bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated multiscale biomaterials experiment and modelling: a perspective
Authors: Buehler Markus J. , Genin Guy M.
Published: December 2015

Advances in multiscale models and computational power have enabled a broad toolset to predict how molecules, cells, tissues and organs behave and develop. A key theme in biological systems is the emergence of macroscale behaviour from collective behaviours across a range of length and timescales, and a key element of these models is therefore hierarchical simulation. However, this predictive capacity has far outstripped our ability to validate predictions experimentally, particularly when multiple hierarchical levels are involved. The state of the art represents careful integration of multiscale experiment and modelling, and yields not only validation, but also insights into deformation and relaxation mechanisms across scales. We present here a sampling of key results that highlight both challenges and opportunities for integrated multiscale experiment and modelling in biological systems.
Yes, one can obtain better quality structures from routine X-ray data collection
Authors: Sanjuan-Szklarz W. Fabiola , Hoser Anna A. , Gutmann Matthias , Madsen Anders Østergaard , Woźniak Krzysztof
Published: December 2015

Single-crystal X-ray diffraction structural results for benzidine dihydrochloride, hydrated and protonatedN,N,N,N-peri(dimethylamino)naphthalene chloride, triptycene, dichlorodimethyltriptycene and decamethylferrocene have been analysed. A critical discussion of the dependence of structural and thermal parameters on resolution for these compounds is presented. Results of refinements against X-ray data, cut off to different resolutions from the high-resolution data files, are compared to structural models derived from neutron diffraction experiments. The Independent Atom Model (IAM) and the Transferable Aspherical Atom Model (TAAM) are tested. The average differences between the X-ray and neutron structural parameters (with the exception of valence angles defined by H atoms) decrease with the increasing 2θmaxangle. The scale of differences between X-ray and neutron geometrical parameters can be significantly reduced when data are collected to the higher, than commonly used, 2θmaxdiffraction angles (for Mo Kα 2θmax > 65°). The final structural and thermal parameters obtained for the studied compounds using TAAM refinement are in better agreement with the neutron values than the IAM results for all resolutions and all compounds. By using TAAM, it is still possible to obtain accurate results even from low-resolution X-ray data. This is particularly important as TAAM is easy to apply and can routinely be used to improve the quality of structural investigations [Dominiak (2015).LSDBfromUBDB.University of Buffalo, USA]. We can recommend that, in order to obtain more adequate (more accurate and precise) structural and displacement parameters during the IAM model refinement, data should be collected up to the larger diffraction angles, at least, for Mo Kα radiation to 2θmax= 65° (sin θmax/λ < 0.75 Å−1). The TAAM approach is a very good option to obtain more adequate results even using data collected to the lower 2θmaxangles. Also the results of translation–libration–screw (TLS) analysis and vibrational entropy values are more reliable for 2θmax > 65°.
Rapid experimental SAD phasing and hot-spot identification with halogenated fragments
Authors: Bauman Joseph D. , Harrison Jerry Joe E. K. , Arnold Eddy
Published: December 2015

Through X-ray crystallographic fragment screening, 4-bromopyrazole was discovered to be a `magic bullet' that is capable of binding at many of the ligand `hot spots' found in HIV-1 reverse transcriptase (RT). The binding locations can be in pockets that are `hidden' in the unliganded crystal form, allowing rapid identification of these sites forin silicoscreening. In addition to hot-spot identification, this ubiquitous yet specific binding provides an avenue for X-ray crystallographic phase determination, which can be a significant bottleneck in the determination of the structures of novel proteins. The anomalous signal from 4-bromopyrazole or 4-iodopyrazole was sufficient to determine the structures of three proteins (HIV-1 RT, influenza A endonuclease and proteinase K) by single-wavelength anomalous dispersion (SAD) from single crystals. Both compounds are inexpensive, readily available, safe and very soluble in DMSO or water, allowing efficient soaking into crystals.
CryoEM at IUCrJ: a new era
Authors: Subramaniam Sriram , Kühlbrandt Werner , Henderson Richard
Published: December 2015

In this overview, we briefly outline recent advances in electron cryomicroscopy (cryoEM) and explain why the journal IUCrJ, published by the International Union of Crystallography, could provide a natural home for publications covering many present and future developments in the cryoEM field.
An unusual coordination polymer containing Cu+ions and featuring possible Cu...Cu `cuprophilic' interactions: poly[di-μ-chlorido-(μ4-3,5-diaminobenzoato-κ4O:O′:N:N′)tricopper(I)(3Cu—Cu)]
Authors: Khosa Muhammad Kaleem , Wood Paul T. , Humphrey Simon M. , Harrison William T. A.
Published: December 2015

Compounds containing copper(I) are of interest for their role in biological processes. The nature of short (< ∼3.2 Å) Cu...Cu contacts within these compounds has been debated, being either described as weakly attractive (bonding) `cuprophilic' interactions, or simply as short metal–metal distances constrained by ligand geometry or largely ionic in nature. The title three-dimensional Cu+-containing coordination polymer, [Cu3(C7H7N2O2)Cl2]n, was formed from thein situreduction of CuCl2in the presence of 3,5-diaminobenzoic acid and KOH under hydrothermal conditions. Its complex crystal structure contains ten distinct CuIatoms, two of which lie on crystallographic inversion centres. The copper coordination geometries include near-linear CuOCl and CuN2, T-shaped CuOCl2and distorted tetrahedral CuOCl3groups. Each CuIatom is also associated with two adjacent metal atoms, with Cu...Cu distances varying from 2.7350 (14) to 3.2142 (13) Å; if all these are regarded as `cuprophilic' interactions, then infinite [\overline{1}01] zigzag chains of CuIatoms occur in the crystal. The structure is consolidated by N—H...Cl hydrogen bonds.
Crystal structure of (RS)-(4-chlorophenyl)(pyridin-2-yl)methanol
Authors: Narayana Badiadka , Sarojini Balladka K. , Yathirajan Hemmige S. , Rathore Ravindranath , Glidewell Christopher
Published: December 2015

In the title racemic compound, C12H10ClNO, the dihedral angle between the benzene and pyridine rings is 74.34 (6)°. In the crystal, the molecules are linked by O—H...N hydrogen bonds, forming zigzagC(5) [001] chains in which alternatingR- andS-configuration molecules are related byc-glide symmetry. In addition, inversion-related pairs of molecules are linked into dimers by pairs of weak C—Cl...π(pyridyl) interactions, which link the hydrogen-bonded chains into (100) sheets. Structural comparisons are drawn with a number of related compounds.
Crystal structure of 3-bromo-9-ethyl-9H-carbazole
Authors: Bezuglyi Mykola , Grybauskaite Gintare , Bagdziunas Gintautas , Grazulevicius Juozas Vidas
Published: December 2015

In the title compound, C14H12BrN, the tricyclic ring system is essentially planar (r.m.s. deviation 0.026 Å). The carbon atoms of the ethyl group deviate from the mean plane by 0.148 (9) (CH2) and 1.59 (1) Å (CH3). In the crystal, H...π contacts [2.698–2.898 Å] shorter than the van der Waals contact distance of 3.70 Å are observed. A scalable to gram quantities selective synthesis of mono-bromine-substituted carbazole derivatives was developed.
Inter-organizational network configurations for ski areas innovations
Authors: Favre-Bonté Véronique , Gardet Elodie , Thevenard-Puthod Catherine
Published: December 2015

Purpose

– Unlike industrial innovations, service innovations cannot be protected by patents or designs. Thus, the implementation of innovation networks is often crucial to generate a sustainable competitive advantage. The focus in this paper is the main forms of inter-organizational networks that have led to service innovations. More precisely, the purpose of this paper is to examine the relationship between the characteristics of inter-organizational networks and the type of service innovations developed.

Design/methodology/approach

– A typology of service innovations and a network analysis framework allowed us to examine the innovations implemented by two major French ski areas: Portes du Soleil and Paradiski. In total, the authors analyse the structure of 12 innovation networks.

Findings

– The results show that, depending on the type of innovation implemented, networks differ in terms of type of partners involved and geographical scope. However, regardless of the innovation developed, it seems necessary to have a central actor to orchestrate the various partners and to use an economic regulation mode.

Practical implications

– This paper gives advice to managers involved in touristic innovations management about the network they may build. For example, ski resorts that want to develop new offers must be open to external partners (companies that do not belong to the tourism industry and/or are not geographically localized in the resort).

Originality/value

– The research documents characteristics of services innovation networks, a type of industry little studied as innovation researchers focused mainly on manufacturing firms.
Competitive advantage through innovation: the case of Nespresso
Authors: Brem Alexander , Maier Maximilian , Wimschneider Christine
Published: December 2015

Purpose

– The purpose of this paper is to describe how Nespresso achieved competitive advantage through innovation by changing the rules of the game in its industry.

Design/methodology/approach

– Nespresso was analyzed based on public available secondary data, in combination with related academic concepts on innovation and competitive advantage.

Findings

– The company succeeded by the thorough application of a strategy that, through perfect alignment, allowed the company to reach a unique market position. However, as described in the case, it took a relatively long time and the company came close to failure several times. Before the current situation of the company, it remains challenging in the future as well. Hence, the Nespresso story provides interesting space for discussion and learning about what innovation is, how innovation emerges, and under which circumstances innovation can serve as a source for competitive advantage.

Research limitations/implications

– Especially given the current market situation, the case offers different starting points for discussion about innovation and long-term company success.

Practical implications

– Especially before the current market situation, the case offers different starting points for discussion about innovation and the success of a company on the long term. The case is designed to give practitioners a better understanding on what an innovation as, and how competitive advantages can be linked to innovation.

Originality/value

– This case of Nespresso is a unique combination of the concepts of innovation and competitive advantage. It serves as an example of an innovation, which was not successful from the scratch, but evolved over time and is still developing. As many innovations went through such a non-linear process, this case offers interesting lessons learned for academics as well as for practitioners.
Regional Comparison of Foreign Direct Investment to Africa: Empirical Analysis
Authors: Anyanwu John C. , Yaméogo Nadège D.
Published: December 2015

This paper analyzed the factors that drive foreign direct investments (FDI) by looking at regional heterogeneity among the five African regions. For the first time, FDI drivers are analyzed for each of the five regions of Africa contrary to previous studies which focused on Africa as a whole. The paper used a panel dataset from 1970 to 2010 of 53 African countries divided into: Central, East, North, Southern, and West Africa. Ordinary least squares (OLS) and generalized method of moments (GMM) techniques are used for the estimations. The main results indicate that: (i) agglomeration has a strong positive relationship with FDI inflows in all the regions except Central Africa. However, in West Africa, the second lag of FDI is significantly negative; (ii) there is a negative relationship between FDI inflows and GDP per capita in all the five regions, but a U‐shaped relationship is observed in Central, North, and West Africa. But GDP growth rate has a strongly positive relationship with FDI inflows in Central Africa but negatively significant in West Africa; (iii) FDI follows domestic investment in East, Southern, and West Africa; (iv) democracy is a major factor in attracting FDI to Southern Africa, being upward concave; (v) infrastructure development has a positive impact on FDI inflows in East and North Africa; (vi) trade openness has a positive relationship with FDI inflows in all the five regions except in East Africa; (vii) inflation deters FDI inflows to East Africa; (viii) the level of urbanization has a strong positive relationship with FDI inflows only in West Africa; (ix) net foreign aid has a negative relationship with FDI inflows to East, North, and Southern Africa; (x) higher life expectancy deters FDI inflows to Central Africa but promotes the same to East and North Africa; (xi) metal production and exportation attract significant FDI to Central Africa while oil production and exportation attract higher FDI to West Africa; (xii) monetary union attracts greater FDI to Central and West Africa; and (xiii) political instability is a strong hindrance to FDI inflows to West Africa.
Access to Schooling and Staying in School in Selected Sub‐Saharan African Countries
Authors: Kuépié Mathias , Shapiro David , Tenikue Michel
Published: December 2015

This study jointly investigates factors driving the processes of accessing and staying in school in sub‐Saharan Africa. We explicitly account for the fact that staying in school or its converse, dropping out, is observed only among children who ever attend school. We use data from Demographic and Health Surveys from 12 countries. We find that access to school is typically lower for females, rural youth, and those from poorer households. Conditional on having ever attended school, these factors, as well as age in grade – an indicator of performance in school – typically help account for staying in school. We also find that keeping girls at school is very sensitive to school performance: girls with comparatively weak performance in school are more likely than their male counterparts to drop out of school, while girls who do relatively well in school are more likely to remain in school than boys, other things being equal.
Inclusive Human Development in Pre‐crisis Times of Globalization‐driven Debts
Authors: Asongu Simplice , Efobi Uchenna , Beecroft Ibukun
Published: December 2015

The paper verifies the Azzimonti et al. () conclusions on a sample of 53 African countries for the period 1996–2008. Authors of the underlying study have established theoretical underpinnings for a negative nexus between rising public debt and inequality in OECD nations. We assess the effects of four debt dynamics on Inequality Adjusted Human Development. Instrumental variable and interactive regressions were employed as empirical strategies. Two main findings were established which depend on whether debt is endogenous to or interactive with globalization. First, when external debt is endogenous to globalization, the effect on inclusive human development is negative, whereas when it is interactive with globalization, the effect is positive. This may reflect the false economics of preconditions. The magnitudes of negative estimates from endogenous related effects were higher than the positive marginal interactive effects. Policy implications were discussed in light of the post‐2015 development agenda.
Winning Friends, Influencing People: Soviet Cultural Diplomacy in Australia, 1928–1968
Authors: McNair John
Published: December 2015

This article draws on largely unpublished archive materials to examine the strategies employed by the USSR to manage its cultural relations with Australia as a means of extending its influence beyond its traditional supporters in trade union and socialist movements. The activities of key players like the All‐Union Society for Cultural Relations with Foreign Countries (VOKS), the Union of Soviet Friendship Societies (SSOD) and the International Commission of the Union of Soviet Writers and their interaction with Australian organizations and individuals identified and cultivated as contacts of influence are reviewed in the context of the changing international situation and an often problematic bilateral political relationship.
Civilisation: A Concept and its Uses in Australian Public Discourse
Authors: Berryman Jim
Published: December 2015

This article examines the concept of civilisation in Australian public discourse, focussing on some recent political uses. Rhetoric defending Australia's traditional attachment to Western civilisation has focussed on three themes — the role of the British heritage in Australian public life, the moral foundations of Australia's “Judeo‐Christian” belief system, and the rational principles of the Enlightenment. Although the language of civilisation is not confined to centre‐right political discourse, it has been most vocal among conservative‐leaning commentators. This article highlights examples of civilisation and its uses in the contemporary Australian context and attempts to give meaning to civilisation in light of debates about Australian history and national identity. I argue in the course of this article that civilisation is differentiated from culture, and that the culture‐civilisation distinction correlates with left‐right political leanings.
Dynamics of circulating tumor DNA represented by the activating and resistant mutations in epidermal growth factor receptor tyrosine kinase inhibitor treatment
Authors: Uchida Junji , Imamura Fumio , Kukita Yoji , Oba Shigeyuki , Kumagai Toru , Nishino Kazumi , Inoue Takako , Kimura Madoka , Kato Kikuya
Published: December 2015

Circulating tumor DNA (ctDNA) is an emerging field of cancer research. For lung cancer, non‐invasive genotyping of EGFR is the foremost application. The activating mutations represent the ctDNA from all cancer cells, and the T790M‐resistant mutation represents that from resistant cells. We examined the ctDNA dynamics of EGFR mutations by using deep sequencing with a massively parallel DNA sequencer. We obtained 190 plasma samples from 57 patients at various times during the treatment course and classified them according to treatment status. The mutation detection rate of exon 19 deletion/L858R in plasma was high at the initiation of treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI; P = 0.001), suppressed during EGFR‐TKI treatment before disease progression, and elevated after the onset of disease progression (P = 0.023). The mutation detection rate of T790M was low until the onset of disease progression and elevated thereafter (P = 0.01). Samples across the development of disease progression were obtained from 10 patients and showed a correlation between increased ctDNA level and disease progression. Decreased ctDNA level in response to the initiation of EGFR‐TKI was observed in 4 of 6 eligible patients. In two patients, the ctDNA dynamics suggested the presence of cancer cell populations only with the T790M mutation. In another patient, the T790M ctDNA represented cell subpopulations that respond to cytotoxic agents differently from the major population. Considering the high incidence, ctDNA could be a clinical parameter to complement information from image analyses.
Cyclic vomiting syndrome versus inborn errors of metabolism: A review with clinical recommendations
Authors: Gelfand Amy A. , Gallagher Renata C.
Published: December 2015

Background

Inborn errors of metabolism are on the differential for patients presenting with a cyclic vomiting syndrome phenotype. Classes of disorders to consider include: mitochondrial disorders, fatty acid oxidation disorders, urea cycle defects, organic acidurias, and acute intermittent porphyria.

Aim

This article reviews the metabolic differential diagnosis and approach to screening for inborn errors in children and adults presenting with a cyclic or recurrent vomiting phenotype.

Conclusion

Cyclic vomiting syndrome is thought to be an episodic syndrome that may be associated with migraine. It is a diagnosis of exclusion. Inborn errors of metabolism should be considered in the patient presenting with a recurrent vomiting phenotype. Mitochondrial dysfunction may play a role in cyclic vomiting syndrome, and true mitochondrial disorders can present with a true cyclic vomiting phenotype.
Clinical and histopathologic analysis of 46 cases of cutaneous adverse reactions to imatinib
Authors: Lee Woo Jin , Lee Ji Hyun , Won Chong Hyun , Chang Sung Eun , Choi Jee Ho , Moon Kee Chan , Kang Yoon‐Koo , Lee Mi Woo
Published: December 2015

Background

Although many cases of cutaneous adverse reactions to imatinib have been reported, their clinical and histopathologic characteristics are not well documented.

Objectives

The present study investigated clinical and histopathologic characteristics of cutaneous adverse reactions to imatinib.

Methods

This retrospective study referred to 46 patients who experienced cutaneous adverse reactions to imatinib. Clinical data including age, sex, skin lesion morphology, underlying disorders, and imatinib treatment parameters (duration of imatinib medication, initial dose, and treatment modifications at the time of the study) were collected. Histopathologic data were available for all patients.

Results

Cutaneous adverse reactions to imatinib developed at 1–24 weeks (median onset: 8 weeks) after imatinib administration. The severity of the reaction was categorized as grade 1 in 22%, grade 2 in 41%, and grade 3 in 37% of patients. Onset was earlier in high‐severity reactions than in low‐severity reactions. The severity of the reaction was dependent on imatinib dose. Grade 3 reactions were noted in nine of 16 (56%) patients administered “high‐dose” (600 mg/d) imatinib. Spongiosis (78% of patients) and papillary dermal edema (83% of patients) were common histopathologic findings in the epidermis and dermis, respectively. Lymphohistiocytes were more predominant than eosinophils in dermal inflammatory infiltration. Histopathologic findings did not differ according to dose of imatinib or severity of the reaction.

Conclusions

Although the clinical features of cutaneous adverse reactions to imatinib depend on imatinib dose and the severity of the reaction, histopathologic findings are not associated with these clinical variables.
Morphological Description and Molecular Phylogeny of Two Species of Levicoleps (Ciliophora, Prostomatida), L. taehwae nov. spec. and L. biwae jejuensis nov. subspec., collected in Korea
Authors: Chen Xiangrui , Shazib Shahed Uddin Ahmed , Kim Ji Hye , Jang Seok Won , Shin Mann Kyoon
Published: December 2015

Two colepid ciliates, Levicoleps taehwae nov. spec. and L. biwae jejuensis nov. subspec., were collected from the brackish water of the Taehwa River and a small freshwater pond in Jeju Island, South Korea, respectively. Their living morphology, infraciliature, and small subunit (SSU) rRNA gene sequences were determined using standard methods. Barrel‐shaped L. taehwae nov. spec. is a small ciliate with an average size of 45 × 25 μm in vivo, about 15 ciliary rows each composed of 12 monokinetids and two perioral dikinetids, and two 20 μm‐long caudal cilia. The sequence length and GC content of the SSU rRNA gene are 1,669 bp, 44.5%. This novel species is similar in body size to Coleps hirtus, and has six armor tiers and hirtus‐type tier plates, and the same number of ciliary rows as C. hirtus; however, it can be distinguished from the latter by the absence of armor spines and its sequence similarity of SSU rRNA gene is about 92.8% which indicates that it is a distinct form. Levicoleps biwae jejuensis nov. subspec., is a medium colepid ciliate which has a barrel‐shaped body, about 22 somatic kineties and 16 transverse ciliary rows, three mini adoral organelles, and four 15 μm‐long caudal cilia. The sequence length and GC content of the SSU rRNA gene are 1,666 bp and 44.4%.
Prevalence of celiac disease in Asia: A systematic review and meta‐analysis
Authors: Singh Prashant , Arora Shubhangi , Singh Alka , Strand Tor A , Makharia Govind K
Published: December 2015

Background and Aim

Celiac disease (CD) is emerging in Asia. While a few population‐based studies from Asia have reported a prevalence of CD from 0.1% to 1.3%, the exact prevalence of CD in Asia is not known. We conducted a systematic review and meta‐analysis to estimate the prevalence of CD in Asia.

Methods

On search of literature, we found 1213 articles, of which 18 articles were included. Diagnosis of CD was based on European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines.

Results

Pooled sero‐prevalence of CD in Asia was 1.6% in 47 873 individuals based on positive anti‐tissue transglutaminase and/or anti‐endomysial antibodies. Pooled prevalence of biopsy proven CD in Asia was 0.5% in 43 955 individuals. The prevalence of CD among women was higher than in men (0.5% vs 0.4%, P = 0.04). The pooled prevalence of CD was 0.3% in Iran, 0.5% in Turkey, 0.6% in India, and 0.7% in Israel. The pooled prevalence of CD was significantly higher in Israel and India as compared with that in Iran.

Conclusions

Celiac disease is not uncommon in Asia, and the sero‐prevalence and prevalence of CD in Asia are 1.6% and 0.5%, respectively. The prevalence of CD varies with gender and geographic location. There is a need for population‐based prevalence studies in many Asian countries to properly estimate the burden of CD in Asia.
Follicle‐stimulating hormone is associated with non‐alcoholic fatty liver disease in Chinese women over 55 years old
Authors: Wang Ningjian , Li Qin , Han Bing , Chen Yi , Zhu Chunfang , Chen Yingchao , Xia Fangzhen , Lu Meng , Meng Ying , Guo Yuyu , Ye Lin , Sui Chunhua , Kuang Lin , Lin Dongping , Lu Yingli
Published: December 2015

Background and Aim

Obesity and diabetes are related to non‐alcoholic fatty liver disease (NAFLD). A reduction in follicle‐stimulating hormone (FSH) is associated with obesity and diabetes in postmenopausal women. Thus, we aim to investigate whether FSH is associated with NAFLD in women over 55 who were postmenopausal with a high probability.

Methods

Our data were obtained from the 2014 Survey on Prevalence in East China for Metabolic Diseases and Risk Factors. A total of 1635 women at the age of 55–89 years were selected. The degrees of fatty liver were categorized into mild and moderate‐severe hepatic steatosis groups by ultrasonography. FSH and other sex hormones were measured by chemiluminescence.

Results

A total of 366 (22.4%) and 417 (25.5%) women had mild and moderate‐severe hepatic steatosis, respectively. FSH was negatively correlated with waist circumference, homeostasis model assessment of insulin resistance (HOMA‐IR), and other metabolic factors (all P < 0.05). After adjusting for age, estradiol, and total testosterone, increased quartiles of FSH were associated with significantly decreased odds ratios of mild and moderate‐severe groups (both P for trends <0.05). After further adjustment for waist circumference and HOMA‐IR, FSH was no longer associated with mild hepatic steatosis. The association of FSH with moderate‐severe hepatic steatosis was attenuated by waist circumference and HOMA‐IR but persisted in the fully adjusted model (P for trend <0.01).

Conclusion

Follicle‐stimulating hormone was negatively associated with NAFLD in women over 55 years old. Adiposity and insulin resistance explained most of the association of mild hepatic steatosis and partially explained the association of moderate‐severe hepatic steatosis with FSH.
Attenuated presenilin‐1 endoproteolysis enhances store‐operated calcium currents in neuronal cells
Authors: Ryazantseva Maria , Skobeleva Ksenia , Glushankova Lyubov , Kaznacheyeva Elena
Published: December 2015

Presenilins have been reported to regulate calcium homeostasis in the endoplasmic reticulum, and dysregulation of intracellular calcium has been implicated in the pathogenesis of Alzheimer's disease (AD). Reduced endoproteolysis levels of presenilin‐1 (PS1) have been detected in postmortem brains of patients carrying familial Alzheimer's disease PS1 mutations. This study deals with the effect of attenuated endoproteolysis of PS1 on store‐operated calcium (SOC) entry in neuronal cells and mouse fibroblasts with double knockouts of PS1 and PS2. Significant enhancement of SOC channel activation has been detected by electrophysiological measurements in cells with reduced PS1 endoproteolysis. The increase in SOC entry was not accompanied by any changes in protein levels of channels subunits or stromal interaction molecule. These data are important for understanding the role of PS1 in AD, apart from its involvement in γ‐secretase cleavage of amyloid precursor protein into Aβ. Taking into account that most of familial AD‐connected mutations in PS1 are loss‐of‐function, the observed effects may well be general for familial AD.

image

Reduced endoproteolysis levels of presenilin‐1 (PS1) have been detected in postmortem brains of patients carrying familial Alzheimer's disease PS1 mutations. Significant enhancement of SOC channel activation has been detected by electrophysiological measurements in cells with reduced PS1 endoproteolysis. The data obtained shed light on Alzheimer's disease pathogenesis and implicates to the future drugs development.
Neurosteroidogenesis Today: Novel Targets for Neuroactive Steroid Synthesis and Action and Their Relevance for Translational Research
Authors: Porcu P. , Barron A. M. , Frye C. A. , Walf A. A. , Yang S.‐Y. , He X.‐Y. , Morrow A. L. , Panzica G. C. , Melcangi R. C.
Published: December 2015

Neuroactive steroids are endogenous neuromodulators synthesised in the brain that rapidly alter neuronal excitability by binding to membrane receptors, in addition to the regulation of gene expression via intracellular steroid receptors. Neuroactive steroids induce potent anxiolytic, antidepressant, anticonvulsant, sedative, analgesic and amnesic effects, mainly through interaction with the GABAA receptor. They also exert neuroprotective, neurotrophic and antiapoptotic effects in several animal models of neurodegenerative diseases. Neuroactive steroids regulate many physiological functions, such as the stress response, puberty, the ovarian cycle, pregnancy and reward. Their levels are altered in several neuropsychiatric and neurological diseases and both preclinical and clinical studies emphasise a therapeutic potential of neuroactive steroids for these diseases, whereby symptomatology ameliorates upon restoration of neuroactive steroid concentrations. However, direct administration of neuroactive steroids has several challenges, including pharmacokinetics, low bioavailability, addiction potential, safety and tolerability, which limit its therapeutic use. Therefore, modulation of neurosteroidogenesis to restore the altered endogenous neuroactive steroid tone may represent a better therapeutic approach. This review summarises recent approaches that target the neuroactive steroid biosynthetic pathway at different levels aiming to promote neurosteroidogenesis. These include modulation of neurosteroidogenesis through ligands of the translocator protein 18 kDa and the pregnane xenobiotic receptor, as well as targeting of specific neurosteroidogenic enzymes such as 17β‐hydroxysteroid dehydrogenase type 10 or P450 side chain cleavage. Enhanced neurosteroidogenesis through these targets may be beneficial not only for neurodegenerative diseases, such as Alzheimer's disease and age‐related dementia, but also for neuropsychiatric diseases, including alcohol use disorders.
Same molecule but different expression: aging and sepsis trigger NLRP3 inflammasome activation, a target of melatonin
Authors: Volt Huayqui , García José A. , Doerrier Carolina , Díaz‐Casado María E. , Guerra‐Librero Ana , López Luis C. , Escames Germaine , Tresguerres Jesús A. , Acuña‐Castroviejo Darío
Published: December 2015

The connection between the innate immune system, clock genes, and mitochondrial bioenergetics was analyzed during aging and sepsis in mouse heart. Our results suggest that the sole NF‐κB activation does not explain the inflammatory process underlying aging; the former also triggers the NLRP3 inflammasome that enhances caspase‐1‐dependent maturation of IL‐1β. In this way, aged mice enter into a vicious cycle as IL‐1β further activates the NF‐κB/NLRP3 inflammasome link. The origin of NF‐κB activation was related to the age‐dependent Bmal1/Clock/RORα/Rev‐Erbα loop disruption, which lowers NAD+ levels, reducing the SIRT1 deacetylase ability to inactivate NF‐κB. Consequently, NF‐κB binding to DNA increases, raising the formation of proinflammatory mediators and inducing mitochondrial impairment. The cycle is then closed with the subsequent NLRP3 inflammasome activation. This paired contribution of the innate immune pathways serves as a catalyst to magnify the response to sepsis in aged compared with young mice. Melatonin administration blunted the septic response, reducing inflammation and oxidative stress, and enhancing mitochondrial function at the levels of nonseptic aged mice, but it did not counteract the age‐related inflammation. Together, our results suggest that, although with different strengths, chronoinflammaging constitutes the biochemical substrate of aging and sepsis, and identifies the NLRP3 inflammasome as a new molecular target for melatonin, providing a rationale for its use in NLRP3‐dependent diseases.
Glutathione‐dependent induction of local and systemic defense against oxidative stress by exogenous melatonin in cucumber (Cucumis sativus L.)
Authors: Li Hao , He Jie , Yang Xiaozhen , Li Xin , Luo Dan , Wei Chunhua , Ma Jianxiang , Zhang Yong , Yang Jianqiang , Zhang Xian
Published: December 2015

Melatonin is involved in defending against oxidative stress caused by various environmental stresses in plants. In this study, the roles of exogenous melatonin in regulating local and systemic defense against photooxidative stress in cucumber (Cucumis sativus) and the involvement of redox signaling were examined. Foliar or rhizospheric treatment with melatonin enhanced tolerance to photooxidative stress in both melatonin‐treated leaves and untreated systemic leaves. Increased melatonin levels are capable of increasing glutathione (reduced glutathione [GSH]) redox status. Application of H2O2 and GSH also induced tolerance to photooxidative stress, while inhibition of H2O2 accumulation and GSH synthesis compromised melatonin‐induced local and systemic tolerance to photooxidative stress. H2O2 treatment increased the GSH/oxidized glutathione (GSSG) ratio, while inhibition of H2O2 accumulation prevented a melatonin‐induced increase in the GSH/GSSG ratio. Additionally, inhibition of GSH synthesis blocked H2O2‐induced photooxidative stress tolerance, whereas scavenging or inhibition of H2O2 production attenuated but did not abolish GSH‐induced tolerance to photooxidative stress. These results strongly suggest that exogenous melatonin is capable of inducing both local and systemic defense against photooxidative stress and melatonin‐enhanced GSH/GSSG ratio in a H2O2‐dependent manner is critical in the induction of tolerance.
Efficacy evaluation of clonazepam for symptom remission in burning mouth syndrome: a meta‐analysis
Authors: Cui Y , Xu H , Chen FM , Liu JL , Jiang L , Zhou Y , Chen QM
Published: December 2015

Objectives

Clonazepam has been used in the treatment of burning mouth syndrome (BMS) for several decades. We conducted a meta‐analysis to investigate the efficacy of clonazepam in the treatment of BMS.

Methods

We conducted a search of the PubMed, MEDLINE, EMBASE, Web of Science (TS), and the Cochrane Library databases for relevant studies that met our eligibility criteria (up to September 22, 2015). Statistical analyses were conducted using RevMan 5.2 and STATA 11.0 software.

Results

Three randomized controlled trials (RCTs) and two high‐quality case–control studies involving 195 BMS patients were selected for this study. Our results show that clonazepam can reduce the oral pain sensation in patients with BMS (WMD: −3.72, 95% CI: −4.57, −2.86; P < 0.05; for all five studies). A positive therapeutic effect was demonstrated for both short‐term (≤10 weeks) application (WMD: −1.44, 95% CI: −2.06, −0.82; P < 0.05) and long‐term (>10 weeks) application (WMD: −4.50, 95% CI: −4.98, −4.03; P < 0.05). Both topical (WMD: −1.50, 95% CI: −2.14, −0.85; P < 0.05) and systemic (WMD: −3.81, 95% CI: −4.63, −2.98; P < 0.05) administration of clonazepam were confirmed to be effective.

Conclusion

Clonazepam is effective in inducing symptom remission in patients with BMS.
Psychological disorders and oral lichen planus: matched case–control study and literature review
Authors: Pippi R , Romeo U , Santoro M , Del Vecchio A , Scully C , Petti S
Published: December 2015

Objective

Oral lichen planus (OLP) may be linked to psychological disorders. This study investigated psychological factors associated with OLP.

Methods

A case–control study with incident OLP case patients and age–gender–socio‐economic status‐matched controls, recruited from among relatives, accompanying persons, and departmental staff, investigated psychological traits using the Psychological General Well‐Being Index‐Short form. Common factor analysis was used to generate a set of psychological dimensions. The association between these dimensions and OLP adjusted for confounders (education, number of lifetime sexual partners, drinking–smoking) and interactions was assessed through conditional logistic regression and odds ratios (OR) were estimated.

Results

A total of 67 case–control pairs were recruited. Psychological dimensions generated were: dimension‐1 (anxiety, low vitality), dimension‐2 (negative well‐being, low vitality), dimension‐3 (depressed mood, low self‐control). The ORs for OLP were, dimension‐1, 1.0 (95% confidence interval ‐95CI, 0.3–2.6); dimension‐2, 0.5 (95CI, 0.2–1.2); dimension‐3, 4.8 (95CI, 1.8–12.9). Dimension‐3 was highly associated with mild, but not associated with severe, OLP. Literature searching provided 21 studies, with anxiety and depression principally associated with OLP.

Conclusions

Depressed mood and low self‐control were highly associated with OLP, particularly the reticular–papular forms. These traits could have a causative role in OLP development‐progression, but further investigations are necessary.
Patient quality of life following induction of oral immunotherapy for food allergy
Authors: Epstein Rigbi Na'ama , Katz Yitzhak , Goldberg Michael R. , Levy Michael B. , Nachshon Liat , Elizur Arnon
Published: December 2015

Background

Patient quality of life improves following successful completion of oral immunotherapy (OIT), but the process itself might have undesirable effects. We aimed to evaluate patient quality of life following OIT initial induction.

Methods

The Hebrew version of the Food Allergy Quality of Life Questionnaire‐Parental Form (FAQLQ‐PF) was validated and administered to the parents of children following the first week of OIT for food allergy (n = 119). Patient demographics and clinical history as well as the course of initial induction week were reviewed.

Results

Pre‐OIT severity of food allergy, defined as severity of reactions due to accidental exposure to the allergenic food (anaphylactic reactions, p = 0.017; epinephrine use, p = 0.049; emergency room referrals p = 0.003; and hospital admissions, p = 0.015) and a lower number of tolerated doses during initial induction, reflective of a lower maximal tolerated dose for the different allergens (p = 0.011) were associated with worse total FAQLQ‐PF scores. The number of tolerated doses during induction and pre‐OIT emergency room referrals remained significantly associated with worse total score of the FAQLQ‐PF on multivariate analysis (p = 0.016 and p = 0.005, respectively). The correlation between the number of tolerated doses and quality of life scores was moderate–strong primarily in children aged 6–12 years (Total score, r = −0.41, p = 0.001; Emotional Impact r = −0.42, p = 0.001; Food Anxiety, r = −0.38, p = 0.002; Social and Dietary Limitations, r = −0.33, p = 0.009).

Conclusions

Pre‐OIT reaction severity affects quality of life in both preschool and school‐aged food‐allergic children. In contrast, a lower maximal tolerated dose during OIT induction is associated with worse indices of quality of life primarily in children aged 6–12 years.
Four receptor‐like cytoplasmic kinases regulate development and immunity in rice
Authors: Zhou Xiaogang , Wang Jing , Peng Chunfang , Zhu Xiaobo , Yin Junjie , Li Weitao , He Min , Wang Jichun , Chern Mawsheng , Yuan Can , Wu Wenguan , Ma Weiwei , Qin Peng , Ma Bintian , Wu Xianjun , Li Shigui , Ronald Pamela , Chen Xuewei
Published: December 2015

Receptor‐like cytoplasmic kinases (RLCKs) represent a large family of proteins in plants. However, few RLCKs have been well characterized. Here, we report the functional characterization of four rice RLCKs – OsRLCK57, OsRLCK107, OsRLCK118 and OsRLCK176 from subfamily VII. These OsRLCKs interact with the rice brassinosteroid receptor, OsBRI1 in yeast cell, but not the XA21 immune receptor. Transgenic lines silenced for each of these genes have enlarged leaf angles and are hypersensitive to brassinolide treatment compared to wild type rice. Transgenic plants silenced for OsRLCK57 had significantly fewer tillers and reduced panicle secondary branching, and lines silenced for OsRLCK107 and OsRLCK118 produce fewer seeds. Silencing of these genes decreased Xa21 gene expression and compromised XA21‐mediated immunity to Xanthomonas oryzae pv. oryzae. Our study demonstrates that these OsRLCKs negatively regulate BR signalling, while positively regulating immune responses by contributing to the expression of the immune receptor XA21.
Incomplete Kawasaki disease in a 12‐month‐old girl presenting with cardiac murmur and iron deficiency anemia
Authors: Choi Yunjung , Eun Lucy Youngmin , Oh Seung Hwan
Published: December 2015

Kawasaki disease (KD) is an acute necrotizing vasculitis that occurs in children <5 years of age. The cause of KD remains unknown, but various complications, including dilatation of the coronary arteries, can occur. Coronary artery aneurysm or ectasia are the most important complications of KD. Children with suspected KD who do not fulfill the diagnostic criteria may have incomplete KD. Given that incomplete KD is associated with delayed diagnosis and treatment, children with incomplete KD have a high risk of cardiovascular complications. Meanwhile, iron deficiency anemia (IDA) is one of the most prevalent micronutrient deficiencies in the world. Children with IDA are prone to infection and inflammation. We report the case of a 12‐month‐old girl with incomplete KD who presented with cardiac murmur and severe IDA.
The Backyard Politics of Attitudes Toward Immigration
Authors: Ostfeld Mara
Published: December 2015

Using two survey experiments, I reconsider the role that the racialized physical traits and level of assimilation of salient immigrants play in shaping attitudes toward immigration. In the first experiment, a nationwide sample of 767 White, non‐Latino adults was exposed to a story about a family of undocumented immigrants living in the Unites States who were at risk of deportation. Subjects were randomly assigned to view a version of the story in which the immigrants were depicted with light skin and stereotypically Eurocentric features, or dark skin and stereotypically Afrocentric features, and their level of assimilation to mainstream American culture was suggested to be high or low. Similar to previous research, the study's results show that assimilation has a direct effect on attitudes toward immigration. Yet in contrast to previous studies, the racialized physical traits proved to be a much more important factor in shaping attitudes toward immigration than previously demonstrated. The role of an immigrant's racialized physical traits was replicated in a second survey experiment of 902 White, non‐Latino adults. Overall, the findings shed new light on how media depictions of immigrants are affecting immigration attitudes, as well as the nuanced ways that race continues to shape public opinion in the United States today.
Neurological damage disrupts normal sex differences in psychophysiological responsiveness to music
Authors: Belfi Amy M. , Chen Kuan‐Hua , Schneider Brett , Tranel Daniel
Published: December 2015

Men and women often display different physiological responses to emotional stimuli, and these responses can be affected by brain damage. Here, we investigated how brain damage differentially affects electrodermal responses based on sex. We studied neurologically normal, healthy adults and a sample of neurological patients. Participants listened to music, an emotional stimulus that reliably elicits skin conductance responses (SCRs). Electrodermal activity was recorded while participants listened to musical clips. When analyzing the data without regard to sex, there were no differences between healthy and brain‐damaged participants in their SCRs. However, we found a significant interaction between brain injury status and sex. For men, brain damage significantly reduced SCRs. For women, there were no differences between brain‐damaged participants and neurologically healthy participants. These findings illustrate the importance of including demographic variables, such as sex, when investigating brain‐behavior relationships with a psychophysiological dependent variable.
Ethnic/racial differences in the association between social support and levels of C‐reactive proteins in the North Texas Heart Study
Authors: Uchino Bert N. , Ruiz John M. , Smith Timothy W. , Smyth Joshua M. , Taylor Daniel J. , Allison Matthew , Ahn Chul
Published: December 2015

Perceived social support has been reliably related to lower rates of morbidity and mortality. However, studies modeling C‐reactive protein (CRP) as an important biological pathway linking social support to health have produced inconsistent results. Given purported ethnic/racial differences in sensitivity to social resources, the present study tested if ethnicity/race moderated the link between perceived support and CRP in a diverse community sample of 300 participants from the North Texas Heart Study. Consistent with prior research, there was no overall link between social support and CRP levels. However, the association between social support and high sensitivity (hs)‐CRP levels was moderated by ethnicity/race as perceived support predicted lower hs‐CRP levels primarily in African Americans. These results suggest the importance of considering how ethnicity/race may inform models on the complex biological mechanisms linking social support to health.