Prolylcarboxypeptidase (PRCP) as a new target for obesity treatment

Recently, we serendipitously discovered that mice with the deficiency of the enzyme prolylcarboxypeptidase (PRCP) have elevated α-melanocyte-stimulating hormone (α-MSH) levels which lead to decreased food intake and weight loss. This suggests that PRCP is an endogenous inactivator of α-MSH and an appetite stimulant. Since a modest weight loss can have the most profound influence on reducing cardiovascular risk factors, the inhibitors of PRCP would be emerging as a possible alternative for pharmacotherapy in high-risk patients with obesity and obesity-related disorders. The discovery of a new biological activity of PRCP in the PRCP-deficient mice and studies of α-MSH function indicate the importance and complexity of the hypothalamic pro-opiomelanocortin (POMC) system in altering food intake. Identifying a role for PRCP in regulating α-MSH in the brain may be a critical step in enhancing our understanding of how the brain controls food intake and body weight. In light of recent findings, the potential role of PRCP in regulating fuel homeostasis is critically evaluated. Further studies of the role of PRCP in obesity are much needed

Adaptation of the application waspar to new linux distributions

Peer Reviewe

High-Resolution Identification of Multiple Salmonella Serovars in a Single Sample by Using CRISPR-SeroSeq

Salmonella enterica is represented by \u3e2,600 serovars that can differ in routes of transmission, host colonization, and in resistance to antimicrobials. S. enterica is the leading bacterial cause of foodborne illness in the United States, with well-established detection methodology. Current surveillance protocols rely on the characterization of a few colonies to represent an entire sample; thus, minority serovars remain undetected. Salmonella contains two CRISPR loci, CRISPR1 and CRISPR2, and the spacer contents of these can be considered serovar specific. We exploited this property to develop an amplicon-based and multiplexed sequencing approach, CRISPR-SeroSeq (serotyping by sequencing of the CRISPR loci), to identify multiple serovars present in a single sample. Using mixed genomic DNA from two Salmonella serovars, we were able to confidently detect a serovar that constituted 0.01% of the sample. Poultry is a major reservoir of Salmonella spp., including serovars that are frequently associated with human illness, as well as those that are not. Numerous studies have examined the prevalence and diversity of Salmonella spp. in poultry, though these studies were limited to culture-based approaches and therefore only identified abundant serovars. CRISPR-SeroSeq was used to investigate samples from broiler houses and a processing facility. Ninety-one percent of samples harbored multiple serovars, and there was one sample in which four different serovars were detected. In another sample, reads for the minority serovar comprised 0.003% of the total number of Salmonella spacer reads. The most abundant serovars identified were Salmonella enterica serovars Montevideo, Kentucky, Enteritidis, and Typhimurium. CRISPR-SeroSeq also differentiated between multiple strains of some serovars. This high resolution of serovar populations has the potential to be utilized as a powerful tool in the surveillance of Salmonella species

Recombinant prolylcarboxypeptidase activates plasma prekallikrein

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106127/1/jth03969.pd

Mapping the interaction between uPAR and high molecular weight kininogen

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106070/1/jth03972.pd

A randomized controlled trial to establish the impact of aquatic exercise training on functional capacity, balance, and perceptions of fatigue in female patients with multiple sclerosis

Objective: To assess the effects of 8-weeks aquatic exercise training on functional capacity, balance, and perceptions of fatigue in women with multiple sclerosis (MS). Design: A randomized controlled design. Setting: Referral center of a multiple sclerosis society. Participants: Women (age:36.4 ±8.2; BMI:24.5 ±1.9) diagnosed with RR-type (relapsing-remitting) MS. After undergoing baseline testing, participants were allocated to either an intervention (aquatic training programme) or a control group. Interventions: The intervention consisted of an 8-week aquatic training programme (3 supervised training sessions per week; session duration; 45-60 min; 50-75% heart rate reserve). Main measures: Six-minute walk test (6-MWT); balance (Berg Balance Scale; BBS), and perceptions of fatigue (Modified Fatigue Impact Scale; MFIS), at baseline and after an 8 week intervention. Differences over time between the experimental and control groups were assessed by a 2x2 (group by time) repeated measures analysis of variance (ANOVA). Results: 32 women (age:36.4 ±8.2; BMI:24.5 ±1.9) completed the 8-week aquatic training intervention (experimental group, n=17; controls, n = 15). All outcome measures improved in the experimental group; 6-MWT performance (451±58 m to 503±57 m; P<0.001); BBS (pre-test mean, 53.59±1.70; post-test mean, 55.18±1.18; P<0.001), and in the MFIS (pre-test mean, 43.1±14.6, post-test mean, 32.8 ±5.9;P<0.01). A significant group-by-time interaction was evident between the experimental and controls groups for 6-MWT:P<0.001, ηp²=0.551; BBS:P<0.001, ηp²=0.423; and MFIS: P<0.001, ηp²=0.679. Conclusions: Aquatic exercise training improves functional capacity, balance, and perceptions of fatigue in women with MS

Ocean Bottom Seismometer: Design and Test of a Measurement System for Marine Seismology

The Ocean Bottom Seismometer (OBS) is a key instrument for the geophysical study of sea sub-bottom layers. At present, more reliable autonomous instruments capable of recording underwater for long periods of time and therefore handling large data storage are needed. This paper presents a new Ocean Bottom Seismometer designed to be used in long duration seismic surveys. Power consumption and noise level of the acquisition system are the key points to optimize the autonomy and the data quality. To achieve our goals, a new low power data logger with high resolution and Signal–to-Noise Ratio (SNR) based on Compact Flash memory card is designed to enable continuous data acquisition. The equipment represents the achievement of joint work from different scientific and technological disciplines as electronics, mechanics, acoustics, communications, information technology, marine geophysics, etc. This easy to handle and sophisticated equipment allows the recording of useful controlled source and passive seismic data, as well as other time varying data, with multiple applications in marine environment research. We have been working on a series of prototypes for ten years to improve many of the aspects that make the equipment easy to handle and useful to work in deep-water areas. Ocean Bottom Seismometers (OBS) have received growing attention from the geoscience community during the last forty years. OBS sensors recording motion of the ocean floor hold key information in order to study offshore seismicity and to explore the Earth’s crust. In a seismic survey, a series of OBSs are placed on the seabed of the area under study, where they record either natural seismic activity or acoustic signals generated by compressed air-guns on the ocean surface. The resulting data sets are subsequently used to model both the earthquake locations and the crustal structure

Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma.

BACKGROUND: Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC). METHODS: Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months. RESULTS: Median pretherapeutic serum GGT level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l(-1) was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l(-1)), normal high (17.5 to <34.5 U l(-1)), elevated (34.5 to <181.5 U l(-1)), and highly elevated (⩾181.5 U l(-1)). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit. CONCLUSIONS: Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design