bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of Next-Generation G Protein–Coupled Receptor Drugs: Linking Novel Pharmacology and In Vivo Animal Models
Authors: Bradley Sophie J. , Tobin Andrew B.
Published: January 2016

Despite the fact that G protein–coupled receptors (GPCRs) are the most successful drug targets in history, this supergene family of cell surface receptors has yet to be fully exploited as targets in the treatment of human disease. Here, we present optimism that this may change in the future by reviewing the substantial progress made in the understanding of GPCR molecular pharmacology that has generated an extensive toolbox of ligand types that include orthosteric, allosteric, and bitopic ligands, many of which show signaling bias. We discuss how combining these advances with recently described transgenic, chemical genetic, and optogenetic animal models will provide the framework to allow for the rational design of next-generation GPCR drugs that possess increased therapeutic efficacy and decreased adverse/toxic responses.
Exendin-4 induces myocardial protection through MKK3 and Akt-1 in infarcted hearts
Authors: Du Jianfeng , Zhang Ling , Wang Zhengke , Yano Naohiro , Zhao Yu Tina , Wei Lei , Dubielecka-Szczerba Patrycja , Liu Paul Y. , Zhuang Shougang , Qin Gangjian , Zhao Ting C.
Published: January 2016

We have demonstrated that glucagon like peptide-1 (GLP-1) protects the heart against ischemic injury. However, the physiological mechanism by which GLP-1 receptor (GLP-1R) initiates cardioprotection remains to be determined. The objective of this study is to elucidate the functional roles of MAPK kinase 3 (MKK3) and Akt-1 in mediating exendin-4-elicited protection in the infarcted hearts. Adult mouse myocardial infarction (MI) was created by ligation of the left descending artery. Wild-type, MKK3−/−, Akt-1−/−, and Akt-1−/−;MKK3−/− mice were divided into one of several groups: 1) sham: animals underwent thoracotomy without ligation; 2) MI: animals underwent MI and received a daily dose of intraperitoneal injection of vehicle (saline); 3) MI + exendin-4: infarcted mice received daily injections of exendin-4, a GLP-1R agonist (0.1 mg/kg, ip). Echocardiographic measurements indicate that exendin-4 treatment resulted in the preservation of ventricular function and increases in the survival rate, but these effects were diminished in MKK3−/−, Akt-1−/−, and Akt-1−/−;MKK3−/− mice. Exendin-4 treatments suppressed cardiac hypotrophy and reduced scar size and cardiac interstitial fibrosis, respectively, but these beneficial effects were lost in genetic elimination of MKK3, Akt-1, or Akt-1−/−;MKK3−/− mice. GLP-1R stimulation stimulated angiogenic responses, which were also mitigated by deletion of MKK3 and Akt-1. Exendin-4 treatment increased phosphorylation of MKK3, p38, and Akt-1 at Ser129 but decreased levels of active caspase-3 and cleaved poly (ADP-ribose) polymerase; these proteins were diminished in MKK3−/−, Akt-1−/−, and Akt-1−/−;MKK3−/− mice. These results reveal that exendin-4 treatment improves cardiac function, attenuates cardiac remodeling, and promotes angiogenesis in the infarcted myocardium through MKK3 and Akt-1 pathway.
Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing
Authors: Rukov Jakob L. , Gravesen Eva , Mace Maria L. , Hofman-Bang Jacob , Vinther Jeppe , Andersen Claus B. , Lewin Ewa , Olgaard Klaus
Published: January 2016

The development of vascular calcification (VC) in chronic uremia (CU) is a tightly regulated process controlled by factors promoting and inhibiting mineralization. Next-generation high-throughput RNA sequencing (RNA-seq) is a powerful and sensitive tool for quantitative gene expression profiling and the detection of differentially expressed genes. In the present study, we, for the first time, used RNA-seq to examine rat aorta transcriptomes from CU rats compared with control rats. Severe VC was induced in CU rats, which lead to extensive changes in the transcriptional profile. Among the 10,153 genes with an expression level of >1 reads/kilobase transcript/million mapped reads, 2,663 genes were differentially expressed with 47% upregulated genes and 53% downregulated genes in uremic rats. Significantly deregulated genes were enriched for ontologies related to the extracellular matrix, response to wounding, organic substance, and ossification. The individually affected genes were of relevance to osteogenic transformation, tissue calcification, and Wnt modulation. Downregulation of the Klotho gene in uremia is believed to be involved in the development of VC, but it is debated whether the effect is caused by circulating Klotho only or if Klotho is produced locally in the vasculature. We found that Klotho was neither expressed in the normal aorta nor calcified aorta by RNA-seq. In conclusion, we demonstrated extensive changes in the transcriptional profile of the uremic calcified aorta, which were consistent with a shift in phenotype from vascular tissue toward an osteochondrocytic transcriptome profile. Moreover, neither the normal vasculature nor calcified vasculature in CU expresses Klotho.
Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State
Authors: Patricelli Matthew P. , Janes Matthew R. , Li Lian-Sheng , Hansen Rasmus , Peters Ulf , Kessler Linda V. , Chen Yuching , Kucharski Jeff M. , Feng Jun , Ely Tess , Chen Jeffrey H. , Firdaus Sarah J. , Babbar Anjali , Ren Pingda , Liu Yi
Published: January 2016

KRAS gain-of-function mutations occur in approximately 30% of all human cancers. Despite more than 30 years of KRAS-focused research and development efforts, no targeted therapy has been discovered for cancers with KRAS mutations. Here, we describe ARS-853, a selective, covalent inhibitor of KRASG12C that inhibits mutant KRAS–driven signaling by binding to the GDP-bound oncoprotein and preventing activation. Based on the rates of engagement and inhibition observed for ARS-853, along with a mutant-specific mass spectrometry–based assay for assessing KRAS activation status, we show that the nucleotide state of KRASG12C is in a state of dynamic flux that can be modulated by upstream signaling factors. These studies provide convincing evidence that the KRASG12C mutation generates a “hyperexcitable” rather than a “statically active” state and that targeting the inactive, GDP-bound form is a promising approach for generating novel anti-RAS therapeutics.

Significance: A cell-active, mutant-specific, covalent inhibitor of KRASG12C is described that targets the GDP-bound, inactive state and prevents subsequent activation. Using this novel compound, we demonstrate that KRASG12C oncoprotein rapidly cycles bound nucleotide and responds to upstream signaling inputs to maintain a highly active state. Cancer Discov; 6(3); 316–29. ©2016 AACR.

See related commentary by Westover et al., p. 233.

This article is highlighted in the In This Issue feature, p. 217
The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV) Infected Glioblastoma Cells
Authors: Tseliou Melpomeni , Al-Qahtani Ahmed , Alarifi Saud , Alkahtani Saad H. , Stournaras Christos , Sourvinos George
Published: January 2016

Background/Aims: Rho GTPases are crucial regulators of the actin cytoskeleton, membrane trafficking and cell signaling and their importance in cell migration and invasion is well- established. The human cytomegalovirus (HCMV) is a widespread pathogen responsible for generally asymptomatic and persistent infections in healthy people. Recent evidence indicates that HCMV gene products are expressed in over 90% of malignant type glioblastomas (GBM). In addition, the HCMV Immediate Early-1 protein (IE1) is expressed in >90% of tumors analyzed. Methods: RhoA, RhoB and RhoC were individually depleted in U373MG glioblastoma cells as well as U373MG cells stably expressing the HCMV IE1 protein (named U373MG-IE1 cells) shRNA lentivirus vectors. Cell proliferation assays, migration as well as wound-healing assays were performed in uninfected and HCMV-infected cells. Results: The depletion of RhoA, RhoB and RhoC protein resulted in significant alterations in the morphology of the uninfected cells, which were further enhanced by the cytopathic effect caused by HCMV. Furthermore, in the absence or presence of HCMV, the knockdown of RhoB and RhoC proteins decreased the proliferation rate of the parental and the IE1-expressing glioblastoma cells, whereas the knockdown of RhoA protein in the HCMV infected cell lines restored their proliferation rate. In addition, wound healing assays in U373MG cells revealed that depletion of RhoA, RhoB and RhoC differentially reduced their migration rate, even in the presence or the absence of HCMV. Conclusion: Collectively, these data show for the first time a differential implication of Rho GTPases in morphology, proliferation rate and motility of human glioblastoma cells during HCMV infection, further supporting an oncomodulatory role of HCMV depending on the Rho isoforms' state.
Cerebral and Cutaneous Involvements of Xanthoma Disseminatum Successfully Treated with an Interleukin-1 Receptor Antagonist: A Case Report and Minireview
Authors: Campero Mario , Campero Sebastián , Guerrero Julia , Aouba Achille , Castro Alex
Published: January 2016

A young male presented with panhypopituitarism (including diabetes insipidus) and temporal lobe epilepsy. A histology specimen of cutaneous papules was diagnostic of non-Langerhans histiocytosis. The diagnosis of xanthoma granulomata was considered based on the clinical and brain MRI findings. Brain lesions significantly worsened over time despite radiotherapy until anakinra induced a complete clinical and radiological remission of all active lesions. Although a single case, the outcome of this patient with xanthoma disseminatum treated with an interleukin-1 receptor antagonist opens and strengthens new and recent physiopathogenic and treatment perspectives for the otherwise difficult-to-treat non-Langerhans cell histiocytosis. Similar results with anakinra have been observed in patients with Erdheim-Chester disease and in multicentric reticulohistiocytosis.
Successful Treatment of Dual-Positive Anti-Myeloperoxidase and Anti-Glomerular Basement Membrane Antibody Vasculitis with Pulmonary-Renal Syndrome
Authors: Huang Jinxian , Wu Ling , Huang Xiaoyan , Xie Yan , Yu Jinquan , Yang Jin , Fang Huiqiong , Zhang Lijun
Published: January 2016

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and anti-glomerular basement membrane (GBM) disease are two separate diseases, while sometimes they can coexist together. The exact mechanisms are not clear, but due to the rapid progression and poor prognosis, prompt and aggressive treatment is usually required. We treated with steroids combined with cyclophosphamide and rituximab an 84-year-old man with ANCA-associated vasculitis and anti-GBM disease who had prior pulmonary fibrosis and a coexisting anterosuperior mediastinal mass. Conventional therapy including steroids, plasmapheresis and cyclophosphamide failed to attenuate the anti-GBM disease, yet he responded to an alternative treatment of rituximab. This case suggests the efficacy of steroids and immunosuppressant for the treatment of a dual-positive case with an anterosuperior mediastinal mass.
Scald-Induced Necrobiosis Lipoidica in a Patient with Diabetes Mellitus and Psoriasis
Authors: Ito Hoshiko , Imamura Sadao
Published: January 2016

The Koebner phenomenon (KP) was first introduced by Heinrich Koebner in the 1870s to describe the appearance of psoriatic lesions following trauma in psoriasis patients. KP has since been defined in numerous diseases, including necrobiosis lipoidica diabeticorum (NLD). Since most Koebnerized dermatological lesions can localise to a site of previous trauma, Weiss et al. (Eur Acad Dermatol Venereol 2002;16:241-248) classified them into four categories (I-IV) according to the Boyd-Nelder classification (Int J Dermatol 1990;29:401-410) system. In this system, necrobiosis lipoidica is classified as category III, which includes diseases that occasionally localise at the site of trauma. We report a case of NLD that developed after scald in a psoriasis patient. NLD after trauma has often been reported, but this is the first case of NLD that coincidentally occurred at a scald site in a psoriasis patient.
Peripheral Ulcerative Keratitis following Laser in situ Keratomileusis
Authors: Burkholder Bryn M. , Kuo Irene C.
Published: January 2016

Purpose: We report a case of a patient with a history of glomerulonephropathy, not disclosed prior to laser in situ keratomileusis (LASIK), who developed severe postoperative peripheral ulcerative keratitis (PUK) soon after surgery. Method: Case report. Results: Within a week of surgery, the patient, who had no blepharitis or ocular surface disease, also developed diffuse lamellar keratitis (DLK) that was not contiguous with the PUK. Microbiologic evaluation of the flap interface disclosed no organisms, and no epithelial ingrowth was found. Both PUK and DLK resolved with topical and oral steroid therapy, and the patient's induced refractive error improved over the 12 months following LASIK. Conclusions: Necrotizing keratitis has been described after LASIK surgery in patients with or without autoimmune disease. However, to our knowledge, there has been no case of PUK following LASIK. As shown by our patient's clinical course and the typical association of PUK with systemic conditions, patients with a history of atypical postinfectious sequelae may require additional preoperative counseling, vigilant postoperative monitoring, and possibly additional intervention. Because patients do not always divulge medical details, especially if an extraocular site was involved or illness occurred many years prior, this case demonstrates the importance of performing a diligent history that excludes autoimmune disorders or atypical postinfectious sequelae prior to proceeding with keratorefractive intervention.
Ankle-Brachial Index and cardiovascular events in atrial fibrillation
Authors: Davi Giovanni , Proietti Marco , Pastori Daniele , Hiatt William R. , Corazza Gino Roberto , Perticone Francesco , Pignatelli Pasquale , Farcomeni Alessio , Vestri Anna Rita , Lip Gregory Y. H. , Basili Stefania , Violi Francesco ,   The ARAPACIS (Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study) STUDY Investigators
Published: January 2016

Atrial fibrillation (AF) patients are at high risk for thrombotic and vascular events related to their cardiac arrhythmia and underlying systemic atherosclerosis. Ankle-Brachial Index (ABI) is a non-invasive tool in evaluating systemic atherosclerosis, useful in predicting cardiovascular events in general population; no data are available in AF patients. ARAPACIS is a prospective multicentre observational study performed by the Italian Society of Internal Medicine, analysing association between low ABI (≤0.90) and vascular events in NVAF out- or in-patients, enrolled in 136 Italian centres. A total of 2,027 non-valvular AF (NVAF) patients aged > 18 years from both sexes followed for a median time of 34.7 (interquartile range: 22.0–36.0) months, yielding a total of 4,614 patient-years of observation. Mean age was 73 ± 10 years old with 55% male patients. A total of 176 patients (8.7%) experienced a vascular event, with a cumulative incidence of 3.81%/patient-year. ABI≤ 0.90 was more prevalent in patients with a vascular event compared with patients free of vascular events (32.2 vs 20.2%, p< 0.05). On Cox proportional hazard analysis, ABI≤ 0.90 was an independent predictor of vascular events (hazard ratio (HR): 1.394, 95% confidence interval (CI): 1.042–1.866; p=0.02), vascular death (HR: 2.047, 95% CI: 1.255-3.338; p=0.004) and MI (HR: 2.709, 95%> CI: 1.485-5.083; p=0.001). This latter association was also confirmed after excluding patients with previous MI (HR: 2.901, 95% CI: 1.408-5.990, p=0.004). No association was observed between low ABI and stroke/transient ischaemic attack (p=0.91). In conclusion, low ABI is useful to predict MI and vascular death in NVAF patients and may independently facilitate cardiovascular risk assessment in NVAF patients.

Note: The review process for this paper was fully handled by C. Weber, Editor in Chief.

Listed in the Supplementary Online Appendix Material which is available online at www.thrombosis-online.com.
Effectiveness of prognosticating pulmonary embolism using the ESC algorithm and the Bova score
Authors: Lobo Jose Luis , Fernandez-Golfin Covadonga , Portillo Ana K. , Nieto Rosa , Lankeit Mareike , Konstantinides Stavros , Prandoni Paolo , Muriel Alfonso , Yusen Roger D. , Jimenez David ,   the PROTECT investigators
Published: January 2016

The prognostic value of the European Society of Cardiology (ESC) 2014 algorithm and the Bova score has lacked adequate validation. According to the ESC 2014 guidelines and the Bova score, we retrospectively risk stratified normotensive patients with PE who were enrolled in the PROTECT study. This study used a complicated course (which consisted of death from any cause, haemodynamic collapse, or recurrent PE) as the primary endpoint, and follow-up occurred through 30 days after the PE diagnosis. Of 848 patients, 37 % had a sPESI of 0 and 5 (1.6 %; 95 % confidence interval [CI], 0.5-3.7 %) experienced a complicated course. Of 143 patients with a sPESI of 0 points and negative computed tomographic pulmonary angiography (CTPA) for right ventricle (RV) dysfunction, three (2.1 %; 95 % CI, 0.4-6.0 %) experienced a complicated course. Four hundred seventy-eight (56 %) patients with a sPESI ≥ 1 had echocardiographic evidence of RV dysfunction or elevated troponin level or none, and 48 (10 %, 95 % CI, 7.5-13.1 %) experienced a complicated course. Fifty-seven (6.7 %) patients with a sPESI ≥ 1 had echocardiographic RV dysfunction and elevated troponin level, and 10 (17.5 %; 95 % CI, 8.8-29.9 %) experienced a complicated course, compared to 21.6 % (8 of 37 patients, 21.6 %; 95 % CI, 9.8-38.2 %) in Bova risk class III. In conclusion, the ESC 2014 prognostic algorithm is effective in the risk stratification of normotensive patients with PE. Use of CTPA did not improve the ability for identification of low-risk PE. Bova risk scoring did not significantly improve identification of intermediate-high risk PE.

Jiménez et al. Validation of the ESC 2014 prognostication algorithm
The Human Microcirculation
Authors: Gutterman David D. , Chabowski Dawid S. , Kadlec Andrew O. , Durand Matthew J. , Freed Julie K. , Ait-Aissa Karima , Beyer Andreas M.
Published: January 2016

The microcirculation is responsible for orchestrating adjustments in vascular tone to match local tissue perfusion with oxygen demand. Beyond this metabolic dilation, the microvasculature plays a critical role in modulating vascular tone by endothelial release of an unusually diverse family of compounds including nitric oxide, other reactive oxygen species, and arachidonic acid metabolites. Animal models have provided excellent insight into mechanisms of vasoregulation in health and disease. However, there are unique aspects of the human microcirculation that serve as the focus of this review. The concept is put forth that vasculoparenchymal communication is multimodal, with vascular release of nitric oxide eliciting dilation and preserving normal parenchymal function by inhibiting inflammation and proliferation. Likewise, in disease or stress, endothelial release of reactive oxygen species mediates both dilation and parenchymal inflammation leading to cellular dysfunction, thrombosis, and fibrosis. Some pathways responsible for this stress-induced shift in mediator of vasodilation are proposed. This paradigm may help explain why microvascular dysfunction is such a powerful predictor of cardiovascular events and help identify new approaches to treatment and prevention.
From C-Reactive Protein to Interleukin-6 to Interleukin-1
Authors: Ridker Paul M
Published: January 2016

Plasma levels of the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) predict vascular risk with an effect estimate as large as that of total or high-density lipoprotein cholesterol. Further, randomized trial data addressing hsCRP have been central to understanding the anti-inflammatory effects of statin therapy and have consistently demonstrated on-treatment hsCRP levels to be as powerful a predictor of residual cardiovascular risk as on-treatment levels of low-density lipoprotein cholesterol. Yet, although hsCRP is clinically useful as a biomarker for risk prediction, most mechanistic studies suggest that CRP itself is unlikely to be a target for intervention. Moving upstream in the inflammatory cascade from CRP to interleukin (IL)-6 to IL-1 provides novel therapeutic opportunities for atheroprotection that focus on the central IL-6 signaling system and ultimately on inhibition of the IL-1β-producing NOD-like receptor family pyrin domain containing 3 inflammasome. Cholesterol crystals, neutrophil extracellular traps, atheroprone flow, and local tissue hypoxia activate the NOD-like receptor family pyrin domain containing 3 inflammasome. As such, a unifying concept of hsCRP as a downstream surrogate biomarker for upstream IL-1β activity has emerged. From a therapeutic perspective, small ischemia studies show reductions in acute-phase hsCRP production with the IL-1 receptor antagonist anakinra and the IL-6 receptor blocker tocilizumab. A phase IIb study conducted among diabetic patients at high vascular risk indicates that canakinumab, a human monoclonal antibody that targets IL-1β, markedly reduces plasma levels of IL-6, hsCRP, and fibrinogen with little change in atherogenic lipids. Canakinumab in now being tested as a method to prevent recurrent cardiovascular events in a randomized trial of 10 065 post-myocardial infarction patients with elevated hsCRP that is fully enrolled and due to complete in 2017. Clinical trials using alternative anti-inflammatory agents active against the CRP/IL-6/IL-1 axis, including low-dose methotrexate and colchicine, are being explored. If successful, these trials will close the loop on the inflammatory hypothesis of atherosclerosis and serve as examples of how fundamental biologic principles can be translated into personalized medical practice.
The Ubiquitin-Like SUMO System and Heart Function
Authors: Mendler Luca , Braun Thomas , Müller Stefan
Published: January 2016

SUMOylation is a ubiquitin-related transient posttranslational modification pathway catalyzing the conjugation of small ubiquitin-like modifier (SUMO) proteins (SUMO1, SUMO2, and SUMO3) to lysine residues of proteins. SUMOylation targets a wide variety of cellular regulators and thereby affects a multitude of different cellular processes. SUMO/sentrin-specific proteases are able to remove SUMOs from targets, contributing to a tight control of SUMOylated proteins. Genetic and cell biological experiments indicate a critical role of balanced SUMOylation/deSUMOylation for proper cardiac development, metabolism, and stress adaptation. Here, we review the current knowledge about SUMOylation/deSUMOylation in the heart and provide an integrated picture of cardiac functions of the SUMO system under physiologic or pathologic conditions. We also describe potential therapeutic approaches targeting the SUMO machinery to combat heart disease.
Are Face and Object Recognition Independent? A Neurocomputational Modeling Exploration
Authors: Wang Panqu , Gauthier Isabel , Cottrell Garrison
Published: January 2016

Are face and object recognition abilities independent? Although it is commonly believed that they are, Gauthier et al. [Gauthier, I., McGugin, R. W., Richler, J. J., Herzmann, G., Speegle, M., & VanGulick, A. E. Experience moderates overlap between object and face recognition, suggesting a common ability. Journal of Vision, 14, 7, 2014] recently showed that these abilities become more correlated as experience with nonface categories increases. They argued that there is a single underlying visual ability, v, that is expressed in performance with both face and nonface categories as experience grows. Using the Cambridge Face Memory Test and the Vanderbilt Expertise Test, they showed that the shared variance between Cambridge Face Memory Test and Vanderbilt Expertise Test performance increases monotonically as experience increases. Here, we address why a shared resource across different visual domains does not lead to competition and to an inverse correlation in abilities? We explain this conundrum using our neurocomputational model of face and object processing [“The Model”, TM, Cottrell, G. W., & Hsiao, J. H. Neurocomputational models of face processing. In A. J. Calder, G. Rhodes, M. Johnson, & J. Haxby (Eds.), The Oxford handbook of face perception. Oxford, UK: Oxford University Press, 2011]. We model the domain general ability v as the available computational resources (number of hidden units) in the mapping from input to label and experience as the frequency of individual exemplars in an object category appearing during network training. Our results show that, as in the behavioral data, the correlation between subordinate level face and object recognition accuracy increases as experience grows. We suggest that different domains do not compete for resources because the relevant features are shared between faces and objects. The essential power of experience is to generate a “spreading transform” for faces (separating them in representational space) that generalizes to objects that must be individuated. Interestingly, when the task of the network is basic level categorization, no increase in the correlation between domains is observed. Hence, our model predicts that it is the type of experience that matters and that the source of the correlation is in the fusiform face area, rather than in cortical areas that subserve basic level categorization. This result is consistent with our previous modeling elucidating why the FFA is recruited for novel domains of expertise [Tong, M. H., Joyce, C. A., & Cottrell, G. W. Why is the fusiform face area recruited for novel categories of expertise? A neurocomputational investigation. Brain Research, 1202, 14–24, 2008].
The Lepidostoma coreanum Species Complex (Trichoptera, Lepidostomatidae) in the Asian Far East
Authors: ITO TOMIKO
Published: January 2016

A total of 68 species of genus Lepidostoma Rambur (Trichoptera; Lepidostomatidae) has been reported from the Asian Far East. L. coreanum (Kumanski & Weaver 1992) was originally described from North Korea. Detail examination of specimens of this species and its related specimens collected in the Asian Far East revealed the hypothetical definition of L. coreanum and the presence of 4 new related species, L. niigataense sp. nov., L. hattorii sp. nov., L. yuwanense sp. nov., and L. ishigakiense sp. nov. The species assemblage is named as the Lepidostoma coreanum Species Complex.
A new species of dwarf gecko in the genus Lygodactylus (squamata: Gekkonidae) from central Kenya
Authors: MALONZA PATRICK K. , GRANTHON CAROLINA , WILLIAMS DEAN A.
Published: January 2016

A new species of Lygodactylus gecko (L. wojnowskii sp. nov.) is described from the vicinity of Chogoria Town on the eastern lower slopes of Mt. Kenya in central Kenya. A phylogeny based on mitochondrial and nuclear DNA shows that the proposed new taxon is distinct within the Lygodactylus picturatus group and is the sister lineage to L. mombasicus and L. kimhowelli. It is morphologically very similar to both L. mombasicus and L. keniensis but its dorsal coloration and pattern is different. Its dorsum is grey with dark stripes while its head has black and white stripes that form a Y-shaped mark. While the male throat pattern is similar to that of L. mombasicus, that of the female is like that of females and some males of Lygodactylus keniensis. Lygodactylus wojnowskii sp. nov. has a higher number of post-postmental scales (6) than do its close relatives (5). The new species is distributed on the lower slopes of mid-altitude areas on eastern Mt. Kenya, but it may occur in other areas at similar elevations in central Kenya. It is associated with short, scattered trees within agricultural areas. It has not yet been recorded within the protected Chogoria forest block of Mt. Kenya forest. It is likely present in Mwea National Reserve as it occurs in nearby areas.
High temperature performance of mullite whisker-reinforced ZTA
Authors: Robertson Taylor , Huang Xiao , Kearsey Rick
Published: January 2016

In this work, an oxide-based ceramic matrix composite (CMC) consisting of a zirconia toughened alumina (ZTA) matrix and reinforced with mullite whiskers is produced with the purpose of providing more oxidation resistance and cost-effective alternative to covalent discontinuously reinforced ceramics. ZTA has enhanced toughness, strength and creep resistance over single-phase alumina or zirconia. ZTA can further be strengthened by the inclusion of SiC whiskers; however, these whiskers are prone to oxidation at temperatures above 1000℃ leading to loss of properties. In this work, mullite whiskers are used as the reinforcement due to its stability in oxidizing atmospheres are high temperatures. Mullite whiskers are grown through the molten salt method and incorporated into the ZTA matrix using a colloidal processing route. The microstructure and room temperature properties have been reported in an earlier paper. Whisker additions have been shown to improve the flexural strength of ZTA at 1200℃ by 59.31%. There is some concern over the stability of large diameter whiskers at high temperatures, especially in environments with excessive moisture content or residual alkali contamination. Further work will be carried out to address these concerns as well as to develop a statistical analysis of the results presented.
Adolescent Life History Strategy in the Intergenerational Transmission and Developmental Stability of Substance Use
Authors: Richardson George B. , Dai Chia-Liang , Chen Ching-Chen , Nedelec Joseph L. , Swoboda Christopher M. , Chen Wei-Wen
Published: January 2016

Research suggests that fast life history strategy (LHS) may be a primary driver of substance use among young adults. However, a recent study reported that (a) young adult fast LHS did not subsume all theorized indicators of LHS during this period and (b) fast LHS among parents did not predict young adult fast LHS or liability for use of common substances. In this study, we used structural equations and national data to test whether these findings generalized to adolescence. In addition, given that LHS and substance use share genetic and neuropsychological bases, we examined whether fast LHS could explain the developmental stability of substance use. Overall, our results extend the findings discussed above and suggest that fast LHS fully explains the developmental stability of substance use among youth. We discuss implications for life history models, research applying life history theory and substance use, and substance abuse prevention and treatment.
Public transportation and the idiocy of urban life
Authors: Attoh Kafui
Published: January 2016

This paper asserts urban transportation’s centrality to debates on ‘the public,’ the ‘right to the city’ and political mobilisation in cities. The paper begins with a re-reading of Marx and Engels’ oft-cited line in the Communist Manifesto on the ‘idiocy of rural life’. Drawing on the work of Hal Draper, who has argued that Marx and Engels used the term ‘idiocy’ as a synonym for ‘privatised isolation’, this paper pulls from two empirical studies on urban transportation to define what I conversely call ‘the idiocy of urban life’. The first case study looks at two transportation programs in Syracuse New York aimed at helping to get welfare recipients to work. The paper argues that such programs not only marked a sharp departure from the public alternative, but that they were programs that enforced the very idiocy and privatised isolation that so worried Marx and Engels. The second case study looks at the East Bay’s transportation justice movement. The paper argues that one of the organising principles of this movement is a rejection of ‘the idiocy of urban life’. The paper concludes by linking debates over ‘the public’, and struggles against urban idiocy to ongoing debates around the right to the city.
Turnover Intentions of Employees With Informal Eldercare Responsibilities
Authors: Greaves Claire E. , Parker Stacey L. , Zacher Hannes , Jimmieson Nerina L.
Published: January 2016

As longevity increases, so does the need for care of older relatives by working family members. This research examined the interactive effect of core self-evaluations and supervisor support on turnover intentions in two samples of employees with informal caregiving responsibilities. Data were obtained from 57 employees from Australia (Study 1) and 66 employees from the United States and India (Study 2). Results of Study 1 revealed a resource compensation effect, that is, an inverse relationship between core self-evaluations and turnover intentions when supervisor care support was low. Results of Study 2 extended these findings by demonstrating resource boosting effects. Specifically, there was an inverse relationship between core self-evaluations and subsequent turnover intentions for those with high supervisor work and care support. In addition, employees' satisfaction and emotional exhaustion from their work mediated the inverse relationship between core self-evaluations and subsequent turnover intentions when supervisor work support and care support were high. Overall, these findings highlight the importance of employee- and supervisor-focused intervention strategies in organizations to support informal caregivers.
When sojourners return: Employment opportunities and challenges facing high-skilled Chinese returnees
Authors: Hao Jie , Wen Wen , Welch Anthony
Published: January 2016

Focusing on the increasingly large numbers of Chinese students undertaking postgraduate programs overseas, this paper examines how international higher education shapes their subsequent career development in China. The specific focus is on their employment status, the impact of Australian higher education, and the challenges they experience upon returning home. A leading Australian university was chosen as the case study, and a mixed research method was adopted. By analyzing questionnaire and interview data, the paper argues that holding an international qualification is no longer adequate for employment success in China’s competitive labor market; rather, different forms of intellectual capital need to be consolidated and utilized. Unlike the previous generation of returnees who gained prestigious positions and made changes to China’s development immediately upon their return, the research finds that the current generation of sojourners faces a different and more complex set of opportunities and challenges. Although the majority of such graduates still retain an advantage in China’s crowded graduate labor market, the context is much more competitive.
Municipal Incorporation
Authors: Leon-Moreta Agustin
Published: January 2016

Using recent census data, this research examines municipal incorporations. The research is guided by the Tiebout model and a reorganization framework: it posits that wider income heterogeneity among county areas raises the probability of incorporation for higher-income communities, and incentives for incorporation include revenue and growth control. Empirically, change in unincorporated places is examined to determine how their income heterogeneity influences initiatives for incorporation, through subsamples of revenue and growth control. Main findings are that income heterogeneity raised the probability of incorporation, particularly where municipal per capita revenue is greater, land-use regulation is nonrestrictive, and population growth is rising.
Depressive symptoms, excessive reassurance seeking, and relationship maintenance
Authors: Fowler Craig , Gasiorek Jessica
Published: January 2016

Using a sample of 143 heterosexual, ethnically diverse couples, we explored the consequences of individuals’ depressive symptomology and excessive reassurance seeking (ERS) for (a) the efforts they and their partners make to maintain their relationship and (b) the satisfaction reported by each relational party. Data were analyzed using an extension of the actor–partner interdependence model. We found actor effects of depression on satisfaction and on relationship maintenance behavior. We also detected significant actor effects of ERS on relationship maintenance behavior. There was inconsistent evidence of partner effects and of the predicted indirect effects. Results suggest that depression and the tendency to engage in ERS may exert countervailing influences on the enactment of relationship maintenance: For both men and women, depression was a negative predictor of self-reported relationship maintenance, whereas ERS was a positive predictor. We suggest that ERS could be considered a form of relationship maintenance in its own right.
A new co-operative revolution in South Africa? Reflections on the outcomes of state support in the Free State Province
Authors: Wessels Johannes , Nel Etienne
Published: January 2016

There has been growing interest in the role and potential which co-operatives can play in terms of economic and community development in the Global South as alternatives to more conventional models of business organisation. One country which has been particularly proactive in this regard is South Africa, where co-operatives feature prominently in national and provincial level development strategies and support. This paper overviews key themes in the literature before proceeding to a case study of the effectiveness of state support for co-operatives in the Free State Province of South Africa. Findings show that the well-intentioned objectives of state interventions are not being realised due to poor business planning, lack of training, poor market links and the seeming prioritisation of political over economic considerations.
Innovation and Local Economic Development Policy in the global South: New South African perspectives
Authors: Ndabeni Lindile L , Rogerson Christian M , Booyens Irma
Published: January 2016

Recently, innovation has become a critical parameter for contemporary regional and local development policy in the global North. In South African debates about regional and local development policy issues of innovation rarely are discussed and the country’s most recent policy documents and frameworks around local economic development (LED) make no mention or acknowledgement of issues around innovation. This disconnect between South Africa’s national innovation policies and those around regional and local development planning is under review as the country’s Department of Science and Technology (DST) with responsibility for innovation policy in the country, released a new strategy document intended to inform the DST’s involvement in the policy space of LED with the mandate of strengthening local systems of innovation and production in a systemic and systematic manner. It is argued that in terms of LED policy and practice across the global South this South African policy document represents a potential benchmark policy intervention which merits scrutiny and discussion. The aim is to examine the shift in national policy thinking towards the use and role of innovation for driving economic and social change in the marginalised spaces of South Africa. Against a background of debates around national, regional and local systems of innovation in the global South and of the emergence of new perspectives around the potential of innovation to contribute to poverty reduction, job creation and LED a critical review is provided of new policy directions and strategic proposals for the application of innovation to drive economic and social change in South Africa’s marginalised spaces.
Apolipoprotein E ɛ2/ɛ3/ɛ4 variant in association with obstructive sleep apnoea and lipid profile: A meta-analysis
Authors: Lu Zhuoqiang , Wu Xuemei , Jin Xueqing , Peng Feng , Lin Jinxiu
Published: January 2016

Objective

A meta-analysis of the association between haplotypical variants of the apolipoprotein E ( APOE) gene (ɛ2/ɛ3/ɛ4) and obstructive sleep apnoea (OSA) risk and changes in lipid profile.

Methods

Electronic databases were searched to retrieve articles that provided data on APOE gene ɛ2/ɛ3/ɛ4 variants in patients with OSA and healthy controls. Data were extracted from eligible articles and statistical analyses were performed.

Results

The meta-analysis included 14 articles involving 19 study populations (3198 patients and 6031 controls). There was no significant association between the presence of the ɛ4 allele and OSA risk. The presence of ɛ4 was associated with significantly increased total cholesterol and decreased high-density lipoprotein cholesterol, compared with ɛ4 allele negative individuals. There was a low probability of publication bias but significant heterogeneity.

Conclusions

There was no association between APOE ɛ2/ɛ3/ɛ4 and OSA susceptibility. The presence of APOE ɛ4 was associated with changes in lipid profile.
A Listening Guide Analysis of Women’s Experiences of Unacknowledged Rape
Authors: Johnstone Dusty J.
Published: January 2016

In the empirical literature, unacknowledged rape has been well documented. But due to ethical and methodological challenges, very few researchers have employed qualitative methods to examine unacknowledged rape. Through pre-screening and careful articulation of interview questions, these barriers were overcome, and 10 undergraduate women from the University of Windsor were interviewed about their experiences of unlabeled sexual assault. I used the Listening Guide to inform both the methodology and the data analysis. I identified three voices pertaining to rape acknowledgment. These voices were labeled the not knowing voice, the knowing voice, and the ambivalent voice, and I illustrate that rape acknowledgment is not dichotomous and that women can both simultaneously recognize and resist the labels of rape and sexual assault. This article addresses the need for a multidimensional understanding of rape acknowledgment. I discuss the implications the findings have for how we understand and respond to women, as they negotiate the labeling of coercive sexual experiences. Online slides for instructors who want to use this article for teaching are available to PWQ subscribers on PWQ's website at http://pwq.sagepub.com/supplemental
Is Sport Activity Possible After Arthroscopic Meniscal Allograft Transplantation?
Authors: Zaffagnini Stefano , Grassi Alberto , Marcheggiani Muccioli Giulio Maria , Benzi Andrea , Roberti di Sarsina Tommaso , Signorelli Cecilia , Raggi Federico , Marcacci Maurilio
Published: January 2016

Background:

Meniscal allograft transplantation (MAT) has produced good to excellent results in the general population; however, few investigations have examined MAT in athletes and sport-related outcomes.

Purpose:

To report midterm clinical outcomes of MAT and the rate of return to sport in a physically active population.

Study Design:

Case series; Level of evidence, 4.

Methods:

The study included all physically active patients who underwent arthroscopic MAT without bone plugs and had a minimum of 2 years of follow-up at a single institution. Clinical evaluation was performed with the Knee injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale, and a 0- to 100-point subjective scale for knee function and satisfaction. Outcomes evaluated included ability to return to sport, time to return to sport, level of sport activity upon return compared with preinjury level, and level of decrease in sport participation or reasons for not returning to sport participation. Comparisons were made between patients who did or did not return to sport and between patients who returned to the same level or a decreased level. Regression analysis was performed to determine the variables affecting the outcomes.

Results:

Eighty-nine patients, whose mean ± SD age at surgery was 38.5 ± 11.2 years, were evaluated to a mean follow-up of 4.2 ± 1.9 years. Total KOOS improved from a mean ± SD of 39.5 ± 18.5 preoperatively to 84.7 ± 14.8 at the latest follow-up ( P < .001). The Tegner score improved significantly from a median of 2 (interquartile range [IQR], 1-4) preoperatively to a median of 4 (IQR, 3-6) at the latest follow-up ( P < .001), although it did not reach the preinjury level of 6 (IQR, 5-7) ( P < .001). Older age at surgery was correlated with the worst clinical results. Sixty-six patients (74%) were able to return to sport after 8.6 ± 4.1 months. Forty-four (49%) returned to the same level as preinjury. Patients who did not return to sport activity and those who reduced their activity level at follow-up had inferior subjective outcomes compared with those who returned to sport and those who returned to their preinjury levels, respectively. Only 11 patients (12%) underwent a surgical procedure during the follow-up period.

Conclusion:

Arthroscopic MAT without bone plugs improved knee function and reduced pain, allowing sport resumption in 74% of patients and return to the preinjury activity level in 49% of patients at midterm follow-up. Of all the demographic and surgical variables, only age at surgery seemed to affect outcomes.
Definitions of Violence: Narratives of Survivors From the War in Bosnia and Herzegovina
Authors: Basic Goran
Published: January 2016

Previous research on violence during the war in Bosnia and Herzegovina has resulted in a one-sided presentation of the phenomenon of “war violence.” Researchers have emphasized the importance of narratives in general but have not analyzed stories on war violence that were the product of interpersonal interaction and meaning-making activity. The aim of this article is to fill this knowledge gap by analyzing survivor narratives of the 1990s war in northwestern Bosnia. The focus is on analyzing interviewees’ descriptions of wartime violence and the discursive patterns that contribute to constructing the phenomenon of “war violence.” My analysis reveals an intimate relationship between how an interviewee interprets the biographical consequences of war violence and the individual’s own war experiences. All interviewees described war violence as something that is morally reprehensible. These narratives, from both perpetrators of violence and those subjected to violence, recount violent situations that not only exist as mental constructions but also live on even after the war; thus, they have real consequences for the individuals and their society.
A Case of Severe, Prolonged, Refractory Hypophosphatemia After Zoledronic Acid Administration
Authors: Clark Sarah L. , Nystrom Erin M.
Published: January 2016

Zoledronic acid (ZA) administration has been associated with electrolyte abnormalities, including hypocalcemia, hypomagnesemia, hypokalemia, and hypophosphatemia. We describe a case of severe, refractory hypophosphatemia in a patient who received ZA for hypercalcemia of malignancy (HCM). Little data are available that describe the incidence or degree of severity of hypophosphatemia that can occur following ZA administration. In addition, no formal recommendations exist to guide monitoring for or management of electrolyte derangements in the setting of bisphosphonate use. Our patient required daily, high-dose phosphorus replacement beginning day 4 following ZA administration. The average daily dose of phosphorus, including both intravenous and enteral administration, was highest in the first 2 weeks after ZA, averaging 77 mmol/d days 4 through 15, and does not include sources of phosphorus from the patient’s nutrition support. Despite this high amount of supplementation, which was well beyond what meets normal daily requirements and the amount expected to treat “usual” hypophosphatemia, the patient did not achieve sustained normal serum phosphorus levels for over 30 days after ZA. ZA is a favorable option for treating HCM because of its longer duration of action, potent serum calcium-lowering effects, and favorable safety profile. The risk of hypophosphatemia with ZA use is reviewed.