bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD6 monoclonal antibodies differ in epitope, kinetics and mechanism of action
Authors: Garner Lee I. , Hartland Andrew , Breuning Johannes , Brown Marion H. 
Published: May 2018

SummaryCD6 is a type I T‐cell surface receptor that modulates antigen receptor signalling. Its activity is regulated by binding of its membrane proximal domain (domain 3) to a cell surface ligand, CD166. CD6 monoclonal antibodies (mAbs) specific for the membrane distal domain (domain 1) perturb CD6 function including itolizumab (Alzumab™), which has reached the clinic for treatment of autoimmune disease. We characterized molecular and functional properties of several CD6 mAbs including itolizumab to define potential mechanisms of action. Epitope mapping using the crystal structure of CD6 to design mutants identified two distinct binding sites on different faces of domain 1, one containing residue R77, crucial for MT605 and T12.1 binding and the other, E63, which is crucial for itolizumab and MEM98. Analysis of binding kinetics revealed that itolizumab has a lower affinity compared with other CD6 domain 1 mAbs. We compared potential agonistic (triggering) and antagonistic (blocking) properties of CD6 mAbs in assays where the mechanism of action was well defined. CD6 domain 1 and 3 mAbs were equally effective in triggering interleukin‐2 production by a cell line expressing a chimeric antigen receptor containing the extracellular region of CD6. CD6 domain 1 mAbs hindered binding of multivalent immobilized CD166 but were inferior compared with blocking by soluble CD166 or a CD6 domain 3 mAb. Characterization of CD6 mAbs provides an insight into how their functional effects in vivo may be interpreted and their therapeutic use optimized.
Two approaches, one goal: How mental health registered nurses' perceive their role and the role of peer support workers in facilitating consumer decision‐making
Authors: Cleary Michelle , Raeburn Toby , West Sancia , Escott Phil , Lopez Violeta 
Published: May 2018

AbstractRecovery‐oriented principles underpin modern‐day mental health care and are enhanced by consumer participation in decision‐making. Understanding how consumer participation can be maximized is central to promoting recovery‐oriented care. This study explored the key strategies used by mental health registered nurses and perceived by nurses to be used by peer support workers in facilitating consumer decision‐making to determine similarities, differences, and possible tensions. A qualitative descriptive approach using semi‐structured interviews was conducted with nine nurses employed in mental health care. Thematic analysis was conducted using open coding. Frequency of views expressed and prevalence of these amongst participants were noted to determine the most common strategies and challenges. Registered nurses use strategies aimed at empowerment, self‐management, and managing expectations to facilitate decision‐making but are challenged by entrenched coercion within the system. These same nurses view peer support workers as using their lived experience to build rapport, role model, and advocate for consumers. Tensions arise in how the peer support workers’ lived experience should be used and how this impacts on professional and therapeutic boundaries. Nurses expressed support for the role of peer support workers and viewed their inclusion in facilitating consumer decision‐making positively. Their own role is perceived as being caught between modern‐day service principles of empowerment and long‐standing practices based on coercion.
Mechanisms and drivers of social inequality in phase II cardiac rehabilitation attendance: A convergent mixed methods study
Authors: Pedersen Maria , Overgaard Dorthe , Andersen Ingelise , Baastrup Marie , Egerod Ingrid 
Published: May 2018

AbstractAimThe aim of this study was to explore the extent to which the qualitative and quantitative data converge and explain mechanisms and drivers of social inequality in cardiac rehabilitation attendance.BackgroundSocial inequality in cardiac rehabilitation attendance has been a recognized problem for many years. However, to date the mechanisms driving these inequalities are still not fully understood.DesignThe study was designed as a convergent mixed methods study.MethodsFrom March 2015—March 2016, patients hospitalized with acute coronary syndrome to two Danish regional hospitals were included in a quantitative prospective observational study (N = 302). Qualitative interview informants (N = 24) were sampled from the quantitative study population and half brought a close relative (N = 12) for dyadic interviews. Interviews were conducted from August 2015 to February 2016. Integrated analyses were conducted in joint displays by merging the quantitative and qualitative findings.ResultsQualitative and quantitative findings primarily confirmed and expanded each other; however, discordant results were also evident. Integrated analyses identified socially differentiated lifestyles, health beliefs, travel barriers and self‐efficacy as potential drivers of social inequality in cardiac rehabilitation.ConclusionOur study adds empirical evidence regarding how a mixed methods study can be used to obtain an understanding of complex healthcare problems. The study provides new knowledge concerning the mechanisms driving social inequality in cardiac rehabilitation attendance. To prevent social inequality, cardiac rehabilitation should be accommodated to patients with a history of unhealthy behaviour and low self‐efficacy. In addition, the rehabilitation programme should be offered in locations not requiring a long commute.
Measuring outcomes of digital technology‐assisted nursing postpartum: A randomized controlled trial
Authors: McCarter Deborah E. , Demidenko Eugene , Hegel Mark T. 
Published: May 2018

AbstractAimTo determine if delivering electronic messages from nurses during the first 6 months postpartum is feasible, acceptable and effective in improving mood and decreasing parenting stress.BackgroundCompeting demands during the postpartum hospitalization make focused time for nurses to provide education and support difficult. Unmet needs following discharge may increase the incidence of postpartum depression. Untreated depression negatively affects families, especially for vulnerable women with limited access to health care.DesignThis is a longitudinal cohort study in three phases. Feasibility and acceptability were assessed during Phases 1 & 2. Phase 3 is a randomized controlled trial (RCT) with three conditions.MethodsThis protocol was approved by the Institutional Review Board of the maternity hospital on 12 May 2015 and reviewed annually. Women are enrolled during the maternity hospitalization, after which randomization occurs. The control group receives usual care. Intervention I participants receive a standardized electronic message four times/week for 6 months postpartum. Intervention II participants receive the messages and the option to request a call from a nurse. Electronic surveys at 3 weeks, 3 months and 6 months postpartum measure depressive symptoms using the Edinburgh Postnatal Depression Scale and parenting stress using the Parenting Stress Index‐Short form. Patient satisfaction, nursing time and expertise required are also measured.DiscussionPhase 1 and 2 have demonstrated the intervention is feasible and acceptable to women. Phase 3 enrolment is completed, and the last follow‐up surveys were emailed to participants in February 2018. Results will help inform efforts to continue nursing care after hospital discharge.
A contextual work‐life experiences model to understand nurse commitment and turnover
Authors: Aluwihare‐Samaranayake Dilmi , Gellatly Ian , Cummings Greta , Ogilvie Emerita Linda 
Published: May 2018

AbstractAimsThe aim of this study was to present a discussion and model depicting most effecting work‐life experience contextual factors that influence commitment and turnover intentions for nurses in Sri Lanka.BackgroundIncreasing demand for nurses has made the retention of experienced, qualified nursing staff a priority for healthcare organizations and highlights the need to capture contextual work‐life experiences that influence nurses’ turnover decisions.DesignDiscussion paper.Data sourcesThis discussion paper and model is based on our experiences and knowledge of Sri Lanka and represents an integration of classic turnover research and commitment theory and others published between 1958 – 2017, contextualized to reflect the reality faced by Sri Lanka nurses.Implications for nursingThe model presents a high‐level view of intrinsic, extrinsic, personal and professional antecedents to nurse turnover where relevance can be used by researchers, policy makers, clinicians and educators to establish focused and limited scope models and examine comprehensive contexts.ConclusionThis model emphasizes the role that work‐life experiences play to fortify (or weaken) nurses’ motivation to remain committed to their organization, profession, family, and country. Understanding of contextual work‐life influences on nurses’ intent to stay should lead to evidence‐based strategies that result in a higher number of nurses wanting to remain in the nursing profession and work in the health sector in Sri Lanka.
Effects of a nanoemulsion with Copaifera officinalis oleoresin against monogenean parasites of Colossoma macropomum: A Neotropical Serrasalmidae
Authors: Valentim D S S , Duarte J L , Oliveira A E M F M , Cruz R A S , Carvalho J C T , Solans C , Fernandes C P , Tavares‐Dias M 
Published: May 2018

AbstractMonogeneans are ectoparasites that may cause losses in production and productivity in the aquaculture of Colossoma macropomum. Chemotherapeutics used in aquaculture usually have major adverse effects on fish; hence, the use of essential oils has been considered advantageous, but these are not soluble in water. Thus, the use of nanostructures to enhance water solubility of compounds and improve bioactivity may be very promising. This study investigated the antiparasitic activity of nanoemulsion prepared with Copaifera officinalis oleoresin (50, 100, 150, 200 and 300 mg/L), against monogenean parasites from the gills of C. macropomum. The particle size distribution and zeta potential suggested that a potentially kinetic stable system was generated. The nanoemulsion from C. officinalis oleoresin achieved high efficacy (100%) at low concentrations (200 and 300 mg/L) after 15 min of exposure. This was the first time that a nanoemulsion was generated from C. officinalis oleoresin using a solvent‐free, non‐heating and low‐energy method. Moreover, this was the first time that an antiparasitic against monogeneans on fish gills, based on nanoemulsion of C. officinalis oleoresin, was tested.
The orphan G‐protein‐coupled receptor 75 signaling is activated by the chemokine CCL5
Authors: Dedoni Simona , Campbell Lee A. , Harvey Brandon K. , Avdoshina Valeria , Mocchetti Italo 
Published: May 2018

AbstractThe chemokine CCL5 prevents neuronal cell death mediated both by amyloid β, as well as the human immunodeficiency virus viral proteins gp120 and Tat. Because CCL5 binds to CCR5, CCR3 and/or CCR1 receptors, it remains unclear which of these receptors plays a role in neuroprotection. Indeed, CCL5 also has neuroprotective activity in cells lacking these receptors. CCL5 may bind to a G‐protein‐coupled receptor 75 (GPR75), which encodes for a 540 amino‐acid orphan receptor of the Gqα family. In this study, we have used SH‐SY5Y human neuroblastoma cells to characterize whether CCL5 could activate a Gq signaling through GPR75. Both qPCR and flow cytometry show that these cells express GPR75 but do not express CCR5, CCR3 or CCR1 receptors. SY‐SY5Y cells were then used to examine CCL5‐mediated signaling. We report that CCL5 promotes a time‐ and concentration‐dependent phosphorylation of protein kinase B (AKT), glycogen synthase kinase 3β, and extracellular signal–regulated kinase (ERK) 1/2. Specific antagonists of CCR5, CCR3, and CCR1 did not prevent CCL5 from increasing phosphorylated AKT or ERK. Moreover, CCL5 promotes a time‐dependent internalization of GPR75. Lastly, knocking down GPR75 expression by a CRISPR‐Cas9 approach inhibited the ability of CCL5 to activate pERK in SH‐SY5Y cells. Therefore, we propose that GPR75 is a novel receptor for CCL5 that could explain some of the pharmacological action of this chemokine. These findings may help in the development of small molecule GPR75 agonists that mimic CCL5.Open PracticesThis article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
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Pueraria tuberosa extract inhibits iNOS and IL-6 through suppression of PKC-α and NF-kB pathway in diabetes-induced nephropathy
Authors: Shukla Rashmi , Banerjee Somanshu , Tripathi Yamini B 
Published: May 2018

Abstract

Objectives
Inflammation plays an important role in the pathogenesis of diabetic nephropathy (DN). The aim of this study was to explore the anti-inflammatory role of PTY-2r (extracted from Pueraria tuberosa), on streptozotocin (STZ)-induced DN rats.

Methods
Diabetes was induced by intraperitoneal injection of STZ (55mg/kg) in rats. After 60 days, the rats were randomly divided into three groups (n = 6/each group), namely DN control group 2, DN rats treated with PTY-2r at dose of 100 mg/100 g, group 3 and 50 mg/100 g, group 4, p.o for 20 days. The normal rats were chosen as a normal control (NC) group 1.

Key findings
In DN rats, the expression of iNOS and inflammatory cytokines (IL-6 and TNF-α) was significantly increased. Raised expression of PKC-α was also found. As NF-kB is the main transcription factor for the inflammatory response-mediated progression of DN, variation in NF-kB expression and its activated phosphorylated derivative (pNF-kB) were also evaluated and increase in expression was obtained in the kidney of DN rats. PTY-2r treatment significantly reversed these changes in dose-dependent manner.

Conclusions
This study suggested that the nephroprotective effect of PTY-2r is possibly due to downregulation of PKC-α and NF-kB pathway and normalizing the expression of inflammatory cytokines and iNOS in the kidney of DN rats.
Inhibitory effect of melatonin on necroptosis via repressing the Ripk3‐PGAM5‐CypD‐mPTP pathway attenuates cardiac microvascular ischemia–reperfusion injury
Authors: Zhou Hao , Li Dandan , Zhu Pingjun , Ma Qiang , Toan Sam , Wang Jin , Hu Shunying , Chen Yundai , Zhang Yingmei 
Published: May 2018

AbstractThe molecular features of necroptosis in cardiac ischemia–reperfusion (IR) injury have been extensively explored. However, there have been no studies investigating the physiological regulatory mechanisms of melatonin acting on necroptosis in cardiac IR injury. This study was designed to determine the role of necroptosis in microvascular IR injury, and investigate the contribution of melatonin in repressing necroptosis and preventing IR‐mediated endothelial system collapse. Our results demonstrated that Ripk3 was primarily activated by IR injury and consequently aggravated endothelial necroptosis, microvessel barrier dysfunction, capillary hyperpermeability, the inflammation response, microcirculatory vasospasms, and microvascular perfusion defects. However, administration of melatonin prevented Ripk3 activation and provided a pro‐survival advantage for the endothelial system in the context of cardiac IR injury, similar to the results obtained via genetic ablation of Ripk3. Functional investigations clearly illustrated that activated Ripk3 upregulated PGAM5 expression, and the latter increased CypD phosphorylation, which obligated endothelial cells to undergo necroptosis via augmenting mPTP (mitochondrial permeability transition pore) opening. Interestingly, melatonin supplementation suppressed mPTP opening and interrupted endothelial necroptosis via blocking the Ripk3‐PGAM5‐CypD signal pathways. Taken together, our studies identified the Ripk3‐PGAM5‐CypD‐mPTP axis as a new pathway responsible for reperfusion‐mediated microvascular damage via initiating endothelial necroptosis. In contrast, melatonin treatment inhibited the Ripk3‐PGAM5‐CypD‐mPTP cascade and thus reduced cellular necroptosis, conferring a protective advantage to the endothelial system in IR stress. These findings establish a new paradigm in microvascular IR injury and update the concept for cell death management handled by melatonin under the burden of reperfusion attack.
RETRACTED: Melatonin modulates dysregulated circadian clocks in mice with diethylnitrosamine‐induced hepatocellular carcinoma
Authors: Sánchez Diana I. , González‐Fernández Bárbara , Crespo Irene , San‐Miguel Beatriz , Álvarez Marcelino , González‐Gallego Javier , Tuñón María Jesús 
Published: May 2018

AbstractDisruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long‐term diseases including hepatocellular carcinoma (HCC). Melatonin has been reported to alleviate promotion and progression of HCC, but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight ip) once a week for 8 weeks. Melatonin was given at 5 or 10 mg kg−1d−1 ip beginning 4 weeks after the onset of DEN administration and ending at the sacrifice time (10, 20, 30, or 40 weeks). Liver expression of Bmal1, Clock, Npas2, Rorα, and Sirt1 increased, whereas Cry1, Per1, Per2, Per3, CK1ε, Rev‐erbα, and Rev‐erbβ decreased following DEN administration. Melatonin treatment prevented changes in the expression of clock genes, and this effect was accompanied by an upregulation of the MT1 receptor and reduced levels of the hypoxia‐inducible factors Hif‐1α and Hif‐2α. An increased expression of p21, p53, and PARP1/2, a higher Bax/Bcl‐2 ratio, and a lower expression of Cyclin D1, CDK6, HSP70, HSP90, and GRP78 proteins were also observed in melatonin‐treated mice. Melatonin significantly potentiated the suppression of proliferation and cell cycle arrest induced by the synthetic REV‐ERB agonist SR9009 in human Hep3B cells, and BMAL1 knocking down attenuated the pro‐apoptotic and antiproliferative effect of melatonin. Results support a contribution of changes in the circadian clock components to the beneficial effects of melatonin in HCC and highlight the usefulness of strategies modulating the circadian machinery in hepatocarcinogenesis.
Hepatitis B virus reactivation in patients with rheumatoid arthritis: Analysis of the National Database of Japan
Authors: Fujita M. , Sugiyama M. , Sato Y. , Nagashima K. , Takahashi S. , Mizokami M. , Hata A. 
Published: May 2018

SummaryThis study aimed to determine the incidence and risk factors for hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) undergoing immunosuppressive therapy. The National Database of Japan, in which insurance claim data have been comprehensively accumulated, was utilized. The subjects were 76 641 RA patients who were plausibly initiated on immunosuppressive therapy from April 2013 to March 2014. Laboratory tests of the hepatitis B surface antigen, anti‐hepatitis B virus surface antibody, and anti‐hepatitis B virus core antibody were performed in 28.23%, 12.52% and 14.63% of patients, respectively, when the therapy was initiated. We found that HBV reactivation and fulminant hepatitis occurred in both the patients with and without HBV DNA monitoring, indicating insufficient monitoring in Japan during the study. The cumulative incidence of HBV reactivation over 24 months was 1.57% (95% confidence interval [CI] = 1.28%‐1.92%) in the monitoring group, which consisted of those with resolved HBV infection. Glucocorticoid administration was a potent risk factor for HBV reactivation (hazard ratio [HR] = 1.70, 95% CI = 1.26‐2.29, P = .001 in all subjects, and HR = 1.82, 95% CI = 1.18‐2.81, P = .007 in the nonmonitoring group), although it was not statistically significant in the monitoring group (HR = 1.49, 95% CI = 0.99‐2.26 and P = .057). No significant risk difference was observed between single administration of methotrexate and biological drugs.
Predicting genotype environmental range from genome–environment associations
Authors: Manel Stéphanie , Andrello Marco , Henry Karine , Verdelet Daphné , Darracq Aude , Guerin Pierre‐Edouard , Desprez Bruno , Devaux Pierre 
Published: May 2018

AbstractGenome–environment association methods aim to detect genetic markers associated with environmental variables. The detected associations are usually analysed separately to identify the genomic regions involved in local adaptation. However, a recent study suggests that single‐locus associations can be combined and used in a predictive way to estimate environmental variables for new individuals on the basis of their genotypes. Here, we introduce an original approach to predict the environmental range (values and upper and lower limits) of species genotypes from the genetic markers significantly associated with those environmental variables in an independent set of individuals. We illustrate this approach to predict aridity in a database constituted of 950 individuals of wild beets and 299 individuals of cultivated beets genotyped at 14,409 random single nucleotide polymorphisms (SNPs). We detected 66 alleles associated with aridity and used them to calculate the fraction (I) of aridity‐associated alleles in each individual. The fraction I correctly predicted the values of aridity in an independent validation set of wild individuals and was then used to predict aridity in the 299 cultivated individuals. Wild individuals had higher median values and a wider range of values of aridity than the cultivated individuals, suggesting that wild individuals have higher ability to resist to stress‐aridity conditions and could be used to improve the resistance of cultivated varieties to aridity.
Signatures of diversifying selection and convergence acting on passerine Toll‐like receptor 4 in an evolutionary context
Authors: Králová Tereza , Albrecht Tomáš , Bryja Josef , Hořák David , Johnsen Arild , Lifjeld Jan T. , Novotný Marian , Sedláček Ondřej , Velová Hana , Vinkler Michal 
Published: May 2018

AbstractPositive selection acting on Toll‐like receptors (TLRs) has been recently investigated to reveal evolutionary mechanisms of host–pathogen molecular co‐adaptation. Much of this research, however, has focused mainly on the identification of sites predicted to be under positive selection, bringing little insight into the functional differences and similarities among species and a limited understanding of convergent evolution in the innate immune molecules. In this study, we provide evidence of phenotypic variability in the avian TLR4 ligand‐binding region (LBR), the direct interface between host and pathogen molecular structures. We show that 55 passerine species vary substantially in the distribution of electrostatic potential on the surface of the receptor, and based on these distinct patterns, we identified four species clusters. Seven of the 34 evolutionarily nonconservative and positively selected residues correspond topologically to sites previously identified as being important for lipopolysaccharide, lipid IVa or MD‐2 binding. Five of these positions codetermine the identity of the charge clusters. Groups of species that host‐related communities of pathogens were predicted to cluster based on their TLR4 LBR charge. Despite some evidence for convergence among taxa, there were no clear associations between the TLR4 LBR charge distribution and any of the general ecological characteristics compared (migration, latitudinal distribution and diet). Closely related species, however, mostly belonged to the same surface charge cluster indicating that phylogenetic constraints are key determinants shaping TLR4 adaptive evolution. Our results suggest that host innate immune evolution is consistent with Fahrenholz's rule on the cospeciation of hosts and their parasites.