bluuebunny/crossref_metadata_2025 huggingface dataset:
F‐actin rearrangement is regulated by mTORC2/Akt/Girdin in mouse fertilized eggs
Authors: Wu Didi , Yu Dahai , Wang Xiuxia , Yu Bingzhi
Published: September 2016

In mouse fertilized eggs, correct assembly and distribution of the actin cytoskeleton are intimately related to cleavage in early‐stage embryos. However, in mouse fertilized eggs, mechanisms and involved factors responsible for regulating the actin cytoskeleton are poorly defined. In this study, mTORC2, PKB/Akt and Girdin were found to modulate division of mouse fertilized eggs by regulating distribution of the actin cytoskeleton. RNA interference (RNAi)‐mediated depletion of mTORC2, Akt1 or Girdin disrupted F‐actin rearrangement and strongly inhibited egg development. PKB/Akt has been proven to be a downstream target of the mTORC2 signalling pathway. Girdin, a newly found actin cross‐linker, has been proven to be a downstream target of the Akt signalling pathway. Furthermore, phosphorylation of both Akt1 and girdin was affected by knockdown of mTORC2. Akt1 positively regulated development of the mouse fertilized eggs by girdin‐mediated F‐actin rearrangement. Thus it seems that girdin could be a downstream target of the Akt1‐mediated signalling pathway. Collectively, this study aimed to prove participation of mTORC2/Akt in F‐actin assembly in early‐stage cleavage of mouse fertilized eggs via the function of girdin.

Objectives

In mouse fertilized eggs, the proper assembly and distribution of actin cytoskeleton is intimately related with the cleavage of early‐stage embryo. However, in mammals, especially in mouse fertilized eggs, the mechanisms and involved factors responsible for regulating the actin cytoskeleton are poorly defined. The aim of this study was to determine the role of mTORC2,PKB/Akt and Girdin in early development of fertilized mouse eggs, via regulating the distribution of actin cytoskeleton.

Materials and methods

Changes of F‐actin after treatting with mTORC2 shRNA, Akt siRNA or Girdin siRNA were observed by Immunofluorescence staining and laser‐scanning confocal microscopy. Levels of phosphorylated Girdin at Se1417 were detected by Western immunoblotting. Percentages of cells undergoing division were determined by counting, using a dissecting microscope.

Results

RNA interference (RNAi)‐mediated depletion of mTORC2, Akt1 or Girdin disrupts F‐actin rearrangement, and remarkably inhibited the development of mouse‐fertilized eggs. PKB/Akt has been proved to be a downstream target of the mTORC2 signaling pathway. Girdin, the newly found actin‐cross linker, has been proved to be a downstream target of the Akt signaling pathway. Furthermore phosphorylation of both Akt1 and Girdin were affected by knockdown of mTORC2. Akt1 positively regulates the development of mouse‐fertilized eggs by Girdin mediated F‐actin rearrangement. Girdin could be a downstream target of the Akt1‐mediated signaling pathway.

Conclusions

Collectively, this study aimed to prove the participation of mTORC2/Akt in F‐actin assembling in early‐stage cleavage of mouse fertilized eggs via the function of Girdin.
p75 neurotrophin receptor regulates differential mineralization of rat ectomesenchymal stem cells
Authors: Yang Kun , Wang Yingying , Ju Yingxin , Li Gang , Liu Chang , Liu Junyu , Liu Qi , Wen Xiujie , Liu Lu Chuan
Published: September 2016

Objectives

The aim of this study was to investigate whether p75NTR (p75 neurotrophin receptor) regulates differential mineralization capacity of rEMSCs (rat ectomesenchymal stem cells) and underlying mechanisms associated with Mage‐D1 (melanoma‐associated antigens‐D1).

Materials and methods

Immunohistochemical staining of p75NTR in developing tooth germs was performed on E12.5d (embryonic 12.5 days) and E19.5d (embryonic 19.5 days). E12.5d EMSCs and E19.5d EMSCs were isolated in the same pregnant Sprague‐Dawley rats from embryonic maxillofacial processes and tooth germs. p75NTR small‐interfering RNA, p75NTR overexpression plasmid, Mage‐D1 small‐interfering RNA and recombined rat NGF were used to transfect cells.

Results

p75NTR was expressed in epithelial‐mesenchymal interaction areas at E12.5d and E19.5d tooth germ development stages. E19.5d EMSCs had higher p75NTR expression levels and differential mineralization capacity but lower levels of cell proliferation. Under induction by mineralized culture medium, the potential of differential mineralization had identical trends in regulation of p75NTR in EMSCs; Mage‐D1 did not fluctuate and TrkA was not expressed. Binding of p75NTR and Mage‐D1 were detected. Mage‐D1 knockdown significantly down‐regulated expression of related genes, which NGF could not rescue.

Conclusion

p75NTR participated in tooth germ development stages and mediated differential mineralization of EMSCs. p75NTR played a critical role in regulating the potential of differential mineralization of EMSCs. Mage‐D1 seemed to act as a bridge in the underlying mechanism of effects of p75NTR.
The JAK/STAT3 signalling pathway regulated angiogenesis in an endothelial cell/adipose‐derived stromal cell co‐culture, 3D gel model
Authors: Xue Changyue , Xie Jiamin , Zhao Dan , Lin Shiyu , Zhou Tengfei , Shi Sirong , Shao Xiaoru , Lin Yunfeng , Zhu Bofeng , Cai Xiaoxiao
Published: September 2016

Objectives

The aim of the study was to investigate the role of the JAK/STAT3 signalling pathway in angiogenesis.

Materials and methods

The model established in vitro, involved a 3D collagen gel being implanted with endothelial cells (ECs) from red fluorescent protein‐labelled mice, and adipose‐derived stromal cells (ASCs) from green fluorescent protein‐labelled mice. Phenomena of angiogenesis, after treatment by the inhibitor and the activator of JAK/STAT3 pathway respectively, were observed using confocal laser scanning microscopy. Transwell co‐culture of ECs and ASCs was used to elucidate mechanisms.

Results

Stattic, inhibitor of JAK/STAT3 pathway, attenuated angiogenesis in the model. In contrast, angiogenesis was promoted after treatment of Olanzapine, an activator. We found that protein levels of VEGFA and cyclin D1 were regulated by the JAK/STAT3 pathway, and flow cytometry further confirmed variations in cell cycle parameters of ECs and ASCs. Genes VEGFA/B, VEGFR2, MMP‐2, MMP‐9, IGF‐1 and b‐FGF were down‐regulated by Stattic in ECs, while Olanzapine significantly up‐regulated mRNA levels of these genes. As for ASCs, genes VEGFA, MMP‐2, MMP‐9, IGF‐1 and b‐FGF were modulated by the JAK/STAT3 pathway.

Conclusions

Angiogenesis in the 3D collagen gel was regulated by the JAK/STAT3 pathway which involved changes in vessel length, vessel diameter and sprout number. The underlying mechanism was that the JAK/STAT3 signalling pathway regulated angiogenesis by modulation of numbers of angiogenesis‐related growth factors and by direct regulation of cell cycle.
Morphology quiz: a 12‐year‐old child with a tumour in the neck
Authors: Bayrak B. , Paksoy N.
Published: September 2016

A 12‐year‐old male patient came to our clinic with a growing neck mass on the right side. A painless mass was observed in the right neck area below the chin in the physical examination. A single, hypoechoic, solid lesion of approximately 3 cm in size, adjacent to the mandibular area, was detected using ultrasonography. An ultrasound‐guided fine‐needle aspiration biopsy was performed.
Optimizing neuronal differentiation of human pluripotent NT2 stem cells in monolayer cultures
Authors: Abolpour Mofrad Sepideh , Kuenzel Katharina , Friedrich Oliver , Gilbert Daniel F.
Published: September 2016

Human pluripotent embryonal carcinoma (NT2) cells are increasingly considered as a suitable model for in vitro developmental toxicity and neurotoxicity (DT/DNT) studies as they undergo neuronal differentiation upon stimulation with retinoic acid (RA) and allow toxicity testing at different stages of maturation. However, differentiation of NT2 cells is not straightforward. There are different protocols available in the literature reporting varying results with regard to differentiation efficiency, expression of neuronal markers and morphological characteristics of differentiated cells. Yet, the efficiency of available protocols has not been systematically compared. To address this question, we quantified the number and size of cell cluster formed during differentiation using published and modified protocols and analyzed the abundance of neuronal and non‐neuronal expression markers using immunocytochemistry. In the course of the experiments we observed that differentiation results strongly depend on the cell density at differentiation‐initiation as well as on the type of used cell culture plastic ware. Based on those observations and the results from our comparative analysis, we created our own optimized and robust protocol that reproducibly reveals differentiated cells with high yield. We conclude that our method may be superior to differentiation of NT2 cells for systematic in vitro‐based primary screening for developmental toxicants and neurotoxicants at different stages of maturation over previous protocols used. Our approach will also contribute to reduce animal testing in the context of the 3Rs.
Participation restriction in childhood phenotype of myotonic dystrophy type 1: a systematic retrospective chart review
Authors: Gagnon Cynthia , Kierkegaard Marie , Blackburn Catherine , Chrestian Nicolas , Lavoie Mélissa , Bouchard Marie‐Frédéric , Mathieu Jean
Published: September 2016

Aim

Myotonic dystrophy type 1 (DM1), a neuromuscular disorder, is divided into four clinical phenotypes: congenital; childhood; adult‐onset, and late‐onset. Publications about the childhood phenotype, especially the long‐term outcome, are scarce. The aims of this study were to assess and describe participation outcomes in adults with the childhood phenotype.

Method

A retrospective chart methodology. Data were extracted from health records for 63 adults with childhoodDM1 (32 males, 31 females; mean age 34y, standard deviation [SD] 11y 6mo; range 18–54y) who had attended the Saguenay Neuromuscular Clinic, Canada.

Results

Thirty‐four adults (54%) lived with their parents or in foster homes, and most patients needed services or help to live independently. A significant proportion (22%) were isolated in regard to friendship. Very few adults had children, although 33% lived with a spouse. The majority of patients (86%) relied on social security and only one person was currently working. Financial responsibilities were often an issue and 13 (21%) were under legal guardianship.

Interpretation

This study showed that patients with the childhood phenotype present a guarded prognosis regarding long‐term social participation. These participation restrictions could be related to behavioural, cognitive, and social stigma problems in childhood. This study illustrates the absolute necessity to pursue an interdisciplinary follow‐up of these patients when they are reaching adulthood.
Turkey and the Palestinian Question: The Shift of Roles in Foreign Policy
Authors: Ertosun Erkan
Published: September 2016

For Turkey, which was seeking a leading role in the Middle East, the Palestinian Question became a priority in its foreign policy during the late 1990s. In this article, it is argued that the role Turkey primarily espoused in the resolution of the Palestinian Question in the period 2000–2009 has mainly been that of a communicator. Nonetheless, in times of crises between Palestine and Israel, Ankara lost its neutrality and credibility to some extent, as it shifted to the role of guardian of Palestinians and proponent of Palestine, thereby undermining its communicator role. Finally, this dilemma in Turkish foreign policy in the Palestinian Question was the fundamental impediment to Turkey's sustainable and constructive contribution to the settlement of the problem in the examined period.
Regulatory B10 cells display an altered homoeostasis in acute graft‐versus‐host disease
Authors: Chakupurakal Geothy , Garcia‐Marquez María Alejandra , Shimabukuro‐Vornhagen Alexander , Kluth Sandra , Schlosser Hans , Theurich Sebastian , Scheid Christof , Hallek Michael , Holtick Udo , von Bergwelt‐Baildon Michael
Published: September 2016

Objective

The role of B cells and the subgroup of IL‐10 producing B cells, known to have a regulatory function, in patients following a haematopoietic stem cell transplant (alloSCT) has not been clearly understood to date.

Methods

We prospectively recruited 95 patients following an alloSCT and studied the B‐cell reconstitution on days 30, 90 and 150. Regulatory B10 cells could be analysed in 22 consecutively recruited patients on day 30 post‐transplant.

Results

The total B‐cell percentages in transplant recipients (median 0.33; range 0.01–5.9) were significantly reduced than the controls (P = 0.0001) and constituted predominantly of transitional CD24high CD38high B cells. Regulatory B10 cells could be analysed in 22 consecutively recruited patients on day 30 post‐transplant. The percentages of B10 cells (median 1.35; 0.0–4.5) were significantly reduced in the transplant recipients in comparison with the control cohort (P < 0.0001). Interestingly, the percentages of B10 cells in patients with acute GvHD (median 1.7; 0.33–4.5) were significantly higher than those without GvHD (median 0.7; 0–1.9) (P = 0.0003).

Conclusion

This is the first report demonstrating B10 cells in stem cell transplant recipients in the early post‐alloSCT (30 d) period. Our data suggest a possible role for B10 cells in the pathophysiology of acute GvHD. Further longitudinal studies are warranted to understand the implications of our findings.
Activation of cannabinoid receptor 2 attenuates mechanical allodynia and neuroinflammatory responses in a chronic post‐ischemic pain model of complex regional pain syndrome type I in rats
Authors: Xu Jijun , Tang Yuying , Xie Mian , Bie Bihua , Wu Jiang , Yang Hui , Foss Joseph F. , Yang Bin , Rosenquist Richard W. , Naguib Mohamed
Published: September 2016

Complex regional pain syndrome type 1 (CRPS‐I) remains one of the most clinically challenging neuropathic pain syndromes and its mechanism has not been fully characterized. Cannabinoid receptor 2 (CB2) has emerged as a promising target for treating different neuropathic pain syndromes. In neuropathic pain models, activated microglia expressing CB2 receptors are seen in the spinal cord. Chemokine fractalkine receptor (CX3CR1) plays a substantial role in microglial activation and neuroinflammation. We hypothesized that a CB2 agonist could modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS by regulating CB2 and CX3CR1 signaling. We used chronic post‐ischemia pain (CPIP) as a model of CRPS‐I. Rats in the CPIP group exhibited significant hyperemia and edema of the ischemic hindpaw and spontaneous pain behaviors (hindpaw shaking and licking). Intraperitoneal administration of MDA7 (a selective CB2 agonist) attenuated mechanical allodynia induced by CPIP. MDA7 treatment was found to interfere with early events in the CRPS‐I neuroinflammatory response by suppressing peripheral edema, spinal microglial activation and expression of CX3CR1 and CB2 receptors on the microglia in the spinal cord. MDA7 also mitigated the loss of intraepidermal nerve fibers induced by CPIP. Neuroprotective effects of MDA7 were blocked by a CB2 antagonist, AM630. Our findings suggest that MDA7, a novel CB2 agonist, may offer an innovative therapeutic approach for treating neuropathic symptoms and neuroinflammatory responses induced by CRPS‐I in the setting of ischemia and reperfusion injury.
The brain‐derived neurotrophic factor Val66Met polymorphism affects encoding of object locations during active navigation
Authors: Wegman Joost , Tyborowska Anna , Hoogman Martine , Arias Vásquez Alejandro , Janzen Gabriele
Published: September 2016

The brain‐derived neurotrophic factor (BDNF) was shown to be involved in spatial memory and spatial strategy preference. A naturally occurring single nucleotide polymorphism of the BDNF gene (Val66Met) affects activity‐dependent secretion of BDNF. The current event‐related fMRI study on preselected groups of ‘Met’ carriers and homozygotes of the ‘Val’ allele investigated the role of this polymorphism on encoding and retrieval in a virtual navigation task in 37 healthy volunteers. In each trial, participants navigated toward a target object. During encoding, three positional cues (columns) with directional cues (shadows) were available. During retrieval, the invisible target had to be replaced while either two objects without shadows (objects trial) or one object with a shadow (shadow trial) were available. The experiment consisted of blocks, informing participants of which trial type would be most likely to occur during retrieval. We observed no differences between genetic groups in task performance or time to complete the navigation tasks. The imaging results show that Met carriers compared to Val homozygotes activate the left hippocampus more during successful object location memory encoding. The observed effects were independent of non‐significant performance differences or volumetric differences in the hippocampus. These results indicate that variations of the BDNF gene affect memory encoding during spatial navigation, suggesting that lower levels of BDNF in the hippocampus results in less efficient spatial memory processing.
The change in the sex ratio in multiple sclerosis is driven by birth cohort effects
Authors: Ajdacic‐Gross V. , Schmid M. , Mutsch M. , Steinemann N. , von Wyl V. , Bopp M.
Published: September 2016

Background and purpose

Birth cohort effects have greatly shaped long‐term trends in multiple sclerosis (MS). This study examined whether birth cohort effects have also determined trends in the sex ratio.

Methods

Age−period−cohort analyses were applied to Swiss mortality data, 1901−2010, using logit models. Sex was introduced as an additional main effect (overall effect) and in interaction terms with A, P and C.

Results

Birth cohort effects strongly impacted the trends of MS risk in Switzerland, with a peak in cohorts born in the 1910s and 1920s. Similarly, birth cohort effects accounted for the change in the sex ratios during the 20th century. The balanced sex ratio at the beginning of the 20th century has been superseded by a ratio with a preponderance of women. Despite similarities in timing, the patterns of overall and sex‐specific birth cohort estimates were not congruent.

Conclusion

The change in the sex ratio in MS is driven by birth cohort related factors. Overall and sex‐specific trends indicate that the appearance of MS has changed dramatically in the 20th century. The driving force behind these trends is related to yet unknown environmental factors.
Fatigue in early Parkinson's disease: the Norwegian ParkWest study
Authors: Ongre S. O. , Larsen J. P. , Tysnes O. B. , Herlofson K.
Published: September 2016

Background and purpose

Fatigue is a common and disabling non‐motor symptom in Parkinson's disease (PD). The pathogenesis is unknown, and the treatment options are limited. The aim of the present study was to investigate the development of fatigue during the first year after diagnosis.

Methods

The study design was a prospective, controlled population‐based longitudinal cohort study, comprising 181 de novo, drug‐naïve patients with PD and 162 control participants. PD was diagnosed according to the Gelb criteria. Fatigue was assessed by the Fatigue Severity Scale (FSS). Both groups were assessed for fatigue at baseline and after 1 year.

Results

Patients reported more fatigue than the control subjects at baseline and at the 1‐year follow‐up evaluation. The FSS scores in the patient group improved from a mean score of 4.4 (SD 1.6) to 4.0 (SD 1.6). Patients with fatigue at baseline received higher doses of dopaminergic medication during follow‐up. Patients who received dopamine agonists improved slightly more than patients who received levodopa. A regression analysis did not show a correlation between an improvement in fatigue and a change in disease severity, depressive symptoms, sleep problems, apathy or cognitive impairment.

Conclusion

Fatigue is a common symptom in PD, also in early, untreated patients. During the first year of observation, an improvement in the fatigue scores was found. The improvement could not be attributed to a change in disease severity or depressive symptoms. The results indicate a better effect of dopamine agonists than of levodopa. This may have implications for treatment in patients with PD‐associated fatigue.
The molecular and phenotypic spectrum of IQSEC2‐related epilepsy
Authors: Zerem Ayelet , Haginoya Kazuhiro , Lev Dorit , Blumkin Lubov , Kivity Sara , Linder Ilan , Shoubridge Cheryl , Palmer Elizabeth Emma , Field Michael , Boyle Jackie , Chitayat David , Gaillard William D. , Kossoff Eric H. , Willems Marjolaine , Geneviève David , Tran‐Mau‐Them Frederic , Epstein Orna , Heyman Eli , Dugan Sarah , Masurel‐Paulet Alice , Piton Ame'lie , Kleefstra Tjitske , Pfundt Rolph , Sato Ryo , Tzschach Andreas , Matsumoto Naomichi , Saitsu Hirotomo , Leshinsky‐Silver Esther , Lerman‐Sagie Tally
Published: September 2016

Objective

IQSEC2 is an X‐linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants.

Methods

Forty‐eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians.

Results

Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male‐to‐female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic–clonic (GTC) seizures. The electroclinical syndromes could be defined in five patients: late‐onset epileptic spasms (three) and Lennox‐Gastaut or Lennox‐Gastaut–like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI) were prominent features.

Significance

The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical feature in sporadic cases. IQSEC2 should be evaluated in both male and female patients with an epileptic encephalopathy.
Postoperative seizure control in patients with tumor‐associated epilepsy
Authors: Neal Andrew , Morokoff Andrew , O'Brien Terence John , Kwan Patrick
Published: September 2016

Objective

The patterns of postoperative seizure control and response to antiepileptic drugs (AEDs) in tumor‐associated epilepsy (TAE) are poorly understood. We aim to document these characteristics in patients with supratentorial gliomas.

Methods

This was a retrospective analysis of 186 patients with supratentorial gliomas. Seizure patterns were classified into four groups: A, no postoperative seizure; B, early postoperative seizure control within 6 months; C, fluctuating seizure control; and D, never seizure‐free. Rates and duration of seizure freedom, subsequent seizure relapse, and response to AED were analyzed.

Results

Among patients included, 49 (26.3%) had grade II, 28 (15.1%) had grade III, and 109 (58.6%) had grade IV glioma. Outcome pattern A was observed in 95 (51.1%), B in 22 (11.8%), C in 45 (24.2%), and D in 24 (12.9%). One hundred nineteen patients had at least one seizure and were classified as having TAE. Compared to pattern A, pattern B was predicted by histologic progression; pattern C by tumor grade, preoperative seizure, and histologic progression, and pattern D by preoperative seizure and gross total resection. Among patients with TAE, 57.5% of grade II, 68.2% of grade III, and 26.3% of grade IV experienced a period of 12‐month seizure freedom. After first 12‐month seizure remission, 39.1%, 60.0%, and 13.3% of grade II, III, and IV gliomas, respectively, experienced subsequent seizure; 22.6% of those with TAE reached terminal seizure freedom of at least 12 months on their first postoperative AED regimen, 6.5% on their second regimen, and 5.4% on subsequent regimens.

Significance

Distinct patterns of postoperative seizure control exist in gliomas; they have specific risk factor profiles, and we hypothesize these correspond to unique pathogenic mechanisms. Twelve‐month seizure freedom with subsequent relapse is frequent in grade II–III gliomas. Response to AEDs is markedly poorer than with non‐TAE, highlighting the complex epileptogenicity of gliomas.
Ghrelin accelerates wound healing in combined radiation and wound injury in mice
Authors: Liu Cong , Hao Yuhui , Huang Jiawei , Li Hong , Yang Zhangyou , Zeng Yiping , Liu Jing , Li Rong
Published: September 2016

Impaired wound healing caused by radiation happens frequently in clinical practice, and the exact mechanisms remain partly unclear. Various countermeasures have been taken to tackle with this issue. Ghrelin was considered as a potent endogenous growth hormone‐releasing peptide, and its role in enhancing wound repair and regeneration was firstly investigated in whole‐body irradiated (γ‐ray) mice in this study. Collagen deposition and neovascularization were mostly discussed. The results demonstrated that ghrelin administration promoted cutaneous wound healing in irradiated mice, followed with reduced average wound closure time, increased spleen index (SI) and improved haematopoiesis. After isolation and analysis of granulation tissues in combined radiation and wound injury (CRWI) mice treated with and without ghrelin, a phenomenon of increased DNA, hexosamine, nitrate and nitrite synthesis, elevated collagen content and enhanced neovascularization was observed after ghrelin treatment. Western blotting indicated that ghrelin also increased the expression of vascular endothelial growth factor (VEGF) and transforming growth factor‐β (TGF‐β), both responsible for wound healing. However, previous administration of growth hormone secretagogue receptor 1a (GHS‐R1a) blocker blunted these therapeutic effects of ghrelin on CRWI mice. Our results identify ghrelin as a novel peptide that could be used for radiation‐induced impaired wound healing.
IL‐36γ has proinflammatory effects on human endothelial cells
Authors: Bridgewood Charlie , Stacey Martin , Alase Adewonuola , Lagos Dimitris , Graham Anne , Wittmann Miriam
Published: September 2016

Interleukin‐36 cytokines are predominantly expressed by epithelial cells. Significant upregulation of epidermal IL‐36 is now a recognised characteristic of psoriatic skin inflammation. IL‐36 is known to induce inflammatory responses in dendritic cells, fibroblasts and epithelial cells. Although vascular alterations are a hallmark of psoriatic lesions and dermal endothelial cells are well known to play a critical role in skin inflammation, the effects of IL‐36 on endothelial cells are unexplored.

We here show that endothelial cells including dermal microvascular cells express a functionally active IL‐36 receptor. Adhesion molecules VCAM‐1 and ICAM‐1 are upregulated by IL‐36γ stimulation, and this is reversed by the presence of the endogenous IL‐36 receptor antagonist. IL‐36γ‐stimulated endothelial cells secrete the proinflammatory chemokines IL‐8, CCL2 and CCL20. Chemotaxis assays showed increased migration of T‐cells following IL‐36γ stimulation of endothelial cells. These results suggest a role for IL‐36γ in the dermal vascular compartment, and it is likely to enhance psoriatic skin inflammation by activating endothelial cells and promoting leucocyte recruitment.
Inferring spatial structure from population genetics and spatial synchrony in demography of Baltic Sea fishes: implications for management
Authors: Östman Örjan , Olsson Jens , Dannewitz Johan , Palm Stefan , Florin Ann‐Britt
Published: September 2016

The spatial structure of species is important for their dynamics and evolution, but also for management and conservation. There are numerous ways of inferring spatial structures, and information from multiple methods is becoming more common to examine how different processes shape the spatial structures of species to improve fish management. Here, we investigate the spatial structure of a suite of Baltic Sea fish species based on the following: (i) spatial (presumably neutral) genetic differentiation, reviewed from the literature, and (ii) spatial synchrony in abundance changes from time series of fishery‐independent surveys, which we currently find to be underused given the amount of data available. For each of these two methods, species were classified as having a distinct, continuous or no/weak spatial structure. In addition, based on each source of information, we estimated the spatial scale of management units for species. The results show that only among species confined to the coastal zone the two sources of information yielded a congruence of the spatial structure (displaying a continuous spatial structure). In contrast, offshore species show weak spatial genetic structure but stronger spatial structure of synchrony in abundance. Based on this, we suggest that population genetic structure and synchrony in abundance should be used as complementary information as they reflect different spatial processes and suggest that management actions should differ with respect to scale depending on the management targets applied. We propose similar analysis should be applied to areas outside the Baltic Sea, and other stock identification methods, to improve management of fish resources.
Alignment of World Language Standards and Assessments: A Multiple Case Study
Authors: Kaplan Carolyn Shemwell
Published: September 2016

Previous research has examined world language classroom‐based assessment practices as well as the impact of the Standards for Foreign Language Learning in the 21st Century (National Standards in Foreign Language Education Project, 1999) on practice. However, the extent to which K–12 teachers’ assessment practices reflect national and state standards has not been made clear. This article presents a multiple case study examining how the classroom‐based assessments used by four secondary world language teachers provided insight into students’ progress toward achieving the competencies that are specified by Ohio's Learning Standards for 9–12 World Language Programs and the five goal areas as they were described in the 1999 version of the nationally accepted standards framework. Qualitative analysis of assessment artifacts and interview transcripts showed that assessments principally targeted presentational writing and interpretive reading and that some assessments did not directly align with any of the goals or standards. Findings provide continuing evidence to support the results of the Standards Impact Survey (ACTFL, 2011) and have implications for world language teachers’ professional development needs and the role of standards in world language education.
Mapping the global state of invasive alien species: patterns of invasion and policy responses
Authors: Turbelin Anna J. , Malamud Bruce D. , Francis Robert A.
Published: September 2016

Aim

To use global databases to (1) provide a visualization of global geographical patterns of species invasions, origins and pathways and (2) depict the international uptake of legislative and policy responses to invasive alien species (IAS).

Location

Global.

Methods

Patterns of recorded species invasions and pathways of introduction were mapped and visualized using data from the Global Invasive Species Database (GISD) and the CABI Invasive Species Compendium (CABI ISC), along with associated legal instruments relevant to IAS compiled from the ECOLEX database. A novel indicator of the asymmetry between each country's ‘ingress/egress’ of IAS (kappa, Κ), was developed to further explore spatial patterns.

Results

Substantial variation in the spatial patterns of invasion was determined, with the Global North, some newly industrialized countries and small tropical islands being the main recipients of IAS and asymmetry (Κ) being highest in New World countries and small islands. Of the 1517 recorded IAS, 39% were introduced only intentionally and 26% only unintentionally, 22% both intentionally and unintentionally, while 13% had no information available. The dominant pathway for species invasions was horticulture and the nursery trade, with 31% of the species introduced outside of their natural geographical range. Large increases in legislation on IAS have occurred since the 1990s, particularly for those countries that have high numbers of species invasions.

Main conclusions

Clear global patterns in the distributions of IAS are determined, supporting arguments emphasizing the role of colonial history, economic development and trade in driving the human‐mediated movement of species. Dominant pathways for species invasions are similar across different regions. Policy responses towards IAS show an increasing desire from the international community to act on species invasions. Current patterns suggest that Africa and Central Asia are priority areas for future IAS research and control.
Method Development and Optimisation of Sodium Peroxide Sintering for Geological Samples
Authors: Bokhari Syed Nadeem Hussain , Meisel Thomas C.
Published: September 2016

This work provides a measurement procedure for the complete digestion of rock samples containing refractory minerals such as zircon and chromite. Their dissolution by wet acid digestion is often incomplete but, although providing complete digestions, alkali fusion techniques can result in solutions with a high blank and total dissolved solid content. It was established by the systematic study with reference material trachyandesite MTA‐1 that a 1:6 sample to sodium peroxide (Na2O2) ratio is conservative for the complete digestion and recovery of all the analytes especially those contained in zircon. The sample decomposition time was 120 min for the zircon‐bearing rhyolite reference material MRH‐1. Complete digestion of chromite was obtained in the harzburgite RM MUH‐1. The sample solutions were stable for at least 1 year. Accurate measurements of SiO2, Al2O3, TiO2, P2O5 and K2O could be made with ICP‐MS by not discarding the supernatant of the sinter solution and by using geological reference materials for external calibration. HF digestions are slow, not universal, and may form new mineral/phases that are insoluble under high temperature conditions. The validated sample decomposition procedure combined with ICP‐MS presents an alternative to the use of HF in routine analysis of difficult to digest geological materials.
Astropedology: palaeosols and the origins of life
Authors: Retallack Gregory J.
Published: September 2016

Palaeosols are ancient soils formed in sedimentary successions between events of sedimentation, erosion and volcanic activity. Soil formation is regulated by circumstances of climate, vegetation, topographic relief, parent material and time. These factors are quantified by nomopedology, in the form of climofunctions, chronofunctions and other relationships useful for interpreting conditions of the past from palaeosols. In deep time, palaeosols reveal the timing and extent of the Great Oxidation Event of 2.4 Ga. There is also circumstantial evidence for life in palaeosols back to 3.5 Ga on Earth and 3.7 Ga on Mars. These are the oldest known intact profiles, but pieces of palaeosols some 4.56 Ga in age may be represented by carbonaceous chondrite meteorites. Astropedology is the study of very ancient palaeosols and meteorites relevant to the origin of life and different planetary soil systems. Complex chemical assembly, metal catalysis of organic compounds, and the course of hydrolytic reactions as a kind of planetary metabolism make soils an attractive theoretical site for the origin of life. Because dilute solutions tend to an equilibrium that undoes organosynthetic reactions, life is more likely to have arisen on a soil planet like Mars than a water planet like Earth.
Victorian geological survey maps of Britain and Ireland
Authors: Nowell David
Published: September 2016

In a farsighted development, the British Geological Survey has brought a new lease of life to its historic material by putting its water‐coloured map sheets online. This new digital archive (http://www.bgs.ac.uk/data/maps/home.html), with introductory notes and downloads, features mainly one inch to the mile 1 : 63 360 geological maps and their related cross‐sections drawn up along the lines that were neatly etched across the sheets, which became increasingly detailed over the decades. Once a map sheet or section is selected online it could not be easier to enlarge it and swiftly pan around, looking at the meticulously engraved topographic base map and the often brightly coloured overlying geology, occasionally annotated, including coastal sheets with descriptive notes. Furthermore, it is then possible to order very high quality reprints to study an area in even more detail or simply put one of the more attractive sheets on the wall, as there are some real gems to choose from. This feature provides a guide to some of its more important maps.
Silurian of the Midland Valley of Scotland and Ireland
Authors: Clarkson Euan N.K. , Harper David A.T.
Published: September 2016

The Silurian rocks and fossils of the Midland Valley of Scotland, and its extension across the northern parts of Ireland, have fascinated and challenged geologists for over 150 years. The spectacular diversity of facies and faunas, displayed in a series of inliers, is matched by contrasts in scenery from the rugged Atlantic coast of western Ireland to the undulating hills and heather moors on the northern margin of the Southern Uplands. Here, tectonic events near the climax of the Caledonian orogenic cycle served to fashion a mosaic of dynamic sedimentary environments on the Laurentian margin, at an exciting time in Earth history, as life established its foothold on the land.
The CLOCK trial, a double‐blinded randomized controlled trial: Trisodium citrate 30% and minocycline 3 mg/mL plus EDTA 30 mg/mL are effective and safe for catheter patency maintenance among CKD 5D patients on hemodialysis
Authors: Luiz Marcus V. S. João , Scavone Cristoforo , Tzanno Carmen
Published: September 2016

Introduction: Poor blood flow rate (PF) is highly prevalent among CKD 5D patients with long‐term central venous catheters. Heparin catheter lock solutions are commonly used to maintain catheter patency, however the incidence of PF remains high. The purpose of the CLOCK Trial was to evaluate two catheter lock solutions on reduction of PF incidence.

Methods: Seventy‐five CKD 5D patients on high‐efficiency hemodialysis at the Integrated Centre of Nephrology (Guarulhos, Brazil) were randomized 1:1:1 to receive a lock solution combining minocycline 3 mg/mL with the anticoagulant/chelation agent EDTA 30 mg/mL (M‐EDTA) or heparin 1000 IU/mL (H) or trisodium citrate 30% (TSC) vs. Hfor 15 weeks. A total of 68 patients completed the trial in which both investigators and patients were blinded to treatment allocation. The primary end‐point was the occurrence of hydraulic resistance and secondary safety end‐point was adverse drug reactions related to the lock solutions.

Findings: At the beginning of the trial, 7 patients were excluded from this trial due to their poor catheter care. The incidence of hydraulic resistance was significantly higher among patients on H (18/23) compared to TSC (4/22) and M‐EDTA (2/23) lock solutions, (P < 0.001).

Discussion: The CLOCK Trial suggests TSC and M‐EDTA may preserve catheter patency better than H. TSC may be a better option due the lack of association with long‐term antimicrobial resistance.
Genetic variant in DICER gene is associated with prognosis of hepatocellular carcinoma in a Chinese cohort
Authors: Wang Zhao , Wang Jiaxiang , Wang Qun , Wang Jiachen , Yuan Jiaxiang , Si Yaqing
Published: September 2016

Aim

MicroRNAs (miRNAs) function as gene regulators and play crucial roles in the pathogenesis and prognosis of hepatocellular carcinoma (HCC). Genetic variants in miRNA processing genes may affect miRNA expression and contribute to HCC risk and survival. We hypothesized that single nucleotide polymorphisms (SNPs) in miRNA processing genes may be associated with HCC susceptibility and prognosis. The study aims to verify whether this hypothesis is right or not.

Methods

We first genotyped the selected three SNPs in miRNA processing genes (RAN rs3803012 A>G, HIWI rs10773771 T>C, and DICER rs1057035 T>C) in 312 HCC patients and 320 cancer‐free controls using the TaqMan assay, and evaluated the associations of the three SNPs with HCC risk. We also investigated the effect of the three SNPs on the overall survival of 312 HCC patients.

Results

There were no significant associations between the three SNPs (RAN rs3803012 A>G, HIWI rs10773771 T>C, and DICER rs1057035 T>C) and HCC risk. However, HCC patients carrying DICER rs1057035 CT + CC genotypes had significantly longer median survival time (log–rank, P = 0.018) and decreased death risk (adjusted hazard ratio = 0.68; 95% confidence interval, 0.49–0.95; P = 0.022) than patients with rs1057035 TT genotypes. The DICER rs1057035 genotype was an independent protective factor for HCC survival (CT + CC vs. TT: hazard ratio = 0.72; 95% confidence interval, 0.55–0.96; P = 0.031).

Conclusion

This study provides evidence that DICER rs1057035 T>C polymorphism may be a prognostic biomarker for HCC patients.
How best to use and evaluate Patient Information Leaflets given during a consultation: a systematic review of literature reviews
Authors: Sustersic Mélanie , Gauchet Aurélie , Foote Alison , Bosson Jean‐Luc
Published: September 2016

Background

In the past, several authors have attempted to review randomized clinical trials (RCT) evaluating the impact of Patient Information Leaflets (PILs) used during a consultation and draw some general conclusions. However, this proved difficult because the clinical situations, size and quality of RCTs were too heterogeneous to pool relevant data.

Objective

To overcome this 30‐year stalemate, we performed a review of reviews and propose general recommendations and suggestions for improving the quality of PILs, how to use them and methods for evaluating them.

Methodology

We searched five databases for reviews, systematic reviews and meta‐analyses describing PILs. We drew general and condition‐linked conclusions concerning the impact of PILs. Checklists summarize criteria for quality PILs, and ways of using and evaluating them.

Results

Of 986 articles found, 24 reviews were pertinent; the five oldest considered the impact of PILs irrespective of the condition the patient consulted for; the 19 more recent ones mostly addressed precise clinical situations.

Discussion

Whatever the clinical situation, PILs improve patients' knowledge and satisfaction. For acute conditions, in the short‐term PILs also improve adherence to treatment. For chronic diseases, invasive procedures or screening situations, their impact on adherence varies depending on the context, how the PILs are given and the invasiveness of the intervention.

Conclusion

PILs are considered to be very useful, especially for acute conditions where the patient is the first to suffer from lack of information. We propose checklists for writing, designing, using and evaluating PILs in RCTs to enable comparisons between different studies.
Les droits des travailleurs migrants, un problème politique, économique et éthique
Authors: RUHS Martin
Published: September 2016

En matière de migrations de main‐d'œuvre, le nombre des travailleurs admis par un pays dépend souvent de l'étendue des droits qui leur sont octroyés. Cette constatation est au cœur de l'ouvrage publié par l'auteur en 2013 sous le titre The price of rights. Ici, celui‐ci revient sur ses principaux arguments et ses grandes conclusions, et il répond à une lecture critique de son ouvrage publiée dans la Revue internationale du Travail en 2015, tout en renouvelant son plaidoyer en faveur d'un débat sans a priori sur les liens entre migrations, droits et développement aux échelons national et international.
L'attitude des employeurs à l'égard des réfugiés: les résultats d'une enquête suédoise
Authors: LUNDBORG Per , SKEDINGER Per
Published: September 2016

En se fondant sur une enquête auprès des entreprises, menée à grande échelle en Suède, les auteurs concluent à une hétérogénéité importante des attitudes par rapport à la main‐d'œuvre immigrée d'origine réfugiée, au comportement professionnel de ces travailleurs, à leur niveau de salaire et à la discrimination à leur égard, même si une expérience préalable en la matière limite les attitudes négatives. Pour la majorité des entreprises, les salaires minima conventionnels ne constituent pas un obstacle majeur au recrutement de réfugiés. Cependant, celles qui emploient beaucoup de réfugiés estiment que la réduction de ces seuils serait très bénéfique à l'emploi.
Have we significantly underestimated the capacity in the Australian health system to treat chronic hepatitis C infection in an interferon‐free era?
Authors: Kaan I. A. , Jones T. , McCaughan G. W.
Published: September 2016

Background

New antiviral therapies for hepatitis C infection may lead to an increase in capacity to treat because of their simplicity and safety.

Aims

To determine the likely current capacity of accredited treatment centres in treating hepatitis C (HCV) patients with interferon (IFN)‐free direct acting antiviral (DAA) agents in Australia.

Method

Data were collected from 22 centres before the introduction of DAA therapy – 11 sites from the Study 1 survey and an additional 11 sites from the Study 2 survey. The sites were selected based on consensus by viral hepatitis experts, in consultation with the NSW Agency for Clinical Innovation. The services were selected as they were experienced in the delivery of IFN‐based treatments and/or had knowledge about IFN‐free regimens. The sites selected offered a mix of metropolitan and regional clinics, opioid substitution clinics, Aboriginal services, general practitioner‐initiated, criminal justice and nurse‐led services. Following the survey, the first 3 months of actual treatment uptake, since listing in March and May 2016, became available for a comparison and were subsequently analysed.

Results

The survey indicated that an average of 27 h would be required to treat patients with IFN‐based regimens. This was reduced to an average of 9 h if IFN‐free regimens were used. The average number of patients on IFN‐based treatment regimens per site was 87 per year compared to 493 per site if IFN‐free therapy was freely available. There is capacity in the current health system to treat five times the numbers of patients with chronic HCV in Australia. When applying a weighted ratio; the results for all centres show a 3.6‐fold increase in the capacity to treat with IFN‐free regimens. However, these numbers may be an underestimate based on the first 3 months of actual treatment uptake since Pharmaceutical Benefits Scheme listing in March and May 2016.

Conclusion

Although current sites have a significant capacity to increase rapidly HCV treatment numbers, expansion of treatment settings and new models of care and training may be required to deliver HCV treatment to all HCV‐infected individuals.