bluuebunny/crossref_metadata_2025 huggingface dataset:
Review article: predictors of response to vedolizumab and ustekinumab in inflammatory bowel disease
Authors: Barré A. , Colombel J.‐F. , Ungaro R.
Published: February 2018

Background

Increased knowledge of pathways involved in the pathogenesis of IBD has led to the development of new treatment options for Crohn's disease (CD) and ulcerative colitis (UC). Two new biological agents have been recently approved for IBD: vedolizumab and ustekinumab. They have different therapeutic targets (α4β7 integrin for vedolizumab and interleukin‐12/23 pathways for ustekinumab) than the primary biological class, anti‐tumour necrosis factor alpha (anti‐TNF) agents. As the armamentarium for IBD increases in coming years, it will become important to understand factors associated with response in order to best position and personalise therapy.

Aim

To summarise the current data on predictors of response to vedolizumab and ustekinumab in IBD patients.

Methods

We conducted a comprehensive literature review. A PubMed search was performed using pre‐defined key words and terms to identify relevant studies on predictors of response.

Results

Patients with severe disease (by clinical activity and inflammatory biomarkers), or prior anti‐TNF exposure are less likely to respond to vedolizumab. Ileocolonic disease, no prior surgery and uncomplicated phenotype were associated with better responses to ustekinumab in CD. Initial response seems to predict a better long‐term maintenance in both therapies (P < 0.001). Contrary to anti‐TNF therapies, immunogenicity appears to play less of a role in response.

Conclusion

As the number of new biological therapies increase in IBD, identifying patients who are most likely to benefit from specific agents is of paramount importance to help best position IBD therapies.
Short‐chain fatty acids induce tissue plasminogen activator in airway epithelial cells via GPR41&43
Authors: Imoto Y. , Kato A. , Takabayashi T. , Sakashita M. , Norton J. E. , Suh L. A. , Carter R. G. , Weibman A. R. , Hulse K. E. , Stevens W. , Harris K. E. , Peters A. T. , Grammer L. C. , Tan B. K. , Welch K. , Conley D. B. , Kern R. C. , Fujieda S. , Schleimer R. P.
Published: February 2018

Background

Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on the presence or absence of nasal polyps (NPs). One of the features of NPs is excessive fibrin deposition, which is associated with down‐regulation of tissue plasminogen activator (t‐PA) in NPs. As t‐PA is expressed in epithelial cells, and epithelium is readily accessible to topical therapies, identifying compounds that can mediate the induction of t‐PA would be a potential new strategy for the treatment of NPs.

Objective

The objective of this study was to determine whether short‐chain fatty acids (SCFAs) can induce t‐PA in airway epithelial cells via their known receptors GPR41 and GPR43.

Methods

We performed immunohistochemistry (IHC) to determine whether receptors for SCFAs, known as G protein‐coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3) and GPR43/FFAR2, are expressed in nasal tissue. Primary normal human bronchial epithelial (NHBE) cells were stimulated with different concentrations of SCFAs to test induction of t‐PA, which was analysed by expression of mRNA and protein. Mediation of responses by SCFA receptors was evaluated by specific receptor gene silencing with siRNA.

Results

Immunohistochemistry study revealed that airway epithelial cells expressed GPR41 and GPR43. Acetic acid, propionic acid, butyric acid and valeric acid significantly induced t‐PA expression from two‐ to tenfolds. The strongest inducer of t‐PA from NHBE cells was propionic acid; cells stimulated with propionic acid released t‐PA into the supernatant in its active form. Gene silencing of GPR41 and GPR43 revealed that induction of t‐PA by SCFAs was dependent upon both GPR41 and GPR43.

Conclusions and Clinical Relevance

Short‐chain fatty acids were shown to induce airway epithelial cell expression of t‐PA via GPR41 and GPR43. Topical delivery of potent compounds that activate these receptors may have value by reducing fibrin deposition and shrinking nasal polyp growth.
Immunoassay methods used in clinical studies for the detection of anti-drug antibodies to adalimumab and infliximab
Authors: Gorovits B , Baltrukonis D J , Bhattacharya I , Birchler M A , Finco D , Sikkema D , Vincent M S , Lula S , Marshall L , Hickling T P
Published: February 2018

We examined the assay formats used to detect anti-drug antibodies (ADA) in clinical studies of the anti-tumour necrosis factor (TNF) monoclonal antibodies adalimumab and infliximab in chronic inflammatory disease and their potential impact on pharmacokinetic and clinical outcomes. Using findings of a recent systematic literature review of the immunogenicity of 11 biological/biosimilar agents, we conducted an ancillary qualitative review of a subset of randomized controlled trials and observational studies of the monoclonal antibodies against anti-TNF factor adalimumab and infliximab. Among studies of adalimumab and infliximab, the immunoassay method used to detect antibodies was reported in 91 of 111 (82%) and 154 of 206 (75%) adalimumab and infliximab studies, respectively. In most adalimumab and infliximab studies, an enzyme-linked immunosorbent assay or radioimmunoassay was used [85 of 91 (93%) and 134 of 154 (87%), respectively]. ADA incidence varied widely among assays and inflammatory diseases (adalimumab, 0–87%; infliximab, 0–79%). Pharmacokinetic and clinical outcomes were only reported for ADA-positive patients in 38 of 91 (42%) and 61 of 154 (40%) adalimumab and infliximab studies, respectively. Regardless of assay format or biological used, ADA formation was associated with lower serum concentrations, reduced efficacy and elevated rates of infusion-related reactions. Consistent with previous recommendations to improve interpretation of immunogenicity data for biologicals, greater consistency in reporting of assay methods and clinical consequences of ADA formation may prove useful. Additional standardization in immunogenicity testing and reporting, application of modern, robust assays that satisfy current regulatory expectations and implementation of international standards for marketed products may help to improve our understanding of the impact of immunogenicity to biologics.
Separation of plasma-derived exosomes into CD3(+) and CD3(−) fractions allows for association of immune cell and tumour cell markers with disease activity in HNSCC patients
Authors: Theodoraki M-N , Hoffmann T K , Whiteside T L
Published: February 2018

Head and neck squamous cell carcinoma (HNSCC) is a highly immunosuppressive malignancy. Exosomes in HNSCC patients' plasma are enriched in inhibitory cargo and mediate immunosuppression. As these exosomes are products of various cells, the cellular origin of immunoregulatory proteins they carry is unknown. To test whether tumour- or T cell-derived exosomes in patients' plasma are immunosuppressive and impact upon disease activity, we separated CD3(−) from CD3(+) exosomes by immunocapture using anti-CD3 antibodies. The exosome protein cargo was evaluated for immunoregulatory proteins using on-bead flow cytometry. Tumour protein-enriched CD3(−) exosomes were CD44v3(+). Surprisingly, mean levels of programmed death ligand 1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4) and cyclooxygenase-2 (COX-2) were similar in CD3(+) and CD3(−) exosomes, although the latter induced higher (P < 0·0025) ex-vivo apoptosis of CD8(+) T cells and greater (P < 0·005) conversion of CD4+ T cells to CD4(+)CD39(+) regulatory T cells (Treg). CD3(+) and CD3(−) exosomes carrying high levels of immunosuppressive proteins were highly effective in mediating these functions. Exosomes of patients with Union for International Cancer Control (UICC) stages III/IV disease had higher levels of PD-L1 and COX-2 than stages I/II patients (P < 0·005). Patients with nodal involvement had exosomes with the higher inhibitory protein content than N0 patients (P < 0·03). CD3(+) and CD3(−) exosomes of HNSCC patients had higher PD-L1, COX-2 and CD15s levels than healthy donors' exosomes (P < 0·009), although levels of immunostimulatory OX40 or OX40L were not different. By isolating CD3(−)/CD44v3-enriched and CD3(+) exosomes from plasma, the cellular origins of immunoregulatory proteins they carry were identified. Association of exosome molecular profiles with disease progression supports the exosome potential as future cancer biomarkers.
Correction of T cell deficiency in ZAP-70 knock-out mice by simple intraperitoneal adoptive transfer of thymocytes
Authors: Kugyelka R , Kohl Z , Olasz K , Prenek L , Berki T , Balogh P , Boldizsár F
Published: February 2018

The tyrosine kinase zeta chain-associated protein of 70 kDa (ZAP-70) plays a key role in T cell development and signalling. In the absence of ZAP-70, T cell development is arrested in the CD4+CD8+ double-positive stage, thus ZAP-70 homozygous knockout (ZAP-70−/−) mice have no mature T cells in their peripheral lymphoid organs and blood, causing severe immunodeficiency. We investigated the early kinetics and long-term effects of wild-type thymocyte transfer on T cell repopulation in ZAP-70−/− mice. We used a single intraperitoneal (i.p.) injection to deliver donor thymocytes to the recipients. Here, we show that after i.p. injection donor thymocytes leave the peritoneum through milky spots in the omentum and home to the thymus, where donor-originated CD4−CD8− double-negative thymocytes most probably restore T cell development and the disrupted thymic architecture. Subsequently, newly developed, donor-originated, single-positive αβ T cells appear in peripheral lymphoid organs, where they form organized T cell zones. The established chimerism was found to be stable, as donor-originated cells were present in transferred ZAP-70−/− mice as late as 8 months after i.p. injection. We demonstrate that a simple i.p. injection of ZAP-70+/+ thymocytes is a feasible method for the long-term reconstitution of T cell development in ZAP-70-deficient mice.
Past, present, and future of a freshwater fish metapopulation in a threatened landscape
Authors: Vera‐Escalona Iván , Senthivasan Shreeram , Habit Evelyn , Ruzzante Daniel E.
Published: February 2018

It is well documented that hydropower plants can affect the dynamics of fish populations through landscape alterations and the creation of new barriers. Less emphasis has been placed on the examination of the genetic consequences for fish populations of the construction of dams. The relatively few studies that focus on genetics often do not consider colonization history and even fewer tend to use this information for conservation purposes. As a case study, we used a 3‐pronged approach to study the influence of historical processes, contemporary landscape features, and potential future anthropogenic changes in landscape on the genetic diversity of a fish metapopulation. Our goal was to identify the metapopulation's main attributes, detect priority areas for conservation, and assess the consequences of the construction of hydropower plants for the persistence of the metapopulation. We used microsatellite markers and coalescent approaches to examine historical colonization processes, traditional population genetics, and simulations of future populations under alternate scenarios of population size reduction and gene flow. Historical gene flow appeared to have declined relatively recently and contemporary populations appeared highly susceptible to changes in landscape. Gene flow is critical for population persistence. We found that hydropower plants could lead to a rapid reduction in number of alleles and to population extirpation 50–80 years after their construction. More generally, our 3‐pronged approach for the analyses of empirical genetic data can provide policy makers with information on the potential impacts of landscape changes and thus lead to more robust conservation efforts.
PLCγ2 promotes apoptosis while inhibits proliferation in rat hepatocytes through PKCD/JNK MAPK and PKCD/p38 MAPK signalling
Authors: Chen Xiaoguang , Lv Qiongxia , Ma Jun , Liu Yumei
Published: February 2018

Objectives

The PLCG2 (PLCγ2) gene is a member of PLC gene family encoding transmembrane signalling enzymes involved in various biological processes including cell proliferation and apoptosis. Our earlier study indicated that PLCγ2 may be involved in the termination of regeneration of the liver which is mainly composed of hepatocytes, but its exact biological function and molecular mechanism in liver regeneration termination remains unclear. This study aims to examine the role of PLCγ2 in the growth of hepatocytes.

Materials and methods

A recombinant adenovirus expressing PLCγ2 was used to infect primary rat hepatocytes. PLCγ2 mRNA and protein levels were detected by qRT‐PCR and Western blot. The subcellular location of PLCγ2 protein was tested by an immunofluorescence assay. The proliferation of hepatocytes was measured by MTT assay. The cell cycle and apoptosis were analysed by flow cytometry. Caspase‐3, ‐8 and ‐9 activities were measured by a spectrophotometry method. Phosphorylation levels of PKCD, JNK and p38 in the infected cells were detected by Western blot. The possible mechanism underlying the role of PLCγ2 in hepatocyte growth was also explored by adding a signalling pathway inhibitor.

Results

Hepatocyte proliferation was dramatically reduced, while cell apoptosis was remarkably increased. The results demonstrated that PLCγ2 increased the phosphorylation of PKCD, p38 and JNK in rat hepatocytes. After PKCD activity was inhibited by the inhibitor Go 6983, the levels of both p‐p38 and p‐JNK MAPKs significantly decreased, and PLCγ2‐induced cell proliferation inhibition and cell apoptosis were obviously reversed.

Conclusions

This study showed that PLCγ2 regulates hepatocyte growth through PKCD‐dependently activating p38 MAPK and JNK MAPK pathways; this result was experimentally based on the further exploration of the effect of PLCγ2 on hepatocyte growth in vivo.
Cannabis use is associated with lower rates of initiation of injection drug use among street‐involved youth: A longitudinal analysis
Authors: Reddon Hudson , DeBeck Kora , Socias Maria Eugenia , Dong Huiru , Wood Evan , Montaner Julio , Kerr Thomas , Milloy Michael‐John
Published: February 2018

Introduction and Aims

Street‐involved youth are known to be at elevated risk of initiating injection drug use. However, the impact of so‐called ‘gateway’ drugs, such as cannabis, on injection initiation is unknown. The objective of this study was to examine the association between cannabis use and initiation of injection drug use among a prospective cohort of street‐involved youth in Vancouver, Canada.

Design and Methods

Data for this study were collected from the At‐Risk Youth Study. From September 2005 to May 2015, participants aged 14–26 who reported illicit drug use were recruited into this open prospective cohort study. An extended Cox regression model with time‐updated covariates was used to identify factors independently associated with injection initiation.

Results

During the study period, 481 street‐involved youth were included in this study. Of these, 228 (47.4%) reported at least daily cannabis use, and 103 (21.4%) initiated injection drug use. In a multivariable analysis, ≥daily cannabis use was associated with slower rates of injection initiation (adjusted relative hazard 0.66, 95% confidence interval 0.45–0.98; P = 0.038). Sub‐analyses revealed that cannabis use was negatively associated with initiation of injection stimulants but not initiation of injection opioids.

Discussion and Conclusions

Given the expansion of cannabis legalisation throughout North America, it is encouraging that cannabis use was associated with slower time to initiation of injection drug use in this cohort. This finding challenges the view of cannabis as a gateway substance that precipitates the progression to using harder and more addictive drugs.
SGLT‐2 inhibitors and the risk of lower‐limb amputation: Is this a class effect?
Authors: Khouri Charles , Cracowski Jean‐Luc , Roustit Matthieu
Published: February 2018

Inhibitors of the sodium‐glucose co‐transporter‐2 (SGLT‐2) are a novel class of glucose‐lowering agents that show promising results. However, the use of canagliflozin has been associated with an increased risk of lower‐limb amputation. Whether this risk concerns other SGLT‐2 inhibitors is unclear, and our objective was to address this issue. We performed a disproportionality analysis using the WHO global database of individual case safety reports (VigiBase). Among the 8 293 886 reports available between January 2013 and December 2017, we identified 79 reports of lower‐limb amputation that were associated with SGLT‐2 inhibitors. Among all blood glucose lowering drugs, the proportional reporting ratio (PRR) was increased only for SGLT‐2 inhibitors (5.55 [4.23, 7.29]). While we observed an expected signal for canagliflozin (7.09 [5.25, 9.57]), the PRR was also high for empagliflozin (4.96 [2.89, 8.50]) and, for toe amputations only, for dapagliflozin (2.62 [1.33, 5.14]). In conclusion, our results reveal a positive disproportionality signal for canagliflozin, and also for empagliflozin, and, for toe amputations only, for dapagliflozin. However, our analysis relies on a limited number of cases and is exposed to the biases inherent to pharmacovigilance studies. Further prospective data are therefore needed to better characterize the risk of amputations with different SGLT‐2 inhibitors.
Variation in composition of two bumble bee species across communities affects nectar robbing but maintains pollinator visitation rate to an alpine plant, Salvia przewalskii
Authors: YE ZHONG‐MING , JIN XIAO‐FANG , INOUYE DAVID W. , WANG QING‐FENG , YANG CHUN‐FENG
Published: February 2018

1. In many flowering plants, bumble bees may forage as both pollinators and nectar robbers. This mixed foraging behaviour may be influenced by community context and consequently, potentially affect pollination of the focal plant.

2. Salvia przewalskii is both pollinated and robbed exclusively by bumble bees. In the present study area, it was legitimately visited by two species of bumble bees with different tongue length, Bombus friseanus and Bombus religiosus, but it was only robbed by Bombus friseanus, the shorter‐tongued bumble bee. The intensity of nectar robbing and pollinator visitation rate to the plant were investigated across 26 communities in the Hengduan Mountains in East Himalaya during a 2‐year project. For each of these communities, the floral diversity, and the population size and floral resource of S. przewalskii were quantified. The abundances of the two bumble bee species were also recorded.

3. Both nectar robbing and pollinator visitation rate were influenced by floral diversity. However, pollinator visitation rate was not affected by nectar robbing. The results revealed that relative abundance of the two bumble bee species significantly influenced the incidence of nectar robbing but not the pollinator visitation rate. Increased abundance of B. religiosus, the legitimate visitors, exacerbated nectar robbing, possibly by causing B. friseanus to shift to robbing; however, pollinator visitation remained at a relatively high level.

4. The results may help to explain the persistence of both nectar robbing and pollination, and suggest that, in comparison to pollination, nectar robbing is a more unstable event in a community.
Characteristics associated with outcome in patients with first‐ever posterior fossa stroke
Authors: Villringer K. , Florczak‐Rzepka M. , Grittner U. , Brunecker P. , Tepe H. , Nolte C. H. , Fiebach J. B.
Published: February 2018

Background and purpose

Factors such as infarct volume, infarct location and symptom severity can considerably influence long‐term outcome in posterior fossa strokes. The decision about therapy can sometimes be complicated by discrepancies between infarct volume and clinical severity. We aimed to evaluate imaging and clinical parameters possibly influencing long‐term outcome in patients with first‐ever posterior fossa stroke.

Methods

Imaging was performed on a 3‐T magnetic resonance imaging scanner. Sixty‐one of 1795 patients from the observational 1000Plus and LOBI studies (NCT00715533 and NCT02077582, clinicaltrials.org) were enrolled, meeting the inclusion criteria of first‐ever posterior fossa stroke and magnetic resonance imaging examination within 24 h after symptom onset. Infarcts were classified as belonging to a proximal, middle or distal territory location in the posterior fossa. Good outcome was defined as a modified Rankin scale score of ≤1 at 3 months.

Results

The largest lesion volumes on diffusion‐weighted imaging on day 0 and fluid attenuation inversion recovery (FLAIR) on day 6 were found in the middle territory location with a median volume of 0.4 mL on diffusion‐weighted imaging and 1.0 mL on FLAIR on day 6 versus 0.1/0.3 mL in the proximal and 0.1/0.1 mL in the distal territory location of the posterior fossa, respectively. Parameters associated with poor outcome were older age (P = 0.005), higher National Institutes of Health Stroke Scale score on admission/discharge (P = 0.016; P = 0.001), larger lesion volumes on FLAIR on day 6 (P = 0.013) and dysphagia (P = 0.02). There was no significant association between infarct location and modified Rankin scale score on day 90.

Conclusion

Infarct volume and clinical severity, but not infarct location, were the main contributors to poor long‐term outcome in first‐ever posterior fossa strokes.
Parental Depression and Cooperative Coparenting: A Longitudinal and Dyadic Approach
Authors: Williams Deadric T.
Published: February 2018

Objective

To examine the relationship between parental depression and cooperative coparenting among couples over the first 5 years after a birth.

Background

Previous research has considered how depression affects coparenting but has not focused on the association as a longitudinal and dyadic process. Understanding coparenting is important as it is linked to parents' and children's well‐being.

Method

Data from the Fragile Families and Child Wellbeing (FFCW) study were analyzed using actor–partner interdependence models. The FFCW follows families and their children as part of a birth cohort of children who were born in large urban cities of the United States in the late 1990s.

Results

The actor–partner interdependence models indicated that (a) parents' depression is associated with decreased coparenting perceptions for both mothers and fathers, and the effects endure over time; (b) fathers' depression was also associated with mothers' perceptions of cooperative coparenting over the later years; and (c) differences between mothers and fathers emerged only during the early years, with the effect of depression on coparenting being larger for fathers than mothers.

Conclusion

The results not only highlight the importance of both parents' mental health on coparenting but also the added role that fathers' depression plays in shaping their own and their partners' perceptions of coparenting.

Implications

Policy makers and family practitioners who are invested in building healthy families may find it valuable to screen for and treat mental illness in the context of creating programs to increase cooperative coparenting.
Helicobacter pylori purine nucleoside phosphorylase shows new distribution patterns of open and closed active site conformations and unusual biochemical features
Authors: Narczyk Marta , Bertoša Branimir , Papa Lucija , Vuković Vedran , Leščić Ašler Ivana , Wielgus‐Kutrowska Beata , Bzowska Agnieszka , Luić Marija , Štefanić Zoran
Published: February 2018

Even with decades of research, purine nucleoside phosphorylases (PNPs) are enzymes whose mechanism is yet to be fully understood. This is especially true in the case of hexameric PNPs, and is probably, in part, due to their complex oligomeric nature and a whole spectrum of active site conformations related to interactions with different ligands. Here we report an extensive structural characterization of the apo forms of hexameric PNP from Helicobacter pylori (HpPNP), as well as its complexes with phosphate (Pi) and an inhibitor, formycin A (FA), together with kinetic, binding, docking and molecular dynamics studies. X‐ray structures show previously unseen distributions of open and closed active sites. Microscale thermophoresis results indicate that a two‐site model describes Pi binding, while a three‐site model is needed to characterize FA binding, irrespective of Pi presence. The latter may be related to the newly found nonstandard mode of FA binding. The ternary complex of the enzyme with Pi and FA shows, however, that Pi binding stabilizes the standard mode of FA binding. Surprisingly, HpPNP has low affinity towards the natural substrate adenosine. Molecular dynamics simulations show that Pi moves out of most active sites, in accordance with its weak binding. Conformational changes between nonstandard and standard binding modes of nucleoside are observed during the simulations. Altogether, these findings show some unique features of HpPNP and provide new insights into the functioning of the active sites, with implications for understanding the complex mechanism of catalysis of this enzyme.

Databases

The atomic coordinates and structure factors have been deposited in the Protein Data Bank: with accession codes 6F52 (HpPNPapo_1), 6F5A (HpPNPapo_2), 6F5I (HpPNPapo_3), 5LU0 (HpPNP_PO4), 6F4W (HpPNP_FA) and 6F4X (HpPNP_PO4_FA).

Enzymes

Purine nucleoside orthophosphate ribosyl transferase, EC2.4.2.1, UniProtID: P56463
An assessment of catches of shore sport fishing competitions along the coast of the Maltese Islands: Implications for conservation and management
Authors: Agius Darmanin S. , Vella A.
Published: February 2018

Competitive shore‐based sport fishing is a popular recreational activity in the Maltese Islands. However, prior to this study, no scientific research surveys had been carried out during sport fishing competitions to investigate catches. Collaboration with Maltese sports fishermen was developed to target sustainable management. Recreational fishing catches were recorded between July 2012 and December 2015 by means of 1,633 roving‐access creel surveys, conducted during 79 sport fishing competitions, totalling a fishing effort of 7,548 hr. A total of 29,916 fish belonging to 80 species from 26 different families were caught at a mean catch‐per‐unit‐effort (CPUE) of 4.16 fish angler/hr (SD ± 3.79) and 0.18 kg angler/hr (SD ± 0.17) but with seasonal variation. Catch‐and‐release practices were implemented by all Maltese sport fishing clubs, however, the mean mortality rate stood at 35.5% (SD ± 42.1), indicating that more effort is required to improve survival of fish. The study outcomes provide conservation recommendations.
The persistent decline of patterned woody vegetation: The tiger bush in the context of the regional Sahel greening trend
Authors: Trichon Valérie , Hiernaux Pierre , Walcker Romain , Mougin Eric
Published: February 2018

Following 25 years of below average annual rainfall in the Sahel between 1970 and 1995, the return to more humid conditions has led to rapid postdrought recovery of the woody cover. However, the increase in the woody cover is not spatially homogeneous raising questions about the resilience of some woody vegetation types. Based on the analysis of field and remote sensing data collected on the tiger bush systems in the northern Sahel in Mali, this study noted the current and persistent degradation of these systems in the Sahel since the 1970s despite the recent improvement in rainfall since the mid‐1990s and the general Sahel re‐greening. Profound changes in the woody population pattern, tree density and cover, and floristic composition took place regardless of the site location along the south–north rainfall gradient. Associated with definite structural changes of the woody population, surface hydrology shifted from a sheet to concentrated run‐off accelerating the collapse of the patterned woody population. Currently, there is no evidence in favour of reversing the current degradation process, at least at a decadal scale, although very sparse recolonization by pioneer woody vegetation has been observed in the driest sites along recently formed gullies. These observations support the hypothesis of an ecosystem shift, with long‐term implications for the structure and functioning of the patterned vegetation, as well as the whole watershed landscape through increased run‐off leading to stronger water flows in enlarged wadis, increased soil erosion upstream and sediment deposition downstream, enhanced water storage in ponds, and greater recharge of aquifers, which is an illustration of the “Sahelian paradox”.
Anthropogenic disturbance homogenizes seagrass fish communities
Authors: Iacarella Josephine C. , Adamczyk Emily , Bowen Dan , Chalifour Lia , Eger Aaron , Heath William , Helms Sibylla , Hessing‐Lewis Margot , Hunt Brian P. V. , MacInnis Andrew , O'Connor Mary I. , Robinson Clifford L. K. , Yakimishyn Jennifer , Baum Julia K.
Published: February 2018

Anthropogenic activities have led to the biotic homogenization of many ecological communities, yet in coastal systems this phenomenon remains understudied. In particular, activities that locally affect marine habitat‐forming foundation species may perturb habitat and promote species with generalist, opportunistic traits, in turn affecting spatial patterns of biodiversity. Here, we quantified fish diversity in seagrass communities across 89 sites spanning 6° latitude along the Pacific coast of Canada, to test the hypothesis that anthropogenic disturbances homogenize (i.e., lower beta‐diversity) assemblages within coastal ecosystems. We test for patterns of biotic homogenization at sites within different anthropogenic disturbance categories (low, medium, and high) at two spatial scales (within and across regions) using both abundance‐ and incidence‐based beta‐diversity metrics. Our models provide clear evidence that fish communities in high anthropogenic disturbance seagrass areas are homogenized relative to those in low disturbance areas. These results were consistent across within‐region comparisons using abundance‐ and incidence‐based measures of beta‐diversity, and in across‐region comparisons using incidence‐based measures. Physical and biotic characteristics of seagrass meadows also influenced fish beta‐diversity. Biotic habitat characteristics including seagrass biomass and shoot density were more differentiated among high disturbance sites, potentially indicative of a perturbed environment. Indicator species and trait analyses revealed fishes associated with low disturbance sites had characteristics including stenotopy, lower swimming ability, and egg guarding behavior. Our study is the first to show biotic homogenization of fishes across seagrass meadows within areas of relatively high human impact. These results support the importance of targeting conservation efforts in low anthropogenic disturbance areas across land‐ and seascapes, as well as managing anthropogenic impacts in high activity areas.
Ecological drivers of spatial community dissimilarity, species replacement and species nestedness across temperate forests
Authors: Wang Xugao , Wiegand Thorsten , Anderson‐Teixeira Kristina J. , Bourg Norman A. , Hao Zhanqing , Howe Robert , Jin Guangze , Orwig David A. , Spasojevic Marko J. , Wang Shunzhong , Wolf Amy , Myers Jonathan A.
Published: February 2018

Aims

Patterns of spatial community dissimilarity have inspired a large body of theory in ecology and biogeography. Yet key gaps remain in our understanding of the local‐scale ecological processes underlying species replacement and species nestedness, the two fundamental components of spatial community dissimilarity. Here, we examined the relative influence of dispersal limitation, habitat filtering and interspecific species interactions on local‐scale patterns of the replacement and nestedness components in eight stem‐mapped temperate forest mega‐plots at different ontogenetic stages (large versus small trees).

Location

Eight large (20–35 ha), fully mapped temperate forest plots in northern China and northern U.S.A.

Time period

2004–2016.

Major taxa studied

Woody plants.

Methods

We combined decomposition of community dissimilarity (based on the Ružička index) and spatial point‐pattern analysis to compare the spatial (i.e., distance‐dependent) replacement and nestedness components of each plot with that expected under five spatially explicit null models representing different hypotheses on community‐assembly mechanisms.

Results

Our analyses revealed complex results. In all eight forests, spatial community dissimilarity was best explained by species replacement among local tree assemblages and by a null model based on dispersal limitation. In contrast, spatial nestedness for large and small trees was best explained by random placement and habitat filtering, respectively, in addition to dispersal limitation. However, interspecific interactions did not contribute to local replacement and nestedness.

Main conclusions

Species replacement is the predominant process accounting for spatial community dissimilarity in these temperate forests and caused largely by local‐scale species clustering associated with dispersal limitation. Nestedness, in contrast, is less prevalent and primarily associated with larger variation in local species richness as caused by spatial richness gradients or ‘hotspots’ of local species richness. The novel use of replacement and nestedness measures in point pattern analysis is a promising approach to assess local‐scale biodiversity patterns and to explore their causes.
Roles of the third Ig‐like domain of Necl‐5/PVR and the fifth Ig‐like domain of the PDGF receptor in its signaling
Authors: Ueda Yuki , Kedashiro Shin , Maruoka Masahiro , Mizutani Kiyohito , Takai Yoshimi
Published: February 2018

The immunoglobulin (Ig)‐like cell adhesion molecule nectin‐like molecule (Necl)‐5/poliovirus receptor is up‐regulated in many types of cancer cells and implicated in their abnormally enhanced cell proliferation and movement. We previously showed that Necl‐5 cis‐interacts with the platelet‐derived growth factor (PDGF) receptor β through the extracellular region and enhances its signaling. Although this cis‐interaction does not affect the PDGF‐induced tyrosine phosphorylation of the receptor, the interaction of the cytoplasmic region of Necl‐5 with sprouty2 and the regulation of its activity are required for the enhancement of the PDGF receptor β signaling by Necl‐5. We investigated here the more detailed mechanism for this cis‐interaction of Necl‐5 with the PDGF receptor β. Necl‐5 contains three Ig‐like domains and the PDGF receptor β contains five Ig‐like domains at their extracellular regions. We showed here that the third Ig‐like domain of Necl‐5 cis‐interacted with the fifth Ig‐like domain of the PDGF receptor β. The recombinant protein of the third Ig‐like domain of Necl‐5 inhibited the cis‐interaction of full‐length Necl‐5 with the PDGF receptor β and the PDGF‐induced activation of the ERK signaling pathway that was enhanced by Necl‐5. These results revealed the novel roles of the third Ig‐like domain of Necl‐5 and the fifth Ig‐like domain of the PDGF receptor β in its signaling.
Requirement of the F‐actin‐binding activity of l‐afadin for enhancing the formation of adherens and tight junctions
Authors: Sakakibara Shotaro , Maruo Tomohiko , Miyata Muneaki , Mizutani Kiyohito , Takai Yoshimi
Published: February 2018

The apical junctional complex consists of adherens junctions (AJs) and tight junctions (TJs) in polarized epithelial cells, which are attached to each other to form a sheet. Actin filaments (F‐actin) are associated with AJs and TJs and required for the formation and maintenance of this complex. l‐Afadin is an F‐actin‐binding protein, which is localized at AJs through binding to the cell adhesion molecule nectin, and regulates the formation of AJs and TJs. However, the role of the F‐actin‐binding activity of l‐afadin for the formation of the apical junctional complex remains unknown. We generated here the cultured EpH4 mouse mammary epithelial cells in which afadin was genetically ablated. In the Ca2+ switch assay, the formation of both AJs and TJs was markedly impaired in the afadin‐deficient cells. Re‐expression of l‐afadin in the afadin‐deficient cells fully restored the formation of both AJs and TJs, but the re‐expression of the l‐afadin mutant lacking the FAB domain did not completely restore the formation of AJs or TJs. These results indicate that the F‐actin‐binding activity of l‐afadin is required for enhancing the formation of both AJs and TJs.
Does needle biopsy cause an increased risk of extracapsular extension in the diagnosis of metastatic lymph node in melanoma?
Authors: Claro Gilles , Meyer Nicolas , Meresse Thomas , Gangloff Dimitri , Grolleau Jean‐Louis , Chaput Benoit
Published: February 2018

Background

Needle biopsy is a rapid, reliable, and reproducible procedure for histological confirmation of metastatic melanoma localization. Nonetheless, this procedure presents a theoretical risk of a mechanical weakening of the lymph node capsule with perinodal tumor seeding. The objective of the study was to evaluate the incidence of extracapsular extension after needle biopsy in comparison with surgical adenectomy in patients suspected of metastatic lymph node of melanoma.

Methods

We conducted a retrospective study of 1056 patients who underwent lymphadenectomy for melanoma between 2000 and 2016 in our unit. Sixty‐nine patients were clinically and/or radiologically suspected of metastatic lymph node of melanoma. Patients were divided according to external lymph node biopsy or surgical adenectomy before lymphadenectomy. The primary endpoint was the histopathological identification of extracapsular extension in analyzed lymph nodes.

Results

The two populations were comparable except for the mitotic index, which was more frequently > 1/mm2 in the group with surgical adenectomy (P = 0.005). The proportion of extracapsular extension was significantly greater in the needle biopsy group (28/37) than in patients who underwent surgical adenectomy (14/32) (P = 0.0067; OR = 4 [95% CI: 1.4–11]).

Conclusion

Our results suggest an increased risk of extracapsular extension after external lymph node biopsy in cases of suspicion of metastatic lymph node of melanoma. Thus, this encourages us to prefer surgical adenectomy in patients with suspected adenopathy accessible surgically. In other cases, needle biopsy should be carried out under radiological guidance using devices limiting tumor seeding.
Neutralisation of toxins by probiotics during the transit into the gut: challenges and perspectives
Authors: Corbo Maria Rosaria , Campaniello Daniela , Speranza Barbara , Altieri Clelia , Sinigaglia Milena , Bevilacqua Antonio
Published: February 2018

Food contamination by toxins (both mycotoxins and bacterial toxins) represents a great challenge for their implications on health. Toxins could be removed during production, but many times, they enter the gut and act on the host. To some extents, a benefit of probiotics could be the removal/neutralisation of harmful compounds in the gut with an indirect health effect on the host. Some authors addressed the ability of yeasts and bacteria to remove mycotoxins and other toxins; however, to the best of our knowledge, there is not an overview on how and when mycotoxins and some other bacterial toxins (like cyanotoxins) can be removed by probiotics into the gut. Therefore, this topic is addressed in this paper. The manuscript is organised with an initial overview of the literature about probiotics, mycotoxins and cyanotoxins followed by a section on the ability of probiotics to remove toxins in vitro and in vivo.
Human mast cells and basophils—How are they similar how are they different?
Authors: Varricchi Gilda , Raap Ulrike , Rivellese Felice , Marone Gianni , Gibbs Bernhard F.
Published: February 2018

Mast cells and basophils are key contributors to allergies and other inflammatory diseases since they are the most prominent source of histamine as well as numerous additional inflammatory mediators which drive inflammatory responses. However, a closer understanding of their precise roles in allergies and other pathological conditions has been marred by the considerable heterogeneity that these cells display, not only between mast cells and basophils themselves but also across different tissue locations and species. While both cell types share the ability to rapidly degranulate and release histamine following high‐affinity IgE receptor cross‐linking, they differ markedly in their ability to either react to other stimuli, generate inflammatory eicosanoids or release immunomodulating cytokines and chemokines. Furthermore, these cells display considerable pharmacological heterogeneity which has stifled attempts to develop more effective anti‐allergic therapies. Mast cell‐ and basophil‐specific transcriptional profiling, at rest and after activation by innate and adaptive stimuli, may help to unravel the degree to which these cells differ and facilitate a clearer understanding of their biological functions and how these could be targeted by new therapies.
RBL cells as models for in vitro studies of mast cells and basophils
Authors: Falcone Franco H. , Wan Daniel , Barwary Nafal , Sagi‐Eisenberg Ronit
Published: February 2018

Since their establishment in 1981, RBL‐2H3 cells have been widely used as a mast cell (MC) model. Their ability to be easily grown in culture in large amounts, their responsiveness to FcεRI‐mediated triggers and the fact that they can be genetically manipulated, have provided advantages over primary MCs, in particular for molecular studies relying on genetic screening. Furthermore, the ability to generate clones that stably express proteins of interest, for example, a human receptor, have marked the RBL cells as an attractive MC model for drug screening. Indeed, 3 RBL reporter cell lines (RS‐ATL8, NFAT‐DsRed, and NPY‐mRFP) have been generated providing useful models for drug and allergen screening. Similarly, RBL cells stably expressing the human MrgprX2 receptor provide a unique paradigm for analyzing ligand interactions and signaling pathways of the unique human receptor. Finally, transient co‐transfections of RBL cells allow functional genomic analyses of MC secretion by combining library screening with simultaneous expression of a reporter for exocytosis. RBL cells thus comprise powerful tools for the study of intracellular membrane trafficking and exocytosis and the detection of allergens, vaccine safety studies and diagnosis of allergic sensitization. Their recent uses as an investigative tool are reviewed here.
Role of mast cells and basophils in pruritus
Authors: Steinhoff Martin , Buddenkotte Jörg , Lerner Ethan A.
Published: February 2018

To protect our body systems, there is a constant interactive conversation between the skin nervous and immune system. Important elements of this conversation in the skin include mast cells, basophils, and sensory nerve fibers. These cells employ a vast array of sensors that detect danger and react accordingly. This reaction, summarized as neurogenic inflammation, manifests at the conscious level as sensations including pain and itch. Here we provide a perspective on the blossoming knowledge that is illuminating connections between mast cells, basophils, and sensory nerve fibers in the mediation of itch. We discuss established mediators and receptors, in particular cytokine and neuropeptide pathways, upstream proteases, and proteinase‐activated receptors, and the emerging role of mas‐related G‐protein‐coupled receptors in itch.
Rapid tranquilization: An audit of Irish mental health nursing practice
Authors: Nash Michael , McDonagh Caitriona , Culhane Aisling , Noone Imelda , Higgins Agnes
Published: February 2018

Rapid tranquillization is a pharmacological intervention sometimes employed in mental health care for the management of acute behavioural disturbance. It is a form of restrictive practice, which, along with seclusion and restraint, is a conventional and controversial intervention in the therapeutic management of risk in mental health settings. This study surveyed mental health nurses practice in rapid tranquillization. A self‐report questionnaire was utilized which addressed aspects such as definitions of rapid tranquillization, presence of rapid tranquillization policy, types of incidents where it is used and postintervention monitoring. The results demonstrate that rapid tranquillization is an intervention used in the management of acute behavioural disturbance in various mental health settings in Ireland. Respondents showed a basic understanding of rapid tranquillization as an intervention; however, some areas reported not having a specific rapid tranquillization policy. There was some evidence of a variation in postrapid tranquillization monitoring of psychiatric/mental health and physical health. Service user debriefing following rapid tranquillization was reported to be common; however, the content of this was not elaborated on. In the light of variations in practice, specific training and the development of rapid tranquillization policies are recommended.
Factors associated with nurses’ perceptions about quality of end‐of‐life care
Authors: Hussin E. O. D. , Wong L. P. , Chong M. C. , Subramanian P.
Published: February 2018

Aim

To examine the factors associated with nurses’ perceptions of the quality of end‐of‐life care.

Background

With increasing demand for hospitals to provide end‐of‐life care, the low quality of palliative care provided in hospital settings is an issue of growing concern in developing countries. Most dying patients receive their care from general nurses, irrespective of the nurses’ specialty or level of training.

Method

A structured cross‐sectional questionnaire survey was conducted of 553 nurses working at a teaching hospital in Malaysia.

Results

The mean scores for nurses’ knowledge about end‐of‐life care, their attitudes towards end‐of‐life care and the perceived quality of end‐of‐life care were low. The factors identified as significantly associated with the quality of end‐of‐life care were nurses’ levels of knowledge and their attitudes towards end‐of‐life care.

Discussion

Factors that contributed to the low quality of end‐of‐life care were inadequate knowledge and negative attitudes. These findings may reflect that end‐of‐life care education is not well integrated into nursing education.

Conclusion

The findings of this study suggest that there is a need to increase the nurses’ level of knowledge and improve their attitude towards end‐of‐life care in order to enhance the quality of care provided to dying patients.

Implications for nursing and health policy

Nurse managers and hospital policymakers should develop strategies to enhance nurses’ level of knowledge, as well as providing adequate emotional support for nurses who care for dying patients and their families. Nurses should be proactive in increasing their knowledge and adopting more positive attitudes towards end‐of‐life care.