12 (survey cycles 21 and 22, respectively) when participants were aged 20 and 24 years on average, respectively. In addition to its primary objectives, NDIT has embedded studies on obesity, blood pressure, physical activity, team sports, sedentary behaviour, diet, genetics, alcohol use, use of illicit drugs, second-hand smoke, gambling, sleep and mental health. Results to date are described in 58 publications, 20 manuscripts in preparation, 13 MSc and PhD theses and 111 conference presentations. Access to NDIT data is open to university-appointed or affiliated investigators and to masters, doctoral and postdoctoral students, through their primary supervisor (www.nditstudy.ca)., (© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Human neural progenitor cells (hNPC) derived from the developing brain can be expanded in culture and subsequently differentiated into neurons and glia. They provide an interesting source of tissue for both modeling brain development and developing future cellular replacement therapies. It is becoming clear that hNPC are regionally and temporally specified depending on which brain region they were isolated from and its developmental stage. We show here that hNPC derived from the developing cortex (hNPC(CTX)) and ventral midbrain (hNPC(VM)) have similar morphological characteristics and express the progenitor cell marker nestin. However, hNPC(CTX) cultures were highly proliferative and produced large numbers of neurons, whereas hNPC(VM) divided slowly and produced fewer neurons but more astrocytes. Microarray analysis revealed a similar expression pattern for some stemness markers between the two growing cultures, overlaid with a regionally specific profile that identified some important differentially expressed neurogenic transcription factors. By overexpressing one of these, the transcription factor ASCL1, we were able to regain neurogenesis from hNPC(VM) cultures, which produced larger neurons with more neurites than hNPC(CTX) but no fully mature dopamine neurons. Thus, hNPC are regionally specified and can be induced to undergo neurogenesis following genetic manipulation. Although this restores neuronal production with a region-specific phenotype, it does not restore full neurochemical maturation, which may require additional factors.

The marrows of 10 patients with hematologic malignancies were examined by immunohistochemistry using anti TGF-beta antibody, CC(1-30), which detects secreted TGF-beta, and compared with four normal marrows. TGF-beta was not demonstrated in marrows with a normal level of reticulin fibrosis; however, TGF-beta was observed within collagen in marrows having collagen fibrosis or increased reticulin fibrosis. The extent of TGF-beta deposition paralleled the severity of fibrosis (P < .0001), and occurred even with normal or reduced numbers of megakaryocytes. Using another TGF-beta antibody, LC(1-30), which detects intracellular TGF-beta, TGF-beta was detected by immunofluorescence in discrete sites in the cytoplasm of immature and mature myeloid and large granular lymphocytic leukemia cells. These sites colocalized with areas detected by an anti-granule antibody (D545) suggesting that TGF-beta was stored in granules. However, neither the TGF-beta mRNA content nor the degree of TGF-beta secretion by these leukemic cells correlated with the extent of TGF-beta deposition in the marrow. Thus, TGF-beta deposition in marrow may contribute to myelofibrosis, but the source of this cytokine in the absence of megakaryocytes requires further study.

Plasma zinc, serum albumin and alkaline phosphatase (a zinc-dependent enzyme) were measured in thirty-five psoriatics and their age- and sex-matched controls. No significant difference was seen between these two groups as a whole, but psoriatics with less than 10% surface involvement had significantly higher mean plasma zinc levels than their respective control group. Psoriatic patients also showed a relationship between the extent of surface involvement and the plasma zinc level, those with more extensive involvement having lower levels than those with minimal involvement. The differences were not due to disturbances in serum albumin, and no abnormalities in serum alkaline phosphatase were observed.

A study was performed using monoclonal antibodies and the immunoperoxidase technic to identify T-cells and T-subsets in human tonsil sections. The in situ topographic identification of T-cells, helper cells, and suppressor cells was achieved. This model may therefore be applied to other normal lymphoid tissues. Its potential pathologic importance lies in the fact that certain disorders may be associated with depletion of lymphocyte subsets from their normal areas of "homing," and that lymphoma cells may mirror their putative normal counterparts in their selective metastatic migration pattern. The improved knowledge of normal lymphocyte subset microenvironment afforded by this technic may therefore be of value in applied pathology.

Zinc is a major component of many local skin applications. An investigation into its systemic absorption in thirty-one psoriatic hospital in-patients is reported. Plasma zinc, copper and whole blood delta-aminolaevulinic acid dehydratase were followed before and during in-patient treatment over 14 days. No significant alteration in these parameters was detected. Significantly reduced plasma zinc levels were found in the patients compared to a matched control population.