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Autism spectrum disorders (ASDs) are diagnosed in 1/100 children worldwide, based on two core symptoms: deficits in social interaction and communication, and stereotyped behaviours. G protein‐coupled receptors (GPCRs) are the largest family of cell‐surface receptors that transduce extracellular signals to convergent intracellular signalling and downstream cellular responses that are commonly dysregulated in ASD. Despite hundreds of GPCRs being expressed in the brain, only 23 are genetically associated with ASD according to the Simons Foundation Autism Research Initiative (SFARI) gene database: oxytocin OTR; vasopressin V1A and V1B; metabotropic glutamate mGlu5 and mGlu7; GABAB2; dopamine D1, D2 and D3; serotoninergic 5‐HT1B; β2‐adrenoceptor; cholinergic M3; adenosine A2A and A3; angiotensin AT2; cannabinoid CB1; chemokine CX3CR1; orphan GPR37 and GPR85; and olfactory OR1C1, OR2M4, OR2T10 and OR52M1. Here, we review the therapeutic potential of these 23 GPCRs, as well as 5‐HT2A and 5‐HT7, for ASD. For each GPCR, we discuss its genetic association, genetic and pharmacological manipulation in animal models, pharmacopoeia for core symptoms of ASD and rank them based on these factors. Among these GPCRs, we highlight D2, 5‐HT2A, CB1, OTR and V1A as the more promising targets for ASD. We discuss that the dysregulation of GPCRs and their signalling is a convergent pathological mechanism of ASD. Their therapeutic potential has only begun as multiple GPCRs could mitigate ASD. [ABSTRACT FROM AUTHOR]

We study the decomposition matrices of the unipotent l-blocks of finite special unitary groups SUn(q) for unitary primes l larger than n. Up to few unknown entries, we give a complete solution for n = 2, . . ., 10. We also prove a general result for two-column partitions when l divides q + 1. This is achieved using projective modules coming from the l-adic cohomology of Deligne-Lusztig varieties. [ABSTRACT FROM AUTHOR]

Background: While patient‐reported outcome measures (PROMs) have benefit in cancer clinical trials, real‐world applications are lacking. This study describes the method of implementation of a cancer enterprise‐wide PROMs platform. Methods: After establishing a multispecialty stakeholder group within a large integrated health system, domain‐specific instruments were selected from the National Institutes of Health's Patient‐Reported Outcomes Measurement Information System (PROMIS) instruments (pain interference, fatigue, physical function, and depression) and were administered at varying frequencies throughout each patient's cancer journey. All cancer patients with an oncologic visit were eligible to complete the PROMs prior to the visit using a patient portal, or at the time of the visit using a tablet. PROMs were integrated into clinical workflow. Clinical partnerships were essential for successful implementation. Descriptive preliminary data were compared using multivariable logistic regression to determine the factors associated with method of PROMs completion. Results: From September 16, 2020 to July 23, 2021, 23 of 38 clinical units (60.5%) implemented PROMs over 2392 encounters and 1666 patients. Approximately one third of patients (n = 629, 37.8%) used the patient portal. Black patients (aOR 0.70; 95% CI: 0.51–0.97) and patients residing in zip codes with higher percentage of unemployment (aOR: 0.07, 95% CI: 0.01–0.41) were among the least likely to complete PROMs using the patient portal. Conclusions: Successful system‐wide implementation of PROMs among cancer patients requires engagement from multispecialty stakeholders and investment from clinical partners. Attention to the method of PROMs collection is required in order to reduce the potential for disparities, such as Black populations and those residing in areas with high levels of unemployment. [ABSTRACT FROM AUTHOR]

Background: Tumour necrosis factor α (TNF-α) may exhibit antitumoral activity and can influence the reaction of both tumour and normal tissue to radiation. Aims: To test the effect of TNF-α and/or irradiation on hepatocellular (HepG2, Hep3B, Sk-Hep1, HuH7) and cholangiocellular (Sk-chA1, Mz-chA1) tumour cell lines. Methods: Colony formation, apoptosis analysis and trypan blue exclusion were used to assess cell viability. Doses of radiation (2–25 Gy) and TNF-α (100–50 000 U) as well as their respective sequencing were varied (24 and 12 h before and 6 h after). The expression of TNF-α and TNF receptors 1/2 was determined using real-time polymerase chain reaction and IκBα protein expression was detected by Western blot. Results: Sole irradiation induced a reduction in colony formation in all cell lines and sole TNF-α in HepG2 and Sk-chA1 cells only. No difference in apoptosis induction after TNF-α or irradiation was observed. Cellular death induced by the combination of TNF-α and radiation was not superior to the use of any of the two agents alone. All cell lines revealed that radiation induced upregulation of TNF-α whereas the extent of TNF receptor-specific transcription did not change. Furthermore, radiation-induced changes in IκBα expression were not detectable. Conclusions: Our data suggest that both TNF-α and radiation may be treatment options for hepatocellular and cholangiocellular carcinomas. Because TNF-α and radiation do not interact in terms of radiosensitization, anti-TNF-α treatment may have the potential to protect against hepatocellular injury after abdominal irradiation. However, further in vivo studies are needed to confirm that anti-TNF-α treatment does not compromise tumour control and actually attenuates radiation-induced liver injury. [ABSTRACT FROM AUTHOR]

Whole-rock Sm–Nd isotope systematics of 79 Archean granitoids from the eastern Kaapvaal craton, southern Africa, are used to delineate lithospheric boundaries and to constrain the timescale of crustal growth, assembly and geochemical differentiation c. 3.66–2.70 Ga. Offsets in εNd values for 3.2–3.3 Ga granitoids across the Barberton greenstone belt (BGB) are consistent with existing models for c. 3.23 Ga accretion of newly formed lithosphere north of the BGB onto pre-existing c. 3.66 Ga lithosphere south of the BGB along a doubly verging subduction margin. The Nd isotopic signature of c. 3.3–3.2 Ga magmatic rocks show that significant crustal growth occurred during subduction–accretion. After c. 3.2 Ga, however, the Nd signature of intrusive rocks c. 3.1 and 2.7 Ga is dominated by intracrustal recycling rather than by new additions from the mantle, signalling cratonic stability. [ABSTRACT FROM AUTHOR]

Background: Statins are shown to have cholesterol-independent properties such as anti-inflammation and immunomodulation. Activated hepatic stellate cells (HSCs) acquire the capacity to synthesize matrix proteins in damaged liver. We tested the hypothesis that atorvastatin may be capable of inducing apoptosis in HSCs. Methods: Primary cultures of rat HSCs were exposed to atorvastatin, mevalonic acid and U0126. Quantification of living, apoptotic and necrotic HSCs was performed by flow cytometry and laser-scan microscopy. Cell-cycle analysis was performed by flow cytometry. Pro- and anti-apoptotic factors were investigated by Western blot and electrophoresis mobility shift assay. Protease activity of caspases was calculated using a colorimetric kit. Results: Atorvastatin leads to a G2-arrest and induces apoptosis in activated HSCs. Atorvastatin-mediated apoptosis could be blocked by co-administration of mevalonic acid and U0126. No effects of atorvastatin on gene expression of CD95, CD95L, NF-κB, p53 and p21WAF1 could be observed. Atorvastatin-induced apoptosis in activated HSCs is related to an increased protease activity of caspase-9 and -3. Gene expression of the major proteins of the bcl-system shows that truncated Bid is involved in apoptosis mediated by atorvastatin. By blocking the extracellular signal-regulated protein kinase (ERK1/2) activation by adding U0126, we could prevent the apoptosis induced by atorvastatin. By Western blot we could not detect any change in the activation of c-jun N-terminal kinase (JNK). Conclusions: Atorvastatin induces apoptosis in activated HSCs acting through an ERK-dependent cleavage of Bid and a highly increased protease activity of caspase-9 and -3. JNK is not involved in atorvastatin-mediated apoptosis in HSCs. [ABSTRACT FROM AUTHOR]

Marine invaders have become a significant threat to native biodiversity and ecosystem function. In this study, the invasion of the varnish clam (Nuttallia obscurata) in British Columbia, Canada, is investigated using a matrix modeling approach to identify the life history characteristics most crucial for population growth and to investigate population differences. Mark-recapture analyses and field collections from 2003 to 2004 were used to determine individual growth, survival rates, and fecundity for two sites. A multi-state matrix model was used to determine population growth rates and to conduct sensitivity and elasticity analyses. A life table response experiment was also used to determine what life history stage contributed most to observed differences in population growth rates. Population survey data were used in conjunction with the matrix model to determine plausible recruitment levels and to investigate recruitment scenarios. Both populations are currently declining but are likely sustainable because of the pulsed nature of large recruitment events. Survival of larger clams (>40 mm) is the most important for population growth based on elasticity and sensitivity analyses. Adult survival also had the largest influence on observed differences between site- specific population growth rates. The two populations studied differed in recruitment dynamics; one experiencing annual recruitment with higher post-settlement mortality and the other, episodic recruitment and lower post-settlement mortality. The most influential factor for the successful invasion of the varnish clam appears to be survival of the larger size classes. Therefore, any process that decreases adult survival (e.g., predation, commercial harvest) will have the greatest impact on population growth. [ABSTRACT FROM AUTHOR]

The gonadotrophin-releasing hormone (GnRH) represents the final common pathway of a neuronal network that integrates multiple external and internal factors to control fertility. Among the many inputs GnRH neurones receive, oestrogens play the most important role. In females, oestrogen, in addition to the negative feedback, also exhibits a positive feedback influence upon the activity and output of GnRH neurones to generate the preovulatory luteinising hormone surge and ovulation. Until recently, the belief has been that the GnRH neurones do not contain oestrogen receptors and that the action of oestrogen upon GnRH neurones is indirect, involving several, oestrogen-sensitive neurotransmitter and neuromodulator systems that trans-synaptically regulate the activity of the GnRH neurones. Although this concept still holds for humans, recent studies indicate that oestrogen receptor-beta is expressed in GnRH neurones of the rat. This review provides three dimensional stereoscopic images of GnRH-immunoreactive (IR) and some peptidergic (neuropeptide Y-, substance P-, β-endorphin-, leu-enkaphalin-, corticotrophin hormone-releasing- and galanin-IR) and catecholaminergic neurones and the communication of these potential oestrogen-sensitive neuronal systems with GnRH neurones in the human hypothalamus. Because the post-mortem human tissue does not allow the electron microscopic identification of synapses on GnRH neurones, the data presented here are based on light microscopic immunocytochemical experiments using high magnification with oil immersion, semithin sections or confocal microscopy. [ABSTRACT FROM AUTHOR]

We find a mechanism by which antibranes placed in a warped deformed conifold throat can destroy the stabilization of the size of the sphere at the tip, collapsing it to zero size. This conifold destabilization mechanism can be avoided by turning on a large amount of flux on the sphere, but tadpole cancelation makes this incompatible with a hierarchy of scales in a Type IIB flux compactification. This indicates that antibrane uplift cannot be used to construct stable de Sitter vacua with a small cosmological constant in perturbative String Theory. The values of V and V′ for these KKLT‐like scenarios can be parametrically small, but we find that V′/V is still consistent with the de Sitter swampland conjecture. Our results also suggest that there should exist a Klebanov‐Strassler black hole, holographically dual to a deconfined phase with spontaneously broken chiral symmetry. A mechanism is found by which antibranes placed in a warped deformed conifold throat can destroy the stabilization of the size of the sphere at the tip, collapsing it to zero size. This conifold destabilization mechanism can be avoided by turning on a large amount of ux on the sphere, but tadpole cancelation makes this incompatible with a hierarchy of scales in a Type IIB flux compactification. This indicates that antibrane uplift cannot be used to construct stable de Sitter vacua with a small cosmological constant in perturbative String Theory. The values of V and V′ for these KKLT‐like scenarios can be parametrically small, but it is found that V′/V is still consistent with the de Sitter swampland conjecture. These results also suggest that there should exist a Klebanov‐Strassler black hole, holographically dual to a deconfined phase with spontaneously broken chiral symmetry. [ABSTRACT FROM AUTHOR]

Background: Prospective cohort studies contribute importantly to understanding the role of lifestyle, genetic, and other factors in chronic disease etiology.Methods: The American Cancer Society (ACS) recruited a new prospective cohort study, Cancer Prevention Study 3 (CPS-3), between 2006 and 2013 from 35 states and Puerto Rico. Enrollment took place primarily at ACS community events and at community enrollment "drives." At enrollment sites, participants completed a brief survey that included an informed consent, identifying information necessary for follow-up, and key exposure information. They also provided a waist measure and a nonfasting blood sample. Most participants also completed a more comprehensive baseline survey at home that included extensive medical, lifestyle, and other information. Participants will be followed for incident cancers through linkage with state cancer registries and for cause-specific mortality through linkage with the National Death Index.Results: In total, 303,682 participants were enrolled. Of these, 254,650 completed the baseline survey and are considered "fully" enrolled; they will be sent repeat surveys periodically for at least the next 20 years to update exposure information. The remaining participants (n = 49,032) will not be asked to update exposure information but will be followed for outcomes. Twenty-three percent of participants were men, 17.3% reported a race or ethnicity other than "white," and the median age at enrollment was 47 years.Conclusions: CPS-3 will be a valuable resource for studies of cancer and other outcomes because of its size; its diversity with respect to age, ethnicity, and geography; and the availability of blood samples and detailed questionnaire information collected over time. Cancer 2017;123:2014-2024. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Long‐term data are key to understanding how species, communities, and habitats change over time. Citizen science programs can support data collection at greater spatial and temporal scales than other types of scientifically collected data, which tend to be project specific and are often tied to short funding periods. This is particularly true for environments that are difficult to sample, such as subtidal ecosystems. The Reef Environmental Education Foundation's (REEF) citizen science SCUBA surveyors have been collecting fish, invertebrate, and algae data in British Columbia since 1998. This study demonstrates how citizen science data from REEF can be used to answer scientific questions via two case studies: the first on Lingcod Ophiodon elongatus population responses to management decisions and the second on detecting rockfish Sebastes spp. young‐of‐year abundance pulses. The results of these case studies suggest that data from REEF, despite their limitations, can be used to improve our understanding of nearshore marine ecosystems. [ABSTRACT FROM AUTHOR]

Aim To study prostate cancer zonal differences in TMPRSS2- ERG gene rearrangement. Methods and results We examined 136 well-characterized dominant anterior prostatic tumours, including 61 transition zone ( TZ) and 75 anterior peripheral zone ( PZ) lesions, defined using strict anatomical considerations. TMPRSS2- ERG FISH and ERG protein immunohistochemistry were performed on tissue microarrays. FISH results, available for 56 TZ and 71 anterior PZ samples, were correlated with ERG staining and TZ-associated 'clear cell' histology. Fewer TZ cancers (four of 56; 7%) were rearranged than anterior PZ cancers (18 of 71; 25%) ( P = 0.009); deletion was the sole mechanism of TZ cancer rearrangement. ERG protein overexpression was present in 4% (two of 56; both FISH+) and 30% (21 of 71; 17 FISH+) of TZ and anterior PZ tumours, respectively. 'Clear cell' histology was present in 21 of 56 (38%) TZ and eight of 71 (11%) anterior PZ tumours. Seven per cent of cancers with and 21% without this histology had rearrangement, regardless of zonal origin. Conclusions TMPRSS2- ERG rearrangement occurs in dominant TZ and anterior PZ prostate cancers, with all rearranged TZ cancers in this cohort showing deletion. ERG immunohistochemistry demonstrated excellent sensitivity (86%) and specificity (96%) for TMPRSS2- ERG rearrangement. TMPRSS2- ERG fusion is rare in TZ tumours and present at a low frequency in tumours displaying 'clear cell' histology. [ABSTRACT FROM AUTHOR]

Floral homeotic and flower development mutants of Primula, including double, Hose in Hose, Jack in the Green and Split Perianth, have been cultivated since the late 1500s as ornamental plants but until recently have attracted limited scientific attention. Here we describe the characterization of a new mutant phenotype, sepaloid, that produces flowers comprising only sepals and carpels. The sepaloid mutation is recessive, and is linked to the S locus that controls floral heteromorphy. The phenotype shows developmental variability, with flowers containing three whorls of sepals surrounding fertile carpels, two whorls of sepals with a diminished third whorl of sepals surrounding a fourth whorl of carpels, or three whorls of sepals surrounding abnormal carpels. In some respects, these phenotypes resemble the Arabidopsis and Antirrhinum homeotic B-function mutants apetala3/deficiens ( ap3/ def) and pistillata/globosa ( pi/ glo) . We have isolated the Primula vulgaris B-function genes PvDEFICIENS ( PvDEF) and PvGLOBOSA ( PvGLO), expression of both of which is affected in the sepaloid mutant. PvGLO, like sepaloid, is linked to the S locus, whereas PvDEF is not. However, our analyses reveal that sepaloid and PvGLO represent different genes. We conclude that SEPALOID is an S-linked independent regulator of floral organ identity genes including PvDEF and PvGLO. [ABSTRACT FROM AUTHOR]

For over two decades, the precise role of transforming growth factor-β (TGF-β) isoforms in scarless healing of mammalian fetal skin wounds has generated much interest. Although their exact role remains to be established, it has been suggested that high TGF-β3 activity may correlate with a scarless phenotype. Previously, we showed that plasminogen activator inhibitor-1 (PAI-1), a known TGF-β downstream molecule and marker of fibrosis, is also developmentally regulated during fetal skin development. In this study, the relationship between TGF-β3 and PAI-1 was investigated using embryonic day 14.5 TGF-β3 knockout (ko) mice. The results showed increased PAI-1 expression in the epidermis and dermis of ko mice, using an ex vivo limb-wounding study. Furthermore, increased PAI-1 expression and activity was seen in embryo extracts and conditioned media of ko dermal fibroblasts. When TGF-β3 knockout fibroblasts were placed into three-dimensional collagen matrices, they were found to have decreased collagen gel contraction, suggesting altered cell–matrix interaction. These findings provide a further avenue for the interactive role of TGF-β3 and PAI-1 during fetal scarless repair. [ABSTRACT FROM AUTHOR]

Apart from hepatic stellate cells (HSC), liver myofibroblasts (MF) represent a second mesenchymal cell population involved in hepatic fibrogenesis. The IGF system including the insulin-like growth factors I and II (IGF-I, -II), their receptors (IGF-I receptor, IGF-IR; IGF-II/mannose 6-phosphate receptor, IGF-II/M6-PR), and six high affinity IGF binding proteins (IGFBPs) participate in the regulation of growth and differentiation of cells of the fibroblast lineage, possibly contributing to the fibrogenic process. The aim of this work was to study the expression and regulation of the IGF axis components in rat liver MF. Methods: Cultures of MF from passages 1 to 4 (P1–4) were studied. IGFBP secretion was analyzed by [125I]-IGF-I ligand and immunoblotting. IGF-I, IGF-IR, IGF-II/M6-PR, and IGFBP messenger RNA (mRNA) expression was assessed by Northern blot hybridization. DNA synthesis was evaluated by 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. Results: MF from P1 to 4 constitutively expressed mRNA transcripts specific for IGF-I, IGF-IR, and IGF-II/M6-PR. In MF, biosynthesis of IGFBP-3 and -2 was observed that was stimulated by IGF-I, insulin, and transforming growth factor β (TGF-β), whereas platelet-derived growth factor (PDGF-BB) revealed inhibitory effects. IGF-I and to a lesser extent insulin increased DNA synthesis of MF. Simultaneous addition of recombinant human IGFBP-2 or -3 with IGF-I diminished the mitogenic effect of IGF-I on MF whereas preincubation of MF with IGFBP-2 or -3 further potentiated the IGF-I stimulated DNA synthesis. In conclusion, the present study demonstrates that the IGF axis may play a role in the regulation of MF proliferation in vitro which might be relevant in vivo for the process of fibrogenesis during acute and chronic liver injury. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Spatial subsidies are associated with pronounced ecosystem responses, as nutrients cross ecological boundaries and cascade through food webs. While the importance of subsidies is known, the role of shellfish, specifically molluscs, as a marine subsidy has not been formally described. Focusing primarily on the Pacific coast of North America, we identify vectors that transport shellfish‐derived nutrients into coastal terrestrial environments, including birds, mammals, and over 13 000 yr of marine resource use by people. Evidence from recipient ecosystems suggests shellfish drastically influence soil chemistry, forest productivity and the diversity of primary producers at the regional and landscape level. Responses in higher trophic levels have not yet been investigated, but given documented responses in lower trophic levels, this may be due to a lack of examination. To determine if the processes we describe within the northeast Pacific are pertinent to coastal environments worldwide, we also explore shellfish subsidies globally, with a specific focus on temperate and tropical islands. As shellfish are not as spatially or temporally constrained as other subsidies, our examination suggests our findings are applicable to many other geographical regions along the marine–terrestrial interface. [ABSTRACT FROM AUTHOR]

The Ensemble Mars Atmosphere Reanalysis System (EMARS) dataset version 1.0 contains hourly gridded atmospheric variables for the planet Mars, spanning Mars Year (MY) 24 through 33 (1999 through 2017). A reanalysis represents the best estimate of the state of the atmosphere by combining observations that are sparse in space and time with a dynamical model and weighting them by their uncertainties. EMARS uses the Local Ensemble Transform Kalman Filter (LETKF) for data assimilation with the GFDL/NASA Mars Global Climate Model (MGCM). Observations that are assimilated include the Thermal Emission Spectrometer (TES) and Mars Climate Sounder (MCS) temperature retrievals. The dataset includes gridded fields of temperature, wind, surface pressure, as well as dust, water ice, CO2 surface ice and other atmospheric quantities. Reanalyses are useful for both science and engineering studies, including investigations of transient eddies, the polar vortex, thermal tides and dust storms, and during spacecraft operations. [ABSTRACT FROM AUTHOR]

Purpose: Computed tomography (CT) is an effective method for detecting and characterizing lung nodules in vivo. With the growing use of chest CT, the detection frequency of lung nodules is increasing. Noninvasive methods to distinguish malignant from benign nodules have the potential to decrease the clinical burden, risk, and cost involved in follow‐up procedures on the large number of false‐positive lesions detected. This study examined the benefit of including perinodular parenchymal features in machine learning (ML) tools for pulmonary nodule assessment. Methods: Lung nodule cases with pathology confirmed diagnosis (74 malignant, 289 benign) were used to extract quantitative imaging characteristics from computed tomography scans of the nodule and perinodular parenchyma tissue. A ML tool development pipeline was employed using k‐medoids clustering and information theory to determine efficient predictor sets for different amounts of parenchyma inclusion and build an artificial neural network classifier. The resulting ML tool was validated using an independent cohort (50 malignant, 50 benign). Results: The inclusion of parenchymal imaging features improved the performance of the ML tool over exclusively nodular features (P < 0.01). The best performing ML tool included features derived from nodule diameter‐based surrounding parenchyma tissue quartile bands. We demonstrate similar high‐performance values on the independent validation cohort (AUC‐ROC = 0.965). A comparison using the independent validation cohort with the Fleischner pulmonary nodule follow‐up guidelines demonstrated a theoretical reduction in recommended follow‐up imaging and procedures. Conclusions: Radiomic features extracted from the parenchyma surrounding lung nodules contain valid signals with spatial relevance for the task of lung cancer risk classification. Through standardization of feature extraction regions from the parenchyma, ML tool validation performance of 100% sensitivity and 96% specificity was achieved. [ABSTRACT FROM AUTHOR]

Summary: Background: Recent studies have demonstrated that Th2 responses have the ability to antagonize Th17 responses. In mouse models of allergic asthma, blockade of Th2‐effector cytokines results in elaboration of Th17 responses and associated increases in pulmonary neutrophilia. While these can be controlled by simultaneous blockade of Th17‐associated effector cytokines, clinical trials of anti‐IL‐17/IL‐17RA blocking therapies have demonstrated increased of risk of bacterial and fungal infections. Identification of minimally effective doses of cytokine‐blocking therapies with the goal of reducing the potential emergence of infection‐related complications is a translationally relevant goal. Objective: In the current report, we examine whether combined blockade of IL‐13 and IL‐17A, at individually sub‐therapeutic levels, can limit the development of allergic asthma while sparing expression of IL‐17A‐associated anti‐microbial effectors. Methods: House dust mite was given intratracheally to A/J mice. Anti‐IL‐13 and anti‐IL‐17A antibodies were administered individually, or concomitantly at sub‐therapeutic doses. Airway hyper‐reactivity, lung inflammation, magnitude of Th2‐ and Th17‐associated cytokine production and expression of IL‐13‐ and IL‐17A‐induced genes in the lungs was assessed. Results: Initial dosing studies identified sub‐therapeutic levels of IL‐13 and IL‐17A blocking mAbs that have a limited effect on asthma parameters and do not impair responses to microbial products or infection. Subsequent studies demonstrated that combined sub‐therapeutic dosing with IL‐13 and IL‐17A blocking mAbs resulted in significant improvement in airway hyperresponsiveness (AHR) and expression of IL‐13‐induced gene expression. Importantly, these doses neither exacerbated nor inhibited production of Th17‐associated cytokines, or IL‐17A‐associated gene expression. Conclusion: This study suggests that combining blockade of individual Th2 and Th17 effector cytokines, even at individually sub‐therapeutic levels, may be sufficient to limit disease development while preserving important anti‐microbial pathways. Such a strategy may therefore have reduced potential for adverse events associated with blockade of these pathways. [ABSTRACT FROM AUTHOR]

Abstract: The aquatic environment is increasingly bombarded by a wide variety of noise pollutants whose range and intensity are increasing with each passing decade. Yet, little is known about how aquatic noise affects marine communities. To determine the implications that changes to the soundscape may have on fishes, a meta‐analysis was conducted focusing on the ramifications of noise on fish behavior and physiology. Our meta‐analysis identified 42 studies that produced 2,354 data points, which in turn indicated that anthropogenic noise negatively affects fish behavior and physiology. The most predominate responses occurred within foraging ability, predation risk, and reproductive success. Additionally, anthropogenic noise was shown to increase the hearing thresholds and cortisol levels of numerous species while tones, biological, and environmental noise were most likely to affect complex movements and swimming abilities. These findings suggest that the majority of fish species are sensitive to changes in the aquatic soundscape, and depending on the noise source, species responses may have extreme and negative fitness consequences. As such, this global synthesis should serve as a warning of the potentially dire consequences facing marine ecosystems if alterations to aquatic soundscapes continue on their current trajectory. [ABSTRACT FROM AUTHOR]

Diversity estimates play a key role in ecological assessments. Species richness and abundance are commonly used to generate complex diversity indices that are dependent on the quality of these estimates. As such, there is a long-standing interest in the development of monitoring techniques, their ability to adequately assess species diversity, and the implications for generated indices. To determine the ability of substratum community assessment methods to capture species diversity, we evaluated four methods: photo quadrat, point intercept, random subsampling, and full quadrat assessments. Species density, abundance, richness, Shannon diversity, and Simpson diversity were then calculated for each method. We then conducted a method validation at a subset of locations to serve as an indication for how well each method captured the totality of the diversity present. Density, richness, Shannon diversity, and Simpson diversity estimates varied between methods, despite assessments occurring at the same locations, with photo quadrats detecting the lowest estimates and full quadrat assessments the highest. Abundance estimates were consistent among methods. Sample-based rarefaction and extrapolation curves indicated that differences between Hill numbers (richness, Shannon diversity, and Simpson diversity) were significant in the majority of cases, and coverage-based rarefaction and extrapolation curves confirmed that these dissimilarities were due to differences between the methods, not the sample completeness. Method validation highlighted the inability of the tested methods to capture the totality of the diversity present, while further supporting the notion of extrapolating abundances. Our results highlight the need for consistency across research methods, the advantages of utilizing multiple diversity indices, and potential concerns and considerations when comparing data from multiple sources. [ABSTRACT FROM AUTHOR]

Three alleles have been described in locus K in dogs: I K SP B sp i I > k SP br sp > k SP y sp i (sorted by dominance); the dominant black I K SP B sp i allele (c.231 233) has not yet been found in GSD (Candille et al., 2007; Kerns et al., 2007). Five individuals of the German Shepherd Dog (GSD) breed were referred to us. The five GSD dogs carried the I a SP t sp i / I a SP t sp i genotype instead of the expected I a i / I a i found so far in other black GSD dogs (Table S2). [Extracted from the article]

Recruitment of new propagules into a population can be a critical determinant of adult density. We examined recruitment dynamics in the Olympia oyster ( Ostrea lurida), a species occurring almost entirely in estuaries. We investigated spatial scales of interannual synchrony across 37 sites in eight estuaries along 2,500 km of Pacific North American coastline, predicting that high vs. low recruitment years would coincide among neighboring estuaries due to shared exposure to regional oceanographic factors. Such synchrony in recruitment has been found for many marine species and some migratory estuarine species, but has never been examined across estuaries in a species that can complete its entire life cycle within the same estuary. To inform ongoing restoration efforts for Olympia oysters, which have declined in abundance in many estuaries, we also investigated predictors of recruitment failure. We found striking contrasts in absolute recruitment rate and frequency of recruitment failure among sites, estuaries, and years. Although we found a positive relationship between upwelling and recruitment, there was little evidence of synchrony in recruitment among estuaries along the coast, and only limited synchrony of sites within estuaries, suggesting recruitment rates are affected more strongly by local dynamics within estuaries than by regional oceanographic factors operating at scales encompassing multiple estuaries. This highlights the importance of local wetland and watershed management for the demography of oysters, and perhaps other species that can complete their entire life cycle within estuaries. Estuaries with more homogeneous environmental conditions had greater synchrony among sites, and this led to the potential for estuary-wide failure when all sites had no recruitment in the same year. Environmental heterogeneity within estuaries may thus buffer against estuary-wide recruitment failure, analogous to the portfolio effect for diversity. Recruitment failure was correlated with lower summer water temperature, higher winter salinity, and shorter residence time: all indicators of stronger marine influence on estuaries. Recruitment failure was also more common in estuaries with limited networks of nearby adult oysters. Large existing oyster networks are thus of high conservation value, while estuaries that lack them would benefit from restoration efforts to increase the extent and connectivity of sites supporting oysters. [ABSTRACT FROM AUTHOR]

Electronic grade Czochralski and float zone silicon in the as grown state have a very low concentration of recombination generation centers (typically <1010 cm−3). Consequently, in integrated circuit technologies using such material, electrically active inadvertent impurities and structural defects are rarely detectable. The quest for cheap photovoltaic cells has led to the use of less pure silicon, multi-crystalline material, and low cost processing for solar applications. Cells made in this way have significant extrinsic recombination mechanisms. In this paper we review recombination involving defects and impurities in single crystal and in multi-crystalline solar silicon. Our main techniques for this work are recombination lifetime mapping measurements using microwave detected photoconductivity decay and variants of deep level transient spectroscopy (DLTS). In particular, we use Laplace DLTS to distinguish between isolated point defects, small precipitate complexes and decorated extended defects. We compare the behavior of some common metallic contaminants in solar silicon in relation to their effect on carrier lifetime and cell efficiency. Finally, we consider the role of hydrogen passivation in relation to transition metal contaminants, grain boundaries and dislocations. We conclude that recombination via point defects can be significant but in most multi-crystalline material the dominant recombination path is via decorated dislocation clusters within grains with little contribution to the overall recombination from grain boundaries. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the rationale for using targeted therapies against hypoxia-inducible factor (HIF) and mammalian target of rapamycin (mTOR) pathways in urothelial carcinoma of the bladder, by studying the immunohistochemical expression of molecules of these pathways in urothelial carcinoma, as recent pre-clinical studies and clinical trials have shown the potential utility of such targeted therapies. PATIENTS AND METHODS Immunohistochemical stains were performed on a tissue microarray prepared from 92 cases of ⩾ pT2 urothelial (transitional cell) carcinoma of bladder, using antibodies against HIF-1α and VEGF-R2, and phospho-S6 and phospho-4E BP1, molecules of HIF and activated mTOR pathways, respectively. Immunoreactivity was graded from 0 to 3 + (0, 0-5%; 1 + , 6-25%; 2 + , 26- 50%; 3 + , > 50% tumour cells positive). RESULTS In all, 58, 34, 35 and 17% of the tumours showed grade 2-3 + expression of phospho- 4E BP1, phospho-S6, HIF-1α and VEGF-R2, respectively. Moderate correlation for immunoreactivity was observed between molecules within the same pathway [(phospho-4E BP1 with phospho-S6 (rho = 0.411), and HIF-1 α with VEGF-R2 (rho = 0.265)], but not between molecules across pathways. CONCLUSIONS Urothelial carcinomas of the bladder express molecules of the HIF and mTOR pathways, providing a rationale for clinical trials evaluating agents targeting these pathways. Correlation between molecules within the same pathway, and not across pathways, suggests that investigating the usefulness of a specific targeted agent might benefit from pre-treatment evaluation of pathway marker expression. [ABSTRACT FROM AUTHOR]

An acute-phase response is the systemic reaction of an organism to insult (e.g. infection, trauma and burning). It represents the ‘first line’ of defence of the body to tissue-damaging attacks. In the present work, we used a rat model of an intra-muscular turpentine oil (TO) injection to analyse erythropoietin (EPO) gene expression changes in the liver, one of the main target organs of acute-phase cytokines. EPO began to increase in the serum of TO-treated animals 6 h after injection and reached a maximum at 24 h (125±20 pg/ml). The detection of total RNA by polymerase chain reaction analysis showed that the levels of EPO gene expression in the liver were considerably increased between 2 and 12 h by up to 20-fold at the peak after TO administration, followed by a gradual decrease over the next 48 h, although the values remained significantly higher compared with the control group. In the kidney, after a sudden slight increase, the values declined progressively to 3.5-fold decrease at 12 h after the injection. In the liver, a parallel upregulation of the hypoxia-inducible factor-1 (HIF-1) α gene was observed (up to 4.7-fold increase), while HIF-2 α gene expression remained unaltered. On the other hand, the protein of both genes became detectable after the injection and increased progressively over 24 h, with a subsequent decline. These results suggest that EPO may be added to the increasing group of positive acute-phase proteins and the liver might represent the major source of the hormone under these conditions in the rat. [ABSTRACT FROM AUTHOR]

The sorptive behavior of two surfactants (Triton X-100(R) and Dowfax(R) 8390) with two surface soil samples, a subsurface soil sample, a weathered black shale containing large amounts of aged organic matter, an aeolian sand, and two clay minerals (montmorillonite and kaolinite) was examined. Dowfax 8390 (dianionic surfactant) sorption was notdetected with any of the samples. In contrast, Triton X-100, an ethoxylated nonionic surfactant, sorbed to all the samples. The mole surfactant sorbed/g sorbent (mol surf/g sorbent) was greater for samples containing large amounts of smectite minerals and nonlinearity of theTriton X-100 isotherm increased in samples low in organic carbon. The X-ray diffraction analysis concluded that the ethoxylate group of Triton X-100 intercalates with montmorillonite. The weathered black shale sample also has a high mol surf/g sorbent value when reacted withTriton X-100 but contains less smectite clay. We suggest that TritonX-100 may be reacting via hydrophobic groups (branched alkyl chain) with the shale sample. Consequently, sorption of alcohol ethoxylate surfactants cannot be predicted solely on the basis of soil attributessuch as clay or organic matter content, for it appears that the organic matter-clay organization may predominate in these types of interactions. [ABSTRACT FROM AUTHOR]

Disturbed ecosystems often exhibit increased community heterogeneity when compared to nondisturbed systems. One way to measure community heterogeneity is statistical dispersion, a measure of how variable individual samples are from the multivariate average of the community condition (species presence/absence and density). In more specific manner, dispersion measures the distance between an individual data point and the centroid, the multivariate average of all data points. Statistical dispersion may be an important parameter to include in environmental assessments, or in studies that attempt to understand the role of disturbances in structuring biological systems. However, disturbances have been observed to increase, decrease, or not impact community dispersion (or community heterogeneity). Therefore, the usefulness of dispersion in studying or identifying disturbances is unclear. We tested if a mechanical disturbance increased community dispersion using the infaunal community of the intertidal mudflats along the north coast of British Columbia, Canada. We observed no statistically significant increase in community dispersion with varying frequency and intensity of a mechanical disturbance. This is likely a result of disturbed and nondisturbed treatments being dominated by the same six taxa, thus minimizing dispersion. Therefore, in ecosystems where differences in community successional stages are subtle (a result of changes in relative abundance rather than species replacement), community dispersion may not be an informative parameter when investigating disturbance. Despite this, we suggest that dispersion can be a useful variable to include in studies attempting to understand or identify disturbances; however, dispersion should only be one parameter amongst many used to understand or identify disturbances. [ABSTRACT FROM AUTHOR]

The article focuses on a study on mutation in the TYRP1 gene associated with brown coat colour in the Australian Shepherd Dog Breed. Topics discussed include involvement of loci in coat colour variation in dogs; production of brown eumelanin with presence of two recessive alleles; and mutation in the melanocortin receptor 1 (MC1R) gene.

A letter to the editor is presented regarding the case of a 58-year-old woman diagnosed with sigmoidal diverticulosis during her gynecological three-dimensional (3D) ultrasound examination.