Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review

Proteinase-activated receptor 2 (PAR2) is a cell surface receptor activated by serine proteinases or specific synthetic compounds. Interest in PAR2 as a pharmaceutical target for various diseases is increasing. Here we asked two questions relevant to endothelial dysfunction and diabetes: How is PAR2 function affected in blood vessels? What role does PAR2 have in promoting obesity, diabetes, and/or metabolic syndrome, specifically via the endothelium and adipose tissues? We conducted a systematic review of the published literature in PubMed and Scopus (July 2015; search terms: par2, par-2, f2lr1, adipose, obesity, diabetes, and metabolic syndrome). Seven studies focused on PAR2 and vascular function. The obesity, diabetes, or metabolic syndrome animal models differed amongst studies, but each reported that PAR2-mediated vasodilator actions were preserved in the face of endothelial dysfunction. The remaining studies focused on nonvascular functions and provided evidence supporting the concept that PAR2 activation promoted obesity. Key studies showed that PAR2 activation regulated cellular metabolism, and PAR2 antagonists inhibited adipose gain and metabolic dysfunction in rats.We conclude that PAR2 antagonists for treatment of obesity indeed show early promise as a therapeutic strategy; however, endothelial-specific PAR2 functions, which may offset mechanisms that produce vascular dysfunction in diabetes, warrant additional study

Advances in the identification of novel factors required in soybean nodulation, a process critical to sustainable agriculture and food security

Nodulation is a process of organogenesis that results from a symbiotic relationship between legume plants and soil-dwelling, nitrogen-fixing bacteria, called rhizobia. The rhizobia are housed in newly formed structures on the host roots, called nodules. Within nodules, the rhizobia fix atmospheric N2 into useable forms of nitrogen for the plant. This process is highly important to agriculture, as nitrogen is critical for plant growth and development and is typically the main component of fertilizers. Although fertilizers are effective, they are expensive and often pollute, making biological alternatives, such as legume nodulation, attractive for use in agriculture. Nodulation is regulated by the auto regulation of nodulation (AON) pathway, which enables the host plant to balance its needs between nitrogen acquisition and energy expenditure. Current research is elucidating the nodule development and AON signalling networks. Recent technological advances, such as RNA-sequencing, are revolutionizing the discovery of genes that are critical to nodulation. The discovery of such genes not only enhances our knowledge of the nodulation signalling network, but may help to underpin future work to isolate superior legume crops via modern breeding and engineering practices. Here, recent advances using the cutting-edge technique of RNA sequencing to identify new nodulation genes in soybean are discussed

Isolation of the Paenibacillus phoenicis, a Spore-Forming Bacterium

A microorganism was isolated from the surfaces of the cleanroom facility in which the Phoenix lander was assembled. The isolated bacterial strain was subjected to a comprehensive polyphasic analysis to characterize its taxonomic position. Both phenotypic and phylogenetic analyses clearly indicate that this isolate belongs to the genus Paenibacillus and represents a novel species. Bacillus spores have been utilized to assess the degree and level of microbiological contamination on spacecraft and their associated spacecraft assembly facilities. Spores of Bacillus species are of particular concern to planetary protection due to the extreme resistance of some members of the genus to space environmental conditions such as UV and gamma radiation, vacuum, oxidation, and temperature fluctuation. These resistive spore phenotypes have enhanced potential for transfer, and subsequent proliferation, of terrestrial microbes on another solar body. Due to decreased nutrient conditions within spacecraft assembly facility clean rooms, the vegetative cells of Bacillus species and other spore-forming Paenibacillus species are induced to sporulate, thereby enhancing their survivability of bioreductio

Magnetic Ordering in V-Layers of the Superconducting System of Sr2VFeAsO3

Results of transport, magnetic, thermal, and 75As-NMR measurements are presented for superconducting Sr2VFeAsO3 with an alternating stack of FeAs and perovskite-like block layers. Although apparent anomalies in magnetic and thermal properties have been observed at ~150 K, no anomaly in transport behaviors has been observed at around the same temperature. These results indicate that V ions in the Sr2VO3-block layers have localized magnetic moments and that V-electrons do not contribute to the Fermi surface. The electronic characteristics of Sr2VFeAsO3 are considered to be common to those of other superconducting systems with Fe-pnictogen layers.Comment: 4 pages, 4 figures, To appear in JPSJ 79 (2010) 12371

Physiological responses to cuddling babies with hypoxic–ischaemic encephalopathy during therapeutic hypothermia:an observational study

OBJECTIVES: To determine whether parents cuddling infants during therapeutic hypothermia (TH) would affect cooling therapy, cardiorespiratory or neurophysiological measures. The secondary aim was to explore parent–infant bonding, maternal postnatal depression and breastfeeding. DESIGN: Prospective observational study. SETTING: Two tertiary neonatal intensive care units (NICU). PARTICIPANTS: Parents and their term-born infants (n=27) receiving TH and intensive care for neonatal hypoxic–ischaemic encephalopathy. INTERVENTIONS: Cuddling up to 2 hours during TH using a standard operating procedure developed in the study (CoolCuddle). MAIN OUTCOME MEASURES: Mean difference in temperature, cardiorespiratory and neurophysiological variables before, during and after the cuddle. Secondary outcomes were parental bonding, maternal postnatal depression and breastfeeding. RESULTS: During 70 CoolCuddles (115 cumulative hours), there were measurable increases in rectal temperature (0.07°C (0.03 to 0.10)) and upper margin of amplitude-integrated electroencephalogram (1.80 µV (0.83 to 2.72)) and decreases in oxygen saturations (−0.57% (−1.08 to −0.05)) compared with the precuddle period. After the cuddle, there was an increase in end-tidal CO(2) (0.25 kPa (95% CI 0.14 to 0.35)) and mean blood pressure (4.09 mm Hg (95% CI 0.96 to 7.21)) compared with the precuddle period. From discharge to 8 weeks postpartum, maternal postnatal depression declined (13 (56.5%) vs 5 (23.8%), p=0.007); breastfeeding rate differed (71% vs 50%, p=0.043), but was higher than national average at discharge (70% vs 54.6%) and mother–infant bonding (median (IQR): 3 (0–6) vs 3 (1–4)) remained stable. CONCLUSION: In this small study, CoolCuddle was associated with clinically non-significant, but measurable, changes in temperature, cardiorespiration and neurophysiology. No infant met the criteria to stop the cuddles or had any predefined adverse events. CoolCuddle may improve breastfeeding and requires investigation in different NICU settings

Study of Ni-doping Effect of Specific Heat and Transport Properties for LaFe1-yNiyAsO0.89F0.11

Specific heats and transport quantities of the LaFe1-yNiyAsO0.89F0.11 system have been measured, and the results are discussed together with those reported previously by our group mainly for LaFe1-yCoyAsO0.89F0.11 and LaFeAsO0.89-xF0.11+x systems. The y dependence of the electronic specific heat coefficient gamma can basically be understood by using the rigid-band picture, where Ni ions provide 2 electrons to the host conduction bands and behave as nonmagnetic impurities. The superconducting transition temperature Tc of LaFe1-yNiyAsO0.89F0.11 becomes zero, as the carrier density p (=2y+0.11) doped to LaFeAsO reaches its critical value p_c_ ~0.2. This p_c_ value of ~0.2 is commonly observed for LaFe1-yCoyAsO0.89F0.11 and LaFeAsO0.89-xF0.11+x systems, in which the relations p = x+0.11 and p = y+0.11 hold, respectively. As we pointed out previously, the critical value corresponds to the disappearance of the hole-Fermi surface. These results indicate that the carrier number solely determines the Tc value. We have not observed appreciable effects of pair breaking, which originates from the nonmagnetic impurity scattering of conduction electrons and strongly suppresses T_c_ values of systems with sign-reversing of the order parameter over the Fermi surface(s). On the basis of the results, the so-called s_+-_ symmetry of the order parameter with the sign-reversing is excluded.Comment: 4 pages, 7 figures, submitted to J. Phys. Soc. Jpn, (modified version

Superconductivity in a Ferromagnetic Layered Compound

We examine superconductivity in layered systems with large Fermi-surface splitting due to coexisting ferromagnetic layers. In particular, the hybrid ruthenate-cuprate compound RuSr_2GdCu_2O_8 is examined on the coexistence of the superconductivity and the ferromagnetism, which has been observed recently. We calculate critical fields of the superconductivity taking into account the Fulde-Ferrell-Larkin-Ovchinnikov state in a model with Fermi-surfaces which shapes are similar to those obtained by a band calculation. It is shown that the critical field is enhanced remarkably due to a Fermi-surface effect, and can be high enough to make the coexistence possible in a microscopic scale. We also clarify the direction of the spatial oscillation of the order parameter, which may be observed by scanning tunneling microscope experiments.Comment: 4 pages, 4 figures, (Latex, revtex.sty, epsf.sty

Risk of metastatic disease using [F-18]PSMA-1007 PET/CT for primary prostate cancer staging

Background Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [Ga-68]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [F-18]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [F-18]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis. Results The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78-91%) and 60% (95% CI 50-68%) and a sensitivity of 36% (95% CI 25-49%) and 62% (95% CI 49-74%), respectively, for detection of metastatic disease. Conclusion Metastatic disease according to [F-18]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [F-18]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax

Biomarkers of aging in Drosophila

Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. Dietary restriction thus does not slow accumulation of aging-related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of aging-related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of aging-related damage. Using this approach, we assessed several commonly used biomarkers of aging-related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence, fluorescent AGEs are biomarkers of aging-related damage in flies. In contrast, five oxidized and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of aging-related damage. Our approach provides a powerful method for identification of biomarkers of aging.This work was supported by the Wellcome Trust and in part by I+D grants from the Spanish Ministry of Education and Science (BFU2006-14495 ⁄ BFI), the Spanish Ministry of Health (ISCIII, Red de Envejecimiento y Fragilidad, RD06 ⁄ 0013 ⁄ 0012), and the Generalitat of Catalunya (2005SGR00101) to R.P; the Spanish Ministry of Health (FIS PI081843), Spanish Ministry of Education and Science (AGL2006-12433), and ‘‘La Caixa’’ Foundation to M.P.O. Also supported by the Max Planck Society (J.J. and L.P), COST B-35 Action; Research into Ageing (A.J.L.) and the Medical Research Council and National Institutes of Health (P01 AG025901, PL1 AG032118 and P30 AG025708) (M.D.B.)