Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Collagen concentration and biomechanical properties of samples from the lower uterine cervix in relation to age and parity in non-pregnant women

<p>Abstract</p> <p>Background</p> <p>During normal pregnancy the cervix has a load bearing function. The cervical tissue consists mainly of an extracellular matrix (ECM) rich in collagen; important for the biomechanical properties. The aim of the present study was to evaluate how the biomechanical strength of samples from the distal cervix is associated with collagen content in relation to age and parity. This study demonstrates a method to investigate cervical tissue from women who still have their uterus in situ.</p> <p>Methods</p> <p>Cervical punch biopsies (2 × 15 mm) were obtained from 57 healthy women (median age: 39 years, range: 29-49 years). Biomechanical tensile testing was performed, and collagen concentration (as % of dry defatted weight (DDW)) and content (mg of collagen per mm of specimen length) was determined. Histomorphometry was used to determine the volume densities of extracellular matrix and smooth muscle cells. Smooth muscle cells were identified by immunohistochemistry. Finally, orientation of collagen fibers was estimated. Data are given as mean +/- SD.</p> <p>Results</p> <p>The mean collagen concentration (62.2 +/- 6.6%) increased with age (0.5% per year, r = 0.45, p = 0.003) and decreased with parity (1.7% per birth, r = -0.45, p = 0.033). Maximum load was positively correlated with collagen content (mg of collagen per mm of specimen length) (r = 0.76, p < 0.001). Normalized maximum stiffness was increased with age (r = 0.32, p = 0.017), whereas no correlation was found with regard to parity. In tissue samples with a length of approximately one cm, volume density of smooth muscle cells increased gradually from 8.9% in the distal part near the epithelium, to 15.5% in the proximal part (p < 0.001).</p> <p>Conclusions</p> <p>The present study shows that cervical collagen concentration increases with age and decreases with parity in non-pregnant women. In addition, collagen stiffness increased with age, whereas no change in collagen tensile strength with respect to age and parity was found. These results show that collagen contributes to cervical tissue tensile strength and age and parity should be considered confounding factors.</p

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Developing a feeling for error

This paper is based on ethnographic research of data practices in a public health project called Weather Health and Air Pollution. (All names are pseudonyms.) I examine two different kinds of practices that make air pollution data, focusing on how they relate to particular modes of sensing and articulating air pollution. I begin by describing the interstitial spaces involved in making measurements of air pollution at monitoring sites and in the running of a computer simulation. Specifically, I attend to a shared dimension of these practices, the checking of a numerical reading for error. Checking a measurement for error is routine practice and a fundamental component of making data, yet these are also moments of interpretation, where the form and meaning of numbers are ambiguous. Through two case studies of modelling and monitoring data practices, I show that making a ‘good’ (error free) measurement requires developing a feeling for the instrument–air pollution interaction in terms of the intended functionality of the measurements made. These affective dimensions of practice are useful analytically, making explicit the interaction of standardised ways of knowing and embodied skill in stabilising data. I suggest that environmental data practices can be studied through researchers’ materialisation of error, which complicate normative accounts of Big Data and highlight the non-linear and entangled relations that are at work in the making of stable, accurate data

Fine Scale Analysis of Crossover and Non-Crossover and Detection of Recombination Sequence Motifs in the Honeybee (Apis mellifera)

BACKGROUND: Meiotic exchanges are non-uniformly distributed across the genome of most studied organisms. This uneven distribution suggests that recombination is initiated by specific signals and/or regulations. Some of these signals were recently identified in humans and mice. However, it is unclear whether or not sequence signals are also involved in chromosomal recombination of insects. METHODOLOGY: We analyzed recombination frequencies in the honeybee, in which genome sequencing provided a large amount of SNPs spread over the entire set of chromosomes. As the genome sequences were obtained from a pool of haploid males, which were the progeny of a single queen, an oocyte method (study of recombination on haploid males that develop from unfertilized eggs and hence are the direct reflect of female gametes haplotypes) was developed to detect recombined pairs of SNP sites. Sequences were further compared between recombinant and non-recombinant fragments to detect recombination-specific motifs. CONCLUSIONS: Recombination events between adjacent SNP sites were detected at an average distance of 92 bp and revealed the existence of high rates of recombination events. This study also shows the presence of conversion without crossover (i. e. non-crossover) events, the number of which largely outnumbers that of crossover events. Furthermore the comparison of sequences that have undergone recombination with sequences that have not, led to the discovery of sequence motifs (CGCA, GCCGC, CCGCA), which may correspond to recombination signals

Recent and historical recombination in the admixed Norwegian Red cattle breed

<p>Abstract</p> <p>Background</p> <p>Comparison of recent patterns of recombination derived from linkage maps to historical patterns of recombination from linkage disequilibrium (LD) could help identify genomic regions affected by strong artificial selection, appearing as reduced recent recombination. Norwegian Red cattle (NRF) make an interesting case study for investigating these patterns as it is an admixed breed with an extensively recorded pedigree. NRF have been under strong artificial selection for traits such as milk and meat production, fertility and health.</p> <p>While measures of LD is also crucial for determining the number of markers required for association mapping studies, estimates of recombination rate can be used to assess quality of genomic assemblies.</p> <p>Results</p> <p>A dataset containing more than 17,000 genome-wide distributed SNPs and 2600 animals was used to assess recombination rates and LD in NRF. Although low LD measured by r²was observed in NRF relative to some of the breeds from which this breed originates, reports from breeds other than those assessed in this study have described more rapid decline in r²at short distances than what was found in NRF. Rate of decline in r²for NRF suggested that to obtain an expected r²between markers and a causal polymorphism of at least 0.5 for genome-wide association studies, approximately one SNP every 15 kb or a total of 200,000 SNPs would be required. For well known quantitative trait loci (QTLs) for milk production traits on <it>Bos Taurus </it>chromosomes 1, 6 and 20, map length based on historic recombination was greater than map length based on recent recombination in NRF.</p> <p>Further, positions for 130 previously unpositioned contigs from assembly of the bovine genome sequence (Btau_4.0) found using comparative sequence analysis were validated by linkage analysis, and 28% of these positions corresponded to extreme values of population recombination rate.</p> <p>Conclusion</p> <p>While LD is reduced in NRF compared to some of the breeds from which this admixed breed originated, it is elevated over short distances compared to some other cattle breeds. Genomic regions in NRF where map length based on historic recombination was greater than map length based on recent recombination coincided with some well known QTL regions for milk production traits.</p> <p>Linkage analysis in combination with comparative sequence analysis and detection of regions with extreme values of population recombination rate proved to be valuable for detecting problematic regions in the Btau_4.0 genome assembly.</p

The Drosophila Zinc Finger Protein Trade Embargo Is Required for Double Strand Break Formation in Meiosis

Homologous recombination in meiosis is initiated by the programmed induction of double strand breaks (DSBs). Although the Drosophila Spo11 ortholog Mei-W68 is required for the induction of DSBs during meiotic prophase, only one other protein (Mei-P22) has been shown to be required for Mei-W68 to exert this function. We show here that the chromatin-associated protein Trade Embargo (Trem), a C2H2 zinc finger protein, is required to localize Mei-P22 to discrete foci on meiotic chromosomes, and thus to promote the formation of DSBs, making Trem the earliest known function in the process of DSB formation in Drosophila oocytes. We speculate that Trem may act by either directing the binding of Mei-P22 to preferred sites of DSB formation or by altering chromatin structure in a manner that allows Mei-P22 to form foci

Percepção de autoeficácia, assertividade sexual e uso do preservativo em jovens colombianos

El uso correcto y consistente del condón en las relaciones sexuales es un procedimiento altamente eficaz para la prevención del VIH/SIDA, así como para otras infecciones de transmisión sexual (ITS). Algunos estudios reportan que las habilidades psicosociales y de interrelación favorecen el desarrollo de prácticas sexuales protegidas, como con el uso de preservativos. El objetivo del presente estudio fue determinar en qué medida la percepción de autoeficacia y la asertividad sexual predicen el uso del condón en las relaciones sexuales en un grupo de jóvenes. Se realizó un estudio descriptivo correlacional y predictivo con una muestra de 631 jóvenes con edades entre 19 y 26 años que reportaron haber tenido relaciones o ser activos sexualmente. Los resultados muestran que la percepción de autoeficacia y la asertividad sexual fueron fuertes predictores del uso del condón en las relaciones sexuales de las mujeres, mientras que para el caso de los hombres, solo la asertividad sexual predijo su uso.O uso correto e consistente do preservativo nas relações sexuais é um procedimento altamente eficaz para a prevenção do HIV/ Aids, bem como para outras infecções de transmissão sexual (ITS). Alguns estudos mostram que as habilidades psicossociais e de inter-relação favorecem o desenvolvimento de práticas sexuais protegidas, como com o uso do preservativo. O objetivo do presente estudo foi determinar em que medida a percepção de autoeficácia e a assertividade sexual predizem o uso do preservativo nas relações sexuais em um grupo de jovens. Realizou-se um estudo descritivo correlacional e preditivo com uma amostra de 631 jovens com idades entre 19 e 26 anos que relataram ter tido relações ou ser ativos sexualmente. Os resultados mostram que a percepção de autoeficácia e a assertividade sexual foram fortes indicadores do uso do preservativo nas relações sexuais das mulheres, enquanto para o caso dos homens, só a assertividade sexual predisse seu uso.The correct and consistent use of condoms during sexual intercourse is a highly effective procedure for the prevention of HIV / AIDS as well as other sexually transmitted infections (STIs). Some studies report that psychosocial skills and interaction promote the development of safe sexual relations by using condoms. The objective of this study was to determine to what extent the perception of self-efficacy and sexual assertiveness predicts condom use in sexual activity in a group of young people. The study was descriptive correlational and predictive.The sample consisted of 645 young people aged between 19 and 26 years who reported having had sex or being sexually active. Results showed that, unlike men, the perception of selfefficacy coupled with sexual assertiveness are strong predictors of condom use in women's sexual relations, whereas for men only sexual assertiveness predicts condom use in sexual relations

Social Phobia in an Italian region: do Italian studies show lower frequencies than community surveys conducted in other European countries?

BACKGROUND: The lifetime prevalence of Social Phobia (SP) in European countries other than Italy has been estimated to range from 3.5% to 16.0%. The aim of this study was to assess the frequency of SP in Sardinia (Italy) in order to verify the evidence of a lower frequency of SP in Italy observed in previous studies (from 1.0% to 3.1%). METHODS: A randomised cross sample of 1040 subjects, living in Cagliari, in rural areas, and in a mining district in Sardinia were interviewed using a Simplified version of the Composite International Diagnostic Interview (CIDIS). Diagnoses were made according to the 10(th )International Classification of Diseases (ICD-10). RESULTS: Lifetime prevalence of SP was 2.2% (males: 1.5%, females: 2.8%) whereas 6-month prevalence resulted in 1.5% (males: 0.9%, females: 2.1%). Mean age at onset was 16.2 ± 9.3 years. A statistically significant association was found with Depressive Episode, Dysthymia and Generalized Anxiety Disorder. CONCLUSIONS: The study is consistent with findings reported in several previous studies of a lower prevalence of SP in Italy. Furthermore, the results confirm the fact that SP, due to its early onset, might constitute an ideal target for early treatment aimed at preventing both the accumulation of social disabilities and impairments caused by anxiety and avoidance behaviour, as well as the onset of more serious, associated complications in later stages of the illness