bluuebunny/crossref_metadata_2025 huggingface dataset:
It’s time to make the profession of health about health
Authors: Becker Craig M. , Rhynders Patricia
Published: December 2012

Most professional health publications and presentations are not about health, but about how to avoid, prevent, or treat disease or infirmity. Better health cannot be attained by simply avoiding, preventing, or treating problems. Health efforts, therefore, should be directed toward creating physical, mental, and social wellbeing. To guide these efforts, salutogenesis, a theoretical framework about the origins or creation of health, is needed to complement the traditional pathogenesis framework that focuses on the origins and causes of disease. Salutogenic strategies are necessary to help health professionals promote positive health enhancement by making their practices about health.
Participant selection as a conscious research method: thinking forward and the deliberation of ‘Emergent’ findings
Authors: Reybold L Earle , Lammert Jill D , Stribling Stacia M
Published: December 2012

Participant selection is one of the most invisible and least critiqued methods in qualitative circles. Researchers do not just collect and analyze neutral data; they decide who matters as data. Each choice repositions inquiry, closing down some opportunities while creating others. After reviewing the selection literature, we present critical vignettes of our selection choices in three separate studies, examining how those choices directed meaning making within and beyond the studies. Our analysis across these vignettes uncovered a constant interface—and often a struggle—between our personal situations and social agendas as qualitative researchers. Four aspects of this Reporting In/Reporting Out tension are discussed: trusting qualitative research, building the story, dealing with powerful others, and accepting unintended consequences. We encourage qualitative researchers to critically think forward their selection choices before and during the research process, to be mindful that selection is a constitutive method of the data collection and analysis process.
Intimate Partner Violence Prevention Services and Resources in Los Angeles
Authors: Ford Chandra L. , Slavin Terra , Hilton Karin L. , Holt Susan L.
Published: December 2012

Intimate partner violence (IPV) is as prevalent in lesbian, gay, bisexual, and transgender (LGBT) relationships as it is in heterosexual ones; however, the issues, needs, and challenges associated with assisting or advocating on behalf of LGBT persons are poorly understood. Using community-based participatory approaches, we conducted a brief survey of professionals (e.g., shelter staff, domestic violence prevention and intervention programs, law enforcement) affiliated with one or more domestic violence prevention and/or intervention networks in Los Angeles, California. The sample, which included professionals ( N = 54) from diverse programs/agencies, was obtained using purposive and snowball sampling. Participants self-administered a 33-item, online questionnaire. Analyses primarily involved descriptive statistics (frequencies, proportions). Most respondents had little or no training in LGBT IPV; nevertheless, nearly 50% of them reported having assisted LGBTs “sometimes” or “often” in the past year. Nearly all (92%) reported that their agencies/programs lack staff with dedicated responsibilities to LGBT IPV. The most frequent requests for assistance respondents reported receiving from LGBTs were for counseling, safe housing, legal assistance, and assistance navigating the medical system. The findings suggest that staff believe their agencies/programs inadequately address LGBT IPV but that many of the inadequacies (e.g., lack of staff training on LGBT IPV) are remediable.
An overview of the effectiveness of psychological therapy for depression and stepped care service delivery models
Authors: Ekers David , Webster Lisa
Published: December 2012

Depression is one of the most prevalent health disorders globally and causes significant distress and cost to the sufferer and society. Psychological therapy for depression has been recommended over a number of decades; however, access to these treatments remains limited. Cognitive behaviour therapy, behavioural activation, self-help approaches, interpersonal therapy and non-directive therapy all demonstrate moderate to large effect sizes when compared to treatment as usual. Differences between psychological interventions however are small and unstable when reviewed in meta-analyses suggesting that for most people adding complexity to treatment does not result in improved outcomes. Stepped care is one system used to organise delivery of psychological therapy that stratifies interventions across several levels of symptom severity. There is debate regarding the ideal design and operation of this complex system resulting in considerable variability in its use in clinical settings. Further research is needed to identify the most cost effective approach to the delivery of psychological therapies for depression as we need to continue to reduce the gap between demand and access to therapy.
Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells
Authors: Kinnunen Tuure , Chamberlain Nicolas , Morbach Henner , Choi Jinyoung , Kim Sangtaek , Craft Joseph , Mayer Lloyd , Cancrini Caterina , Passerini Laura , Bacchetta Rosa , Ochs Hans D. , Torgerson Troy R. , Meffre Eric
Published: December 2012

Key Points

Peripheral B-cell tolerance is defective in IPEX patients, suggesting that Tregs are involved in the maintenance of B-cell tolerance. T cells, including Tregs, display an activated phenotype in IPEX patients that may favor the accumulation of autoreactive B cells.
Resolvin D1 attenuates inflammation in lipopolysaccharide-induced acute lung injury through a process involving the PPARγ/NF-κB pathway
Authors: Liao Zenglin , Dong Jiajia , Wu Wei , Yang Ting , Wang Tao , Guo Lingli , Chen Lei , Xu Dan , Wen Fuqiang
Published: December 2012

Background

Docosahexaenoic acid (DHA) and DHA-derived lipid mediators have recently been shown to possess anti-inflammatory and pro-resolving properties. In fact, DHA can down-regulate lipolysaccharide (LPS)-induced activation of NF-κB via a PPARγ-dependent pathway. We sought to investigate the effects of the novel DHA-derived mediator resolvin D1 (RvD1) on LPS-induced acute lung injury and to determine whether these effects occur via a PPARγ-dependent pathway.

Methods

BALB/c mice aged 6–8 weeks were randomly divided into seven groups: two control groups receiving saline or RvD1 (600 ng) without LPS; a control group receiving LPS only; an experimental group receiving RvD1 (300 ng) or RvD1 (600 ng), followed by LPS; a group receiving the PPARγ antagonist GW9662; and a group receiving GW9662, then RvD1 (600 ng) and finally LPS. LPS (50 μM) and saline were administered intratracheally. RvD1 was injected intravenously 24 h and 30 min before LPS, while GW9662 was injected intravenously 30 min before RvD1. Mice were killed at 6, 12, and 24 h. Samples of bronchoalveolar lavage fluid (BALF) were analyzed for cell counts and cytokine analysis. Lung tissues were collected for histology, Western blotting and electrophoretic mobility shift assays (EMSAs).

Results

At all three time points, groups receiving either dose of RvD1 followed by LPS had significantly lower total leukocyte counts and levels of TNF-α and IL-6 levels in BALF than did the group given only LPS. RvD1 markedly attenuated LPS-induced lung inflammation at 24 h, based on hematoxylin-eosin staining of histology sections. RvD1 activated PPARγ and suppressed IκBα degradation and NF-κB p65 nuclear translocation, based on Western blots and EMSAs. The PPARγ inhibitor GW9662 partially reversed RvD1-induced suppression of IκBα degradation and p65 nuclear translocation.

Conclusions

These results suggest that RvD1 may attenuate lung inflammation of LPS-induced acute lung injury by suppressing NF-κB activation through a mechanism partly dependent on PPARγ activation.
Evidence for selection at HIV host susceptibility genes in a West Central African human population
Authors: Zhao Kai , Ishida Yasuko , Oleksyk Taras K , Winkler Cheryl A , Roca Alfred L
Published: December 2012

Background

HIV-1 derives from multiple independent transfers of simian immunodeficiency virus (SIV) strains from chimpanzees to human populations. We hypothesized that human populations in west central Africa may have been exposed to SIV prior to the pandemic, and that previous outbreaks may have selected for genetic resistance to immunodeficiency viruses. To test this hypothesis, we examined the genomes of Biaka Western Pygmies, who historically resided in communities within the geographic range of the central African chimpanzee subspecies (Pan troglodytes troglodytes) that carries strains of SIV ancestral to HIV-1.

Results

SNP genotypes of the Biaka were compared to those of African human populations who historically resided outside the range ofP. t. troglodytes, including the Mbuti Eastern Pygmies. Genomic regions showing signatures of selection were compared to the genomic locations of genes reported to be associated with HIV infection or pathogenesis. In the Biaka, a strong signal of selection was detected atCUL5, which codes for a component of the vif-mediated APOBEC3 degradation pathway. ACUL5allele protective against AIDS progression was fixed in the Biaka. A signal of selection was detected atTRIM5,which codes for an HIV post-entry restriction factor. A protective mis-sense mutation inTRIM5had the highest frequency in Biaka compared to other African populations, as did a protective allele forAPOBEC3G, which codes for an anti-HIV-1 restriction factor. Alleles protective against HIV-1 forAPOBEC3H,CXCR6andHLA-Cwere at higher frequencies in the Biaka than in the Mbuti. Biaka genomes showed a strong signal of selection atTSG101,an inhibitor of HIV-1 viral budding.

Conclusions

We found protective alleles or evidence for selection in the Biaka at a number of genes associated with HIV-1 infection or progression. Pygmies have also been reported to carry genotypes protective against HIV-1 for the genesCCR5andCCL3L1.Our hypothesis that HIV-1 may have shaped the genomes of some human populations in West Central Africa appears to merit further investigation.
The tomato RLK superfamily: phylogeny and functional predictions about the role of the LRRII-RLK subfamily in antiviral defense
Authors: Sakamoto Tetsu , Deguchi Michihito , Brustolini Otávio JB , Santos Anésia A , Silva Fabyano F , Fontes Elizabeth PB
Published: December 2012

Background

Receptor-like kinases (RLKs) play key roles during development and in responses to the environment. Despite the relevance of the RLK family and the completion of the tomato genome sequencing, the tomato RLK family has not yet been characterized, and a framework for functional predictions of the members of the family is lacking.

Results

To generate a complete list of all the members of the tomato RLK family, we performed a phylogenetic analysis using the Arabidopsis family as a template. A total of 647 RLKs were identified in the tomato genome, which were organized into the same subfamily clades as Arabidopsis RLKs. Only eight of 58 RLK subfamilies exhibited specific expansion/reduction compared to their Arabidopsis counterparts. We also characterized the LRRII-RLK family by phylogeny, genomic analysis, expression profile and interaction with the virulence factor from begomoviruses, the nuclear shuttle protein (NSP). The LRRII subfamily members from tomato and Arabidopsis were highly conserved in both sequence and structure. Nevertheless, the majority of the orthologous pairs did not display similar conservation in the gene expression profile, indicating that these orthologs may have diverged in function after speciation. Based on the fact that members of the Arabidopsis LRRII subfamily (AtNIK1, AtNIK2 and AtNIK3) interact with the begomovirus nuclear shuttle protein (NSP), we examined whether the tomato orthologs of NIK, BAK1 and NsAK genes interact with NSP of Tomato Yellow Spot Virus (ToYSV). The tomato orthologs of NSP interactors, SlNIKs and SlNsAK, interacted specifically with NSP in yeast and displayed an expression pattern consistent with the pattern of geminivirus infection. In addition to suggesting a functional analogy between these phylogenetically classified orthologs, these results expand our previous observation that NSP-NIK interactions are neither virus-specific nor host-specific.

Conclusions

The tomato RLK superfamily is made-up of 647 proteins that form a monophyletic tree with the Arabidopsis RLKs and is divided into 58 subfamilies. Few subfamilies have undergone expansion/reduction, and only six proteins were lineage-specific. Therefore, the tomato RLK family shares functional and structural conservation with Arabidopsis. For the LRRII-RLK members SlNIK1 and SlNIK3, we observed functions analogous to those of their Arabidopsis counterparts with respect to protein-protein interactions and similar expression profiles, which predominated in tissues that support high efficiency of begomovirus infection. Therefore, NIK-mediated antiviral signaling is also likely to operate in tomato, suggesting that tomato NIKs may be good targets for engineering resistance against tomato-infecting begomoviruses.
Expression profile and prognostic role of sex hormone receptors in gastric cancer
Authors: Gan Lu , He Jian , Zhang Xia , Zhang Yong-Jie , Yu Guan-Zhen , Chen Ying , Pan Jun , Wang Jie-Jun , Wang Xi
Published: December 2012

Background

Increasing interest has been devoted to the expression and possible role of sex hormone receptors in gastric cancer, but most of these findings are controversial. In the present study, the expression profile of sex hormone receptors in gastric cancer and their clinicopathological and prognostic value were determined in a large Chinese cohort.

Methods

The mRNA and protein expression of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), progesterone receptor (PR), and androgen receptor (AR) in primary gastric tumors and corresponding adjacent normal tissues from 60 and 866 Chinese gastric cancer patients was detected by real-time quantitative PCR and immunohistochemistry method, respectively. The expression profile of the four receptors was compared and their associations with clinicopathological characteristics were assessed by using Chi-square test. The prognostic value of the four receptors in gastric cancer was evaluated by using univariate and multivariate Cox regression analysis.

Results

The presence of ERα, ERβ, PR, and AR in both gastric tumors and normal tissues was confirmed but their expression levels were extremely low except for the predominance of ERβ. The four receptors were expressed independently and showed a decreased expression pattern in gastric tumors compared to adjacent normal tissues. The positive expression of the four receptors all correlated with high tumor grade and intestinal type, and ERα and AR were also associated with early TNM stage and thereby a favorable outcome. However, ERα and AR were not independent prognostic factors for gastric cancer when multivariate survival analysis was performed.

Conclusions

Our findings indicate that the sex hormone receptors may be partly involved in gastric carcinogenesis but their clinicopathological and prognostic significance in gastric cancer appears to be limited.
Intraocular pressure in a cohort of healthy eastern European schoolchildren: variations in method and corneal thickness
Authors: Krzyżanowska-Berkowska Patrycja , Asejczyk-Widlicka Magdalena , Pierscionek Barbara
Published: December 2012

Background

Intraocular pressure (IOP) in the developing eye of a child is not always easy to measure and there is no technique that is known to be the most accurate for the young eye. Measurements are needed on many cohorts of children with different tonometers to determine how the values correlate between instruments, whether corneal parameters affect readings and whether correlations between age and IOP values can be discerned. The aim of this study was to undertake a comparative analysis of three different tonometers on a group of healthy children to see whether differences exist and whether these may be related to central corneal thickness and/or radius of curvature. In addition, the study adds to the relatively small body of literature on IOP in the growing eye which will collectively allow trends to be identified and ultimately norms to be established.

Methods

IOP was measured on 115 eyes in a group of Polish children, aged between 5–17 years (mean ± standard deviation [SD] 11.3 ± 3.0 years) using three different tonometers: non-contact (NCT), the ICare and Goldmann applanation (GAT). Readings obtained were compared between instruments and with central corneal thickness and radius of curvature.

Results

The ICare tonometer provided statistically higher IOP values (16.9 ± 3.4 mmHg) than the GAT (14.7 ± 2.9 mmHg) regardless of corneal thickness and whether or not a correction factor was applied. A correlation was found between central corneal thickness (CCT) and IOP values obtained with all three tonometers but only the IOP values detected with the ICare tonometer showed a statistically significant correlation with radius of curvature (p < 0.004). No correlations with age or gender were found for IOP values measured with any of the instruments.

Conclusions

IOP measurements on children vary significantly between instruments and correlations are affected by the corneal thickness. Further studies on children are needed to determine which instrument is most appropriate and to derive a normative IOP scale for the growing eye.
Rates of undiagnosed attention deficit hyperactivity disorder in London drug and alcohol detoxification units
Authors: Huntley Zoe , Maltezos Stefanos , Williams Charlotte , Morinan Alun , Hammon Amy , Ball David , Marshall E Jane , Keaney Francis , Young Susan , Bolton Patrik , Glaser Karen , Howe-Forbes Raoul , Kuntsi Jonna , Xenitidis Kiriakos , Murphy Declan , J Asherson Philip
Published: December 2012

Background

ADHD is a common childhood onset mental health disorder that persists into adulthood in two-thirds of cases. One of the most prevalent and impairing comorbidities of ADHD in adults are substance use disorders. We estimate rates of ADHD in patients with substance abuse disorders and delineate impairment in the co-morbid group.

Method

Screening for ADHD followed by a research diagnostic interview in people attending in-patient drug and alcohol detoxification units.

Results

We estimated prevalence of undiagnosed ADHD within substance use disorder in-patients in South London around 12%. Those individuals with substance use disorders and ADHD had significantly higher self-rated impairments across several domains of daily life; and higher rates of substance abuse and alcohol consumption, suicide attempts, and depression recorded in their case records.

Conclusions

This study demonstrates the high rates of untreated ADHD within substance use disorder populations and the association of ADHD in such patients with greater levels of impairment. These are likely to be a source of additional impairment to patients and represent an increased burden on clinical services.
Malaria in infants aged less than six months - is it an area of unmet medical need?
Authors: D’Alessandro Umberto , Ubben David , Hamed Kamal , Ceesay Serign Jawo , Okebe Joseph , Taal Makie , Lama Eugene Kaman , Keita Moussa , Koivogui Lamine , Nahum Alain , Bojang Kalifa , Sonko Aja Adam Jagne , Lalya Honorat Francis , Brabin Bernard
Published: December 2012

Despite the protection provided by several factors, including maternal antibodies, the burden of malaria in young infants may be higher than previously thought. Infants with congenital or neonatal malaria may have a different clinical presentation than older children, and diagnosis may be confused with other neonatal diseases due to an overlap of clinical manifestations. In addition, there is little information on the use of artemisinin-based combination therapy in young infants. There is the need for a more accurate estimate of the parasite prevalence and the incidence of clinical malaria in infants under 6 months old, as well as a better characterization of risk factors, pharmacokinetic profiles, safety and efficacy of currently available anti-malarial treatments, in order to develop evidence-based treatment guidelines for this population.
Fabrication and characterization of DNA-loaded zein nanospheres
Authors: Regier Mary C , Taylor Jessica D , Borcyk Tyler , Yang Yiqi , Pannier Angela K
Published: December 2012

Background

Particulates incorporating DNA are promising vehicles for gene delivery, with the ability to protect DNA and provide for controlled, localized, and sustained release and transfection. Zein, a hydrophobic protein from corn, is biocompatible and has properties that make it a promising candidate material for particulate delivery, including its ability to form nanospheres through coacervation and its insolubility under physiological conditions, making it capable of sustained release of encapsulated compounds. Due to the promise of this natural biomaterial for drug delivery, the objective of this study was to formulate zein nanospheres encapsulating DNA as the therapeutic compound, and to characterize size, charge, sustained release, cell cytotoxicity and cellular internalization of these particles.

Results

Zein nanospheres encapsulating DNA were fabricated using a coacervation technique, without the use of harsh solvents or temperatures, resulting in the preservation of DNA integrity and particles with diameters that ranged from 157.8 ± 3.9 nm to 396.8 ± 16.1 nm, depending on zein to DNA ratio. DNA encapsulation efficiencies were maximized to 65.3 ± 1.9% with a maximum loading of 6.1 ± 0.2 mg DNA/g zein. The spheres protected encapsulated DNA from DNase I degradation and exhibited sustained plasmid release for at least 7 days, with minimal burst during the initial phase of release. Zein/DNA nanospheres demonstrated robust biocompatibility, cellular association, and internalization.

Conclusions

This study represents the first report on the formation of zein particles encapsulating plasmid DNA, using simple fabrication techniques resulting in preservation of plasmid integrity and tunable sizes. DNA encapsulation efficiencies were maximized to acceptable levels at higher zein to DNA ratios, while loading was comparable to that of other hydrophilic compounds encapsulated in zein and that of DNA incorporated into PLGA nano- and microspheres. The hydrophobic nature of zein resulted in spheres capable of sustained release of plasmid DNA. Zein particles may be an excellent potential tool for the delivery of DNA with the ability to be fine-tuned for specific applications including oral gene delivery, intramuscular delivery, and in the fabrication of tissue engineering scaffolds.
Use of silver nanowires to determine thresholds for fibre length-dependent pulmonary inflammation and inhibition of macrophage migration in vitro
Authors: Schinwald Anja , Chernova Tanya , Donaldson Ken
Published: December 2012

Background

The objective of this study was to examine the threshold fibre length for the onset of pulmonary inflammation after aspiration exposure in mice to four different lengths of silver nanowires (AgNW). We further examined the effect of fibre length on macrophage locomotion in an in vitro wound healing assay. We hypothesised that exposure to longer fibres causes both increased inflammation and restricted mobility leading to impaired clearance of long fibres from the lower respiratory tract to the mucociliary escalator in vivo.

Methods

Nine week old female C57BL/6 strain mice were exposed to AgNW and controls via pharyngeal aspiration. The dose used in this study was equalised to fibre number and based on 50 μg/ mouse for AgNW14. To examine macrophage migration in vitro a wound healing assay was used. An artificial wound was created in a confluent layer of bone marrow derived macrophages by scraping with a pipette tip and the number of cells migrating into the wound was monitored microscopically. The dose was equalised for fibre number and based on 2.5 μg/cm2 for AgNW14.

Results

Aspiration of AgNW resulted in a length dependent inflammatory response in the lungs with threshold at a fibre length of 14 μm. Shorter fibres including 3, 5 and 10 μm elicited no significant inflammation. Macrophage locomotion was also restricted in a length dependent manner whereby AgNW in the length of ≥5 μm resulted in impaired motility in the wound closure assay.

Conclusion

We demonstrated a 14 μm cut-off length for fibre-induced pulmonary inflammation after aspiration exposure and an in vitro threshold for inhibition of macrophage locomotion of 5 μm. We previously reported a threshold length of 5 μm for fibre-induced pleural inflammation. This difference in pulmonary and pleural fibre- induced inflammation may be explained by differences in clearance mechanism of deposited fibres from the airspaces compared to the pleural space. Inhibition of macrophage migration at long fibre lengths could account for their well-documented long term retention in the lungs compared to short fibres. Knowledge of the threshold length for acute pulmonary inflammation contributes to hazard identification of nanofibres.
Survival of patients with alcoholic and cryptogenic cirrhosis without liver transplantation: a single center retrospective study
Authors: Senanayake Sudul Mananjala , Niriella Madunil Anuk , Weerasinghe Sanjaya Kumara , Kasturiratne Anuradhani , de Alwis Jerome Praneeth , de Silva Arjuna Priyadarsin , Dassanayake Anuradha Supun , de Silva Hithanadura Janaka
Published: December 2012

Background

There is no recent data addressing the long term survival of cirrhosis patients without transplantation, but with the availability of optimal pharmacological and endoscopic therapies. We compared the long term transplant free survival of alcoholic (AC) and cryptogenic (CC) cirrhosis patients in a setting where liver transplantation was, until very recently, not available. AC and CC patient details were extracted from our database, maintained since 1995. For those who had not attended clinics within the past 4 weeks, the patient or families were contacted to obtain survival status. If deceased, cause of death was ascertained from death certificates and patient records. Survival was compared using Kaplan-Meier curves.

Results

Complete details were available in 549/651 (84.3%) patients (AC 306, CC 243). Mean follow up duration (SD) (months) was 29.9 (32.6). 82/96 deaths (85.4%) among AC and 80/94 deaths (85.1%) among CC were liver related. Multivariate analysis showed age at diagnosis and Child’s class predicted overall survival among all groups. The median survival in Child’s class B and C were 53.5 and 25.3 months respectively. Survival was similar among AC and CC. Among AC survival was improved by abstinence [HR = 0.63 (95% CI: 0.40-1.00)] and was worse with diabetes [HR=1.59 (95% CI: 1.02- 2.48)] irrespective of alcohol status.

Conclusions

The overall survival of AC was similar to CC. Death in both groups were predominantly liver related, and was predicated by age at diagnosis and Child class. Among AC, presence of diabetes and non-abstinence from alcohol were independent predictors for poor survival.
Endosperm-specific expression of human acid beta-glucosidase in a waxy rice
Authors: Patti Tamara , Bembi Bruno , Cristin Piero , Mazzarol Flavia , Secco Erika , Pappalardo Carla , Musetti Rita , Martinuzzi Maurizio , Versolatto Serena , Cariati Roberta , Dardis Andrea , Marchetti Stefano
Published: December 2012

Background

The deficiency of human acid beta-glucosidase (hGCase) causes Gaucher disease, a rare genetically-inherited disorder currently treated by enzyme replacement therapy using recombinant CHO-derived GCase. In an attempt to provide an alternative and more efficient production system, a chimeric cDNA coding for hGCase operatively linked to the signal peptide of rice glutelin 4 (GluB4) was put under the control of the GluB4 endosperm-specific promoter and inserted into the genome of a waxy rice.

Results

Molecular, immunological and biochemical analyses showed that recombinant hGCase, targeted to the protein storage vacuoles of rice endosperm cells, is equivalent to the native protein and has a glycosylation pattern compatible with direct therapeutic use. Compared to a previous study carried out on transgenic tobacco seeds, enzyme contents per unit of biomass were drastically increased; in addition, differently from what observed in tobacco, rice seed viability was unaffected by hGCase even at the highest production level. Transgenic seed polishing combined with a pretreatment of seed flour greatly facilitated hGCase extraction and purification with an industrially-scalable procedure.

Conclusions

This study opens up the possibility to efficiently produce in the rice seed pharmaceutical compounds which are available in limited amounts or completely excluded from clinical practice due to the inadequacy of their production systems.
CRIg mediates early Kupffer cell responses to adenovirus
Authors: He Jeannie Q , Katschke Kenneth J , Gribling Peter , Suto Eric , Lee Wyne P , Diehl Lauri , Eastham-Anderson Jeffrey , Ponakala Anusha , Komuves Laszlo , Egen Jackson G , van Lookeren Campagne Menno
Published: December 2012

CRIg plays a critical role in regulating Kupffer cell function and survival in response to adenovirus infection.

Whereas adenoviral vectors are known to activate the complement cascade, leading to fixation of C3 proteins to the viral capsid, the consequences of this activation for viral clearance from the circulation are not known. Liver KCs, the macrophage population responsible for early uptake and elimination of many blood-borne pathogens, express CRIg, a complement receptor for C3 proteins. Here, we find that CRIg is important for the early elimination of C3-coated adenoviral vectors from the sinusoidal bloodstream by KCs. We further demonstrate that by acting as a critical receptor for adenovirus phagocytosis, CRIg plays an important role in regulating virus-induced KC death and depletion of these cells from the liver sinusoidal lumen. Our study thus identifies a critical pathway regulating KC function and survival in response to systemic viral infection.
Mitogen-Inducible Gene 6 Triggers Apoptosis and Exacerbates ER Stress-Induced β-Cell Death
Authors: Chen Yi-Chun , Colvin E. Scott , Maier Bernhard F. , Mirmira Raghavendra G. , Fueger Patrick T.
Published: December 2012

The increased insulin secretory burden placed on pancreatic β-cells during obesity and insulin resistance can ultimately lead to β-cell dysfunction and death and the development of type 2 diabetes. Mitogen-inducible gene 6 (Mig6) is a cellular stress-responsive protein that can negatively regulate the duration and intensity of epidermal growth factor receptor signaling and has been classically viewed as a molecular brake for proliferation. In this study, we used Mig6 heterozygous knockout mice (Mig6+/−) to study the role of Mig6 in regulating β-cell proliferation and survival. Surprisingly, the proliferation rate of Mig6+/− pancreatic islets was lower than wild-type islets despite having comparable β-cell mass and glucose tolerance. We thus speculated that Mig6 regulates cellular death. Using adenoviral vectors to overexpress or knockdown Mig6, we found that caspase 3 activation during apoptosis was dependent on the level of Mig6. Interestingly, Mig6 expression was induced during endoplasmic reticulum (ER) stress, and its protein levels were maintained throughout ER stress. Using polyribosomal profiling, we identified that Mig6 protein translation was maintained, whereas the global protein translation was inhibited during ER stress. In addition, Mig6 overexpression exacerbated ER stress-induced caspase 3 activation in vitro. In conclusion, Mig6 is transcriptionally up-regulated and resistant to global translational inhibition during stressed conditions in β-cells and mediates apoptosis in the form of caspase 3 activation. The sustained production of Mig6 protein exacerbates ER stress-induced β-cell death. Thus, preventing the induction, translation, and/or function of Mig6 is warranted for increasing β-cell survival.
Pragmatic Idealism Revisited: Russia’s Post-1991 Cyprus Policy and Implications for Washington
Authors: Melakopides Costas
Published: December 2012

Having previously applied the concept of pragmatic idealism to the “like-minded middle powers” during the Cold War, the author now aims to extend its application to great powers and even superpowers. This essay challenges the stereotypical realist conception of Russia’s Cyprus policy, demonstrating that, besides its pragmatic features, it reveals idealistic motives, especially since 1991. These motives issue from a rich nexus of historical, religious, and cultural bonds, resulting in support for essentially idealist legal norms and ethical values that defend the rights of the Republic of Cyprus. Moreover, since President Barack Obama’s worldview is widely, and properly, perceived to exhibit pragmatic idealism, it should follow that Washington’s own Cyprus policy should be refashioned along such principled lines.
MicroRNAs 221 and 222 regulate the undifferentiated state in mammalian male germ cells
Authors: Yang Qi-En , Racicot Karen E. , Kaucher Amy V. , Oatley Melissa J. , Oatley Jon M.
Published: December 2012

Continuity of cycling cell lineages relies on the activities of undifferentiated stem cell-containing subpopulations. Transition to a differentiating state must occur periodically in a fraction of the population to supply mature cells, coincident with maintenance of the undifferentiated state in others to sustain a foundational stem cell pool. At present, molecular mechanisms regulating these activities are poorly defined for most cell lineages. Spermatogenesis is a model process that is supported by an undifferentiated spermatogonial population and transition to a differentiating state involves attained expression of the KIT receptor. We found that impaired function of the X chromosome-clustered microRNAs 221 and 222 (miR-221/222) in mouse undifferentiated spermatogonia induces transition from a KIT– to a KIT+ state and loss of stem cell capacity to regenerate spermatogenesis. Both Kit mRNA and KIT protein abundance are influenced by miR-221/222 function in spermatogonia. Growth factors that promote maintenance of undifferentiated spermatogonia upregulate miR-221/222 expression; whereas exposure to retinoic acid, an inducer of spermatogonial differentiation, downregulates miR-221/222 abundance. Furthermore, undifferentiated spermatogonia overexpressing miR-221/222 are resistant to retinoic acid-induced transition to a KIT+ state and are incapable of differentiation in vivo. These findings indicate that miR-221/222 plays a crucial role in maintaining the undifferentiated state of mammalian spermatogonia through repression of KIT expression.
Gel Formation and Characterization of Clay–[Poly(N-isopropylacrylamide)] Nanocomposites with Some Clay Minerals Prepared by Photopolymerization
Authors: Sato Kana , Yamamoto Shota , Ishimaru Shin’ichi
Published: December 2012

Nanocomposites consisting of clay and poly(N-isopropylacrylamide) (PNIPAAm) were synthesized by photopolymerization using several clay minerals. Uniform hydrogels were obtained by adding saponite-, hectorite-, and fluorohectorite-type synthetic clays to whole clay/NIPAAm with weight-ratios ranging from 0.2 to 1.0. No gels or very brittle gels were produced when synthetic mica and natural montmorillonite were used. The appearance of the obtained hydrogel for the composite of saponite was translucent and relatively stiff, whereas that for fluorohectorite was highly transparent and soft. DSC measurements showed an endothermic anomaly at the volume phase transition in each hydrogel upon increasing temperature. The transition heat decreased with increasing clay content. Swelling behaviors were significantly different between the composites of saponite and fluorohectorite. The amount of absorbed water in the fluorohectorite-composite containing 60 wt % of clay versus NIPAAm was 3 times greater than that in the saponite-composite with the same clay content. The equilibrium water content in the hydrogel decreased with increasing amount of saponite; however, an inverse tendency in the composite of fluorohectorite was observed.
Dual Nano-Electrospray for Probing Solution Interactions and Fast Reactions of Complex Biomolecules
Authors: Mark Lewis P. , Gill Matthew C. , Mahut Marek , Derrick Peter J.
Published: December 2012

A novel nano-electrospray emitter has been developed containing two separated channels running throughout the length of the emitter. The emitters have been fabricated from “theta-shaped” borosilicate capillaries. Loading of different solutions into the two different channels opens up the possibility to study short timescale interactions within a Taylor cone common to both channels. The common Taylor cone constitutes an extremely small “mixing volume” of the order of femtolitres. The products of electrospray from the dual-channel emitters have been analysed by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Results are presented for interactions of vancomycin with diacetyl-l-lysyl-d-alanyl-d-alanine and interactions of vancomycin with deuterated vancomycin. On the basis of these results, it is concluded that, during electrospray, specific non-covalent adducts have been formed and that there have been exchange reactions involving making and breaking of covalent bonds.
Strategic Ambidexterity in Small and Medium-Sized Enterprises: Implementing Exploration and Exploitation in Product and Market Domains
Authors: Voss Glenn B. , Voss Zannie Giraud
Published: December 2012

Balancing exploration and exploitation is a critical challenge that is particularly difficult for smaller, nascent organizations that lack the resources, capabilities, and experience necessary to successfully implement ambidexterity. To better understand how small and medium-sized enterprises achieve ambidexterity, we develop theoretical arguments that link organizational performance to strategic combinations of exploration and exploitation in both product and market domains. We test the hypotheses with a longitudinal study in a dynamic industry that combines objective measures of competition, firm size, age, and revenue performance with self-reported measures of product and market exploration and exploitation. The empirical results offer new insights with respect to several tensions at the heart of the ambidexterity challenge: (1) pure strategies that combine product exploration with market exploration or product exploitation with market exploitation have complementary interaction effects on revenue, (2) cross-functional ambidexterity combining product exploitation with market exploration also exerts complementary interaction effects on revenue, (3) product ambidexterity has positive effects on revenue for older and larger—but not younger and smaller—firms, and (4) market ambidexterity has positive effects on revenue for larger—but not smaller, younger, or older—firms. Two ambidexterity paradoxes emerge: (1) larger, older firms have the resources, capabilities, and experience required to benefit from a product ambidexterity strategy, but larger, older firms are less likely to implement product ambidexterity; and (2) only larger firms have the resources and capabilities required to benefit from a market ambidexterity strategy, but developing and sustaining market ambidexterity is necessary to drive long-term growth.
Leisure Time Invention
Authors: Davis Lee N. , Davis Jerome D. , Hoisl Karin
Published: December 2012

This paper studies the contextual factors that influence whether invention occurs during work time or leisure time. Leisure time invention, a potentially important but thus far largely unexplored source of employee creativity, refers to invention where the main underlying idea occurs while the employee is away from the workplace. We build on existing theory in the fields of organizational creativity and knowledge recombination, especially work relating context to creativity. The paper’s main theoretical contribution is to extend our understanding of the boundaries of employee creativity by adding to the discussion of how access to and exploitation of different types of resources—during work hours or during leisure time—may affect creativity. Based on survey data from more than 3,000 inventions from German employee inventors, we find that leisure time inventions are more frequently observed for conceptually based problems, in cases where interactions with people outside the organization are important for making the invention, and for smaller research and development projects. Our findings also suggest that employee inventions during work time may become more “embedded” in an environment of path-dependent resources than those made during leisure time.
Can the Survivor Principle Survive Diversification?
Authors: Lien Lasse B. , Klein Peter G.
Published: December 2012

The survivor principle holds that the competitive process weeds out inefficient firms, so that hypotheses about efficient behavior can be tested by observing what firms actually do. This principle underlies a large body of empirical work in strategy, economics, and management. But do competitive markets really select for efficient behavior? Is the survivor principle reliable? We evaluate the survivor principle in the context of corporate diversification, asking if survivor-based measures of interindustry relatedness are good predictors of firms’ decisions to exit particular lines of business, controlling for other firm and industry characteristics that affect firms’ portfolio choices. We find strong, robust evidence that survivor-based relatedness is an important determinant of exit. This empirical regularity is consistent with an efficiency rationale for firm-level diversification, though we cannot rule out alternative explanations based on firms’ desire for legitimacy by imitation and attempts to temper multimarket competition.
“Does This Sound Like a Fair Deal?”: Antecedents and Consequences of Fairness Expectations in the Individual’s Decision to Participate in Firm Innovation
Authors: Franke Nikolaus , Keinz Peter , Klausberger Katharina
Published: December 2012

The Internet has given rise to new organizational forms of integrating users into firm innovation. Companies willing to make use of external resources can now outsource innovation-related tasks to huge “crowds” outside the company. The extant literature on participation motives assumes a symbiotic relationship between the firm and external contributors in which both parties have largely complementary motives and are only interested in their own utility. In two experimental simulations, we show that this understanding has to be amended: potential contributors not only want a good deal, they also want a fair deal. Fairness expectations with regard to the distribution of value between the firm and contributors (distributive fairness) and the fairness of the procedures leading to this distribution (procedural fairness) impact the likelihood of participation beyond considerations of self-interest. Fairness expectations are formed on the basis of the terms and conditions of the crowdsourcing system and the ex ante level of identification with the firm organizing it. In turn, they impact the individuals’ transaction-specific reactions and also inform their future identification with the firm. These findings contribute not only to research on open and user innovation but also to theories on organizational fairness by enhancing our understanding of the emergent field of fairness expectations.
Deformations of unbounded convex bodies and hypersurfaces
Authors: Ghomi Mohammad
Published: December 2012

We study the topology of the space $\partial{\mathcal K}^n$ of complete
convex hypersurfaces of ${\bf R}^n$ which are homeomorphic to ${\bf
R}^{n-1}$. In particular, using Minkowski sums, we construct a deformation
retraction of $\partial{\mathcal K}^n$ onto the Grassmannian space of
hyperplanes. So every hypersurface in $\partial{\mathcal K}^n$ may be
flattened in a canonical way. Further, the total curvature of each
hypersurface evolves continuously and monotonically under this
deformation. We also show that, modulo proper rotations, the subspaces of
$\partial{\mathcal K}^n$ consisting of smooth, strictly convex, or
positively curved hypersurfaces are each contractible, which settles a
question of H. Rosenberg.
Disk counting on toric varieties via tropical curves
Authors: Nishinou Takeo
Published: December 2012

In this paper, we define two numbers. One is defined by counting tropical curves with a stop, and the other is the number of holomorphic disks in toric varieties with Lagrangian boundary condition. Both of these curves should satisfy some incidence conditions. We show that these numbers coincide. These numbers can be considered as Gromov-Witten type invariants for holomorphic disks, and they have similarities as well as differences to the counting numbers of closed holomorphic curves. We study several aspects of them.
Multiplicity one theorems for Fourier-Jacobi models
Authors: Sun Binyong
Published: December 2012

For every genuine irreducible admissible smooth representation $\pi$ of the metaplectic group
$\widetilde{{\rm Sp}}(2n)$ over a $p$-adic field, and every smooth oscillator representation $\omega_\psi$
of $\widetilde{{\rm Sp}}(2n)$, we prove that the tensor product $\pi\otimes\omega_\psi$ is multiplicity free
as a smooth representation of the symplectic group ${\rm Sp}(2n)$. Similar results are proved for general
linear groups and unitary groups.
Small families of complex lines for testing holomorphic extendibility
Authors: Globevnik Josip
Published: December 2012

Let $B$ be the open unit ball in ${\Bbb C}^2$. This paper deals with the
analog of Hartogs' separate analyticity theorem for CR functions on the
sphere $bB$. We prove such a theorem for functions in $C^\infty (bB)$: If
$a, b\in\overline B$, $a\not=b$ and if $f\in C^\infty (bB)$ extends
holomorphically into $B$ along any complex line passing through either $a$
or $b$, then $f$ extends holomorphically through $B$. On the other hand,
for each $k\in\Bbb{N}$ there is a function $f\in C^k(bB)$ which extends
holomorphically into $B$ along any complex line passing through either $a$
or $b$ yet $f$ does not extend holomorphically through $B$. More
generally, in the paper we obtain a fairly complete description of pairs
of points $a, b\in{\Bbb C}^2$, $a\not= b$, such that if $f\in C^\infty
(bB)$ extends holomorphically into $B$ along every complex line passing
through either $a$ or $b$ that meets $B$, then $f$ extends holomorphically
through $B$.
Unramified Brauer groups of finite and infinite groups
Authors: Moravec Primož
Published: December 2012

The Bogomolov multiplier is a group theoretical invariant isomorphic to the unramified Brauer group of
a given quotient space. We derive a homological version of the Bogomolov multiplier, prove a Hopf-type
formula, find a five term exact sequence corresponding to this invariant, and describe the role of the
Bogomolov multiplier in the theory of central extensions. A new description of the Bogomolov multiplier
of a nilpotent group of class two is obtained. We define the Bogomolov multiplier within $K$-theory and
show that proving its triviality is equivalent to solving a long-standing problem posed by Bass. An
algorithm for computing the Bogomolov multiplier is developed.
Catalan numbers for complex reflection groups
Authors: Gordon Iain G. , Griffeth Stephen
Published: December 2012

We construct $(q,t)$-Catalan polynomials and $q$-Fuss-Catalan polynomials for any irreducible complex
reflection group $W$. The two main ingredients in this construction are Rouquier's formulation of shift
functors for the rational Cherednik algebras of $W$, and Opdam's analysis of permutations of the irreducible
representations of $W$ arising from the Knizhnik-Zamolodchikov connection.
On the non-vanishing of Hecke L -values modulo p
Authors: Hsieh Ming-Lun
Published: December 2012

In this article, we follow Hida's approach to establish an analogue of Washington's
theorem on the non-vanishing modulo $p$ of Hecke $L$-values for CM fields with
anticyclotomic twists.