(±)-3-Carb­oxy-2-(imidazol-3-ium-1-yl)­propanoate

The title compound, C7H8N2O4, crystallizes as a zwitterion, with mol­ecules organized into mol­ecular sheets via carbox­yl–carboxyl­ate and N+—H⋯carboxyl­ate contacts. These sheets are constructed from translationally related mol­ecules that further link to neighboring motifs via π-stacking [centroid–centroid distance 3.504 (3) Å] and weak C—H⋯O contacts

Targeting tumor cell motility as a strategy against invasion and metastasis

Advances in diagnosis and treatment have rendered most solid tumors largely curable if they are diagnosed and treated before dissemination. However, once they spread beyond the initial primary location, these cancers are usually highly morbid, if not fatal. Thus, current efforts focus on both limiting initial dissemination and preventing secondary spread. There are two modes of tumor dissemination – invasion and metastasis – each leading to unique therapeutic challenges and likely to be driven by distinct mechanisms. However, these two forms of dissemination utilize some common strategies to accomplish movement from the primary tumor, establishment in an ectopic site, and survival therein. The adaptive behaviors of motile cancer cells provide an opening for therapeutic approaches if we understand the molecular, cellular, and tissue biology that underlie them. Herein, we review the signaling cascades and organ reactions that lead to dissemination, as these are non-genetic in nature, focusing on cell migration as the key to tumor progression. In this context, the cellular phenotype will also be discussed because the modes of migration are dictated by quantitative and physical aspects of the cell motility machinery.National Institute of General Medical Sciences (U.S.)National Cancer Institute (U.S.

Characteristics of a Broadband Dye Laser Using Pyrromethene and Rhodamine Dyes

A broadband dye laser pumped by a frequency-doubled Nd:YAG laser with a full-width half-maximum (FWHM) from 592 to 610 nm was created for the use in a dual-pump broadband CARS system called WIDECARS. The desired broadband dye laser was generated with a mixture of Pyrromethene dyes as an oscillator gain medium and a spectral selective optic in the oscillator cavity. A mixture of Rhodamine dyes were used in the amplifier dye cell. To create this laser a study was performed to characterize the spectral behavior of broadband dye lasers created with Rhodamine dyes 590, 610, and 640, Pyrromethene dyes 597 and 650 as well as mixture of these dyes

Sibling relationship quality and Mexican-origin adolescents\u27 and young adults\u27 familism values and adjustment

We examined profiles of sibling relationship qualities in 246 Mexican-origin families living in the United States using latent profile analyses. Three profiles were identified: Positive, Negative and Affect-Intense. Links between profiles and youths’ familism values and adjustment were assessed using longitudinal data. Siblings in the Positive profile reported the highest familism values, followed by siblings in the Affect-Intense profile and, finally, siblings in the Negative profile. Older siblings in the Positive and Affect-Intense profiles reported fewer depressive symptoms than siblings in the Negative profile. Further, in the Positive and Negative profiles, older siblings reported less involvement in risky behaviors than younger siblings. In the Negative profile, younger siblings reported greater sexual risk behaviors in late adolescence than older siblings; siblings in opposite-sex dyads, as compared to same-sex dyads, engaged in riskier sexual behaviors. Our findings highlight sibling relationship quality as promotive and risky, depending on sibling characteristics and adjustment outcomes

Romantic Relationship Experiences from Late Adolescence to Young Adulthood: The Role of Older Siblings in Mexican-Origin Families

Youth\u27s experiences with romantic relationships during adolescence and young adulthood have far reaching implications for future relationships, health, and well-being; yet, although scholars have examined potential peer and parent influences, we know little about the role of siblings in youth\u27s romantic relationships. Accordingly, this study examined the prospective longitudinal links between Mexican-origin older and younger siblings\u27 romantic relationship experiences and variation by sibling structural and relationship characteristics (i.e., sibling age and gender similarity, younger siblings\u27 modeling) and cultural values (i.e., younger siblings\u27 familism values). Data from 246 Mexican-origin families with older (M = 20.65 years; SD = 1.57; 50% female) and younger (M = 17.72 years; SD = .57; 51% female) siblings were used to examine the likelihood of younger siblings\u27 involvement in dating relationships, sexual relations, cohabitation, and engagement/marriage with probit path analyses. Findings revealed older siblings\u27 reports of involvement in a dating relationship, cohabitation, and engagement/marriage predicted younger siblings\u27 relationship experiences over a two-year period. These links were moderated by sibling age spacing, younger siblings\u27 reports of modeling and familism values. Our findings suggest the significance of social learning dynamics as well as relational and cultural contexts in understanding the links between older and younger siblings\u27 romantic relationship experiences among Mexican-origin youth

Cortical AAV-CNTF gene therapy combined with intraspinal mesenchymal precursor cell transplantation promotes functional and morphological outcomes after spinal cord injury in adult rats

Ciliary neurotrophic factor (CNTF) promotes survival and enhances long-distance regeneration of injured axons in parts of the adult CNS. Here we tested whether CNTF gene therapy targeting corticospinal neurons (CSN) in motor-related regions of the cerebral cortex promotes plasticity and regrowth of axons projecting into the female adult F344 rat spinal cord after moderate thoracic (T10) contusion injury (SCI). Cortical neurons were transduced with a bicistronic adeno-associated viral vector (AAV1) expressing a secretory form of CNTF coupled to mCHERRY (AAV-CNTFmCherry) or with control AAV only (AAV-GFP) two weeks prior to SCI. In some animals, viable or nonviable F344 rat mesenchymal precursor cells (rMPCs) were injected into the lesion site two weeks after SCI to modulate the inhibitory environment. Treatment with AAV-CNTFmCherry, as well as with AAV-CNTFmCherry combined with rMPCs, yielded functional improvements over AAV-GFP alone, as assessed by open-field and Ladderwalk analyses. Cyst size was significantly reduced in the AAV-CNTFmCherry plus viable rMPC treatment group. Cortical injections of biotinylated dextran amine (BDA) revealed more BDA-stained axons rostral and alongside cysts in the AAV-CNTFmCherry versus AAV-GFP groups. After AAV-CNTFmCherry treatments, many sprouting mCherry-immunopositive axons were seen rostral to the SCI, and axons were also occasionally found caudal to the injury site. These data suggest that CNTF has the potential to enhance corticospinal repair by transducing parent CNS populations

Twenty-Four-Month Longitudinal Study Suggests Little to No Horizontal Gene Transfer In Situ between Third-Generation Cephalosporin-Resistant \u3ci\u3eSalmonella\u3c/i\u3e and Third-Generation Cephalosporin-Resistant \u3ci\u3eEscherichia coli\u3c/i\u3e in a Beef Cattle Feedyard

Third-generation cephalosporins (3GCs) are preferred treatments for serious human Salmonella enterica infections. Beef cattle are suspected to contribute to human 3GC-resistant Salmonella infections. Commensal 3GC-resistant Escherichia coli are thought to act as reservoirs of 3GC resistance because these strains are isolated more frequently than are 3GC-resistant Salmonella strains at beef cattle feedyards. During each of 24 consecutive months, four samples of pen surface material were obtained from five pens (N = 480) at a Nebraska feedyard to determine to the contribution of 3GC-resistant E. coli to the occurrence of 3GC-resistant Salmonella. Illumina whole genome sequencing was performed, and susceptibility to 14 antimicrobial agents was determined for 121 3GC-susceptible Salmonella, 121 3GC-resistant Salmonella, and 203 3GCresistant E. coli isolates. 3GC-susceptible Salmonella isolates were predominantly from serotypes Muenchen (70.2%) and Montevideo clade 1 (23.1%). 3GC-resistant Salmonella isolates were predominantly from serotypes Montevideo clade 2 (84.3%). One bla gene type (blaCMY-2) and the IncC plasmid replicon were present in 100 and 97.5% of the 3GC-resistant Salmonella, respectively. Eleven bla gene types were detected in the 3GC-resistant E. coli, which were distributed across 42 multilocus sequence types. The blaCMY-2 gene and IncC plasmid replicon were present in 37.9 and 9.9% of the 3GC-resistant E. coli, respectively. These results suggest that 3GC resistance in Salmonella was primarily due the persistence of Salmonella Montevideo clade 2 with very minimal or no contribution from 3GC-resistant E. coli via horizontal gene transfer and that 3GCresistant E. coli may not be a useful indicator for 3GC-resistant Salmonella in beef cattle production environments

The effect of FTO variation on increased osteoarthritis risk is mediated through body mass index : a mendelian randomisation study

Objective: Variation in the fat mass and obesity-associated (FTO) gene influences susceptibility to obesity. A variant in the FTO gene has been implicated in genetic risk to osteoarthritis (OA). We examined the role of the FTO polymorphism rs8044769 in risk of knee and hip OA in cases and controls incorporating body mass index (BMI) information. Methods: 5409 knee OA patients, 4355 hip OA patients and up to 5362 healthy controls from 7 independent cohorts from the UK and Australia were genotyped for rs8044769. The association of the FTO variant with OA was investigated in case/control analyses with and without BMI adjustment and in analyses matched for BMI category. A mendelian randomisation approach was employed using the FTO variant as the instrumental variable to evaluate the role of overweight on OA. Results: In the meta-analysis of all overweight (BMI≥25) samples versus normal-weight controls irrespective of OA status the association of rs8044769 with overweight is highly significant (OR[CIs] for allele G=1.14 [01.08 to 1.19], p=7.5×10−7). A significant association with knee OA is present in the analysis without BMI adjustment (OR[CIs]=1.08[1.02 to 1.14], p=0.009) but the signal fully attenuates after BMI adjustment (OR[CIs]=0.99[0.93 to 1.05], p=0.666). We observe no evidence for association in the BMI-matched meta-analyses. Using mendelian randomisation approaches we confirm the causal role of overweight on OA. Conclusions: Our data highlight the contribution of genetic risk to overweight in defining risk to OA but the association is exclusively mediated by the effect on BMI. This is consistent with what is known of the biology of the FTO gene and supports the causative role of high BMI in OA

TNF-α/TNFR1 Signaling Is Required for the Development and Function of Primary Nociceptors

SummaryPrimary nociceptors relay painful touch information from the periphery to the spinal cord. Although it is established that signals generated by receptor tyrosine kinases TrkA and Ret coordinate the development of distinct nociceptive circuits, mechanisms modulating TrkA or Ret pathways in developing nociceptors are unknown. We have identified tumor necrosis factor (TNF) receptor 1 (TNFR1) as a critical modifier of TrkA and Ret signaling in peptidergic and nonpeptidergic nociceptors. Specifically, TrkA+ peptidergic nociceptors require TNF-α-TNFR1 forward signaling to suppress nerve growth factor (NGF)-mediated neurite growth, survival, excitability, and differentiation. Conversely, TNFR1-TNF-α reverse signaling augments the neurite growth and excitability of Ret+ nonpeptidergic nociceptors. The developmental and functional nociceptive defects associated with loss of TNFR1 signaling manifest behaviorally as lower pain thresholds caused by increased sensitivity to NGF. Thus, TNFR1 exerts a dual role in nociceptor information processing by suppressing TrkA and enhancing Ret signaling in peptidergic and nonpeptidergic nociceptors, respectively

A Qualitative Study of Perceived Barriers to Fruit and Vegetable Consumption Among Low-Income Populations, North Carolina, 2011

IntroductionObesity is the leading preventable cause of illness and a major contributor to chronic disease. Eating fresh fruits and vegetables can help manage and prevent weight gain and reduce the risk of chronic diseases. Low-income communities often lack stores that sell fresh fruit and vegetables and have instead stores that sell foods low in nutritional value. The objective of this study was to understand perceived community-level barriers to fruit and vegetable consumption among low-income people.MethodsWe conducted 8 focus groups involving 68 low-income participants in 2 North Carolina counties, from May 2011 through August 2011. The socioecological model of health guided data analysis, and 2 trained researchers coded transcripts and summarized findings. Four focus groups were conducted in each county; 1 was all male, 5 all female, and 2 mixed sexes. Most participants were black (68%), most were women (69.1%), and most had a high school education or less (61.8%). Almost half received support from either the Supplemental Nutrition Assistance Program or another government assistance program.ResultsWe identified 6 major community-level barriers to access to fruits and vegetables: cost, transportation, quality, variety, changing food environment, and changing societal norms on food.ConclusionPolicymakers should consider supporting programs that decrease the cost and increase the supply of high-quality fruits and vegetables in low-income communities