bluuebunny/crossref_metadata_2025 huggingface dataset:
Stem Cell Therapies for Knee Cartilage Repair
Authors: Anderson John A. , Little Dianne , Toth Alison P. , Moorman Claude T. , Tucker Bradford S. , Ciccotti Michael G. , Guilak Farshid
Published: November 2013

Background:

Articular cartilage damage of the knee is common, causing significant morbidity worldwide. Many adult tissues contain cells that are able to differentiate into multiple cell types, including chondrocytes. These stem cells have gained significant attention over the past decade and may become frontline management for cartilage defects in the very near future.

Purpose:

The role of stem cells in the treatment of knee osteochondral defects was reviewed. Recent animal and clinical studies were reviewed to determine the benefits and potential outcomes of using stem cells for cartilage defects.

Study Design:

Literature review.

Methods:

A PubMed search was undertaken. The key phrase “stem cells and knee” was used. The search included reviews and original articles over an unlimited time period. From this search, articles outlining animal and clinical trials were selected. A search of current clinical trials in progress was performed on the clinicaltrials.gov website, and “stem cells and knee” was used as the search phrase.

Results:

Stem cells have been used in many recent in vitro and animal studies. A number of cell-based approaches for cartilage repair have progressed from preclinical animal studies into clinical trials.

Conclusion:

The use of stem cells for the treatment of cartilage defects is increasing in animal and clinical studies. Methods of delivery of stem cells to the knee’s cartilage vary from direct injection to implantation with scaffolds. While these approaches are highly promising, there is currently limited evidence of a direct clinical benefit, and further research is required to assess the overall outcome of stem cell therapies for knee cartilage repair.
“The Blessing” in the Lives of Three Generations of Bedouin Women
Authors: Alhuzail Nuzha Allassad
Published: November 2013

In this article, I address the meaning of the blessing in the lives of Bedouin women in Israel as it is reflected in their life stories and discuss the significance attributed to “the blessing that has vanished.” The Bedouin sector in the State of Israel is undergoing radical changes in terms of types of residence, lifestyle, society, and culture, with far-reaching consequences for Bedouin society in general and for women in particular. In certain respects, Bedouin society is becoming more progressive and open, while in others it is becoming more closed and conservative. In young women, progress stimulates the desire for self-realization, the yearning to determine their own future and assume new roles, while conservatism places obstacles before them. A narrative study conducted among 30 Bedouin women from three generations aimed to examine how they experience the changes that occurred during three periods of settlement. It was found that for each generation these changes have a different meaning. Among the central themes that arose in the study were the home, the good wife, couple’s relationships, means of expression, and others. This article focuses on the theme of the blessing and its significance as it is expressed in the life stories of Bedouin women.
Renaming, Reclaiming, Renewing the Self
Authors: Dziengel Lake
Published: November 2013

This is an autoethnographic account of seeking double mastectomy as a sexual minority due to advanced fibrocystic scarring. Using social construction, feminist, and ambiguous loss theories, themes of the concept of belonging, challenges of health care systems, reconstruction of identity, and responses of others depict the transformative process of gender identity and sense of self. Discussion of the role of resiliency and ambiguity are addressed, as well as ambivalence, and managing external stressors. Recommendations for social work education and practice include advancing sensitivity and competency on gender identity/expression and advocacy role in challenging the gender binary.
Performance degradation analysis of solid lubricated bearings based on Laplace wavelet filter and self-organizing map
Authors: Zhang Chao , Wang Shaoping
Published: November 2013

Solid lubricated bearings are commonly used in space mechanisms and other appliances, and their reliability analysis has drawn more and more attention. This paper focuses on the performance degradation analysis of solid lubricated bearings. Based on the vibration and friction torque signal of solid lubricated bearings, Laplace wavelet filter is adopted to process vibration signal and feature vector is constructed by calculating time-domain parameters of filtered vibration signal and original friction torque signal. Self-organizing map is then adopted to analyze the performance degradation based on extracted feature vectors. Experimental results show that this method can describe performance degradation process effectively.
Symmetry in Cold-to-Hot and Hot-to-Cold Valuation Gaps
Authors: Fisher Geoffrey , Rangel Antonio
Published: November 2013

Individuals commonly mispredict their future preferences when they make decisions in a visceral state different from their anticipated state at consumption. In the research reported here, we asked subjects to bid on different foods while exogenously varying their hunger levels at the time of decision and at the time of consumption. This procedure allowed us to test whether cold-to-hot and hot-to-cold gaps are symmetric in size and driven by similar mechanisms. We found that the effect size was symmetric: Hungry subjects overbid 20¢ for a snack they would eat later when they were satiated, and satiated subjects underbid 19¢ for a snack they would eat later when they were hungry. Furthermore, we found evidence that these gaps were driven by symmetric mechanisms that operate on the evaluation of visceral features of food, such as taste, as opposed to more cognitive features, such as healthiness.
Rhabdomyolysis induced by excessive coffee drinking
Authors: Chiang W-F , Liao M-T , Cheng C-J , Lin S-H
Published: November 2013

Excessive ingestion of caffeine-containing beverages is a rare cause of rhabdomyolysis. Here, we describe the case of a 44-year-old woman presented with nausea, vomiting, palpitations, and tea-colored urine 6 h after drinking a liter of black coffee containing approximately 565 mg of caffeine for mental alertness. Laboratory studies were notable for myoglobinuria and markedly elevated plasma creatine kinase (CK) level of 7315 U/L. With volume expansion and alkalization, her plasma CK level returned to normal within 5 days. Rhabdomyolysis should be considered a potential health hazard from excessive consumption of caffeine-containing products.
The association between serum Dickkopf-1 levels and esophageal squamous cell carcinoma
Authors: Begenik H , Kemik AS , Emre H , Dulger AC , Demirkiran D , Ebinc S , Kemik O
Published: November 2013

Serum Dickkopf-1(DKK-1) is elevated in many malignancies and is an important indicator of malignant potential. However, its significance in esophageal squamous cell cancer (ESCC) has not yet been clarified. We hypothesized a role for DKK-1 in patients with ESCC. The study consisted of 90 ESCC patients and 85 healthy controls. After diagnosis, the level of DKK-1 was measured in the serum samples by enzyme-linked immunosorbent assay and the levels of DKK-1 were much higher in the ESCC patients than in the healthy control group ( p < 0.0001). For serum DKK-1, the sensitivity and specificity of the assay were 70 and 80%, respectively. The preoperative serum DKK-1 level was elevated in the ESCC patients. Although serum DKK-1 is not a specific biomarker for ESCC, it might be a useful marker for the diagnosis and treatment of ESCC.
In vitro study on cytotoxicity and intracellular formaldehyde concentration changes after exposure to formaldehyde and its derivatives
Authors: Ke YJ , Qin XD , Zhang YC , Li H , Li R , Yuan JL , Yang X , Ding SM
Published: November 2013

HeLa cells were exposed to formaldehyde and its metabolic derivatives, methanol, formic acid, and acetaldehyde, to investigate that the toxicity of formaldehyde is not caused by the chemical group. After 1 h of treatment with formaldehyde, mitochondrial assays showed that low concentrations (e.g. 10 μmol/L) of formaldehyde promoted growth of the HeLa cells, while higher concentrations (e.g. ≥62.5 μmol/L) inhibited cell growth; while all four chemicals at a concentration of 125 μmol/L affected cell growth, formaldehyde affected the largest. Reactive oxygen species concentration increased with the concentration of the exposure chemical. The endogenous formaldehyde content increased the most in the formaldehyde group, but in other three groups, it did not increase as the exposure concentration increased. Expression of dehydrogenase (formaldehyde dehydrogenase (FDH)) in the formaldehyde (10.40) and methanol (10.60) groups increased significantly compared with the control (1), while it was similar to the control in formic acid (0.90) and acetaldehyde (1.10) groups. Our results suggest that formaldehyde could affect cell activity and even enter cells. Exposure to formaldehyde changes the endogenous formaldehyde concentration in cells within 24 h, and this induces expression of FDH for formaldehyde degradation to maintain the formaldehyde balance. The toxicity of formaldehyde is not caused by the carbon atoms in the aldehyde, hydroxyl, or carboxyl groups. Formaldehyde is hypothesized to be an important signaling molecule in the regulation of cell growth and maintenance of the endogenous formaldehyde level.
EU-Limboscapes: Ceuta and the proliferation of migrant detention spaces across the European Union
Authors: Ferrer-Gallardo Xavier , Albet-Mas Abel
Published: November 2013

This Euro-commentary puts the lens on the European Union (EU) North-African city of Ceuta. In so doing, it introduces the notion of EU limboscapes. In the 1990s and early 2000s the iconic twin-metal fencing of Ceuta’s borders added powerful visual strength to the metaphorical Fortress Europe. Today, Ceuta is still (or even more) central when it comes to the conceptual understanding of the socio-spatial articulation of the EU project vis-à-vis migration management. In this respect, we suggest that the limboscape profile drawn by Ceuta’s spatial dynamics is now iconic in terms of current EU b/ordering practices. The notion of limboscape helps us conceptually grasp/map the expanding archipelago of migrant confinement spaces scattered within and beyond EU space.
Combined Mesothelial Cyst and Lymphangioma of the Small Bowel
Authors: Wang Jayson , Fisher Cyril , Thway Khin
Published: November 2013

Intra-abdominal cysts have a variety of origins, of which lymphatic and mesothelial types are the most commonly encountered. Here we describe a combined mesothelial cyst and lymphangioma arising within the small bowel subserosa of an 80-year-old woman. This was found incidentally at laparotomy performed for an unrelated condition. To date, such a hybrid lesion has not been previously reported. The ways by which this lesion might have arisen are discussed.
Assessing DSM-5 Section III Personality Traits and Disorders With the MMPI-2-RF
Authors: Sellbom Martin , Anderson Jaime L. , Bagby R. Michael
Published: November 2013

An alternative model for diagnosing personality disorders (PDs) appears in DSM-5 Section III. This model includes a set of dimensional personality traits, which along with impairment in personality functioning can be configured to represent one of six PDs. Although specific assessment instruments for these personality traits have already been developed (e.g., the Personality Inventory for DSM-5 [PID-5]), clinicians will likely continue to use omnibus measures of psychopathology that are familiar to them to inform diagnostic decision making. One such measure, the Minnesota Multiphasic Personality Inventory–2–Restructured Form (MMPI-2-RF), will likely remain in the test armamentarium of many practitioners and be employed to assess the DSM-5 dimensional traits. In the current investigation, we examined the associations between MMPI-2-RF scale scores and the PID-5 trait scores and DSM-5 Section III PDs in a combined sample of university students ( n = 668) from the United States and Canada. Our results indicated that the MMPI-2-RF scale scores mostly converge with PID-5 dimensional traits as well as the Section III PDs in a conceptually expected manner. As such, we conclude that the MMPI-2-RF is a potentially useful instrument in assessing personality psychopathology as conceptualized in DSM-5 Section III.
The Effect of a Platform Swing on the Independent Work Behaviors of Children With Autism Spectrum Disorders
Authors: Murdock Linda C. , Dantzler John A. , Walker Anne N. , Wood L. Becca
Published: November 2013

A randomized pretest–posttest control group design was utilized to measure the effects of a platform swing on independent work behaviors of 30 children with Autism Spectrum Disorders (ASD). Participants engaged in two 5-min intervals of independent work. Between the intervals, participants in the treatment group received 5 min of vestibular stimulation using a platform swing and children in the control group watched a video. No significant differences were evidenced between the treatment and control groups on engagement, on-task behavior, stereotyped/repetitive behavior, or out-of-seat behavior. Changes noted for individual participants could not be linked to age, diagnosis, or sensory profile patterns.
Marginal but Modern: Young Nepali Labour Migrants in India
Authors: Sharma Jeevan Raj
Published: November 2013

Migration to India has been one of the key livelihood strategies amongst marginal households in the middle hills of Nepal. Based on ethnographic fieldwork in western and far-western hill villages in Nepal, including tracing the experience of young men who take on adult responsibility to travel to find work opportunities in Mumbai and Nainital in India, this article discusses how the steady flow of marginal migrants from the middle hills is shaped and sustained by gendered and generational considerations. An intriguing aspect of young migrants’ lives in India is their participation in consumption of modern commodities despite their marginal position and difficult working condition.
Alcohol Use Among Young Adolescents in Belgium, the Netherlands, Germany and Austria: The Effects of Type of Education
Authors: Berten Hans , Cardoen Dries , Van Rossem Ronan , Brondeel Ruben , Vettenburg Nicole
Published: November 2013

The present study elucidates the association between students’ education type and alcohol use, controlling for other socio-economic background characteristics. A subsample of data from the second International Self-Reported Delinquency Study was used (N= 10,525), collected among adolescents in the seventh to ninth grades of secondary school in four Western European countries (Belgium, the Netherlands, Germany and Austria). Data were analyzed with multilevel logistic regression techniques. There is an indication that type of education affects prevalence rates of drunkenness and heavy episodic drinking; these effects prove robust for differences in socio-economic backgrounds. The results of this study support the literature regarding the role of the educational system in the reproduction of health inequalities and underscore the finding that students from education types of lower status are at greater risk than those from higher status types.
Interrogating cultural narratives about ‘honour’- based violence
Authors: Gill Aisha K , Brah Avtar
Published: November 2013

On 3 August 2012, Shafilea Ahmed’s parents were convicted of her murder, nine years after the brutal ‘honour’ killing. The case offers important insights into how ‘honour’-based violence might be tackled without constructing non-Western cultures as inherently uncivilised. Critiquing the framing devices that structure British debates about ‘honour’-based violence demonstrates the prevalence of Orientalist tropes, revealing the need for new ways of thinking about culture that do not reify it or treat it as a singular entity that can only be tackled in its entirety; instead, it is important to recognise that cultures consist of multiple, intersecting signifying practices that are continually ‘creolising’. Thus, rather than talking purely about culture, debates on ‘honour’-based violence should explore the intersection of culture with gender and other axes of differentiation and inequality.
Seniors in shopping centres
Authors: White Rob , Toohey Julie-Anne , Asquith Nicole
Published: November 2013

Many studies have examined issues of youth and public spaces; however, less attention has been devoted to seniors and their navigation and experience of community spaces, particularly in relation to their sense of inclusion in, or exclusion from, consumptive spaces. This article explores the everyday experiences of seniors in four Australian shopping centres, two in Melbourne and two in Hobart. Based on a survey of 260 seniors (the majority aged 75 years or more), respondents’ perceptions of this environment are considered, including the reasons for visiting the shopping centre, and the challenges of accessing and negotiating the shopping centre ‘terrain’. The research findings indicate that how seniors engage with and navigate the shopping centre is influenced not only by the nature of the space itself, but also by their personal historical and cultural experiences. Where and why seniors choose to ‘hang out’ in shopping centres has implications for research into the social landscapes of ageing, along with public policy and shopping centre procedures. There is a need to consider both the social and physical well-being of older people in the shopping centre locus, and to take positive steps towards improving and enhancing their experience in an environment that is often used to provide a range of experiences that go beyond mere ‘retail therapy’.
Proliferative changes of renal arteriolar walls induced by administration of angiotensin II receptor blocker are frequent in juvenile rats
Authors: Nagai Yohko , Nakanishi Kazushige , Akimoto Tatsuo , Yamanaka Nobuaki
Published: November 2013

Introduction:

Our previous study of angiotensin II receptor blocker (ARB) administration in rats induced unusual proliferative changes of smooth muscle cells in renal arteriolar walls. The present study examined if the incidence of the changes depended on the rats’ age, and how long it would take to find changes.

Materials and methods:

Six-week-old (juvenile spontaneous hypertensive rats (SHRs)+ARB group, n=15) and 20-week-old (adult SHRs+ARB group, n=10) male SHRs were fed a standard diet (0.4% NaCl) containing valsartan (10 mg/kg/day; Novartis Co.). Fifteen age-matched SHRs were studied as controls. After 4, 8, and 12 weeks, the rat kidneys were examined under light and electron microscopes and through immunohistochemical studies.

Results:

Extremely concentric proliferative changes in afferent arteriolar walls were frequently observed in the juvenile SHR+ARB group compared to the adult SHR+ARB group (48.7±6.8% vs 19.3±6.9%; p=0.0307) at the 12th week. Increased renin expression and arteriolar changes were found from the 4th week in the juvenile SHR+ARB group.

Conclusion:

This study indicates that ARB administration induces unusual proliferative changes and a marked renin-producing cell increase in afferent arterioles more frequently in juveniles than adult rats. It is suggested that the treatment of ARB in juveniles might have a higher risk of changes in renal afferent arterioles.
Narcolepsy Goes to School
Authors: Gow Monica
Published: November 2013

The sleep disorder narcolepsy most often first appears in the teen years. It can dash the dreams of optimistic, intelligent students. It can make some students the target of nasty jokes and bullying, leaving them depressed and socially isolated. It can challenge children’s self-esteem, and lowered self-esteem may last a lifetime. Typically, children with narcolepsy gain weight and have no interest in participating in anything. Many constantly feel extreme tiredness, and they may experience cataplexy. School nurses and teachers can help if they know the symptoms and practice the 3 Rs of narcolepsy: Recognize the symptoms of narcolepsy; Respect that narcolepsy is a lifelong, serious sleep disorder that needs treatment; and Refer students who exhibit symptoms to medical professionals. The 3 Rs will help students living with this lifelong disorder to get a fair shake in life’s academic, social, and career arenas.
Genome-wide survey and expression profiles of the AP2/ERF family in castor bean (Ricinus communis L.)
Authors: Xu Wei , Li Fei , Ling Lizhen , Liu Aizhong
Published: November 2013

Background

The AP2/ERF transcription factor, one of the largest gene families in plants, plays a crucial role in the regulation of growth and development, metabolism, and responses to biotic and abiotic stresses. Castor bean (Ricinus communisL., Euphobiaceae) is one of most important non-edible oilseed crops and its seed oil is broadly used for industrial applications. The available genome provides a great chance to identify and characterize the global information on AP2/ERF transcription factors in castor bean, which might provide insights in understanding the molecular basis of the AP2/ERF family in castor bean.

Results

A total of 114 AP2/ERF transcription factors were identified based on the genome in castor bean. According to the number of the AP2/ERF domain, the conserved amino acid residues within AP2/ERF domain, the conserved motifs and gene organization in structure, and phylogenetical analysis, the identified 114 AP2/ERF transcription factors were characterized. Global expression profiles among different tissues using high-throughput sequencing of digital gene expression profiles (DGEs) displayed diverse expression patterns that may provide basic information in understanding the function of the AP2/ERF gene family in castor bean.

Conclusions

The current study is the first report on identification and characterization of the AP2/ERF transcription factors based on the genome of castor bean in the family Euphobiaceae. Results obtained from this study provide valuable information in understanding the molecular basis of the AP2/ERF family in castor bean.
Lipopolysaccharide (LPS)-induced autophagy is involved in the restriction of Escherichia coliin peritoneal mesothelial cells
Authors: Wang Juan , Feng Xiaoran , Zeng Youjia , Fan Jinjin , Wu Juan , Li Zhijian , Liu Xinhui , Huang Rong , Huang Fengxian , Yu Xueqing , Yang Xiao
Published: November 2013

Background

Host cell autophagy is implicated in the control of intracellular pathogen. Escherichia coli (E.coli) is the most common organism caused single-germ enterobacterial peritonitis during peritoneal dialysis. In this study, we investigated autophagy of peritoneal mesothelial cells and its role in defense against E.coli.

Results

Autophagy in human peritoneal mesothelial cell line (HMrSV5) was induced by lipopolysaccharide (LPS) in a dose-dependent and time-dependent way, which was demonstrated by increased expression of Beclin-1 and light chain 3 (LC3)-II, the accumulation of punctate green fluorescent protein-LC3, and a higher number of monodansylcadaverine-labeled autophagic vacuoles. After incubation of HMrSV5 cells with E.coli following LPS stimulation, both the intracellular bactericidal activity and the co-localization of E.coli (K12-strain) with autophagosomes were enhanced. Conversely, blockade of autophagy with 3-methyladenine, wortmannin or Beclin-1 small-interfering RNA (siRNA) led to a significant reduction in autophagy-associated protein expression, attenuation of intracellular bactericidal activity, and reduced co-localization of E.coli with monodansylcadaverine-labeled autophagosomes. In addition, treatment of HMrSV5 cells with LPS caused a dose-dependent and time-dependent increase in Toll-like receptor 4 (TLR4) expression. Both knockdown of TLR4 with siRNA and pharmacological inhibition of TLR4 with Polymyxin B significantly decreased LPS-induced autophagy. Furthermore, TLR4 siRNA attenuated remarkably LPS-induced intracellular bactericidal activity.

Conclusions

Our findings demonstrated for the first time that LPS-induced autophagy in peritoneal mesothelial cells could enhance the intracellular bactericidal activity and the co-localization of E.coli with autophagosomes. The activation of TLR4 signaling was involved in this process. These results indicate that LPS-induced autophagy may be a cell-autonomous defense mechanism triggered in peritoneal mesothelial cells in response to E.coli infection.
Hospital process orientation from an operations management perspective: development of a measurement tool and practical testing in three ophthalmic practices
Authors: Gonçalves Pedro D , Hagenbeek Marie Louise , Vissers Jan M H
Published: November 2013

Background

Although research interest in hospital process orientation (HPO) is growing, the development of a measurement tool to assess process orientation (PO) has not been very successful yet. To view a hospital as a series of processes organized around patients with a similar demand seems to be an attractive proposition, but it is hard to operationalize this idea in a measurement tool that can actually measure the level of PO. This research contributes to HPO from an operations management (OM) perspective by addressing the alignment, integration and coordination of activities within patient care processes. The objective of this study was to develop and practically test a new measurement tool for assessing the degree of PO within hospitals using existing tools.

Methods

Through a literature search we identified a number of constructs to measure PO in hospital settings. These constructs were further operationalized, using an OM perspective. Based on five dimensions of an existing questionnaire a new HPO-measurement tool was developed to measure the degree of PO within hospitals on the basis of respondents’ perception. The HPO-measurement tool was pre-tested in a non-participating hospital and discussed with experts in a focus group. The multicentre exploratory case study was conducted in the ophthalmic practices of three different types of Dutch hospitals. In total 26 employees from three disciplines participated. After filling in the questionnaire an interview was held with each participant to check the validity and the reliability of the measurement tool.

Results

The application of the HPO-measurement tool, analysis of the scores and interviews with the participants resulted in the possibility to identify differences of PO performance and the areas of improvement – from a PO point of view – within each hospital. The result of refinement of the items of the measurement tool after practical testing is a set of 41 items to assess the degree of PO from an OM perspective within hospitals.

Conclusions

The development and practically testing of a new HPO-measurement tool improves the understanding and application of PO in hospitals and the reliability of the measurement tool. The study shows that PO is a complex concept and appears still hard to objectify.
Researching male circumcision for HIV prevention in Papua New Guinea: a process that incorporates science, faith and culture
Authors: Tommbe Rachael , MacLaren David J , Redman-MacLaren Michelle L , Mafile’o Tracie A , Asugeni Lester , McBride William John H
Published: November 2013

Background

Undertaking HIV research in the culturally diverse Pacific nation of Papua New Guinea (PNG) requires careful consideration of social, cultural and religious beliefs and practices. Here, we share a detailed description of culturally informed research processes and lessons learned from the first ever study undertaken on male circumcision for HIV prevention at a faith-based university in PNG.

Methods

Male and female staff and students at Pacific Adventist University were invited to complete an anonymous self-administered questionnaire, and/or participate in a semi-structured interview or focus group discussion. Male participants were invited for clinical examination. Results were collated and disseminated to the university community in gender segregated sessions. The study deliberately partnered with student leaders and centralised social, cultural, and religious paradigms. Student leaders were interviewed about their experience of partnering in sensitive health research.

Results

The student leaders reported that pre-existing relationships, cultural ties, gendered sensitivity and regular communication reinforced trust between researchers, student leaders and participants, and helped the success of the study. The amount of time, complex logistics and social and cultural relationships between single and married staff and students were highlighted as challenges.

Conclusions

Partnering with regional student leaders to plan and implement the study gave a legitimate and immediate mechanism for involving PNG staff and students in this sensitive health research. Gendered research processes utilised established social and cultural structures and ensured the safety of participants; all of these factors contributed to the acceptability of the study. Capacity was strengthened in PNG and Australian researchers to undertake sensitive HIV research in PNG. The study demonstrated that it is possible to conduct sensitive sexual health research at a faith-based university in PNG.
Mutational analysis of the rotavirus NSP4 enterotoxic domain that binds to caveolin-1
Authors: Ball Judith M , Schroeder Megan E , Williams Cecelia V , Schroeder Friedhelm , Parr Rebecca D
Published: November 2013

Background

Rotavirus (RV) nonstructural protein 4 (NSP4) is the first described viral enterotoxin, which induces early secretory diarrhea in neonatal rodents. Our previous data show a direct interaction between RV NSP4 and the structural protein of caveolae, caveolin-1 (cav-1), in yeast and mammalian cells. The binding site of cav-1 mapped to the NSP4 amphipathic helix, and led us to examine which helical face was responsible for the interaction.

Methods

A panel of NSP4 mutants were prepared and tested for binding to cav-1 by yeast two hybrid and direct binding assays. The charged residues of the NSP4 amphipathic helix were changed to alanine (NSP446-175-ala6); and three residues in the hydrophobic face were altered to charged amino acids (NSP446-175-HydroMut). In total, twelve mutants of NSP4 were generated to define the cav-1 binding site. Synthetic peptides corresponding to the hydrophobic and charged faces of NSP4 were examined for structural changes by circular dichroism (CD) and diarrhea induction by a neonatal mouse study.

Results

Mutations of the hydrophilic face (NSP446-175-Ala6) bound cav-1 akin to wild type NSP4. In contrast, disruption of the hydrophobic face (NSP446-175-HydroMut) failed to bind cav-1. These data suggest NSP4 and cav-1 associate via a hydrophobic interaction. Analyses of mutant synthetic peptides in which the hydrophobic residues in the enterotoxic domain of NSP4 were altered suggested a critical hydrophobic residue. Both NSP4HydroMut112-140, that contains three charged amino acids (aa113, 124, 131) changed from the original hydrophobic residues and NSP4AlaAcidic112-140 that contained three alanine residues substituted for negatively charged (aa114, 125, 132) amino acids failed to induce diarrhea. Whereas peptides NSP4wild type 112
−140 and NSP4AlaBasic112-140 that contained three alanine substituted for positively charged (aa115, 119, 133) amino acids, induced diarrhea.

Conclusions

These data show that the cav-1 binding domain is within the hydrophobic face of the NSP4 amphipathic helix. The integrity of the helical structure is important for both cav-1 binding and diarrhea induction implying a connection between NSP4 functional and binding activities.
Defining traumatic brain injury in children and youth using International Classification of Diseases version 10 codes: a systematic review protocol
Authors: Chan Vincy , Thurairajah Pravheen , Colantonio Angela
Published: November 2013

Background

Although healthcare administrative data are commonly used for traumatic brain injury research, there is currently no consensus or consistency on using the International Classification of Diseases version 10 codes to define traumatic brain injury among children and youth. This protocol is for a systematic review of the literature to explore the range of International Classification of Diseases version 10 codes that are used to define traumatic brain injury in this population.

Methods/design

The databases MEDLINE, MEDLINE In-Process, Embase, PsychINFO, CINAHL, SPORTDiscus, and Cochrane Database of Systematic Reviews will be systematically searched. Grey literature will be searched using Grey Matters and Google. Reference lists of included articles will also be searched. Articles will be screened using predefined inclusion and exclusion criteria and all full-text articles that meet the predefined inclusion criteria will be included for analysis. The study selection process and reasons for exclusion at the full-text level will be presented using a PRISMA study flow diagram. Information on the data source of included studies, year and location of study, age of study population, range of incidence, and study purpose will be abstracted into a separate table and synthesized for analysis. All International Classification of Diseases version 10 codes will be listed in tables and the codes that are used to define concussion, acquired traumatic brain injury, head injury, or head trauma will be identified.

Discussion

The identification of the optimal International Classification of Diseases version 10 codes to define this population in administrative data is crucial, as it has implications for policy, resource allocation, planning of healthcare services, and prevention strategies. It also allows for comparisons across countries and studies. This protocol is for a review that identifies the range and most common diagnoses used to conduct surveillance for traumatic brain injury in children and youth. This is an important first step in reaching an appropriate definition using International Classification of Diseases version 10 codes and can inform future work on reaching consensus on the codes to define traumatic brain injury for this vulnerable population.
Suppression of eukaryotic initiation factor 4E prevents chemotherapy-induced alopecia
Authors: Nasr Zeina , Dow Lukas E , Paquet Marilene , Chu Jennifer , Ravindar Kontham , Somaiah Ragam , Deslongchamps Pierre , Porco Jr John A , Lowe Scott W , Pelletier Jerry
Published: November 2013

Background

Chemotherapy-induced hair loss (alopecia) (CIA) is one of the most feared side effects of chemotherapy among cancer patients. There is currently no pharmacological approach to minimize CIA, although one strategy that has been proposed involves protecting normal cells from chemotherapy by transiently inducing cell cycle arrest. Proof-of-concept for this approach, known as cyclotherapy, has been demonstrated in cell culture settings.

Methods

The eukaryotic initiation factor (eIF) 4E is a cap binding protein that stimulates ribosome recruitment to mRNA templates during the initiation phase of translation. Suppression of eIF4E is known to induce cell cycle arrest. Using a novel inducible and reversible transgenic mouse model that enables RNAi-mediated suppression of eIF4E in vivo, we assessed the consequences of temporal eIF4E suppression on CIA.

Results

Our results demonstrate that transient inhibition of eIF4E protects against cyclophosphamide-induced alopecia at the organismal level. At the cellular level, this protection is associated with an accumulation of cells in G1, reduced apoptotic indices, and was phenocopied using small molecule inhibitors targeting the process of translation initiation.

Conclusions

Our data provide a rationale for exploring suppression of translation initiation as an approach to prevent or minimize cyclophosphamide-induced alopecia.
Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma
Authors: Magee Kelsey E , Kelsey Christina E , Kurzinski Katherine L , Ho Jonhan , Mlakar Logan R , Feghali-Bostwick Carol A , Torok Kathryn S
Published: November 2013

Introduction

The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures.

Methods

The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC).

Results

IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control.

Conclusions

Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS.
Follow-Up Care, Surveillance Protocol, and Secondary Prevention Measures for Survivors of Colorectal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement
Authors: Meyerhardt Jeffrey A. , Mangu Pamela B. , Flynn Patrick J. , Korde Larissa , Loprinzi Charles L. , Minsky Bruce D. , Petrelli Nicholas J. , Ryan Kim , Schrag Deborah H. , Wong Sandra L. , Benson Al B.
Published: November 2013

Purpose

The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing recent clinical practice guidelines that have been developed by other professional organizations.

Methods

The Cancer Care Ontario (CCO) Guideline on Follow-up Care, Surveillance Protocol, and Secondary Prevention Measures for Survivors of Colorectal Cancer was reviewed by ASCO for methodologic rigor and considered for endorsement.

Results

The ASCO Panel concurred with the CCO recommendations and recommended endorsement, with the addition of several qualifying statements.

Conclusion

Surveillance should be guided by presumed risk of recurrence and functional status of the patient (important within the first 2 to 4 years). Medical history, physical examination, and carcinoembryonic antigen testing should be performed every 3 to 6 months for 5 years. Patients at higher risk of recurrence should be considered for testing in the more frequent end of the range. A computed tomography scan (abdominal and chest) is recommended annually for 3 years, in most cases. Positron emission tomography scans should not be used for surveillance outside of a clinical trial. A surveillance colonoscopy should be performed 1 year after the initial surgery and then every 5 years, dictated by the findings of the previous one. If a colonoscopy was not preformed before diagnosis, it should be done after completion of adjuvant therapy (before 1 year). Secondary prevention (maintaining a healthy body weight and active lifestyle) is recommended. If a patient is not a candidate for surgery or systemic therapy because of severe comorbid conditions, surveillance tests should not be performed. A treatment plan from the specialist should have clear directions on appropriate follow-up by a nonspecialist.
Homologous electron transport components fail to increase fatty acid hydroxylation in transgenic Arabidopsis thaliana
Authors: Wayne Laura L. , Browse John
Published: November 2013

Ricinoleic acid, a hydroxylated fatty acid (HFA) present in castor (Ricinus communis) seeds, is an important industrial commodity used in products ranging from inks and paints to polymers and fuels. However, due to the deadly toxin ricin and allergens also present in castor, it would be advantageous to produce ricinoleic acid in a different agricultural crop. Unfortunately, repeated efforts at heterologous expression of the castor fatty acid hydroxylase (RcFAH12) in the model plantArabidopsis thalianahave produced only 17-19% HFA in the seed triacylglycerols (TAG), whereas castor seeds accumulate up to 90% ricinoleic acid in the endosperm TAG. RcFAH12 requires an electron supply from NADH:cytochrome b5 reductase (CBR1) and cytochrome b5 (Cb5) to synthesize ricinoleic acid. Previously, our laboratory found a mutation in theArabidopsis CBR1gene,cbr1-1, that caused an 85% decrease in HFA levels in the RcFAH12Arabidopsisline. These results raise the possibility that electron supply to the heterologous RcFAH12 may limit the production of HFA. Therefore, we hypothesized that by heterologously expressing RcCb5, the reductant supply to RcFAH12 would be improved and lead to increased HFA accumulation inArabidopsisseeds. Contrary to this proposal, heterologous expression of the top three RcCb5 candidates did not increase HFA accumulation. Furthermore, coexpression of RcCBR1 and RcCb5 in RcFAH12 Arabidopsis also did not increase in HFA levels compared to the parental lines. These results demonstrate that theArabidopsiselectron transfer system is supplying sufficient reductant to RcFAH12 and that there must be other bottlenecks limiting the accumulation of HFA.
Syndicated Landing in Russian and English Law
Authors: Гравин Дмитрий , Gravin Dmitriy
Published: November 2013

This article deals with syndicated loans governed by Russian law, analyses legal nature of such agreements. It also relates to inter-­creditors arrangements and amendments to be proposed to Russian law.
How Judges Think: Judicial Reasoning in Tort Cases from a Comparative Perspective
Authors: Griss Irmgard
Published: November 2013

Are judges la bouche de la loi or are they the oracles of the law? An answer to this question is sought by comparing the different styles of reasoning of French, German, Austrian and UK courts of last resort in tort cases. Whereas UK judges state overtly what they think, French judges keep secret their motives. German and Austrian judges tend to maintain that legal doctrine provides an answer to even the most difficult questions. But, as regards the outcome, there are no real differences. Judges are nowhere merely the mouth of the law.
The Protein Kinase A Regulatory Subunit R1A (Prkar1a) Plays Critical Roles in Peripheral Nerve Development
Authors: Guo Li , Lee Audrey A. , Rizvi Tilat A. , Ratner Nancy , Kirschner Lawrence S.
Published: November 2013

Signaling through cAMP has been implicated in Schwann cell (SC) proliferation and myelination, but the signaling pathway components downstream of cAMP required for SC function remain unknown. Protein kinase A (PKA) is a potential downstream effector of cAMP. Here, we induced loss ofPrkar1a, the gene encoding the type 1A regulatory subunit of PKA, in SC to study its role in nerve development; loss of Prkar1a is predicted to elevate PKA activity. ConditionalPrkar1aknock-out in mouse SC (Prkar1a-SCKO) resulted in a dramatic and persistent axonal sorting defect, and unexpectedly decreased SC proliferation in Prkar1a-SCKO nervesin vivo. Effects were cell autonomous as they were recapitulatedin vitroin Prkar1a-SCKO SC, which showed elevated PKA activity. In the few SCs sorted into 1:1 relationships with axonsin vivo, SC myelination was premature in Prkar1a-SCKO nerves, correlating with global increase in the cAMP-regulated transcription factor Oct-6 and expression of myelin basic protein. These data reveal a previously unknown role of PKA in axon sorting, an unexpected inhibitory role of PKA on SC cell proliferationin vivoand define the importance ofPrkar1ain peripheral nerve development.
The Fragile X Mental Retardation Protein Regulates Matrix Metalloproteinase 9 mRNA at Synapses
Authors: Janusz Aleksandra , Miłek Jacek , Perycz Małgorzata , Pacini Laura , Bagni Claudia , Kaczmarek Leszek , Dziembowska Magdalena
Published: November 2013

Activity-dependent protein synthesis at synapses is dysregulated in the Fragile X syndrome (FXS). This process contributes to dendritic spine dysmorphogenesis and synaptic dysfunction in FXS. Matrix Metalloproteinase 9 (MMP-9) is an enzyme involved in activity-dependent reorganization of dendritic spine architecture and was shown to regulate spine morphology in a mouse model of FXS, the Fmr1 knock-out mice. Here we show that MMP-9 mRNA is part of the FMRP complex and colocalizes in dendrites. In the absence of FMRP MMP-9 mRNA translation is increased at synapses, suggesting that this mechanism contributes to the increased metalloproteinase level at synapses of Fmr1 knock-out mice. We propose that such a local effect can contribute to the aberrant dendritic spine morphology observed in the Fmr1 knock-out mice and in patients with FXS.
Convergent Rhythm Generation from Divergent Cellular Mechanisms
Authors: Rodriguez Jason C. , Blitz Dawn M. , Nusbaum Michael P.
Published: November 2013

Different modulatory inputs commonly elicit distinct rhythmic motor patterns from a central pattern generator (CPG), but they can instead elicit the same pattern. We are determining the rhythm-generating mechanisms in this latter situation, using the gastric mill (chewing) CPG in the crab (Cancer borealis) stomatogastric ganglion, where stimulating the projection neuron MCN1 (modulatory commissural neuron 1) or bath applying CabPK (C. borealispyrokinin) peptide elicits the same gastric mill motor pattern, despite configuring different gastric mill circuits. In both cases, the core rhythm generator includes the same reciprocally inhibitory neurons LG (lateral gastric) and Int1 (interneuron 1), but the pyloric (food-filtering) circuit pacemaker neuron AB (anterior burster) is additionally necessary only for CabPK rhythm generation. MCN1 drives this rhythm generator by activating in the LG neuron the modulator-activated inward current (IMI), which waxes and wanes periodically due to phasic feedback inhibition of MCN1 transmitter release. Each buildup ofIMIenables the LG neuron to generate a self-terminating burst and thereby alternate with Int1 activity. Here we establish that CabPK drives gastric mill rhythm generation by activating in the LG neuronIMIplus a slowly activating transient, low-threshold inward current (ITrans-LTS) that is voltage, time, and Ca2+dependent. Unlike MCN1, CabPK maintains a steadyIMIactivation, causing a subthreshold depolarization in LG that facilitates a periodic postinhibitory rebound burst caused by the regular buildup and decay of the availability ofITrans-LTS. Thus, different modulatory inputs can use different rhythm-generating mechanisms to drive the same neuronal rhythm. Additionally, the same ionic current (IMI) can play different roles under these different conditions, while different currents (IMI,ITrans-LTS) can play the same role.