Repurposing of Meropenem and Nadifloxacin for Treatment of Burn Patients?

The escalating number of multidrug resistant pathogens has demanded the swift development of new and potent antibiotics (ref. 2). Metallo-[beta]-lactamases (MBLs) continue to evolve, rendering the latest generation of carbapenem antibiotics useless (ref. 8). SPM-1, a recently discovered MBL, was isolated from a juvenile leukemia patient residing in a hospital in San Palo, Brazil just prior to the patient succumbing to septicemia brought on by Pseudomonas aeruginosa expressing SPM-1 (ref. 8). Screening of the Johns Hopkins Compound library of 1,514 FDA or FAD approved drugs (ref. 1) identified a novel SPM-1 inhibitor that is synergistically compatible with meropenem. Using clinically achievable concentrations, meropenem coupled with nadifloxacin inhibits Pseudomonas aeruginosa expressing SPM-1. This shotgun approach to new drug discovery provided a prompt solution to the grave problem of antibiotic resistant pathogens that are thriving in hospitals today

It takes a village to break up a match: a systemic analysis of formal youth mentoring relationship endings

BACKGROUND Although early closure of formal youth mentoring relationships has recently begun to receive some attention, more information about factors that contribute to premature endings, and how those factors interact, is needed so that empirically-based program practices can be developed and disseminated to prevent such endings and to ensure that youth reap the benefits mentoring can provide. OBJECTIVE This qualitative interview study applies a systemic model of youth mentoring relationships (Keller in J Prim Prev 26:169–188, 2005a) to the study of mentoring relationship endings in community-based mentoring matches to understand why these matches ended. METHOD Mentors, parents/guardians and program staff associated with 36 mentoring matches that had ended were interviewed about their experiences of these relationships and their understanding of why they had ended. Thematic analysis of the interview transcripts and mentoring program case notes for each match followed by systemic modeling of the relationships yielded three major findings. RESULTS A strong mentor–youth relationship is necessary but not sufficient for match longevity. The mentor–youth relationship, even when relatively strong, is unlikely to withstand disruptions in other relationships in the system. Agency contextual factors, such as program practices and policies and staffing patterns, have a critical role to play in sustaining mentoring matches, as they directly influence all of the relationships in the mentoring system. CONCLUSION These findings highlight the importance of considering not just the mentoring dyad but also the parent/guardian and program context when trying to prevent match closures. They also point to several program practices that may support longer mentoring relationships.Accepted manuscrip

Optical Spectroscopic Survey of High Latitude WISE Selected Sources

We report on the results of an optical spectroscopic survey at high Galactic latitude (b\geq30{\deg}) of a sample of WISE-selected targets, grouped by WISE W1 ({\lambda}_eff = 3.4 \mum) flux, which we use to characterize the sources WISE detected. We observed 762 targets in 10 disjoint fields centered on ultra-luminous infrared galaxy (ULIRG) candidates using the DEIMOS spectrograph on Keck II. We find 0.30 \pm 0.02 galaxies arcmin^-2 with a median redshift of z=0.33 \pm 0.01 for the sample with W1 \geq 120 \muJy. The foreground stellar densities in our survey range from 0.23 \pm 0.07 arcmin^(-2) to 1.1 \pm 0.1 arcmin^(-2) for the same sample. We obtained spectra that produced science grade redshifts for \geq 90% of our targets for sources with W1 flux \geq 120 \muJy that also had i-band flux \geq 18 \muJy. We used for targeting very preliminary data reductions available to the team in August of 2010. Our results therefore present a conservative estimate of what is possible to achieve using WISE's Preliminary Data Release for the study of field galaxies.Comment: 29 pages, 10 figures, 8 table

Amino acids in the uterine luminal fluid reflects the temporal changes in transporter expression in the endometrium and conceptus during early pregnancy in cattle

In cattle, conceptus-maternal interactions are critical for the establishment and maintenance of pregnancy. A major component of this early interaction involves the transport of nutrients and secretion of key molecules by uterine epithelial cells to help support conceptus development during the peri-implantation period of pregnancy. Objectives were to: 1) analyze temporal changes in the amino acid (AA) content of uterine luminal fluid (ULF) during the bovine estrous cycle; 2) understand conceptus-induced alterations in AA content; 3) determine expression of AA transporters in the endometrium and conceptus; and 4) determine how these transporters are modulated by (Progesterone) P4. Concentrations of aspartic acid, arginine, glutamine, histidine, lysine, isoleucine, leucine, phenylalanine and tyrosine decreased on Day 16 of the estrous cycle but increased on Day 19 in pregnant heifers (P < 0.05). Glutamic acid only increased in pregnant heifers on Day 19 (P,0.001). Asparagine concentrations were greater in ULF of cyclic compared to pregnant heifers on Day 7 (P < 0.05) while valine concentrations were higher in pregnant heifers on Day 16 (P < 0.05). Temporal changes in expression of the cationic AA transporters SLC7A1 SLC7A4 and SLC7A6 occurred in the endometrium during the estrous cycle/early pregnancy coordinate with changes in conceptus expression of SLC7A4, SLC7A2 and SLC7A1 (P < 0.05). Only one acidic AA transporter (SLC1A5) increased in the endometrium while conceptus expression of SLC1A4 increased (P < 0.05). The neutral AA transporters SLC38A2 and SLC7A5 increased in the endometrium in a temporal manner while conceptus expression of SLC38A7, SLC43A2, SLC38A11 and SLC7A8 also increased (P < 0.05). P4 modified the expression of SLC1A1, -1A4, -1A5, -38A2 , -38A4, -38A7, -43A2, -6A14, -7A1, -7A5 and -7A7 in the endometrium. Results demonstrate that temporal changes in AA in the ULF reflect changes in transporter expression in the endometrium and conceptus during early pregnancy in cattle, some of which are modified by P4. © 2014 Forde et al

Coordinated thermal and optical observations of Trans-Neptunian object (20000) Varuna from Sierra Nevada

We report on coordinated thermal and optical measurements of trans-Neptunian object (20000) Varuna obtained in January-February 2002, respectively from the IRAM 30-m and IAA 1.5 m telescopes. The optical data show a lightcurve with a period of 3.176+/-0.010 hr, a mean V magnitude of 20.37+/-0.08 and a 0.42+/-0.01 magnitude amplitude. They also tentatively indicate that the lightcurve is asymmetric and double-peaked. The thermal observations indicate a 1.12+/-0.41 mJy flux, averaged over the object's rotation. Combining the two datasets, we infer that Varuna has a mean 1060(+180/-220) km diameter and a mean 0.038(+0.022/-0.010) V geometric albedo, in general agreement with an earlier determination using the same technique.Comment: Accepted for publication in Astronomy & Astrophysics (7 pages, including 3 figures

iDNA from terrestrial haematophagous leeches as a wildlife surveying and monitoring tool - prospects, pitfalls and avenues to be developed

Invertebrate-derived DNA (iDNA) from terrestrial haematophagous leeches has recently been proposed as a powerful non-invasive tool with which to detect vertebrate species and thus to survey their populations. However, to date little attention has been given to whether and how this, or indeed any other iDNA-derived data, can be combined with state-of-the-art analytical tools to estimate wildlife abundances, population dynamics and distributions. In this review, we discuss the challenges that face the application of existing analytical methods such as site-occupancy and spatial capture-recapture (SCR) models to terrestrial leech iDNA, in particular, possible violations of key assumptions arising from factors intrinsic to invertebrate parasite biology. Specifically, we review the advantages and disadvantages of terrestrial leeches as a source of iDNA and summarize the utility of leeches for presence, occupancy, and spatial capture-recapture models. The main source of uncertainty that attends species detections derived from leech gut contents is attributable to uncertainty about the spatio-temporal sampling frame, since leeches retain host-blood for months and can move after feeding. Subsequently, we briefly address how the analytical challenges associated with leeches may apply to other sources of iDNA. Our review highlights that despite the considerable potential of leech (and indeed any) iDNA as a new survey tool, further pilot studies are needed to assess how analytical methods can overcome or not the potential biases and assumption violations of the new field of iDNA. Specifically we argue that studies to compare iDNA sampling with standard survey methods such as camera trapping, and those to improve our knowledge on leech (and other invertebrate parasite) physiology, taxonomy, and ecology will be of immense future value

Comparison of the Effects of Early Pregnancy with Human Interferon, Alpha 2 (IFNA2), on Gene Expression in Bovine Endometrium

Interferon tau (IFNT), a type I IFN similar to alpha IFNs (IFNA), is the pregnancy recognition signal produced by the ruminant conceptus. To elucidate specific effects of bovine IFNT and of other conceptus-derived factors, endometrial gene expression changes during early pregnancy were compared to gene expression changes after intrauterine application of human IFNA2. In experiment 1, endometrial tissue samples were obtained on Day (D) 12, D15, and D18 postmating from nonpregnant or pregnant heifers. In experiment 2, heifers were treated from D14 to D16 of the estrous cycle with an intrauterine device releasing IFNA2 or, as controls, placebo lipid extrudates or PBS only. Endometrial biopsies were performed after flushing the uterus. All samples from both experiments were analyzed with an Affymetrix Bovine Genome Array. Experiment 1 revealed differential gene expression between pregnant and nonpregnant endometria on D15 and D18. In experiment 2, IFNA2 treatment resulted in differential gene expression in the bovine endometrium. Comparison of the data sets from both studies identified genes that were differentially expressed in response to IFNA2 but not in response to pregnancy on D15 or D18. In addition, genes were found that were differentially expressed during pregnancy but not after IFNA2 treatment. In experiment 3, spatiotemporal alterations in expression of selected genes were determined in uteri from nonpregnant and early pregnant heifers using in situ hybridization. The overall findings of this study suggest differential effects of bovine IFNT compared to human IFNA2 and that some pregnancy-specific changes in the endometrium are elicited by conceptus-derived factors other than IFNT

Dwarf Tomato and Pepper Cultivars for Space Crops

Several dwarf tomato and pepper varieties were evaluated under ISS-simulated growth conditions (22C, 50% RH, 1500 ppm CO2, and 300 mol m(exp -2) s(exp -1) of light for 16 h per day) with the goal of selecting those with the best growth, nutrition, and organoleptic potential for use in a pick and eat salad crop system on ISS and future exploration flights. Testing included six cultivars of tomato (Red Robin, Scarlet Sweet N Neat, Tiny Tim, Mohamed, Patio Princess, and Tumbler) and six cultivars of pepper (Red Skin, Fruit Basket, Cajun Belle, Chablis, Sweet Pickle, and Pompeii). Plants were grown to an age sufficient to produce fruit (70 to 106 days for tomato and 109 days for pepper). Tomato fruits were harvested when they showed full red color, beginning ca. 70-days age and then at weekly intervals thereafter, while peppers were grown until numerous fruits showed color and all fruits (green and colored) were harvested once at the end of the test. Plant sizes, yields, and nutritional attributes were measured and used to down-select to three cultivars for each species. In particular, we were interested in cultivars that were short (dwarf) but still produced high yields. Nutritional data included elemental (Ca, Mg, Fe, and K) composition, vitamin K, phenolics, lycopene, anthocyanin, lutein, and zeaxanthin. The three down-selected cultivars for each species were evaluated for sensory attributes, including overall acceptability, appearance, color intensity aroma, flavor and texture. The combined data were compared and given weighting factors to rank the cultivars as potential candidates for testing in space. For tomato, the ranking was 1) cv. Mohamed, 2) cv. Red Robin, and 3) cv. Sweet N Neat. For pepper, the ranking was 1) cv. Pompeii, 2) cv. Red Skin, and 3) cv. Fruit Basket. These rankings are somewhat subjective but provide a good starting point for conducting higher fidelity testing with these crops (e.g., testing with LED lighting similar to the Veggie plant unit), and ultimately conducting flight experiments

N-Methylimidazole Promotes The Reaction Of Homophthalic Anhydride With Imines

The addition of N-methylimidazole (NMI) to the reaction of homophthalic anhydride with imines such as pyridine-3-carboxaldehyde-N-trifluoroethylimine (9) reduces the amount of elimination byproduct and improves the yield of the formal cycloadduct, tetrahydroisoquinolonic carboxylate 10. Carboxanilides of such compounds are of interest as potential antimalarial agents. A mechanism that rationalizes the role of NMI is proposed, and a gram-scale procedure for the synthesis and resolution of 10 is also described