bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban built environment configuration and psychological distress in older men: Results from the Caerphilly study
Authors: Sarkar Chinmoy , Gallacher John , Webster Chris
Published: July 2013

Background

Few studies have examined the impact of the built environment configuration upon mental health. The study examines the impact of objectively assessed land use and street network configuration upon psychological distress and whether this association is moderated by the natural environment and area-level deprivation.

Methods

In a community sample of 687 older men from the Caerphilly Prospective Study, built environment morphological metrics (morphometrics) were related to differences in psychological distress as measured by the General Health Questionnaire. Cross-sectional data were taken from the most recent (5th) phase. A multi-level analysis with individuals nested within census-defined neighbourhoods was conducted. Environmental measures comprised GIS-constructed land use and street network metrics, slope variability and a satellite derived measure of greenness.

Results

Reduced psychological distress was associated with residing in a terraced dwelling (OR = 0.48, p = 0.03), higher degrees of land-use mix (OR = 0.42, p = 0.03 for the high tertile) and having higher local-level street-network accessibility (‘movement potential’) (OR = 0.54, p = 0.03). Hillier topography with higher slope variability was associated with increased risks of psychological distress (OR = 1.38, p = 0.05).

Conclusions

The findings support our hypothesis that built environment configuration is independently associated with psychological distress. The study underscores the need for effective intervention in the planning and design of residential built environment to achieve the goal of health-sustaining communities.
Cell-cycle synchronization reverses Taxol resistance of human ovarian cancer cell lines
Authors: Wang Xueqing , Pan Lingya , Mao Ning , Sun Lifang , Qin Xiangjuan , Yin Jie
Published: July 2013

Background

Taxol is a powerful chemotherapy agent leading to mitotic arrest and cell death; however, its clinical efficacy has been hampered due to the development of drug resistance. Taxol specifically targets the cell cycle. Progress through mitosis (M stage) is an absolute requirement for drug-induced death because cell death is markedly reduced in cells blocked at the G1-S transition. The measured doubling time for ovarian cancer cells is about 27 h. As such, during treatment with Taxol most of the cells are not in the M stage of the cell cycle. Thus, the effect of cell-cycle synchronization was investigated in regard to reversing Taxol resistance in ovarian cancer cells.

Methods

Giemsa-Wright staining was used for assessing the morphology of the cells. The doubling time of the cells was calculated using formula as follows: Td = In2/slope. The resistant index and cell cycle were measured via MTT assays and flow cytometry. Thymidine was used to induce cell-cycle synchronization, and cell apoptosis rates following exposure to Taxol were measured using a flow cytometer.

Results

The growth doubling time of two Taxol-resistant cell lines were longer than that of Taxol-sensitive cells. Apoptotic rates in Taxol-sensitive and -resistant cell lines after synchronization and exposure to Taxol were all higher compared to unsynchronized controls (p <0.05).

Conclusions

Synchronization of the cell-cycle resulted in an increased effectiveness of Taxol toward ovarian cancer cell lines. We speculated that formation of drug resistance toward Taxol in ovarian cancer could be partly attributed to the longer doubling time of these cells.
A sparse-projection computed tomography reconstruction method for in vivo application of in-line phase-contrast imaging
Authors: Wang Liting , Li Xueli , Wu Mingshu , Zhang Lu , Luo Shuqian
Published: July 2013

Background

In recent years, X-ray phase-contrast imaging techniques have been extensively studied to visualize weakly absorbing objects. One of the most popular methods for phase-contrast imaging is in-line phase-contrast imaging (ILPCI). Combined with computed tomography (CT), phase-contrast CT can produce 3D volumetric images of samples. To date, the most common reconstruction method for phase-contrast X-ray CT imaging has been filtered back projection (FBP). However, because of the impact of respiration, lung slices cannot be reconstructed in vivo for a mouse using this method. Methods for reducing the radiation dose and the sampling time must also be considered.

Methods

This paper proposes a novel method of in vivo mouse lung in-line phase-contrast imaging that has two primary improvements compared with recent methods: 1) using a compressed sensing (CS) theory-based CT reconstruction method for the in vivo in-line phase-contrast imaging application and 2) using the breathing phase extraction method to address the lung and rib cage movement caused by a live mouse’s breathing.

Results

Experiments were performed to test the breathing phase extraction method as applied to the lung and rib cage movement of a live mouse. Results with a live mouse specimen demonstrate that our method can reconstruct images of in vivo mouse lung.

Conclusions

The results demonstrate that our method could deal with vivo mouse’s breathing and movements, meanwhile, using less sampling data than FBP while maintaining the same high quality.
Development of a panel of seven duplex real-time PCR assays for detecting 13 streptococcal superantigens
Authors: Yang Peng , Peng Xiaomin , Cui Shujuan , Shao Junbin , Zhu Xuping , Zhang Daitao , Liang Huijie , Wang Quanyi
Published: July 2013

Background

Streptococcal superantigens (SAgs) are the major virulence factors of infection in humans for group A Streptococcus (GAS) bacteria. A panel consisting of seven duplex real-time PCR assays was developed to simultaneously detect 13 streptococcal SAgs and one internal control which may be important in the control of GAS-mediated diseases.

Methods

Primer and probe sequences were selected based on the highly conserved region from an alignment of nucleotide sequences of the 13 streptococcal SAgs. The reaction conditions of the duplex real-time PCR were optimized and the specificity of the duplex assays was evaluated using SAg positive strains. The limit of detection of the duplex assays was determined by using 10-fold serial dilutions of the DNA of 13 streptococcal SAgs and compared to a conventional polymerase chain reaction (PCR) method for evaluating the duplex assays sensitivity.

Results

Using the duplex assays, we were able to differentiate between 13 SAgs from Streptococcus strains and other non-Streptococcus bacteria without cross-reaction. On the other hand, the limit of detection of the duplex assays was at least one or two log dilutions lower than that of the conventional PCR.

Conclusions

The panel was highly specific (100%) and the limit of detection of these duplex groups was at least ten times lower than that obtained by using a conventional PCR method.
Distinction of subtype-specific antibodies against European porcine influenza viruses by indirect ELISA based on recombinant hemagglutinin protein fragment-1
Authors: Zhao Na , Lange Elke , Kubald Sybille , Grund Christian , Beer Martin , Harder Timm C
Published: July 2013

Background

Serological investigations of swine influenza virus infections and epidemiological conclusions thereof are challenging due to the complex and regionally variable pattern of co-circulating viral subtypes and lineages and varying vaccination regimes. Detection of subtype-specific antibodies currently depends on hemagglutination inhibition (HI) assays which are difficult to standardize and unsuitable for large scale investigations.

Methods

The nucleocapsid protein (NP) and HA1 fragments of the hemagglutinin protein (HA) of five different lineages (H1N1av, H1N1pdm, H1pdmN2, H1N2, H3N2) of swine influenza viruses were bacterially expressed and used as diagnostic antigens in indirect ELISA.

Results

Proteins were co-translationally mono-biotinylated and refolded in vitro into an antigenically authentic conformation. Western blotting and indirect ELISA revealed highly subtype-specific antigenic characteristics of the recombinant HA1 proteins although some cross reactivity especially among antigens of the H1 subtype were evident. Discrimination of antibodies directed against four swine influenza virus subtypes co-circulating in Germany was feasible using the indirect ELISA format.

Conclusions

Bacterially expressed recombinant NP and HA1 swine influenza virus proteins served as antigens in indirect ELISAs and provided an alternative to commercial blocking NP ELISA and HI assays concerning generic (NP-specific) and HA subtype-specific sero-diagnostics, respectively, on a herd basis.
Comprehensive characterization of malignant phyllodes tumor by whole genomic and proteomic analysis: biological implications for targeted therapy opportunities
Authors: Jardim Denis L Fontes , Conley Anthony , Subbiah Vivek
Published: July 2013

Background

Phyllodes tumors are uncommon breast tumors that account for less than 0.5% of all breast malignancies. After metastases develop, the prognosis is poor, with very few patients living more than 1 year. The biology of this unusual cancer is not understood and, consequently, no potential targets for treatments are currently available. There has been an exponential increase in the number of commercially available tumor profiling services. Herein, we report a case of metastatic malignant phyllodes tumor for which a comprehensive molecular analysis was performed by using Clinical Laboratory Improvement Amendments (CLIA)-certified labs, providing new insights into the potential opportunities for molecularly targeted therapies for this extremely rare disease.

Methods

Next-generation sequencing was performed by using the FoundationOne™ platform (Foundation Medicine, Cambridge, MA). Whole-genome array-based comparative genomic hybridization (array CGH) was performed by using the DNAarray™ (CombiMatrix Diagnostics, Irvine, CA). Immunohistochemical and morphoproteomics analysis were performed at Consultative proteomics®, The University of Texas, UT Health Medical School, Houston,TX (Robert E Brown Lab); Clarient Diagnostics, Aliso Viejo, CA; and Caris Life Sciences Target one, Irving, TX, USA.

Results

Next-generation sequencing showed 3 aberrant genes: activating mutation Q61L onNRAS; inactivating mutations Q504* and K740* onRB1; andTP53loss. Whole-genome array-based comparative genomic hybridization (array CGH) revealed amplifications of chromosome (chr.) 1 (CKS1Bgene), chr. 8 (MYCgene), and chr. 9 (CDKN2Agene) Deletions of chr. 17 (TP53), chr. 10 (GATA3), chr. 11 (FGF4andCCND1genes), and chr.22 (PDGFβ). Immunohistochemical analysis for relevant markers showed a positive staining for transducing-like enhancer of split (TLE) 3; secreted protein acidic and rich in cysteine (SPARC) was expressed at 2-3+ in the cytoplasm of the tumors cells, whereas mammalian target of rapamycin (mTOR) was expressed up to 2+ in the nuclei of the tumor cells.

Conclusions

We describe for the first time anNRASmutation with concomitant activation ofPI3K/Akt/mTORin phyllodes tumor. We also found markers for sensitivity to taxane-based therapies, especially albumin-bound paclitaxel. Exploring the biology of rare malignancies by CLIA certified labs may be reasonable strategy for the development of targeted treatments.
Developing an evidence‐based clinical pathway for the assessment, diagnosis and management of acute Charcot Neuro‐Arthropathy: a systematic review
Authors: Milne Tamara E , Rogers Joseph R , Kinnear Ewan M , Martin Helen V , Lazzarini Peter A , Quinton Thomas R , Boyle Frances M
Published: July 2013

Background

Charcot Neuro‐Arthropathy (CN) is one of the more devastating complications of diabetes. To the best of the authors' knowledge, it appears that no clinical tools based on a systematic review of existing literature have been developed to manage acute CN. Thus, the aim of this paper was to systematically review existing literature and develop an evidence‐based clinical pathway for the assessment, diagnosis and management of acute CN in patients with diabetes.

Methods

Electronic databases (Medline, PubMed, CINAHL, Embase and Cochrane Library), reference lists, and relevant key websites were systematically searched for literature discussing the assessment, diagnosis and/or management of acute CN published between 2002‐2012. At least two independent investigators then quality rated and graded the evidence of each included paper. Consistent recommendations emanating from the included papers were then fashioned in a clinical pathway.

Results

The systematic search identified 267 manuscripts, of which 117 (44%) met the inclusion criteria for this study. Most manuscripts discussing the assessment, diagnosis and/or management of acute CN constituted level IV (case series) or EO (expert opinion) evidence. The included literature was used to develop an evidence‐based clinical pathway for the assessment, investigations, diagnosis and management of acute CN.

Conclusions

This research has assisted in developing a comprehensive, evidence‐based clinical pathway to promote consistent and optimal practice in the assessment, diagnosis and management of acute CN. The pathway aims to support health professionals in making early diagnosis and providing appropriate immediate management of acute CN, ultimately reducing its associated complications such as amputations and hospitalisations.
An investigation of objective and subjective types of binge eating episodes in a clinical sample of people with co-morbid obesity
Authors: Palavras Marly Amorim , Morgan Christina Marcondes , Borges Ferrari Maria Beatriz , Claudino Angélica Medeiros , Hay Phillipa J
Published: July 2013

Background

Objective binge eating episodes (OBEs) refer to binge eating on an unusually large amount of food and are the core symptom in current definitions of bulimia nervosa (BN) and binge eating disorder (BED). Subjective binge eating episodes (SBEs) refer to eating on a small or moderate amount of food (that is perceived as large) and like OBEs are associated with loss of control (LOC). Reaching consensus on what is considered a large amount of food can however be problematic and it remains unclear if the size of a binge is an essential component for defining a binge eating episode. The aim of this study was to compare the eating disorder features and general psychopathology of subjects reporting OBEs with those reporting only SBEs.

Methods

This is a retrospective secondary analysis of data from 70 obese participants at the recruitment phase of a multicentre trial for BED. Individuals who answered positively to the presence of binge eating and LOC over eating had their binge eating episodes further explored by interview and self-report. Two groups, those who reported current OBEs (with or without SBEs) and those who reported current SBEs only were compared for age, gender, marital status, body mass index (BMI), indicators of LOC over eating, severity of binge-eating and associated psychopathology.

Results

The majority of participants in both the OBE and SBE groups endorsed the experience of at least four indicators of LOC. There were no significant differences between the groups. Both groups had high levels of binge-eating severity, moderate severity of associated depressive symptoms and frequent psychiatric co-morbidity.

Conclusion

Treatment seeking participants with obesity who reported SBEs alone were similar to those who reported OBEs in terms of eating disorder features and general psychopathology. These findings suggest that classificatory systems of mental illnesses should consider introducing SBEs as a feature of the diagnostic criteria for binge eating and, thus, facilitate the inclusion of participants with SBEs in treatment trials.
Factors associated with compliance to adjuvant hormone therapy in Black and White women with breast cancer
Authors: Bhatta Sumita S , Hou Ningqi , Moton Zakiya N , Polite Blase N , Fleming Gini F , Olopade Olufunmilayo I , Huo Dezheng , Hong Susan
Published: July 2013

Background

Studies have demonstrated lower rates of breast cancer survival for Black versus White women. Factors implicated include later stages at diagnosis, differences in tumor biology, and lower compliance rates to adjuvant hormone therapy (AHT) among Black women with hormone sensitive breast cancer. We examined factors associated with compliance to AHT among Black and White women with invasive breast cancer.

Methods

Women with estrogen receptor positive (ER+), non-metastatic breast cancer were identified by the cancer registry at the University of Chicago Hospital and asked to complete a mail-in survey. Compliance was defined by self-reported adherence to AHT ≥80% at the time of the survey plus medical record verification of persistence (completion of 5 years of AHT). Logistic regression was used to determine factors associated with compliance to AHT.

Results

197 (135 White and 62 Black) women were included in the analysis. 97.4% of patients reported adherence to therapy. 87.4% were found to be persistent to therapy. Overall compliance was 87.7% with no statistically significant racial difference seen (87.9% in White and 87.0% in Black, P = 0.87). For both Black and White women, compliance was strongly associated with both perceived importance of AHT (OR =2.1, 95% CI:1.21-3.68, P = 0.009) and the value placed on their doctor’s opinion about the importance of AHT (OR = 4.80, 95% CI: 2.03-11.4, P < 0.001).

Conclusions

In our cohort of Black and White women, perceived importance of AHT and the degree to which they valued their doctor’s opinion correlated with overall compliance. This suggests that Black and White women consider similar factors in their decision to take AHT.
Diagnostic and prognostic value of presepsin in the management of sepsis in the emergency department: a multicenter prospective study
Authors: Ulla Marco , Pizzolato Elisa , Lucchiari Manuela , Loiacono Maria , Soardo Flavia , Forno Daniela , Morello Fulvio , Lupia Enrico , Moiraghi Corrado , Mengozzi Giulio , Battista Stefania
Published: July 2013

Introduction

Sepsis, severe sepsis and septic shock are common conditions with high mortality. Their early diagnosis in the Emergency Department (ED) is one of the keys to improving survival. Procalcitonin (PCT) has been used as a biomarker in septic patients but has limited specificity and can be elevated in other scenarios of systemic inflammatory response syndrome (SIRS). Soluble CD14 (sCD14) or presepsin is the free fragment of a glycoprotein expressed on monocytes and macrophages. Preliminary reports suggest that levels of presepsin are significantly higher in septic patients than in healthy individuals. The aim of this study is to investigate the diagnostic and prognostic value of presepsin compared to PCT in people presenting at the ED with SIRS and suspected sepsis or septic shock.

Methods

This study was conducted in two major hospitals in Turin, Italy. One hundred six patients presenting to the EDs with suspected sepsis or septic shock were included, and another eighty-three patients affected by SIRS, but with no clinical evidence of infection, were recruited as controls. Blood samples were collected at first medical evaluation and for some patients after 24 and 72 h. The samples were analyzed using the PATHFAST Presepsin assay for sCD14, and commercial kits were used for other determinations (for example, PCT). Definitive diagnosis and survival rates were obtained afterward by analysis of digital medical records.

Results

Elevated concentrations of presepsin at presentation were observed in septic patients compared to control patients. The same trend was observed for mean values of PCT. Higher values of presepsin were observed in septic patients at presentation (time 0). The diagnostic accuracy of PCT was generally higher, and areas under the curve (AUCs) were 0.875 for PCT and 0.701 for presepsin. Mean presepsin values were significantly higher in nonsurvivor septic patients (60-day mortality) than in survivors. No significant correlation was noted between PCT and survival.

Conclusions

In our experience, presepsin was useful in the early diagnosis of infection in a complex population of patients with SIRS, sepsis, severe sepsis and septic shock who presented to the ED. Presepsin showed a significant prognostic value, and initial values were significantly correlated with in-hospital mortality of patients affected by sepsis, severe sepsis or septic shock.
Tpl2 kinase regulates FcγR signaling and immune thrombocytopenia in mice
Authors: Kyrmizi Irene , Ioannou Marianna , Hatziapostolou Maria , Tsichlis Philip N , Boumpas Dimitrios T , Tassiulas Ioannis
Published: July 2013

The MAPK3 Tpl2 controls innate and adaptive immunity by regulating TLR, TNF-α, and GPCR signaling in a variety of cell types. Its ablation gives rise to an anti-inflammatory phenotype characterized by resistance to LPS-induced endotoxin shock, DSS-induced colitis, and TNF-α-induced IBD. Here, we address the role of Tpl2 in autoimmunity. Our data show that the ablation and the pharmacological inhibition of Tpl2 protect mice from antiplatelet antibody-induced thrombocytopenia, a model of ITP. Thrombocytopenia in this model and in ITP is caused by phagocytosis of platelets opsonized with antiplatelet antibodies and depends on FcγR activation in splenic and hepatic myeloid cells. Further studies explained how Tpl2 inhibition protects from antibody-induced thrombocytopenia, by showing that Tpl2 is activated by FcγR signals in macrophages and that its activation by these signals is required for ERK activation, cytoplasmic Ca2+ influx, the induction of cytokine and coreceptor gene expression, and phagocytosis.
Macrophage migration arrest due to a winning balance of Rac2/Sp1 repression over β-catenin-induced PLD expression
Authors: Speranza Francis J , Mahankali Madhu , Gomez-Cambronero Julian
Published: July 2013

Monocytes and neutrophils infiltrate into tissues during inflammation and stay for extended periods of time until the initial insult is resolved or sometimes remain even longer in the case of chronic inflammation. The mechanism as to why phagocytes become immobilized after the initial cell migration event is not understood completely. Here, we show that overexpression or hyperactivation of Rac2 decreases sustained chemotactic responses of macrophages to MCP-1/CCL2. The resulting leukocyte arrest is not caused by a diminished availability of the cytokine receptor CCR2 that remains intact during MCP-1 stimulation. We show a novel mechanism that links the Rac2-dependent arrest of chemotaxis to decreased expression of PLD2 through the transcription regulator Sp1. Prolonged Rac2 activity leads to nuclear overactivation of Sp1, which acts as a repressor for PLD2. Also, another signaling component plays a regulatory role: β-catenin. Although early times of stimulation (∼20 min) with MCP-1/CCL2 resulted in activation of β-catenin with a positive effect on PLD2, after ∼3 h of stimulation, the levels of β-catenin were reduced and not able to prevent the negative effect of Rac2 on PLD2 activity. This is a novel molecular mechanism underlying immobilization of monocyte/macrophage migration that is important for the physiological maintenance of leukocytes at the site of inflammation. If this immobilization is prolonged enough, it could lead to chronic inflammation.
Randomized Controlled Trial of a Structured Intervention to Facilitate End-of-Life Decision Making in Patients With Advanced Cancer
Authors: Stein Rhea A. , Sharpe Louise , Bell Melanie L. , Boyle Fran M. , Dunn Stewart M. , Clarke Stephen J.
Published: July 2013

Purpose

This study tested the efficacy of an intervention on end-of-life decision making for patients with advanced cancer.

Patients and Methods

One hundred twenty patients with metastatic cancer who were no longer being treated with curative intent (and 87 caregivers) were randomly assigned to the intervention (n = 55) or treatment as usual (n = 65). Primary outcome measures were the proportion of patients with do-not-resuscitate (DNR) orders, timing of DNR orders, and place of death. Secondary outcome measures were completed at study enrollment, 3 weeks later, and 3 months later, including patients' knowledge, mood, and caregiver burden.

Results

High, but equivalent, rates of DNR orders were observed in both groups. In per-protocol analyses, DNR orders were placed earlier for patients who received the intervention (median, 27 v 12.5 days; 95% CI, 1.1 to 5.9; P = .03) and they were more likely to avoid a hospital death (19% v 50% (95% CI, 11% to 50%; P = .004). Differences between the groups over time were evident for estimates of cardiopulmonary rehabilitation (CPR) success rates (P = .01) but not knowledge of CPR (P = .2). There was no evidence that the intervention resulted in more anxious or depressive symptoms. Caregivers experienced less burden in terms of disruption to schedule if the patient received the intervention (P = .05).

Conclusion

An intervention, consisting of an informational pamphlet and discussion, was associated with earlier placement of DNR orders relative to death and less likelihood of death in hospital. There was no negative impact of the intervention on secondary outcomes, although the sample may have been too small to detect differences.
Patterns of Recurrence and Outcome According to Breast Cancer Subtypes in Lymph Node–Negative Disease: Results From International Breast Cancer Study Group Trials VIII and IX
Authors: Metzger-Filho Otto , Sun Zhuoxin , Viale Giuseppe , Price Karen N. , Crivellari Diana , Snyder Raymond D. , Gelber Richard D. , Castiglione-Gertsch Monica , Coates Alan S. , Goldhirsch Aron , Cardoso Fatima
Published: July 2013

Purpose

To retrospectively evaluate the pattern of recurrence and outcome of node-negative breast cancer (BC) according to major subtypes.

Patients and Methods

In all, 1,951 patients with node-negative, early-stage BC randomly assigned in International Breast Cancer Study Group Trials VIII and IX with centrally reviewed pathology data were included. BC subtypes were defined as triple negative (TN; n = 310), human epidermal growth factor receptor 2 (HER2) positive (n = 369), and hormone receptor positive with high (luminal B–like [LB-like]; n = 763) or low (luminal A–like [LA-like]; n = 509) proliferative activity by Ki-67 labeling index. BC-free interval (BCFI) events were invasive BC recurrence in local, contralateral breast, nodal, bone, or visceral sites. Time to first site–specific recurrence was evaluated by using cumulative incidence and competing risks regression analysis.

Results

Median follow-up was 12.5 years. The 10-year BCFI was higher for patients with LA-like (86%) BC compared with LB-like (76%), HER2 (73%), and TN (71%; P < .001) BC. TN and HER2 cohorts had higher hazard of BCFI event in the first 4 years after diagnosis (pre-trastuzumab). LB-like cohorts had a continuously higher hazard of BCFI event over time compared with LA-like cohorts. Ten-year overall survival was higher for LA-like (89%) compared with LB-like (83%), HER2 (77%), and TN (75%; P < .001) BC. LB-like subtypes had higher rates of bone as first recurrence site than other subtypes (P = .005). Visceral recurrence as first site was lower for the LA-like subgroup, with similar incidence among the other subgroups when treated with chemotherapy (P = .003).

Conclusion

BC subtypes have different distant recurrence patterns over time. Defining different patterns of BC recurrence can improve BC care through surveillance guidelines and can guide the design of clinical studies.
Clustered protocadherins
Authors: Chen Weisheng V. , Maniatis Tom
Published: July 2013

The majority of vertebrate protocadherin (Pcdh) genes are clustered in a single genomic locus, and this remarkable genomic organization is highly conserved from teleosts to humans. These clustered Pcdhs are differentially expressed in individual neurons, they engage in homophilic trans-interactions as multimers and they are required for diverse neurodevelopmental processes, including neurite self-avoidance. Here, we provide a concise overview of the molecular and cellular biology of clustered Pcdhs, highlighting how they generate single cell diversity in the vertebrate nervous system and how such diversity may be used in neural circuit assembly.
Mutual control of intracellular localisation of the patterning proteins AtMYC1, GL1 and TRY/CPC inArabidopsis
Authors: Pesch Martina , Schultheiß Ilka , Digiuni Simona , Uhrig Joachim F. , Hülskamp Martin
Published: July 2013

Trichome and root hair patterning is governed by a gene regulatory network involving TTG1 and several homologous MYB and bHLH proteins. The bHLH proteins GL3 and EGL3 are core components that serve as a regulatory platform for the activation of downstream genes. In this study we show that a homologue of GL3 and EGL3, AtMYC1, can regulate the intracellular localisation of GL1 and TRY. AtMYC1 protein is predominantly localised in the cytoplasm and can relocate GL1 from the nucleus into the cytoplasm. Conversely, AtMYC1 can be recruited into the nucleus by TRY and CPC, concomitant with a strong accumulation of TRY and CPC in the nucleus. When AtMYC1 is targeted to the nucleus or cytoplasm by nuclear localisation or export signals (NLS or NES), respectively, the intracellular localisation of GL1 and TRY also changes accordingly. The biological significance of this intracellular localisation is suggested by the finding that the efficiency of rescue of trichome number is significantly altered in NES and NLS fusions as compared with wild-type AtMYC1. Genetic analysis of mutants and overexpression lines supports the hypothesis that AtMYC1 represses the activity of TRY and CPC.
Prdm1a directly activates foxd3 and tfap2a during zebrafish neural crest specification
Authors: Powell Davalyn R. , Hernandez-Lagunas Laura , LaMonica Kristi , Artinger Kristin Bruk
Published: July 2013

The neural crest comprises multipotent precursor cells that are induced at the neural plate border by a series of complex signaling and genetic interactions. Several transcription factors, termed neural crest specifiers, are necessary for early neural crest development; however, the nature of their interactions and regulation is not well understood. Here, we have established that the PR/SET domain-containing transcription factor Prdm1a is co-expressed with two essential neural crest specifiers, foxd3 and tfap2a, at the neural plate border. Through rescue experiments, chromatin immunoprecipitation and reporter assays, we have determined that Prdm1a directly binds to and transcriptionally activates enhancers for foxd3 and tfap2a and that they are functional, direct targets of Prdm1a at the neural plate border. Additionally, analysis of dominant activator and dominant repressor Prdm1a constructs suggests that Prdm1a is required both as a transcriptional activator and transcriptional repressor for neural crest development in zebrafish embryos.
Bbof1 is required to maintain cilia orientation
Authors: Chien Yuan-Hung , Werner Michael E. , Stubbs Jennifer , Joens Matt S. , Li Julie , Chien Shu , Fitzpatrick James A. J. , Mitchell Brian J. , Kintner Chris
Published: July 2013

Multiciliate cells (MCCs) are highly specialized epithelial cells that employ hundreds of motile cilia to produce a vigorous directed flow in a variety of organ systems. The production of this flow requires the establishment of planar cell polarity (PCP) whereby MCCs align hundreds of beating cilia along a common planar axis. The planar axis of cilia in MCCs is known to be established via the PCP pathway and hydrodynamic cues, but the downstream steps required for cilia orientation remain poorly defined. Here, we describe a new component of cilia orientation, based on the phenotypic analysis of an uncharacterized coiled-coil protein, called bbof1. We show that the expression of bbof1 is induced during the early phases of MCC differentiation by the master regulator foxj1. MCC differentiation and ciliogenesis occurs normally in embryos where bbof1 activity is reduced, but cilia orientation is severely disrupted. We show that cilia in bbof1 mutants can still respond to patterning and hydrodynamic cues, but lack the ability to maintain their precise orientation. Misexpression of bbof1 promotes cilia alignment, even in the absence of flow or in embryos where microtubules and actin filaments are disrupted. Bbof1 appears to mediate cilia alignment by localizing to a polar structure adjacent to the basal body. Together, these results suggest that bbof1 is a basal body component required in MCCs to align and maintain cilia orientation in response to flow.
The histone H3-K27 demethylase Utx regulates HOX gene expression in Drosophila in a temporally restricted manner
Authors: Copur Ömer , Müller Jürg
Published: July 2013

Trimethylation of histone H3 at lysine 27 (H3-K27me3) by Polycomb repressive complex 2 (PRC2) is a key step for transcriptional repression by the Polycomb system. Demethylation of H3-K27me3 by Utx and/or its paralogs has consequently been proposed to be important for counteracting Polycomb repression. To study the phenotype of Drosophila mutants that lack H3-K27me3 demethylase activity, we created UtxΔ, a deletion allele of the single Drosophila Utx gene. UtxΔ homozygotes that contain maternally deposited wild-type Utx protein develop into adults with normal epidermal morphology but die shortly after hatching. By contrast, UtxΔ homozygotes that are derived from Utx mutant germ cells and therefore lack both maternal and zygotic Utx protein, die as larvae and show partial loss of expression of HOX genes in tissues in which these genes are normally active. This phenotype classifies Utx as a trithorax group regulator. We propose that Utx is needed in the early embryo to prevent inappropriate instalment of long-term Polycomb repression at HOX genes in cells in which these genes must be kept active. In contrast to PRC2, which is essential for, and continuously required during, germ cell, embryonic and larval development, Utx therefore appears to have a more limited and specific function during development. This argues against a continuous interplay between H3-K27me3 methylation and demethylation in the control of gene transcription in Drosophila. Furthermore, our analyses do not support the recent proposal that Utx would regulate cell proliferation in Drosophila as Utx mutant cells generated in wild-type animals proliferate like wild-type cells.
Role of forefinger and thumb loops in production of Ψ54 and Ψ55 in tRNAs by archaeal Pus10
Authors: Joardar Archi , Jana Sujata , Fitzek Elisabeth , Gurha Priyatansh , Majumder Mrinmoyee , Chatterjee Kunal , Geisler Matt , Gupta Ramesh
Published: July 2013

Pseudouridines (Ψ) are found in structurally and functionally important regions of RNAs. Six families of Ψ synthases, TruA, TruB, TruD, RsuA, RluA, and Pus10 have been identified. Pus10 is present in Archaea and Eukarya. While most archaeal Pus10 produce both tRNA Ψ54 and Ψ55, some produce only Ψ55. Interestingly, human PUS10 has been implicated in apoptosis and Crohn’s and Celiac diseases. Homology models of archaeal Pus10 proteins based on the crystal structure of human PUS10 reveal that there are subtle structural differences in all of these Pus10 proteins. These observations suggest that structural changes in homologous proteins may lead to loss, gain, or change of their functions, warranting the need to study the structure-function relationship of these proteins. Using comparison of structural models and a series of mutations, we identified forefinger loop (reminiscent of that of RluA) and an Arg and a Tyr residue of archaeal Pus10 as critical determinants for its Ψ54, but not for its Ψ55 activity. We also found that a Leu residue, in addition to the catalytic Asp, is essential for both activities. Since forefinger loop is needed for both rRNA and tRNA Ψ synthase activities of RluA, but only for tRNA Ψ54 activity of Pus10, archaeal Pus10 proteins must use a different mechanism of recognition for Ψ55 activity. We propose that archaeal Pus10 uses two distinct mechanisms for substrate uridine recognition and binding. However, since we did not observe any mutation that affected only Ψ55 activity, both mechanisms for archaeal Pus10 activities must share some common features.
The role of resiliency in the process of adaptation to life after heart transplantation
Authors: Baran Agnieszka
Published: July 2013

Aim of the study

The aim of the research was to find out if resiliency is a potentially significant factor in the process of adaptation after heart transplantation.

Subject or material and methods

The research included 53 people after heart transplantation, hospitalized in the John Paul II Hospital in Krakow. Measures included a self-made interview questionnaire; the Acceptance of Illness Scale, the Polish Resiliency Assessment Scale SPP-25. The necessary statistics were conducted by means of SPSS program.

Results

Examined group of heart transplant patients appeared to be well adapted to living with a transplanted heart and was characterized by an average level of resiliency. The results supported the hypotheses regarding the relationship between resiliency and adaptation after heart transplantation. A special role in the process of adapting to life with new heart seems to play a personal skills to cope, tolerate negative emotions and failures, and the ability to view life as a challenge.

Discussion

.

Conclusions

Resiliency is a factor significantly related to adaptation after heart transplantation, and it has implications for clinical practice, especially for the rehabilitation of patients after transplantation. It seems to be important to shape and develop these elements of resiliency which are mostly related to positive adaptation after heart transplantation.
“Impatience of the Heart”:
Parenting counter-transference and its neurobiological roots
Authors: Aleksandrowicz Dov R.
Published: July 2013

“Impatience of the heart”: Parenting counter-transference and its neurobiological roots
Abstract:
“Impatience of the Heart” (“Beware of pity” in English translation) is a novel by Stefan Zweig about the relationship between an Austrian cavalry officer and a paraplegic Hungarian girl. The officer tries to comfort the girl but his misdirected compassion leads to a tragic result.
This paper discusses the instinctive urge to relieve distress (which the author compares to the “parenting response” of the caregiver to an infant) and its potentially harmful manifestations in counter-transference. Such counter-transference and its negative manifestations may not necessarily be an expression of the therapist’s unresolved problems, but an over-expression of that innate urge. That urge is not merely a social value, but a part of our mammalian heritage and the author presents evidence from animal studies to that effect.
Finally, the author discusses the implication of his conclusions for the training and supervision of psychotherapists.
Status Inertia and Member Replacement in Role-Differentiated Teams
Authors: Bunderson J. Stuart , Van der Vegt Gerben S. , Sparrowe Raymond T.
Published: July 2013

The arrival of a new member can provide the impetus for learning and performance improvement in groups, but only if the newcomer is accorded status within the new group. We examine newcomer status in cases of member replacement, i.e., when a newcomer assumes an existing role within an established group. Drawing from status characteristics and status construction theories, we suggest that status in role-differentiated groups is inertial—nominal roles acquire status value, and these role-related status attributions carry forward to affect the status of a replacement newcomer. We also suggest that these inertial status dynamics can be affected by the relative performance of the host versus donor group and that they will have consequences for group performance. These hypotheses were supported in a controlled setting using teams engaged in several rounds of a management simulation exercise. The theory and results of this study have important implications for research on intragroup status, membership change in groups, and the transfer of knowledge through member rotation.
Temporal Elements in Career Selection Decisions: An Archival Study Investigating Career Decisions in Medicine
Authors: Shah Priti Pradhan , Bechara John P. , Kolars Joseph , Drefahl Monica , LaRusso Nicholas , Wood Douglas , Spurrier Barbara
Published: July 2013

Time is a ubiquitous but often omitted variable in career selection decisions. This study investigates the impact of temporal elements on career selection decisions, thus advancing our understanding of both career decision making and the impact of timing on decision making. We investigate the influence of timing and duration of experience with career options on career selection decisions in an archival study using medical residents’ rotation schedules. We also investigate factors that mitigate the influence of timing on career selection decisions by examining the interaction of timing with the duration of experience and the diversity of options that an individual experiences. Conditional logit results indicate that decisions often based on career and individual attributes are significantly influenced by the timing and duration of options even when controlling for option attributes. Additionally, significant interactions between timing and diversity of experience and timing and duration of experience revealed boundary conditions for timing. Individuals were more likely to select later-appearing career options when they appeared for a greater duration or when they experienced a greater diversity of options in their schedule. Results illustrate that schedules over which individuals have no control can influence consequential decisions.
[Cali] Fornication by False Pretences—No Penalty for Partner Personation under California's Penal Code
Authors: Davies Mitchell C.
Published: July 2013

This article considers the recent decision of the Second District Court of Appeal of California in People v Julio Morales. The California Court of Appeal controversially quashed the conviction for rape of the appellant who had had sexual intercourse with the victim seemingly whilst she had initially been asleep. With there being conflicting accounts as to whether the victim had been awake or asleep during the intercourse, the appellant had been convicted of rape by the jury on the alternative bases of her either: (1) having been unconscious (asleep) during the intercourse or; (2) having been awake during the intercourse, but mistaken as to the identity of her sexual partner, believing him to be her boyfriend. In a restrictive judgment, displaying more concern for principles of statutory interpretation than criminal justice, the appeal court quashed the appellant's conviction. The reasoning of the court was that the jury might have convicted on the basis of (2) above and that the California Penal Code recognised the offence of rape as being possible in personation cases only where the person being impersonated is the spouse of the victim. This article suggests a number of ways that were open to the appeal court to avoid this unsatisfactory outcome, both by application of other provisions of the Penal Code itself and by reference to the history of the spousal impersonation rule traceable back to old English common law.
Laminin and Type IV Collagen Isoform Substitutions Occur in Temporally and Spatially Distinct Patterns in Developing Kidney Glomerular Basement Membranes
Authors: Abrahamson Dale R. , St. John Patricia L. , Stroganova Larysa , Zelenchuk Adrian , Steenhard Brooke M.
Published: July 2013

Kidney glomerular basement membranes (GBMs) undergo laminin and type IV collagen isoform substitutions during glomerular development, which are believed to be required for maturation of the filtration barrier. Specifically, GBMs of earliest glomeruli contain laminin α1β1γ1 and collagen α1α2α1(IV), whereas mature glomeruli contain laminin α5β2γ1 and collagen α3α4α5(IV). Here, we used confocal microscopy to simultaneously evaluate expression of different laminin and collagen IV isoforms in newborn mouse GBMs. Our results show loss of laminin α1 from GBMs in early capillary loop stages and continuous linear deposition of laminin bearing the α5 chain thereafter. In contrast, collagen α1α2α1(IV) persisted in linear patterns into late capillary loop stages, when collagen α3α4α5(IV) first appeared in discontinuous, non-linear patterns. This patchy pattern for collagen α3α4α5(IV) continued into maturing glomeruli where there were lengths of linear, laminin α5-positive GBM entirely lacking either isoform of collagen IV. Relative abundance of laminin and collagen IV mRNAs in newborn and 5-week-old mouse kidneys also differed, with those encoding laminin α1, α5, β1, β2, and γ1, and collagen α1(IV) and α2(IV) chains all significantly declining at 5 weeks, but α3(IV) and α4(IV) were significantly upregulated. We conclude that different biosynthetic mechanisms control laminin and type IV collagen expression in developing glomeruli.
Journalism, climate science and the public: Towards better practices
Authors: McIlwaine Steve
Published: July 2013

Media reporting and analysis of climate-change science is a fundamental and vital requirement for public understanding and engagement in the increasingly serious issue of global climate change. However, journalists have largely failed to come to grips with the science and its practitioners: they have generally failed to obtain an adequate understanding of what the science is about, they have used inappropriate reporting and framing techniques and have been unduly influenced by vested interests. The result is that media audiences have been left confused, apathetic and even hostile about climate-change news. This article analyses the major shortcomings in media reporting of climate-change science and proposes means by which journalists can, without great difficulty, better serve their audiences, their organizations and themselves in this area of major professional importance.
Public engagement with climate change: What do we know and where do we go from here?
Authors: Whitmarsh Lorraine , O’Neill Saffron , Lorenzoni Irene
Published: July 2013

Climate change is an issue with fundamental implications for societies and individuals. These implications range from our everyday choices about resource use and lifestyles, through how we adjust to an unprecedented rate of environmental change, to our role in debating and enacting accompanying social transitions. This article outlines the various ways in which members of society (‘publics’) may be engaged in efforts to mitigate and adapt to climate change, and then provides a synthesis of lessons about public engagement which span both theoretical and practical insights. These include the diverse drivers of, and barriers to, engagement; the importance of multiple forms of engagement and messages; and a critical need to evaluate and identify successful examples of engagement. We conclude by outlining priorities for future research, policy and practice.