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Objective: Development of brown-like/beige adipocytes in white adipose tissue (WAT) helps to reduce obesity. Thus we investigated the effects of resveratrol, a dietary polyphenol capable of preventing obesity and related complications in humans and animal models, on brown-like adipocyte formation in inguinal WAT (iWAT). Methods: CD1 female mice (5-month old) were fed a high-fat diet with/without 0.1% resveratrol. In addition, primary stromal vascular cells separated from iWAT were subjected to resveratrol treatment. Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) α1 was assessed using conditional knockout. Results: Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers, including uncoupling protein 1 (UCP1), PR domain-containing 16, cell death-inducing DFFA-like effector A, elongation of very long-chain fatty acids protein 3, peroxisome proliferator-activated receptor-γ coactivator 1α, cytochrome c and pyruvate dehydrogenase, in differentiated iWAT stromal vascular cells (SVCs), suggesting that resveratrol induced brown-like adipocyte formation in vitro . Concomitantly, resveratrol markedly enhanced AMPKα1 phosphorylation and differentiated SVC oxygen consumption. Such changes were absent in cells lacking AMPKα1, showing that AMPKα1 is a critical mediator of resveratrol action. Resveratrol also induced beige adipogenesis in vivo along with the appearance of multiocular adipocytes, increased UCP1 expression and enhanced fatty acid oxidation. Conclusions: Resveratrol induces brown-like adipocyte formation in iWAT via AMPKα1 activation and suggest that its beneficial antiobesity effects may be partly due to the browning of WAT and, as a consequence, increased oxygen consumption.

Background: Obesity in women of childbearing age is increasing at an alarming rate. Growing evidence shows that maternal obesity induces detrimental effects on offspring health, including pre-disposition to obesity. We have shown that maternal obesity increases fetal intramuscular adipogenesis at mid-gestation. However, the mechanisms are poorly understood. MicroRNAs (miRNAs) regulate mRNA stability. We hypothesized that maternal obesity alters fetal muscle miRNA expression, thereby influencing intramuscular adipogenesis. Methods: Non-pregnant ewes received a control diet (Con, fed 100% of National Research Council (NRC) recommendations, n =6) or obesogenic diet (OB; 150% NRC recommendations, n =6) from 60 days before to 75 days after conception when the fetal longissimus dorsi (LD) muscle was sampled and miRNA expression analyzed by miRNA microarray. One of miRNAs with differential expression between Con and OB fetal muscle, let-7g , was further tested for its role in adipogenesis and cell proliferation in C3H10T1/2 cells. Results: A total of 155 miRNAs were found with a signal above 500, among which, three miRNAs, hsa-miR-381 , hsa-let-7g and bta-miR-376d , were differentially expressed between Con and OB fetuses, and confirmed by quantitative real-time PCR (QRT-PCR) analyses. Reduced expression of miRNA let-7g , an abundantly expressed miRNA, in OB fetal muscle was correlated with higher expression of its target genes. Overexpression of let-7g in C3H10T1/2 cells reduced their proliferation rate. Expression of adipogenic markers decreased in cells overexpressing let-7g , and the formation of adipocytes was also reduced. Overexpression of let-7g decreased expression of inflammatory cytokines. Conclusion: Fetal muscle miRNA expression was altered due to maternal obesity, and let-7g downregulation may enhance intramuscular adipogenesis during fetal muscle development in the setting of maternal obesity.

While bipolar disorder (BD) is a leading cause of disability, and an important contributor to disability in BD is cognitive impairment, there is little systematic research on the longitudinal course of cognitive function and instrumental activities of daily living (IADLs) in late-life. In this report, we characterize the 2-year course of cognitive function and IADLs in older adults with BD. Method We recruited non-demented individuals 50 years and older with BD I or BD II (n = 47) from out-patient clinics or treatment studies at the University of Pittsburgh. Comparator subjects ('controls') were 22 individuals of comparable age and education with no psychiatric or neurologic history, but similar levels of cardiovascular disease. We assessed cognitive function and IADLs at baseline, 1- and 2-year time-points. The neuropsychological evaluation comprised 21 well-established and validated tests assessing multiple cognitive domains. We assessed IADLs using a criterion-referenced, performance-based instrument. We employed repeated-measures mixed-effects linear models to examine trajectory of cognitive function. We employed non-parametric tests for analysis of IADLs. The BD group displayed worse cognitive function in all domains and worse IADL performance than the comparator group at baseline and over follow-up. Global cognitive function and IADLs were correlated at all time-points. The BD group did not exhibit accelerated cognitive decline over 2 years. Over 2 years, cognitive impairment and associated functional disability of older adults with BD appear to be due to long-standing neuroprogressive processes compounded by normal cognitive aging rather than accelerated cognitive loss in old age.

The primary mode of North Atlantic storm track variability is identified using rotated principal component analysis (RPCA) on monthly fields of root-mean-squares of daily high-pass filtered (2–8-day periods) sea level pressures (SLP) for winters (December–February) 1900–92. It is examined in terms of its association with 1) monthly mean SLP fields, 2) regional low-frequency teleconnections, and 3) the seesaw in winter temperatures between Greenland and northern Europe. The principal storm track component is characterized by high synoptic variability preferring one of two areas at any given time. The northeastern Atlantic center (identified by positive RPCA scores) is characterized by deep cyclones in the area extending from Iceland northeastward to the Norwegian and Barents Seas, whereas the Bay of Biscay center (negative scores) is linked to cyclone activity around that area and into the Mediterranean basin. Combined principal component analysis is used to link the high-frequency storm track pressure variability with that of lower frequencies (monthly mean pressures). In this, the primary storm track pattern is linked to large monthly mean SLP variations around the Bay of Biscay and near northern Scandinavia and the Barents Sea. This pattern does not suggest a strong storm track link to the North Atlantic Oscillation (NAO). Instead, the results presented indicate that the dominant mode of variability in the storm track is associated with low-frequency SLP anomalies in the extreme northeastern Atlantic. When the component scores reach their highest positive values, both the mean Atlantic subpolar low and subtropical high are unusually strong and displaced farther northeast than normal. The pressure field intensifies to the northeast and produces strong zonal flow extending into Europe, bringing abnormally high surface air temperatures as far east as Siberia and below normal temperatures over Greenland and northern Africa (the “Greenland below” seesaw mode, GB). Besides this eastward extension of the mean pressure field, anomalously high European winter temperatures can also be somewhat less frequently caused by mild return flow around the Siberian high, which is displaced farther west than normal. In this situation the Icelandic low is in its normal Denmark Strait location and cyclones move along the more southerly storm track toward the Mediterranean basin, contributing to the synoptic forcing that helps develop the westward extended high. The NAO appears to be only indirectly linked to the European component of the GB mode of the winter surface air temperature seesaw.

•Published opinion about Human Taphonomy Facilities has been analysed.•The UK does not currently have a Human Taphonomy Facility.•Animal models cannot be used to study the effect of human conditions on decay.•Human remains are necessary for effective training of police, students, and dogs.•Cadaver donation based on informed consent is unobjectionable on ethical grounds. Human Taphonomy Facilities (HTFs) are outdoor laboratories where scientific research is carried out on donated human cadavers in order to understand how human decomposition progresses in a variety of conditions. There are currently eight such facilities in the USA, one in Australia and one on mainland Europe. Forensic scientists in the UK have started to ask the question ‘Does the UK need a Human Taphonomy Facility?’. A review of the literature produced by the existing HTFs, as well as published opinion and commentaries about these facilities and the feasibility of one in the UK has been undertaken. The existing arguments for and against the establishment of a Human Taphonomy Facility in the UK have been examined. Given recent media interest in the possibility of the establishment of a Human Taphonomy Facility in the UK, and the surrounding controversy, it is important to evaluate the potential benefit or harm of the creation of such a facility to Society and the scientific community.

BP-80 is a type I integral membrane protein abundant in pea (Pisum sativum) clathrin-coated vesicles (CCVs) that binds with high affinity to vacuole-targeting determinants containing asparagine-proline-isoleucine-arginine. Here we present results from cDNA cloning and studies of its intracellular localization. Its sequence and sequences of homologs from Arabidopsis, rice (Oryza sativa), and maize (Zea mays) define a novel family of proteins unique to plants that is highly conserved in both monocotyledons and dicotyledons. The BP-80 protein is present in dilated ends of Golgi cisternae and in \"prevacuoles,\" which are small vacuoles separate from but capable of fusing with lytic vacuoles. Its cytoplasmic tail contains a Tyr-X-X-hydrophobic residue motif associated with transmembrane proteins incorporated into CCVs. When transiently expressed in tobacco (Nicotiana tabacum) suspension-culture protoplasts, a truncated form lacking transmembrane and cytoplasmic domains was secreted. These results, coupled with previous studies of ligand-binding specificity and pH dependence, strongly support our hypothesis that BP-80 is a vacuolar sorting receptor that trafficks in CCVs between Golgi and a newly described prevacuolar compartment.

Hypoestrogenism triggers increased production of inflammatory mediators, which contribute to bone loss during postmenopausal osteoporosis. This study aimed to investigate the association between circulating inflammatory markers and bone outcomes in postmenopausal women. We conducted a cross-sectional, secondary analysis of baseline data from participants who completed a 12-month randomized controlled trial, The Prune Study (NCT02822378), which included healthy postmenopausal women (n=183, 55-75 years old) with bone mineral density (BMD) T-score between 0.0 and -3.0 at any site. BMD was measured using dual-energy X-ray absorptiometry, and bone geometry and strength were measured using peripheral quantitative computed tomography. Blood was collected at baseline to measure (1) serum biomarkers of bone turnover, including procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide and (2) inflammatory markers, including serum high-sensitivity C-reactive protein (hs-CRP) and plasma pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1, using enzyme-linked immunosorbent assay. The associations between bone and inflammatory outcomes at baseline were analyzed using correlation and regression analyses. Serum hs-CRP negatively correlated with P1NP ( =-0.197, =0.042). Plasma IL-1β, IL-6, IL-8, and TNF-α negatively correlated with trabecular bone score at the lumbar spine (all <0.05). In normal-weight women, plasma IL-1β, IL-6, and IL-8 negatively correlated ( <0.05) with trabecular and cortical bone area, content, and density at various sites in the tibia and radius. Serum hs-CRP positively predicted lumbar spine BMD ( =0.078, =0.028). Plasma IL-6 negatively predicted BMD at the total body ( =-0.131, =0.027) and lumbar spine ( =-0.151, =0.036), whereas plasma TNF-α negatively predicted total hip BMD ( =-0.114, =0.028). At baseline, inflammatory markers were inversely associated with various estimates of bone density, geometry, and strength in postmenopausal women. These findings suggest that inflammatory markers may be an important mediator for postmenopausal bone loss.

We address the issue of whether the Arctic (AO), and North Atlantic oscillations (NAO) are inseparable, forming an annular mode in the Northern Hemisphere atmospheric circulation. This annular mode is the leading empirical orthogonal function of hemispheric sea level pressure (SLP) data, explaining the largest amount of its variability. We examine whether the NAO and AO are inseparable spatial modes of the atmospheric circulation using rotated principal component analysis (RPCA), a methodology that identifies simple and unique patterns of spatial dataset variability. RPCA of the spring, summer, and autumn SLP fields from 1946-1998 reveal NAO and AO-like patterns, occurring as separate regional teleconnections forming the first and second principal components respectively. The RPCA-based NAO dipole pattern is like that observed in many prior studies, while the AO-like pattern exhibits high SLP variability over the Kara and Laptev seas. During winter however, and in annual analyses, a distinct AO-like pattern is not obtained and the two patterns may be inseparable using commonly accepted RPCA methods. The RPCA-based AO-like mode is significantly linked to north-central Siberian seasonal air temperatures and to the prevailing direction of motion of the underlying Arctic Ocean in summer, suggesting that the non-winter AO-like pattern, as a stand alone teleconnection separate from the NAO, contributes significantly to high-latitude climate and ocean variability. The winter NAO/AO inseparability is discussed as a possible effect of a shared winter storm track between the northeastern Atlantic and the Arctic.[PUBLICATION ABSTRACT]

General characteristics of the dynamical and thermal structure and evolution of strong explosive cyclones in the northwestern Atlantic near North America (18 cases) and the extreme northeastern Atlantic near Iceland (19 cases) are compared and contrasted through a composite study. Twice-daily gridded analyses from the European Centre for Medium-Range Weather Forecasts at 2.5 degrees resolution from January 1985 to March 1996 are used. In the process of case selection, it is found that the frequency of rapid cyclogenesis in the Greenland-Iceland region is higher than previously thought, and some of the events can be extremely violent. Many dynamically consistent differences are found when composite cyclones in the two sectors of the North Atlantic are compared. The upper-level forcing that triggers the development in the northeast Atlantic (NEA) is no less intense at the onset of rapid deepening. The NEA cyclones are also associated with lower static stability and locally concentrated but shallower thermal gradient, with less overall environmental baroclinicity. These factors lead to rapid depletion of available potential energy and result in a faster evolution and a shorter life cycle. Therefore, low-level thermal gradient and upper-level forcing components all weaken immediately after rapid deepening. The low-level incipient low in the NEA composite is also stronger, with a distinct potential vorticity (PV) anomaly visible at least 24 h prior to most rapid deepening, and the development produces a more pronounced warm core seclusion. Explosive cyclones in the northwest Atlantic, on the other hand, tend to have a higher stability and a greater amount of environmental baroclinicity, with temperature gradients in a broader area and deeper layers. These factors correspond to slower evolution and a longer life cycle. For cases in the NEA near Iceland, it appears that both upper-level forcing and initial system strengths affect the maximum deepening rate. The close proximity of this region to the high PV reservoir in the lower stratosphere is helpful in the generation of very strong forcing and a violent development under favorable synoptic conditions, when a ``parent cyclone'' with appreciable strength exists to the north/northeast of the incipient system.

Clathrin-coated vesicles are known to be involved in the transport of proteins from the Golgi to the vacuole in plant cells. The mechanisms by which proteins are directed into this pathway are not known. Here we identify an integral membrane protein of approximately 80 kDa, extracted from clathrin-coated vesicles of developing pea (Pisum sativum L.) cotyledons, that bound at neutral pH to an affinity column prepared with the N-terminal targeting determinant of the vacuolar thiol protease, proaleurain, and eluted when the pH was lowered to 4. The protein was not retained on a control column prepared with the N-terminal sequence of a homologous, secreted thiol protease, endopeptidase B. The 80-kDa protein also accumulated in a membrane fraction that is less dense than clathrin-coated vesicles. In vitro studies demonstrated a binding constant of 37 nM between the approximately 80-kDa protein and the proaleurain targeting determinant. A peptide with a vacuolar targeting determinant from prosporamin weakly competed for binding to the approximately 80-kDa protein, while a peptide carrying a single amino acid substitution known to abolish prosporamin vacuolar targeting had no measurable binding affinity for the protein. The binding protein is a glycoprotein with a transmembrane orientation in which the C terminus is exposed to the cytoplasm. The binding domain is located in the N-terminal luminal portion of the protein. These properties of the binding protein are consistent with the function of a receptor that would select proteins in the trans-Golgi for sorting to clathrin-coated vesicles and delivery to the vacuole.