bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering Platforms for Directed Evolution of Laccase from Pycnoporus cinnabarinus
Authors: Camarero S. , Pardo I. , Cañas A. I. , Molina P. , Record E. , Martínez A. T. , Martínez M. J. , Alcalde M.
Published: December 2011

While the
Pycnoporus cinnabarinus
laccase (PcL) is one of the most promising high-redox-potential enzymes for environmental biocatalysis, its practical use has to date remained limited due to the lack of directed evolution platforms with which to improve its features. Here, we describe the construction of a PcL fusion gene and the optimization of conditions to induce its functional expression in
Saccharomyces cerevisiae
, facilitating its directed evolution and semirational engineering. The native PcL signal peptide was replaced by the α-factor preproleader, and this construct was subjected to six rounds of evolution coupled to a multiscreening assay based on the oxidation of natural and synthetic redox mediators at more neutral pHs. The laccase total activity was enhanced 8,000-fold: the evolved α-factor preproleader improved secretion levels 40-fold, and several mutations in mature laccase provided a 13.7-fold increase in
k
cat
. While the pH activity profile was shifted to more neutral values, the thermostability and the broad substrate specificity of PcL were retained. Evolved variants were highly secreted by
Aspergillus niger
(∼23 mg/liter), which addresses the potential use of this combined-expression system for protein engineering. The mapping of mutations onto the PcL crystal structure shed new light on the oxidation of phenolic and nonphenolic substrates. Furthermore, some mutations arising in the evolved preproleader highlighted its potential for heterologous expression of fungal laccases in yeast (
S. cerevisiae
).
Genetic Characterization of Escherichia coli O104 Isolates from Different Sources in the United States
Authors: Rump Lydia V. , Bodeis-Jones Sonya , Abbott Jason , Zhao Shaohua , Kase Julie , Lorenz Sandra , Fischer Markus , Brown Eric , Meng Jianghong
Published: December 2011

Escherichia coli
O104 isolates collected from different sources in the United States were examined for virulence genes typical of enterohemorrhagic
E. coli
and those identified in the O104:H4 isolate associated with the 2011 German outbreak. The unexpected presence of virulence markers in these isolates highlights the importance of screening unusual and potentially pathogenic Shiga toxin-producing
E. coli
serotypes.
Vacuolar H
+
-ATPase Works in Parallel with the HOG Pathway To Adapt Saccharomyces cerevisiae Cells to Osmotic Stress
Authors: Li Sheena Claire , Diakov Theodore T. , Rizzo Jason M. , Kane Patricia M.
Published: December 2011

Hyperosmotic stress activates an array of cellular detoxification mechanisms, including the high-osmolarity glycerol (HOG) pathway. We report here that vacuolar H
+
-ATPase (V-ATPase) activity helps provide osmotic tolerance in
Saccharomyces cerevisiae
. V-ATPase subunit genes exhibit complex haploinsufficiency interactions with HOG pathway components.
vma
mutants lacking V-ATPase function are sensitive to high concentrations of salt and exhibit Hog1p activation even at low salt concentrations, as demonstrated by phosphorylation of Hog1p, a shift in Hog1-green fluorescent protein localization, transcriptional activation of a subset of HOG pathway effectors, and transcriptional inhibition of parallel mitogen-activated protein kinase pathway targets.
vma2Δ hog1Δ
and
vma3Δ pbs2Δ
double mutants have a synthetic growth phenotype, poor salt tolerance, and an aberrant, hyper-elongated morphology on solid media, accompanied by activation of a filamentous response element-LacZ construct, indicating cross talk into the filamentous growth pathway. Vacuoles isolated from wild-type cells briefly exposed to salt show higher levels of V-ATPase activity, and Na
+
/H
+
exchange in isolated vacuolar vesicles suggests a biochemical basis for the genetic interactions observed. V-ATPase activity is upregulated during salt stress by increasing assembly of the catalytic V
1
sector with the membrane-bound V
o
sector. Together, these data suggest that the V-ATPase acts in parallel with the HOG pathway in order to mediate salt detoxification.
Transcriptome and Functional Analysis of Mating in the Basidiomycete Schizophyllum commune
Authors: Erdmann Susann , Freihorst Daniela , Raudaskoski Marjatta , Schmidt-Heck Wolfgang , Jung Elke-Martina , Senftleben Dominik , Kothe Erika
Published: December 2011

In this study, we undertook a functional characterization and transcriptome analysis that enabled a comprehensive study of the mating type loci of the mushroom
Schizophyllum commune
. Induced expression of both the
bar2
receptor and the
bap2(2)
pheromone gene within 6 to 12 h after mates' contact was demonstrated by quantitative real-time PCR. Similar temporal expression patterns were confirmed for the allelic
bbr1
receptor and
bbp1
pheromone-encoding genes by Northern hybridization. Interestingly, the fusion of clamp connections to the subterminal cell was delayed in mating interactions in which one of the compatible partners expressed the
bar2
receptor with a truncated C terminus. This developmental delay allowed the visualization of a green fluorescent protein (Gfp)-labeled truncated receptor at the cell periphery, consistent with a localization in the plasma membrane of unfused pseudoclamps. This finding does not support hypotheses envisioning a receptor localization to the nuclear membrane facilitating recognition between the two different nuclei present in each dikaryotic cell. Rather, Gfp fluorescence observed in such pseudoclamps indicated a role of receptor-pheromone interaction in clamp fusion. Transcriptome changes associated with mating interactions were analyzed in order to identify a role for pheromone-receptor interactions. We detected a total of 89 genes that were transcriptionally regulated in a mating type locus
A
-dependent manner, employing a cutoff of 5-fold changes in transcript abundance. Upregulation in cell cycle-related genes and downregulation of genes involved in metabolism were seen with this set of experiments. In contrast, mating type locus
B
-dependent transcriptome changes were observed in 208 genes, with a specific impact on genes related to cell wall and membrane metabolism, stress response, and the redox status of the cell.
Interplay of a Ligand Sensor and an Enzyme in Controlling Expression of the Saccharomyces cerevisiae
GAL
Genes
Authors: Abramczyk Dariusz , Holden Stacey , Page Christopher J. , Reece Richard J.
Published: December 2011

The regulation of the
Saccharomyces cerevisiae
GAL
genes in response to galactose as a source of carbon has served as a paradigm for eukaryotic transcriptional control over the last 50 years. Three proteins—a transcriptional activator (Gal4p), an inhibitor (Gal80p), and a ligand sensor (Gal3p)—control the switch between inert and active gene expression. The molecular mechanism by which the recognition of galactose within the cell is converted into a transcriptional response has been the subject of considerable debate. In this study, using a novel and powerful method of localizing active transcription factors within the nuclei of cells, we show that a short-lived complex between Gal4p, Gal80p, and Gal3p occurs soon after the addition of galactose to cells to activate
GAL
gene expression. Gal3p is subsequently replaced in this complex by Gal1p, and a Gal4p-Gal80p-Gal1p complex is responsible for the continued expression of the
GAL
genes. The transient role of the ligand sensor indicates that current models for the induction and continued expression of the yeast
GAL
genes need to be reevaluated.
Integration of σ
B
Activity into the Decision-Making Process of Sporulation Initiation in Bacillus subtilis
Authors: Reder Alexander , Gerth Ulf , Hecker Michael
Published: December 2011

Spo0A∼P is the master regulator of sporulation in
Bacillus subtilis
. Activity of Spo0A is regulated by a phosphorelay integrating multiple positive and negative signals by the action of kinases and phosphatases. The phosphatase Spo0E specifically inactivates the response regulator Spo0A∼P by dephosphorylation. We identified a σ
B
-type promoter adjacent to
spo0E
that is activated by the general stress response sigma factor σ
B
and is responsible for
spo0E
induction
in vivo
. Ectopic expression of σ
B
and subsequent induction of
spo0E
cause a σ
B
-dependent block of sporulation-specific transcription of the
spo0A
and
spoIIE
genes and produces a sporulation-deficient phenotype. This effect could be erased by a deletion of the σ
B
promoter of
spo0E
and thus solely addresses σ
B
activity. Here, a molecular mechanism is shown that integrates σ
B
activity into the decision-making process of sporulation and provides a link to interconnect these two dominant and probably mutually exclusive adaptive responses in the regulatory network of
B. subtilis
.
Paediatric trauma patients and attention deficit hyperactivity disorder: correlation and significance
Authors: Ertan Cem , Özcan Özlem Özel , Pepele Mustafa Safa
Published: January 2012

Introduction

Trauma is one of the leading reasons for emergency department (ED) visits in children. Hyperactivity, inattentiveness and impulsiveness may contribute to injury proneness. The aim of this study was to evaluate the prevalence and role of attention deficit hyperactivity disorder (ADHD) in children with trauma.

Methods

Trauma patients aged 3–17 attending the ED were included in the study group. Parents were informed after medical care had been given to their children, and demographic data and information about the trauma were collected. Later, parents were asked to complete the Conners' Parent Rating Scales-Revised questionnaire for ADHD symptoms. The control group consisted of children of similar age and sociocultural characteristics who attended the hospital for reasons other than trauma. Cases in which the child apparently had no active role in the trauma or where the parents did not complete the Conners' Parent Rating Scales-Revised questionnaire were excluded from the study.

Results

Fifty-five children were included in the study group (mean age 7.49 (range 3–14; SD 3.3); 33 (60%) were male). The control group was statistically similar to the study group. The most common trauma mechanism was falls (n=31, 56.4%). All the subscale scores were significantly higher in the study group, and previous trauma-related ED visits were associated with significantly higher subscale scores.

Conclusion

The data suggest that children who make repeated trauma-related ED visits have a predisposition to ADHD, and they may benefit from screening for this disorder while in the ED.
Data sharing for prevention: a case study in the development of a comprehensive emergency department injury surveillance system and its use in preventing violence and alcohol-related harms
Authors: Quigg Zara , Hughes Karen , Bellis Mark A
Published: January 2012

Objective

To examine emergency department (ED) data sharing via a local injury surveillance system and assess its contribution to the prevention of violence and alcohol-related harms.

Methods

6-year (2004–2010) exploratory study analysing injury attendances to one ED in the North West of England using descriptive and trend analyses.

Results

Over the 6-year period, there were 242 796 ED injury attendances, including 21 683 for intentional injuries. Compared with unintentional injury patients, intentional injury patients were more likely to be men, aged 18–34 years, live in the most deprived communities, have attended the ED at night/weekends, have been injured in a public place and have consumed alcohol prior to the injury. Detailed data collected on alcohol and violence-related ED attendances were shared with local partners to monitor local trends and inform prevention activity including targeted policing and licensing enforcement. Over the 6-year period, intentional ED injury attendances decreased by 35.6% and alcohol-related assault attendances decreased by 30.3%.

Conclusions

The collection of additional ED data on assault details and alcohol use prior to injury, and its integration into multi-agency policy and practice, played an important role in driving local violence prevention activity. Further research is needed to assess the direct contribution ED data sharing makes to reductions in violence.
CHARACTERIZING ENGLISH POETIC STYLE USING COMPLEX NETWORKS
Authors: ROXAS-VILLANUEVA RANZIVELLE MARIANNE , NAMBATAC MAELORI KRISTA , TAPANG GIOVANNI
Published: January 2012

Complex networks have been proven useful in characterizing written texts. Here, we use networks to probe if there exist a similarity within, and difference across, era as reflected within the poem's structure. In literary history, boundary lines are set to distinguish the change in writing styles through time. We obtain the network parameters and motif frequencies of 845 poems published from 1522 to 1931 and relate this to the writing of the Elizabethan, 17th Century, Augustan, Romantic and Victorian eras. Analysis of the different network parameters shows a significant difference of the Augustan era (1667–1780) with the rest. The network parameters and the convex hull and centroids of the motif frequencies reflect the adjectival sequence pattern of the poems of the Augustan era.
WHITE NOISE DRIVEN SPDEs WITH TWO REFLECTING WALLS
Authors: ZHANG TUSHENG , YANG JUAN
Published: January 2012

In this paper, we study stochastic partial differential equations with two reflecting smooth walls h1 and h2, driven by space-time white noise with non-constant diffusion coefficients. The existence and uniqueness of the solutions are established.
Definition and Risk Factors of Rapidly Declining Residual Renal Function in Peritoneal Dialysis: An Observational Study
Authors: Herget-Rosenthal Stefan , von Ostrowski Michael , Kribben Andreas
Published: January 2012

Background: It is critical to preserve residual renal function (RRF) in peritoneal dialysis (PD), as RRF is associated with lower morbidity and mortality. There is no uniform definition of RRF, and rapidly declining RRF has rarely been studied and predominately limited to single factor analysis and not corrected for lead-time bias. Methods: An observational study in 71 incident PD patients. RRF was defined as urine output (UO) ≥500 ml/day and renal glomerular filtration rate (rGFR) ≥2 ml/min/1.73 m2, rapid declining RRF as UO <500 ml/day and rGFR <2 ml/min/1.73 m2 occurring within 6 months which were separately evaluated. Independent risk factors associated with rapid RRF decline were identified while correcting for lead-time bias. Results: RRF declined rapidly by both definitions in 65% patients 2.5 years after PD start. Both definitions of RRF decline were consistent in 96%. Nephrotoxic drugs, renal transplant failure and absent angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) were independent risk factors associated with rapidly declining RRF defined both by definitions, intravascular radiocontrast additionally for UO decline. Conclusions: Most PD patients demonstrated rapid RRF decline, independent of its definition. Both definitions are highly consistent and interchangeable. Nephrotoxic drugs and radiocontrast were identified as risk factors of acute, absent ACEI or ARB, and renal transplant failure of chronic renal injury.
Ultrastructure of the Anterior Lens Capsule and Epithelium in Cataracts Associated with Uveitis
Authors: Stunf Spela , Hvala Anastazija , Vidovič Valentinčič Nataša , Kraut Aleksandra , Hawlina Marko
Published: January 2012

Aims: To study the ultrastructure of the anterior lens capsule and epithelium, and capsular thickness in uveitic cataracts. Methods: Capsulorhexis samples from 20 uveitic cataracts were compared to 20 nuclear cataracts using the semi- and ultra-thin techniques. Results: Extensive epithelial and capsular-epithelial border changes and epithelial-mesenchymal transition in some fibrotic capsules were found only in the uveitic group. All these changes were observed predominately in white uveitic cataracts. Mild and moderate ultrastructural changes were seen in both groups. Surface deposition of amorphous material was also found only in uveitic cataracts. Capsular thickness was not different between the two groups. Conclusions: Uveitic capsules showed more extensive and different ultrastructural changes that probably occurred because of inflammation in the eye and epithelial-mesenchymal transition. These changes might be an additional reason for altered behavior of the lens capsule at capsulorhexis.
Surgical Treatment of Metabolic Syndrome
Authors: Williams Sharon , Cunningham Emily , Pories Walter J.
Published: January 2012

This article explores the surprising finding that bariatric surgery can produce full and durable remission of the metabolic syndrome as well as other comorbidities of obesity including type II diabetes, hypertension, polycystic ovary syndrome, gastroesophageal reflux disease, nonalcoholic steatotic hepatitis, adult asthma and improvement in weight-bearing arthropathy. Such an outcome was previously deemed impossible. One effect of the surgery is the correction of hyperinsulinemia, a common denominator in the various expressions of the metabolic syndrome. Basal insulin levels return to normal levels within a matter of days following surgery, allowing a return of the first phase of insulin secretion. This effect is ‘dose related’ to the extent of the reduction of contact between food and the gut. The resolution of the spectrum of diseases that comprise the metabolic syndrome following bariatric surgery suggests that hyperinsulinemia may be the common cause that is corrected by lowering contact between food and the gut. If this concept is true, then the cause of the syndrome, including diabetes, could be a diabetogenic signal from the gut that forces the islets to produce excessive and harmful levels of insulin, or the cause could be the removal of a signal that blocks excessive insulin secretion. If either of these mechanisms is proven correct, the current treatment of diabetes with long-term insulin administration deserves review.
Review of Emotion Recognition in Mild Cognitive Impairment
Authors: McCade Donna , Savage Greg , Naismith Sharon L.
Published: January 2012

Background: While dysfunction in emotion recognition is sometimes apparent with aging, and is frequently evident in Alzheimer’s disease, it is unclear whether individuals who have a high risk of developing dementia exhibit demonstrable changes. Method: A review of the literature pertaining to mild cognitive impairment was undertaken to discern the extent to which emotion recognition deficits are evident in this prodromal period. Results: A search of Medline, Psycinfo and Psyextra databases using specific key words identified only six relevant studies. These studies suggest that the ability to accurately identify facial expressions of affect is compromised. Conclusions: Research in this area is in its infancy. Suggestions are made for furthering our knowledge about this important ability which affects interpersonal relationships, daily functioning, mental well-being and quality of life.
Basal Cerebral Computed Tomography as Diagnostic Tool to Improve Patient Selection in Asymptomatic Carotid Artery Stenosis
Authors: Pecoraro Felice , Dinoto Ettore , Mirabella Domenico , Corte Giuseppe , Bracale Umberto Marcello , Bajardi Guido
Published: December 2011

One-hundred patients were included to evaluate the role of cerebral computed tomography (CT) to improve patient selection in asymptomatic internal carotid stenosis. Symptomatic patients were assigned to group A, asymptomatic patients to group B. A cerebral CT pattern A was observed in groups A and B in 60% and 20%, respectively ( P < .0001). Between A and B groups, type 6 plaques were found, respectively, in 26.7% and 7.5% of patients ( P = .01); a type 5 in 51.7% and 45% ( P = .32) of patients; and a type 4 in 21.7% and 47.5% of patients, respectively ( P = .006). Within B group, the association of CT pattern A and histological plaque level 4, 5, and 6 was, respectively, 25% ( P = .15), 50% ( P = .53), and 25% ( P = .16). In group B, a 7-fold risk increase in CT pattern A was found in patients with level 6 plaque. In asymptomatic patients with high-risk plaque, a basal cerebral CT scan can be used as diagnostic tool to improve patient selection for intervention.
Socialization and the Acquisition of Professional Discourse
Authors: Bremner Stephen
Published: December 2011

This article tracks the socialization of a Chinese intern into a Hong Kong PR company and considers the factors that enabled her to move toward acquiring the discourse of the profession. Taking a case study approach, the research is based on a detailed daily journal written by the intern during her internship, and two interviews. Over the 3-month period of the internship, her written discourse changed considerably, revealing the extent of her socialization into the organization. Specifically, the intern’s writing changed from detailed general descriptions of her activity to discourse resembling that of PR practitioners. The study demonstrates the power of the workplace as a context for learning, yet data show that the academy, by providing tools for understanding and reflecting on organizational culture, also has a role to play in socialization processes.
Relationship of Hyperactivity/Inattention With Adiposity and Lifestyle Characteristics in Preschool Children
Authors: Ebenegger Vincent , Marques-Vidal Pedro-Manuel , Munsch Simone , Quartier Vincent , Nydegger Andreas , Barral Jérôme , Hartmann Tim , Dubnov-Raz Gal , Kriemler Susi , Puder Jardena J.
Published: December 2011

We performed a cross-sectional study in 450 nonreferred preschool children aged 4 to 6 years to assess the association between hyperactivity/inattention with adiposity and lifestyle characteristics. Measurements included scores of hyperactivity/inattention, adiposity, objectively measured physical activity, television viewing, and eating habits. Higher scores of hyperactivity/inattention were associated with lower percentage body fat, higher levels of physical activity, and less time spent in sedentary activity (all P ≤ .01). However, higher scores of hyperactivity/inattention were also associated with more television viewing and less healthy eating habits (all P ≤ .04). Except for some selected eating habits ( P ≥ .07), those relationships remained significant after adjustment for age, sex, and sociodemographic confounders. To conclude, higher scores of hyperactivity/inattention are linked to different lifestyle characteristics that may in part contribute to a future development of overweight/obesity. Precise mechanisms explaining these associations and possible preventive approaches should be further investigated.
Histomorphometrical and clinical study of connective tissue around titanium dental implants with porous surfaces in a canine model
Authors: Zhao Bao Hong , Cui Fu Zhai , Liu Yang , Deng Chun Fu
Published: December 2011

Connective tissue (CT) reactions and collagen fiber orientation were evaluated on titanium implants with porous surfaces made by a laser method. Three groups in which the diameters of pores were 10 ± 5 µm, 40 ± 5 µm, and 70 ± 5 µm were involved in this test, together with a machined group as control. A total of 24 implants were randomly placed in mandibles after 3 months of premolars and the first molar extraction in beagle dogs. All the implants were firmly anchored in the bone after 3-month insertion. Histological sections showed that the gingival tissue was attached tightly to implant surface and there was no significant difference in inflammatory cell invasion and probing depth among all groups ( p > 0.05). Histomorphometric analysis demonstrated that no significant difference in total CT length was observed among four groups ( p > 0.05), however, the gingival recession in the 40 ± 5 µm and 70 ± 5 µm porous groups was less than in the 10 ± 5 µm porous group and control group ( p < 0.05). Collagen fibers at the inner zone of the CT around the 40 ± 5 µm and 70 ± 5 µm porous implants aligned mostly in an oblique orientation, while there was a mainly parallel fiber direction around the 10 ± 5 µm porous and control implants. It was noted that some fibroblasts and fibers in the 70 ± 5 µm porous group was inserted into the pores of implant surface, indicating that pores of a proper size on the implant surface could induce the insertion of CT and prevent gingival recession.
In vitro assessment of blood compatibility: Residual and dynamic markers of cellular activation
Authors: Johnson Greg , Curry Benjamin , Cahalan Linda , Prater Roni , Beeler Michael , Gartner Mark , Biggerstaff John , Cahalan Patrick
Published: December 2011

The blood compatibility of materials and surfaces used for medical device fabrication is a crucial factor in their function and effectiveness. Expansion of device use into more sensitive and longer term applications warrants increasingly detailed evaluations of blood compatibility that reach beyond the customary measures mandated by regulatory requirements. A panel of tests that assess both deposition on the surface and activation of circulating blood in contact with the surface has been developed. Specifically, the ability of a surface to modulate the biological response of blood is assessed by measuring: (1) dynamic thrombin generation; (2) surface-bound thrombin activity after exposure to blood; (3) activation of monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets; (4) activation of complement; and (5) adherent monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets on blood-contacting surfaces. The tests were used to evaluate surfaces modified with immobilized heparin (Ension’s proprietary bioactive surface) and demonstrated that the modified surfaces reduced platelet activation, leukocyte activation, and complement activation in flowing human blood. Perfusion of the surfaces with human platelet-rich plasma showed that the immobilized heparin surfaces also reduce both dynamic thrombin levels in the circulating plasma and residual thrombin generated at the material surface.
Comparing Reports From Hip-Fracture Patients and Their Proxies
Authors: Shardell Michelle , Alley Dawn E. , Miller Ram R. , Hicks Gregory E. , Magaziner Jay
Published: December 2011

Objective: This study compared sex differences in disability and depressive symptoms using reports from hip fracture patients and their proxies. Method: Hip fracture patients (49 men, 183 women) aged ≥65 years and proxies were interviewed 1 year postfracture. Outcomes were Center for Epidemiological Studies Depression (CES-D) and number of dependencies in performing activities of daily living and instrumental activities of daily living. Results: Mean ADL sex differences (men minus women) were 0.40 ( p = .37) using proxy reports and 0.70 ( p = .08) using patient self-reports. Mean CES-D sex differences were −3.60 ( p = .02) using proxy reports and −1.26 ( p = .38) using patient self-reports. Discrepancies between patients and proxies were smallest for proxies who have lived with the patient ≥ 1 year. Discussion: Patients and proxies produced conflicting conclusions about sex differences. Results suggest that ideal proxies to recruit are those who have been cohabitating with the patients for an extended length of time.
Accountability of Transnational NGOs
Authors: Schmitz Hans Peter , Raggo Paloma , Bruno-van Vijfeijken Tosca
Published: December 2011

Nongovernmental organizations (NGOs) working across borders face increased accountability demands. Although many have proposed ways of changing accountability practices, the debate is rarely informed by leaders’ perspectives of how accountability is perceived and practiced across different organizational settings. In interviews with NGO leaders we find aspirations to make accountability more meaningful and integrated, in particular by listening more to stakeholders other than donors. However, these aspirations are rarely put in practice and leaders continue to highlight traditional means such as financial accounting. This gap is particularly pronounced for smaller organizations and reflects an increasingly competitive environment shaped by rating agencies and a focus on financial metrics. To move from aspirations to practice, NGOs have to be willing to share more meaningful information about their work and outcomes with stakeholders. Practicing transparency that empowers beneficiaries is central to effective organizational learning and balancing demands from different stakeholders.
Social Expectations, Constraints, and Their Effect on Nonprofit Strategies
Authors: Sosin Michael R.
Published: December 2011

A comprehensive analysis of the strategies pursued by nonprofit agencies must take into account not only the conventional market forces but also the social expectations and constraints that the agencies regularly confront. This study reports on a theoretically guided, qualitative analysis of the strategies that develop in the context of such factors. Data stem from interviews with officials from 12 agencies, the agencies’ prime funding agency, and interest groups. The results suggest that sampled agencies occasionally use conventionally described strategies as well as the social and political strategies covered in several previous studies, but that they most frequently rely on rarely considered “relationship” strategies by which they seek to establish and preserve an image or status. The results are argued to inform strategic decision making and to suggest ways in which agency officials may take into account two sources of social expectations and constraints: institutional arrangements and organizational identities.
On anholonomic deformation, geometry, and differentiation
Authors: Clayton JD
Published: December 2011

In geometrically nonlinear theories of inelasticity of solids, the deformation gradient is typically split multiplicatively into two (or more terms), none of which need be integrable to a motion or displacement field. Such terms, when not integrable, are termed anholonomic, and can be associated with intermediate configuration(s) of a deformed material element. In this work, aspects of tensor calculus associated with anholonomic deformation are analyzed in general curvilinear coordinates. Various linear connection coefficients for intermediate configurations are posited or derived; of particular interest are those mapped coefficients corresponding to the choice of identical basis vectors in multiple configurations. It is shown that torsion and curvature associated with such mapped coefficients do not necessarily vanish, even though torsion and curvature tensors of the original connections vanish by definition in reference or current configurations. Intermediate connection coefficients defined in this way exhibit vanishing covariant derivatives of corresponding metric tensors, but are time dependent even when reference (current) configuration connections are fixed in time at a given material (spatial) location. Formulae are derived for total covariant derivatives of two- and three-point tensors with one or more components referred to the intermediate configuration. It is shown that in intermediate coordinates, neither the divergence of the curl of a vector field nor the curl of the gradient of a scalar field need always vanish. The balance of linear momentum for a hyperelastic–plastic material is examined in the context of curvilinear intermediate coordinates.
Self-Concept of College Students With ADHD
Authors: Nelson Jason M.
Published: December 2011

Objective: To investigate the self-concept of college students with ADHD. Method: College students with ADHD and their parents completed self-report and observer-report measures of self-concept, respectively. Results: Results indicated that college students with ADHD did not report problems with self-concept but their parents did for them. This difference was statistically significant and large in magnitude ( d = .84). Conclusion: Perceptions of the self-concept of college students with ADHD appear to vary by informant source. Hypotheses for the discordance between self- and parent-reports are discussed. Multi-informant assessment is recommended as a way to obtain a more complete clinical picture than reliance on self- or parent-report alone.
Validation of the Chinese Strengths and Weaknesses of ADHD-Symptoms and Normal-Behaviors Questionnaire in Hong Kong
Authors: Lai Kelly Y. C. , Leung Patrick W. L. , Luk Ernest S. L. , Wong Ann S. Y. , Law Lawrence S. C. , Ho Karen K. Y.
Published: December 2011

Objective: Unlike rating scales that focus on the severity of ADHD symptoms, the Strengths and Weaknesses of ADHD-Symptoms and Normal-Behaviors (SWAN) rating scale is phrased in neutral or positive terms for carers to compare the index child’s behaviors with that of their peers. This study explores its psychometric properties when applied to Chinese children in Hong Kong. Method: Ratings from the Chinese SWAN scale collected from parents and teachers of a community sample of 3,722 6- to 12-year-old students recruited by stratified random sampling were compared with 247 clinic children with a diagnosis of ADHD. Reliability, validity, factor structure, and cutoff scores were calculated. Results: Favorable psychometrics and a two-factor structure identical to the original were reproduced. Cutoff scores were supported by satisfactory sensitivities and specificities. Conclusion: The SWAN scale is a reliable and valid instrument for the assessment of ADHD symptoms in Chinese children in Hong Kong.
Cross-cultural conflict and affirmative action: Inter- and intra-ethnic dilemmas of Malaysia’s heterogeneous workplace
Authors: Montesino Max U
Published: December 2011

This article, a combination of field research report and literature review, looks at affirmative-action policies both as a mechanism for managing cross-cultural conflict and as creator of other types of conflicts in multi-ethnic Malaysia. Socioeconomic imbalances and post-independence rioting prompted the implementation of these policies to reduce ethnic confrontations and uplift the majority Bumiputras. They were reluctantly accepted by the minority immigrant communities, but managed to change Malaysia’s pre-independence ethnic disparities. The article identifies some of the cross-cultural conflicts the nation still faces, after four decades of affirmative action: (a) the existence of a highly segregated educational system with little opportunity for intercultural interactions; (b) the ghost of latent inter-ethnic tensions beneath the surface; (c) the accentuation of intra-ethnic disparities; (d) complaints about alleged Malay cultural hegemony and Chinese economic hegemony; (e) the visible marginalization of ethnic Indians due to alleged discrimination; (f) the formation of ethnic enclaves in the market; (g) fierce debate about the effects of the affirmative policies; and (h) some challenging by-products of ethno-politics. It also identifies some of the positive factors that work in favor of a better management of these cross-cultural conflicts: (a) the capacity of the country to withstand the changing winds of the global economy; (b) the relative stability of the societal balance produced by the affirmative economic policies since 1970; (c) the reduction of poverty as a direct result of affirmative action; (d) the accentuation of the Malaysian character of the nation among new generations of immigrants; (e) the promise of formal programs to promote national unity; and (f) contemporary trends that promise mindset changes.
Participants’ motivations and co-construction of the qualitative research process
Authors: Bell Karen
Published: December 2011

This article explores what motivated participants to volunteer for a qualitative social work research project as well as the co-construction of the researcher-participant relationship. In social work research methodology literature, much attention has been given to the importance of engaging participants in democratized research relationships, but less attention has been given to the process from participants’ perspectives. Often, little is known about the meanings attributed by participants to the process. Based on information from participants in a doctoral research project on psychosocial support needs in relation to assisted reproductive service use, this article considers participants’ motivations to volunteer for research. Twenty-eight women were interviewed and all were asked about their motivations to volunteer; their responses highlight the mutuality of exchange and the complexity of the researcher-participant relationship. The need for social work researchers to carefully negotiate this relationship and to acknowledge and actively respond to participants’ motivations is reinforced.
Antipodean Performativity
Authors: Rinehart Robert E.
Published: December 2011

In this article introducing the special issue, I argue for ethnographic research and research traditions that are simultaneously global and local, that are universal and singular, that are a mish-mash of cultural and individual negotiations. Further, in this piece, I locate a Performative Ethnography that is both vital and thriving, and offer as exemplars the authors’ works.
Killing by neutrophil extracellular traps: fact or folklore?
Authors: Menegazzi Renzo , Decleva Eva , Dri Pietro
Published: December 2011

Neutrophil extracellular traps (NETs) are DNA structures released by dying neutrophils and claimed to constitute a new microbicidal mechanism. Killing by NET-forming cells is ascribed to these structures because it is prevented by preincubation with DNase, which has been shown to dismantle NETs, before addition of the target microorganisms. Curiously, the possibility that the microorganisms ensnared in NETs are alive has not been considered. Using Staphylococcus aureus and Candida albicans blastospores, we demonstrate that the microorganisms captured by NETs and thought to be killed are alive because they are released and recovered in cell medium by incubation with DNase. It is concluded that NETs entrap but do not kill microbes.
PI3Kδ inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma
Authors: Meadows Sarah A. , Vega Francisco , Kashishian Adam , Johnson Dave , Diehl Volker , Miller Langdon L. , Younes Anas , Lannutti Brian J.
Published: December 2011

GS-1101 (CAL-101) is an oral PI3Kδ-specific inhibitor that has shown preclinical and clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. To investigate the potential role of PI3Kδ in Hodgkin lymphoma (HL), we screened 5 HL cell lines and primary samples from patients with HL for PI3Kδ isoform expression and constitutive PI3K pathway activation. Inhibition of PI3Kδ by GS-1101 resulted in the inhibition of Akt phosphorylation. Cocultures with stroma cells induced Akt activation in HL cells, and this effect was blocked by GS-1101. Conversely, production of the stroma-stimulating chemokine, CCL5, by HL cells was reduced by GS-1101. GS-1101 also induced dose-dependent apoptosis of HL cells at 48 hours. Reductions in cell viability and apoptosis were enhanced when combining GS-1101 with the mTOR inhibitor everolimus. Our findings suggest that excessive PI3Kδ activity is characteristic in HL and support clinical evaluation of GS-1101, alone and in combination, as targeted therapy for HL.
A newly identified complex of spinophilin and the tyrosine phosphatase, SHP-1, modulates platelet activation by regulating G protein–dependent signaling
Authors: Ma Peisong , Cierniewska Aleksandra , Signarvic Rachel , Cieslak Marcin , Kong Hong , Sinnamon Andrew J. , Neubig Richard R. , Newman Debra K. , Stalker Timothy J. , Brass Lawrence F.
Published: December 2011

Platelets are essential for normal hemostasis, but close regulation is required to avoid the destructive effects of either inappropriate platelet activation or excessive responses to injury. Here, we describe a novel complex comprising the scaffold protein, spinophilin (SPL), and the tyrosine phosphatase, SHP-1, and show that it can modulate platelet activation by sequestering RGS10 and RGS18, 2 members of the regulator of G protein signaling family. We also show that SPL/RGS/SHP1 complexes are present in resting platelets where constitutive phosphorylation of SPL(Y398) creates an atypical binding site for SHP-1. Activation of the SHP-1 occurs on agonist-induced phosphorylation of SHP-1(Y536), triggering dephosphorylation and decay of the SPL/RGS/SHP1 complex. Preventing SHP-1 activation blocks decay of the complex and produces a gain of function. Conversely, deleting spinophilin in mice inhibits platelet activation. It also attenuates the rise in platelet cAMP normally caused by endothelial prostacyclin (PGI2). Thus, we propose that the role of the SPL/RGS/SHP1 complex in platelets is time and context dependent. Before injury, the complex helps maintain the quiescence of circulating platelets by maximizing the impact of PGI2. After injury, the complex gradually releases RGS proteins, limiting platelet activation and providing a mechanism for temporal coordination of pro thrombotic and antithrombotic inputs.
Selection of optimal alternative graft source: mismatched unrelated donor, umbilical cord blood, or haploidentical transplant
Authors: Ballen Karen K. , Koreth John , Chen Yi-Bin , Dey Bimalangshu R. , Spitzer Thomas R.
Published: December 2011

Only 30% of patients who require an allogeneic hematopoietic cell transplant will have an HLA-matched sibling donor. A search for an unrelated donor will be undertaken for patients without a matched family donor. However, many patients, particularly patients of diverse racial and ethnic backgrounds, may not be able to rapidly identify a suitably matched unrelated donor. Three alternative graft sources, umbilical cord blood (UCB), haploidentical (haplo)–related donor, and mismatched unrelated donor (MMUD) are available. UCB is associated with decreased GVHD, but hematologic recovery and immune reconstitution are slow. Haplo-HCT is characterized by donor availability for transplantation and after transplantation adoptive cellular immunotherapy but may be complicated by a high risk of graft failure and relapse. A MMUD transplant may also be an option, but GVHD may be of greater concern. Phase 2 studies have documented advances in HLA typing, GVHD prophylaxis, and infection prevention, which have improved survival. The same patient evaluated in different transplant centers may be offered MMUD, UCB, or haplo-HCT depending on center preference. In this review, we discuss the rationale for donor choice and the need of phase 3 studies to help answer this important question.
Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma
Authors: Kridel Robert , Meissner Barbara , Rogic Sanja , Boyle Merrill , Telenius Adele , Woolcock Bruce , Gunawardana Jay , Jenkins Christopher , Cochrane Chris , Ben-Neriah Susana , Tan King , Morin Ryan D. , Opat Stephen , Sehn Laurie H. , Connors Joseph M. , Marra Marco A. , Weng Andrew P. , Steidl Christian , Gascoyne Randy D.
Published: December 2011

Mantle cell lymphoma (MCL), an aggressive subtype of non-Hodgkin lymphoma, is characterized by the hallmark translocation t(11;14)(q13;q32) and the resulting overexpression of cyclin D1 (CCND1). Our current knowledge of this disease encompasses frequent secondary cytogenetic aberrations and the recurrent mutation of a handful of genes, such as TP53, ATM, and CCND1. However, these findings insufficiently explain the biologic underpinnings of MCL. Here, we performed whole transcriptome sequencing on a discovery cohort of 18 primary tissue MCL samples and 2 cell lines. We found recurrent mutations in NOTCH1, a finding that we confirmed in an extension cohort of 108 clinical samples and 8 cell lines. In total, 12% of clinical samples and 20% of cell lines harbored somatic NOTCH1 coding sequence mutations that clustered in the PEST domain and predominantly consisted of truncating mutations or small frame-shifting indels. NOTCH1 mutations were associated with poor overall survival (P = .003). Furthermore, we showed that inhibition of the NOTCH pathway reduced proliferation and induced apoptosis in 2 MCL cell lines. In summary, we have identified recurrent NOTCH1 mutations that provide the preclinical rationale for therapeutic inhibition of the NOTCH pathway in a subset of patients with MCL.
Genesis of a novel Shigella flexneri serotype by sequential infection of serotype-converting bacteriophages SfX and SfI
Authors: Sun Qiangzheng , Lan Ruiting , Wang Yiting , Wang Jianping , Luo Xia , Zhang Shaomin , Li Peijing , Wang Yan , Ye Changyun , Jing Huaiqi , Xu Jianguo
Published: December 2011

Background

Shigella flexneri is the major pathogen causing bacillary dysentery. Fifteen serotypes have been recognized up to now. The genesis of new S. flexneri serotypes is commonly mediated by serotype-converting bacteriophages. Untypeable or novel serotypes from natural infections had been reported worldwide but have not been generated in laboratory.

Results

A new S. flexneri serotype-serotype 1 d was generated when a S. flexneri serotype Y strain (native LPS) was sequentially infected with 2 serotype-converting bacteriophages, SfX first and then SfI. The new serotype 1 d strain agglutinated with both serotype X-specific anti-7;8 grouping serum and serotype 1a-specific anti- I typing serum, and differed from subserotypes 1a, 1b and 1c. Twenty four S. flexneri clinical isolates of serotype X were all converted to serotype 1 d by infection with phage SfI. PCR and sequencing revealed that SfI and SfX were integrated in tandem into the proA-yaiC region of the host chromosome.

Conclusions

These findings suggest a new S. flexneri serotype could be created in nature. Such a conversion may be constrained by susceptibility of a strain to infection by a given serotype-converting bacteriophage. This finding has significant implications in the emergence of new S. flexneri serotypes in nature.
The nuclear factor-κB inhibitor pyrrolidine dithiocarbamate reduces polyinosinic-polycytidilic acid-induced immune response in pregnant rats and the behavioral defects of their adult offspring
Authors: Song Xueqin , Li Wenqiang , Yang Yongfeng , Zhao Jingping , Jiang Chengdi , Li Wei , Lv Luxian
Published: December 2011

Background

Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C) treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia.

Methods

We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) levels was determined by enzyme-linked immunosorbent assays (ELISA). The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI), passive avoidance, and active avoidance tests.

Results

PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring.

Conclusions

Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring.