bluuebunny/crossref_metadata_2025 huggingface dataset:
Myeloid Cell Receptor LRP1/CD91 Regulates Monocyte Recruitment and Angiogenesis in Tumors
Authors: Staudt Nicole D. , Jo Minji , Hu Jingjing , Bristow Jeanne M. , Pizzo Donald P. , Gaultier Alban , VandenBerg Scott R. , Gonias Steven L.
Published: May 2013

Recruitment of monocytes into sites of inflammation is essential in the immune response. In cancer, recruited monocytes promote invasion, metastasis, and possibly angiogenesis. LDL receptor-related protein (LRP1) is an endocytic and cell-signaling receptor that regulates cell migration. In this study, we isografted PanO2 pancreatic carcinoma cells into mice in which LRP1 was deleted in myeloid lineage cells. Recruitment of monocytes into orthotopic and subcutaneous tumors was significantly increased in these mice, compared with control mice. LRP1-deficient bone marrow–derived macrophages (BMDM) expressed higher levels of multiple chemokines, including, most prominently, macrophage inflammatory protein-1α/CCL3, which is known to amplify inflammation. Increased levels of CCL3 were detected in LRP1-deficient tumor-associated macrophages (TAM), isolated from PanO2 tumors, and in RAW 264.7 macrophage-like cells in which LRP1 was silenced. LRP1-deficient BMDMs migrated more rapidly than LRP1-expressing cells in vitro. The difference in migration was reversed by CCL3-neutralizing antibody, by CCR5-neutralizing antibody, and by inhibiting NF-κB with JSH-23. Inhibiting NF-κB reversed the increase in CCL3 expression associated with LRP1 gene silencing in RAW 264.7 cells. Tumors formed in mice with LRP1-deficient myeloid cells showed increased angiogenesis. Although VEGF mRNA expression was not increased in LRP1-deficient TAMs, at the single-cell level, the increase in TAM density in tumors with LRP1-deficient myeloid cells may have allowed these TAMs to contribute an increased amount of VEGF to the tumor microenvironment. Our results show that macrophage density in tumors is correlated with cancer angiogenesis in a novel model system. Myeloid cell LRP1 may be an important regulator of cancer progression. Cancer Res; 73(13); 3902–12. ©2013 AACR.
Disrupting Protein NEDDylation with MLN4924 Is a Novel Strategy to Target Cisplatin Resistance in Ovarian Cancer
Authors: Nawrocki Steffan T. , Kelly Kevin R. , Smith Peter G. , Espitia Claudia M. , Possemato Anthony , Beausoleil Sean A. , Milhollen Michael , Blakemore Stephen , Thomas Michael , Berger Allison , Carew Jennifer S.
Published: May 2013

Purpose: Ovarian cancer has the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure and novel therapeutic strategies are urgently needed. MLN4924 is a NEDDylation inhibitor currently under investigation in multiple phase I studies. We investigated its anticancer activity in cisplatin-sensitive and -resistant ovarian cancer models.

Experimental Design: Cellular sensitivity to MLN4924/cisplatin was determined by measuring viability, clonogenic survival, and apoptosis. The effects of drug treatment on global protein expression, DNA damage, and reactive oxygen species generation were determined. RNA interference established natural born killer/bcl-2–interacting killer (NBK/BIK) as a regulator of therapeutic sensitivity. The in vivo effects of MLN4924/cisplatin on tumor burden and key pharmacodynamics were assessed in cisplatin-sensitive and -resistant xenograft models.

Results: MLN4924 possessed significant activity against both cisplatin-sensitive and -resistant ovarian cancer cells and provoked the stabilization of key NEDD8 substrates and regulators of cellular redox status. Notably, MLN4924 significantly augmented the activity of cisplatin against cisplatin-resistant cells, suggesting that aberrant NEDDylation may contribute to drug resistance. MLN4924 and cisplatin cooperated to induce DNA damage, oxidative stress, and increased expression of the BH3-only protein NBK/BIK. Targeted NBK/BIK knockdown diminished the proapoptotic effects of the MLN4924/cisplatin combination. Administration of MLN4924 to mice bearing ovarian tumor xenografts significantly increased the efficacy of cisplatin against both cisplatin-sensitive and -resistant tumors.

Conclusions: Our collective data provide a rationale for the clinical investigation of NEDD8-activating enzyme (NAE) inhibition as a novel strategy to augment cisplatin efficacy in patients with ovarian cancer and other malignancies. Clin Cancer Res; 19(13); 3577–90. ©2013 AACR.
Nonequivalent Gene Expression and Copy Number Alterations in High-Grade Serous Ovarian Cancers with BRCA1 and BRCA2 Mutations
Authors: George Joshy , Alsop Kathryn , Etemadmoghadam Dariush , Hondow Heather , Mikeska Thomas , Dobrovic Alexander , deFazio Anna ,   for the Australian Ovarian Cancer Study Group, Smyth Gordon K. , Levine Douglas A. , Mitchell Gillian , Bowtell David D.
Published: May 2013

Purpose: High-grade serous carcinoma (HGSC) accounts for the majority of epithelial ovarian cancer deaths. Genomic and functional data suggest that approximately half of unselected HGSC have disruption of the BRCA pathway and defects in homologous recombination repair (HRR). Pathway disruption is regarded as imparting a BRCAness phenotype. We explored the molecular changes in HGSC arising in association with specific BRCA1/BRCA2 somatic or germline mutations and in those with BRCA1 DNA promoter methylation.

Experimental Design: We describe gene expression and copy number analysis of two large cohorts of HGSC in which both germline and somatic inactivation of HRR has been measured.

Results: BRCA1 disruptions were associated with the C2 (immunoreactive) molecular subtype of HGSC, characterized by intense intratumoral T-cell infiltration. We derived and validated a predictor of BRCA1 mutation or methylation status, but could not distinguish BRCA2 from wild-type tumors. DNA copy number analysis showed that cases with BRCA1 mutation were significantly associated with amplification both at 8q24 (frequencies: BRCA1 tumors 50%, BRCA2 tumors 32%, and wild-type tumors 9%) and regions of the X-chromosome specifically dysregulated in basal-like breast cancer (BLBC; BRCA1 62%, BRCA2 34%, and wild-type 35%). Tumors associated with BRCA1/BRCA2 mutations shared a negative association with amplification at 19p13 (BRCA1 0%, BRCA2 3%, and wild-type 20%) and 19q12 (BRCA1 6%, BRCA2 3%, and wild-type 29%).

Conclusion: The molecular differences between tumors associated with BRCA1 compared with BRCA2 mutations are in accord with emerging clinical and pathologic data and support a growing appreciation of the relationship between HGSC and BLBC. Clin Cancer Res; 19(13); 3474–84. ©2013 AACR.
Does Maliseet-Passamaquoddy Have VP-Ellipsis?
Authors: LeSourd Philip S.
Published: May 2013

Richards (2009) proposes that VP-Ellipsis relates pairs of sentences in the Eastern Algonquian language Maliseet-Passamaquoddy that contain morphologically related verbs, one of which lacks a stem component that appears in the other. Under his proposal, the polysynthetic verbs of the language are decomposed into abstract syntactic structures, and VP-Ellipsis is applicable within the word. I argue that his data are better explained without postulating VP-Ellipsis for Maliseet-Passamaquoddy. The verbs that he sees as derived via ellipsis are independently occurring lexical items. There are in fact no ellipsis gaps in the structures he considers, only null pronouns, and overt pronouns may always occur in the relevant positions. My conclusions are fully consistent with the Lexical Integrity Hypothesis of Bresnan and Mchombo (1995) .
Notes on Early Land Plants Today. 34. Validation of Scapania gaochii (Scapaniaceae, Marchantiophyta)
Authors: CAO TONG , SÖDERSTRÖM LARS , HAGBORG ANDERS , VON KONRAT MATT
Published: May 2013

Scapania gaochii was described from Yunnan without indication of the herbarium where the type was conserved. Therefore, this name was invalidly published (ICN Art. 37.7; McNeill et al. 2012) and needs validation.The format of this note follows Söderström et al. (2012) except that we use the Melbourne International Code of Nomenclature for algae, fungi, and plants (ICN; McNeill et al. 2012) instead of the Vienna International Botanical Code of Nomenclature (ICBN; McNeill et al. 2006).
Notes on Early Land Plants Today. 39. Microlejeunea indica (Marchantiophyta, Lejeuneaceae)
Authors: WEI YU-MEI , ZHU RUI-LIANG
Published: May 2013

The systematic position of the pantropical genus Microlejeunea Stephani (1888: 61) has been debated. Grolle (1995) first defined the precise generic concept of Microlejeunea, which was also confirmed by molecular studies (Wilson et al. 2004; Dong et al. 2013). This concept has recently been followed by various authors (e.g., He & Zhu 2011; Lavocat & Schäfer-Verwimp 2011; Thouvenot et al. 2011; Marline et al. 2012; Thiers et al. 2012). Microlejeunea is well characterized and easily separated from Lejeunea Libert (1820: 372) by the presence of ocelli in the leaf lobe, transverse section of stem consisting of seven cortical cells and three medullary cells, and keel of female bract usually winged (Wei & Zhu 2013). Lejeunea indica Udar & Awasthi (1981: 345), known only from India (Udar & Awasthi 1981; Joshi 1995; Zhu & Long 2003; Dey et al. 2008), has all essential characters of Microlejeunea. Thus, a new combination is needed.
Three new earthworm species of the genus Amynthas (Clitellata: Megascolecidae) from Mt. Chiak National Park, Korea
Authors: HONG YONG , JAMES SAMUEL W.
Published: May 2013

Earthworm specimens collected from Mt. Chiak, National Park, Korea were found to represent three new species of megascolecid earthworms: Amynthas chiakensis sp. nov., Amynthas gyeongriae sp. nov., and Amynthas wonjuensis sp. nov. Amynthas chiakensis sp. nov. has two pairs of spermathecae in VII and VIII, small transverse oval male porophores each with C-shaped small patches of genital papillae, 0.22–0.31 circumference apart. Amynthas gyeongriae sp. nov. has spermathecae in VI–VIII, male field with large circular-shaped raised pads and seminal grooves, with pores 0.16–0.28 circumference apart. Amynthas wonjuensis sp. nov. has spermathecae in VI and VII, male pores superficial in XVIII on small oval-shaped white porophores lateral to large roughly circular raised genital papillae, 0.15 circumference apart.
Nomenclatural and bibliographic corrections to the Catalog of Nabidae (Hemiptera: Heteroptera) for the Neotropical Region
Authors: COSCARÓN MARIA DEL CARMEN , VOLPI LORENA N.
Published: May 2013

The recent catalog of Neotropical Nabidae is corrected and updated. Synonymies, species, and references that were overlooked are now included. 11 genera and 83 species are presently known from this region.
The influence of social expectations on strategies for coping with moral transgressions
Authors: Nencini Alessio , Meneghini Anna-Maria
Published: May 2013

Guilt has been found to accomplish important relational functions, thus promoting reparative behaviours through other- directed strategies. However, when one's self-image is at risk, self-directed strategies may be adaptively preferred. We thus wondered whether social expectations towards morally relevant roles would affect the emotional response to moral transgressions and, consequently, the choice of coping strategies to restore the original emotional status. In two studies, two groups of participants were asked to imagine themselves in guilt-evoking situations and to think of ways of reducing their negative feelings. In study 1, social expectations regarding the transgressor were manipulated by comparing a group of Catholic priests and of lay people. In study 2, we repeated the same design adding a manipulation of perspective (first/third person). Overall, results showed that the priests reported more feelings of shame when in the first person condition, and were more likely to cope with their negative feelings by means of self-directed strategies than the lay people. In these cases, self- directed coping strategies may be adaptively chosen in order to restore a positive self-image.
An intervention with firefighters to promote psychological occupational health according to the Job Demands-Resources Model
Authors: Ângelo Rui-Pedro , Chambel Maria-José
Published: May 2013

This study reports an intervention programme to promote job resources (social support) to increase firefighters' psychological well-being (burnout and engagement), using the Job Demand-Resource Model as the theoretical model. Participants were firefighters from an elite Portuguese organization. The intervention consisted of a leadership stress management workshop for middle supervisors that lasted 21 hours spread over 3 days. The intervention group (n = 67) were subordinates whose immediate supervisors participated in the workshop, and the control group (n = 37) were subordinates whose supervisors did not. All participants filled out questionnaires before the workshop and 4 months after. The repeated measures ANOVA revealed as expected that Time x Intervention interaction increased colleagues' social support, and marginally also increased firefighters' vigor. However, contrary to expected the intervention also increased chronic demands. Discussion focuses on the importance of understanding the process underpinning change in occupational stress management interventions, especially in emergency professionals.
Effects of a question prompt sheet on active patient behaviour: A randomized controlled trial with depressed outpatients
Authors: Hamann Johannes , Maris Nikolaos , Iosifidou Paraskevi , Mendel Rosmarie , Cohen Rudolf , Wolf Petra , Kissling Werner
Published: May 2013

Background:

A deeper engagement into medical decision-making is demanded by treatment guidelines for patients with affective disorders. There is to date little evidence on what facilitates active behaviour of patients with depression. In general medicine ‘question prompt sheets’ (QPSs) have been shown to change patients’ behaviour in the consultation and improve treatment satisfaction but there is no evidence for such interventions for mental health settings.

Aims:

To study the effects of a QPS on active patient behaviour in the consultation.

Methods:

Randomized controlled trial (involving N = 100 outpatients with depression) evaluating the effects of a QPS on patients’ behaviour in the consultation.

Results:

The QPS showed no influence on the number of topics raised by patients ( p = .13) nor on the external rater’s perception of ‘Who made the decisions in today’s consultation?’ ( p = .50).

Conclusions:

A QPS did not change depressed patients’ behaviour in the consultation. More complex interventions might be needed to change depressed patients’ behaviour within an established doctor–patient dyad. Patient seminars addressing behavioural aspects have been shown to be effective in other settings and may also be feasible for outpatients with affective disorders.
An investigation of the effect of thiamine pyrophosphate on cisplatin-induced oxidative stress and DNA damage in rat brain tissue compared with thiamine
Authors: Turan MI , Cayir A , Cetin N , Suleyman H , Turan I Siltelioglu , Tan H
Published: May 2013

This study investigated the effects of thiamine pyrophosphate (TPP) at dosages of 10 and 20 mg/kg on oxidative stress induced in rat brain tissue with cisplatin and compared this with thiamine. Cisplatin neurotoxicity represents one of the main restrictions on the drug being given in effective doses. Oxidative stress is considered responsible for cisplatin toxicity. Our results showed that cisplatin increased the levels of oxidant parameters such as lipid peroxidation (thio barbituric acid reactive substance (TBARS)) and myeloperoxidase (MPO) in brain tissue and suppressed the effects of antioxidants such as total glutathione (GSH) and superoxide dismutase (SOD). TPP, especially at a dosage of 20 mg/kg, significantly reduced TBARS and MPO levels that increase with cisplatin administration compared with the thiamine group, while TPP significantly increases GSH and SOD levels. In addition, the level of 8-Gua (guanine), a product of DNA damage, was 1.7 ± 0.12 8-hydroxyl guanine (8-OH Gua)/105 Gua in brain tissue in the control group receiving cisplatin, compared with 0.97 ± 0.03 8-OH Gua/105 Gua in the thiamine pyrophosphate (20 mg/kg) group and 1.55 ± 0.11 8-OH Gua/105 Gua in the thiamine (20 mg/kg) group. These results show that thiamine pyrophosphate significantly prevents oxidative damage induced by cisplatin in brain tissue, while the protective effect of thiamine is insignificant.
Effect of subacute exposure to silver nanoparticle on some hematological and plasma biochemical indices in silver carp (Hypophthalmichthys molitrix)
Authors: Shaluei F , Hedayati A , Jahanbakhshi A , Kolangi H , Fotovat M
Published: May 2013

The use of silver nanoparticles (Ag-NPs) is rapidly increasing, but there are limited data on their effects on the aquatic environment. The present study aimed to determine the acute toxicity and evaluate the effect of subacute concentrations of Ag-NPs (Nanocid®: average particle size of 61 nm) on hematological and plasma biochemical indices of silver carp, Hypophthalmichthys molitrix, after 3, 7 and 14 days. The 24-, 48-, 72- and 96-h median lethal concentration (LC50) values of Nanocid for silver carp were estimated at 0.810, 0.648, 0.383 and 0.202 mg/L, respectively; 20% and 10% of the 96-h LC50 values (0.04 and 0.02 mg/L) were selected for subacute study. Red blood cell (RBC) count, hemoglobin (Hb) count and hematocrit (Hct) level were significantly reduced at both concentrations tested ( p < 0.05). White blood cell (WBC), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), cortisol and glucose levels in Nanocid-treated groups were significantly higher than the controlled group at experimental periods ( p < 0.05). In conclusion, Ag-NPs intoxication resulted in erythrocyte reduction, hematological disturbances, leucocytosis and stress response in silver carp and offered a simple tool to evaluate toxicity-derived alterations.
From Qualitative Work to Intervention Development in Pediatric Oncology Palliative Care Research
Authors: Akard Terrah Foster , Gilmer Mary Jo , Friedman Debra L. , Given Barbara , Hendricks-Ferguson Verna L. , Hinds Pamela S.
Published: May 2013

Qualitative methods can be particularly useful approaches to use with individuals who are experiencing a rare disease and thus who comprise a small sample (such as children with cancer) and are at points in care that few experience (such as end of life). This data-based methods article describes how findings from a qualitative study were used to guide and shape a pediatric oncology palliative care intervention. Qualitative data can lay a strong foundation for subsequent pilot intervention work by facilitating the development of an underlying study conceptualization, providing recruitment feasibility estimates, helping establish clinically meaningful inclusion criteria, establishing staff acceptability of a research intervention, and providing support for face validity of newly developed interventions. These benefits of preliminary qualitative research are described in the context of this study on legacy-making, which involves reports of children (7-12 years of age) living with advanced cancer and of their parent caregivers.
Sonographic Detection and Follow-up of a Persistent Ectopic Pregnancy
Authors: Lindauer Stephanie R.
Published: May 2013

Ectopic pregnancy is a life-threatening condition if not detected early, prior to it rupturing. This case study presents a situation where an ectopic pregnancy is sonographically detected prerupture and treated with methotrexate. Based on serial sonograms, a salpingectomy was performed several weeks later when the pregnancy had not resolved. Sonographic findings indicative of an ectopic pregnancy are presented, along with the importance of correlating findings between serial sonograms and β–human chorionic gonadotropin serum levels.
Imatinib disrupts lymphoma angiogenesis by targeting vascular pericytes
Authors: Ruan Jia , Luo Min , Wang Chunjie , Fan Lei , Yang Shao Ning , Cardenas Mariano , Geng Huimin , Leonard John P. , Melnick Ari , Cerchietti Leandro , Hajjar Katherine A.
Published: May 2013

Key Points

Blockade of PDGFRβ impairs lymphoma growth by depleting vascular mural cells. Pericytes may represent a novel, antiangiogenic target for lymphoma therapy.
Transthoracic echocardiography reference values in juvenile and adult 129/Sv mice
Authors: Vinhas Maurícia , Araújo Ana Carolina , Ribeiro Sónia , Rosário Luís Brás , Belo José António
Published: May 2013

Background

In the recent years, the use of Doppler-echocardiography has become a standard non-invasive technique in the analysis of cardiac malformations in genetically modified mice. Therefore, normal values have to be established for the most commonly used inbred strains in whose genetic background those mutations are generated. Here we provide reference values for transthoracic echocardiography measurements in juvenile (3 weeks) and adult (8 weeks) 129/Sv mice.

Methods

Echocardiographic measurements were performed using B-mode, M-mode and Doppler-mode in 15 juvenile (3 weeks) and 15 adult (8 weeks) mice, during isoflurane anesthesia. M-mode measurements variability of left ventricle (LV) was determined.

Results

Several echocardiographic measurements significantly differ between juvenile and adult mice. Most of these measurements are related with cardiac dimensions. All B-mode measurements were different between juveniles and adults (higher in the adults), except for fractional area change (FAC). Ejection fraction (EF) and fractional shortening (FS), calculated from M-mode parameters, do not differ between juvenile and adult mice. Stroke volume (SV) and cardiac output (CO) were significantly different between juvenile and adult mice. SV was 31.93 ± 8.67 μl in juveniles vs 70.61 ± 24.66 μl in adults, ρ < 0.001. CO was 12.06 ± 4.05 ml/min in juveniles vs 29.71 ± 10.13 ml/min in adults, ρ < 0.001. No difference was found in mitral valve (MV) and tricuspid valve (TV) related parameters between juvenile and adult mice. It was demonstrated that variability of M-mode measurements of LV is minimal.

Conclusions

This study suggests that differences in cardiac dimensions, as wells as in pulmonary and aorta outflow parameters, were found between juvenile and adult mice. However, mitral and tricuspid inflow parameters seem to be similar between 3 weeks and 8 weeks mice. The reference values established in this study would contribute as a basis to future studies in post-natal cardiovascular development and diagnosing cardiovascular disorders in genetically modified mouse mutant lines.
Dynamic modeling of yeast meiotic initiation
Authors: Ray Debjit , Su Yongchun , Ye Ping
Published: May 2013

Background

Meiosis is the sexual reproduction process common to eukaryotes. The diploid yeast Saccharomyces cerevisiae undergoes meiosis in sporulation medium to form four haploid spores. Initiation of the process is tightly controlled by intricate networks of positive and negative feedback loops. Intriguingly, expression of early meiotic proteins occurs within a narrow time window. Further, sporulation efficiency is strikingly different for yeast strains with distinct mutations or genetic backgrounds. To investigate signal transduction pathways that regulate transient protein expression and sporulation efficiency, we develop a mathematical model using ordinary differential equations. The model describes early meiotic events, particularly feedback mechanisms at the system level and phosphorylation of signaling molecules for regulating protein activities.

Results

The mathematical model is capable of simulating the orderly and transient dynamics of meiotic proteins including Ime1, the master regulator of meiotic initiation, and Ime2, a kinase encoded by an early gene. The model is validated by quantitative sporulation phenotypes of single-gene knockouts. Thus, we can use the model to make novel predictions on the cooperation between proteins in the signaling pathway. Virtual perturbations on feedback loops suggest that both positive and negative feedback loops are required to terminate expression of early meiotic proteins. Bifurcation analyses on feedback loops indicate that multiple feedback loops are coordinated to modulate sporulation efficiency. In particular, positive auto-regulation of Ime2 produces a bistable system with a normal meiotic state and a more efficient meiotic state.

Conclusions

By systematically scanning through feedback loops in the mathematical model, we demonstrate that, in yeast, the decisions to terminate protein expression and to sporulate at different efficiencies stem from feedback signals toward the master regulator Ime1 and the early meiotic protein Ime2. We argue that the architecture of meiotic initiation pathway generates a robust mechanism that assures a rapid and complete transition into meiosis. This type of systems-level regulation is a commonly used mechanism controlling developmental programs in yeast and other organisms. Our mathematical model uncovers key regulations that can be manipulated to enhance sporulation efficiency, an important first step in the development of new strategies for producing gametes with high quality and quantity.
Genome-wide search for the genes accountable for the induced resistance to HIV-1 infection in activated CD4+ T cells: apparent transcriptional signatures, co-expression networks and possible cellular processes
Authors: Xu Wen-Wen , Han Miao-Jun , Chen Dai , Chen Ling , Guo Yan , Willden Andrew , Liu Di-Qiu , Zhang Hua-Tang
Published: May 2013

Background

Upon co-stimulation with CD3/CD28 antibodies, activated CD4 + T cells were found to lose their susceptibility to HIV-1 infection, exhibiting an induced resistant phenotype. This rather unexpected phenomenon has been repeatedly confirmed but the underlying cell and molecular mechanisms are still unknown.

Methods

We first replicated the reported system using the specified Dynal beads with PHA/IL-2-stimulated and un-stimulated cells as controls. Genome-wide expression and analysis were then performed by using Agilent whole genome microarrays and established bioinformatics tools.

Results

We showed that following CD3/CD28 co-stimulation, a homogeneous population emerged with uniform expression of activation markers CD25 and CD69 as well as a memory marker CD45RO at high levels. These cells differentially expressed 7,824 genes when compared with the controls on microarrays. Series-Cluster analysis identified 6 distinct expression profiles containing 1,345 genes as the representative signatures in the permissive and resistant cells. Of them, 245 (101 potentially permissive and 144 potentially resistant) were significant in gene ontology categories related to immune response, cell adhesion and metabolism. Co-expression networks analysis identified 137 “key regulatory” genes (84 potentially permissive and 53 potentially resistant), holding hub positions in the gene interactions. By mapping these genes on KEGG pathways, the predominance of actin cytoskeleton functions, proteasomes, and cell cycle arrest in induced resistance emerged. We also revealed an entire set of previously unreported novel genes for further mining and functional validation.

Conclusions

This initial microarray study will stimulate renewed interest in exploring this system and open new avenues for research into HIV-1 susceptibility and its reversal in target cells, serving as a foundation for the development of novel therapeutic and clinical treatments.
A leading role for the immune system in the pathophysiology of preeclampsia
Authors: Laresgoiti-Servitje Estibalitz
Published: May 2013

Preeclampsia syndrome is characterized by inadequate placentation, because of deficient trophoblastic invasion of the uterine spiral arteries, leading to placental hypoxia, secretion of proinflammatory cytokines, the release of angiogenic and antiangiogenic factors and miRNAs. Although immune-system alterations are associated with the origin of preeclampsia, other factors, including proinflammatory cytokines, neutrophil activation, and endothelial dysfunction, are also related to the pathophysiology of this syndrome. The pathophysiology of preeclampsia may involve several factors, including persistent hypoxia at the placental level and the release of high amounts of STBMs. DAMP molecules released under hypoxic conditions and STBMs, which bind TLRs, may activate monocytes, DCs, NK cells, and neutrophils, promoting persistent inflammatory conditions in this syndrome. The development of hypertension in preeclamptic women is also associated with endothelial dysfunction, which may be mediated by various mechanisms, including neutrophil activation and NET formation. Furthermore, preeclamptic women have higher levels of nonclassic and intermediate monocytes and lower levels of lymphoid BDCA-2+ DCs. The cytokines secreted by these cells may contribute to the inflammatory process and to changes in adaptive-immune system cells, which are also modulated in preeclampsia. The changes in T cell subsets that may be seen in preeclampsia include low Treg activity, a shift toward Th1 responses, and the presence of Th17 lymphocytes. B cells can participate in the pathophysiology of preeclampsia by producing autoantibodies against adrenoreceptors and autoantibodies that bind the AT1-R.
Using psychodynamic principles in formulation in everyday practice
Authors: Summers Alison , Martindale Brian
Published: May 2013

We try to demonstrate that using psychodynamic principles as part of case formulation is both possible and useful in everyday practice. We consider steps to developing a psychodynamically informed formulation, frameworks that can be used to structure this, and processes and resources needed to support good-quality formulation. We discuss the potential value of incorporating psychodynamic thinking and emphasise that this is complementary to other frameworks for understanding psychosis. Detailed case studies are provided.
Influence of problematic child-teacher relationships on future psychiatric disorder: population survey with 3-year follow-up
Authors: Lang lain A. , Marlow Ruth , Goodman Robert , Meltzer Howard , Ford Tamsin
Published: May 2013

Background

Teacher-pupil relationships have been found to mediate behavioural, social and psychological outcomes for children at different ages according to teacher and child report but most studies have been small.

Aims

To explore later psychiatric disorder among children with problematic teacher-pupil relationships.

Method

Secondary analysis of a population-based cross-sectional survey of children aged 5-16 with a 3-year follow-up.

Results

Of the 3799 primary-school pupils assessed, 2.5% of parents reported problematic teacher-pupil relationships; for secondary-school pupils (n=3817) this rose to 6.6%. Among secondary-school pupils, even when children with psychiatric disorder at baseline were excluded and we adjusted for baseline psychopathology score, problematic teacher-pupil relationships were statistically significantly related to higher levels of psychiatric disorder at 3-year follow-up (odds ratio (OR) = 1.93, 95% CI 1.07-3.51 for any psychiatric disorder, OR=3.00, 95% CI 1.37-6.58 for conduct disorder). Results for primary-school pupils were similar but non-significant at this level of adjustment.

Conclusions

This study underlines the need to support teachers and schools to develop positive relationships with their pupils.
Psychiatrists' access to electronic laboratory results
Authors: Skelton Mike , Thacker Simon , Forbes-Haley Andrew , Kumar Mahendra , Holliday Eleanor
Published: May 2013

Aims and method

A completed audit cycle, consisting of email surveys of all psychiatrists and a review of acute trust information technology registers was undertaken in Derbyshire Healthcare NHS Foundation Trust, to assess whether psychiatrists could access electronic laboratory results from the neighbouring acute trust laboratory. This was replicated in Nottinghamshire Healthcare NHS Trust, with an initial audit; plans were then implemented to increase access.

Results

In Derbyshire, 14% of psychiatrists could access electronic results initially, with limited ward access. By re-audit, all wards had access, and 28% used those systems. The later initial audit in Nottinghamshire Healthcare Trust revealed 6% access.

Clinical implications

Benefits of electronic results include clinical (faster decisions, safer monitoring, prompt detection of acute problems); efficiency savings (less wasted time telephoning); and other (improved relationships with general practitioners and laboratories, reduced marginalisation of patients with mental illness and professionals). There may be considerable clinical and efficiency savings for trusts.
Stories of Water
Authors: Borowick Nancy
Published: May 2013

Nearly 1 billion people do not have access to safe or clean drinking water. The people of Ghana are reflected in this statistic, and, as a photojournalist, Nancy Borowick advocates for these communities through her images.
The EITC, Tax Refunds, and Unemployment Spells
Authors: LaLumia Sara
Published: May 2013

The earned income tax credit generates large average tax refunds for low-income parents, and these refunds are distributed in a narrow time frame. I rely on this plausibly exogenous source of variation in liquidity to investigate the effect of cash on hand on unemployment duration. Among EITC-eligible women, unemployment spells beginning just after tax refund receipt last longer than unemployment spells beginning at other times of year. There is no evidence that tax refund receipt is associated with longer unemployment duration for men, or that the longer durations for women are associated with higher-quality subsequent job matches. (JEL H24, J64)
Energy Intensity Convergence in OECD Countries
Authors: Kiran Burcu
Published: May 2013

This paper investigates the energy intensity convergence for 21 OECD countries over the period 1980-2010. To achieve this aim, fractional cointegration definition suggested by Cheung and Lai (1993), which requires only a mean reverting ( d < 1) relationship between a set of I(1) variables, is used. Following their suggestion, we employ Geweke and Porter-Hudak test for estimating the fractional parameter of the residuals obtained from cointegrating regressions. The results reveal the presence of energy intensity convergence for 9 countries namely Canada, Chile, Denmark, Finland, Germany, Iceland, Ireland, the Netherlands and Turkey.
Physical Characterization of the Pore-Fracture System in Coals, Northeastern China
Authors: Li Junqian , Liu Dameng , Yao Yanbin , Cai Yidong , Guo Xiaoqian
Published: May 2013

Usually mercury intrusion/extrusion curves reflect the characteristics of open pore-fracture system of coals. Using this method, the nature of the open pore-fractures of 18 Chinese coals (varying in vitrinite reflectance from 0.65 to 1.76% Ro, max) was studied. A quantitative evaluation method for micropore (0-0.1 μm, in diameter), mesopore (0.1-1 μm), macropore (1-10 μm) and fracture (>10 μm) within coals was established by the mercury intrusion curves. The method was verified by the fractal geometry theory. Moreover, three Types (I, II and III) of the open pore-fracture systems of coals were analyzed by combining mercury withdrawal efficiency and permeability with pore size distribution. Results show that (a) Type I coals are characterized by abundant open micropores (mean 62.8 vol. %) and rarely open fractures, which leads to a large minable potential but very low production rate for coalbed methane (CBM); (b) Type II coals have low minable potential and high production rate for CBM, mainly because of the distribution of a few micropores (mean 35.5 vol. %) and a large number fractures (mean 19.7 vol. %) in coals; (c) Type III coals are the most appropriate to exploit CBM due to the existence of optimal open pore-fracture system (micropores, mean 58.5 vol. %; fractures, mean 15.4 vol. %) within coals.
An Experimental Investigation into the Effect of Flap Angles for a Piezo-Driven Wing
Authors: DeLuca Anthony M. , Reeder Mark F. , Cobb Richard G.
Published: May 2013

This article presents a comparison of results from six degree of freedom force and moment measurements and Particle Image Velocimetry (PIV) data taken on the Air Force Institute of Technology's (AFIT) piezoelectrically actuated, biomimetically designed Hawkmoth, Manduca Sexta, class engineered wing, at varying amplitudes and flapping frequencies, for both trimmed and asymmetric flapping conditions to assess control moment changes. To preserve test specimen integrity, the wing was driven at a voltage amplitude 50% below the maximum necessary to achieve the maximal Hawkmoth total stroke angle. 86° and 65° stroke angles were achieved for the trimmed and asymmetric tests respectively. Flapping tests were performed at system structural resonance, and at ±10% off system resonance at a single amplitude, and PZT power consumption was calculated for each test condition. Two-dimensional PIV visualization measurements were taken transverse to the wing planform, recorded at the mid-span, for a single frequency and amplitude setting, for both trimmed and asymmetric flapping to correlate with the 6-DoF balance data. Linear velocity data was extracted from the 2-D PIV imagery at ± 1/2 and ±1 chord locations above and below the wing, and the mean velocities were calculated for four separate wing phases during the flap cycle. The mean forces developed during a flap cycle were approximated using a modification of the Rankine-Froude axial actuator disk model to calculate the transport of momentum flux as a measure of vertical thrust produced during a static hover flight condition. Values of vertical force calculated from the 2-D PIV measurements were within 20% of the 6-DOF force balance experiments. Power calculations confirmed flapping at system resonance required less power than at off resonance frequencies, which is a critical finding necessary for future vehicle design considerations.
Integrated Survey to Extract Date for Structural Investigations
Authors: Costantino D. , Angelini M. G.
Published: May 2013

This paper presents some results of a integrated survey, aimed to 3D modeling and the subsequent representation of the collapse of part of a historical building. The survey of a building in Salerno it has been made, built in Art Nouveau style, has the name taken from “Società Anonima per l'Edilizia”, which undertook its construction. The results have been a support characterized by metric valence for structural engineers who have examined the stability of the structure and determined the cause of the collapse. The collapse occurred during the night and covered the South-West corner of the building. However, there were no neither victims nor injured because the zone of the building housed the living room or rather the kitchen, and not the bedrooms. For this case study a integrated survey it has been conducted; in particular, laser scanning, topographical and terrestrial photogrammetry techniques in order to obtain the 3D model of buildings, plans and prospects and the particular of the collapsed area have been adopted. The experimental algorithm, developed by authors, in order to obtain 2D representation of whole building and the area of collapse, it has been used. The results has been an aid for the structural engineers. Of considerable support to the above analyzes were both the topographical survey of the collapse site, that the laboratory tests, some of them inferred by three-dimensional metric knowledge and by graphical representation provided.
Gestão de Mudanças nas Organizações do Terceiro Setor: O Desafio da Sustentabilidade Financeira
Authors: Parente Tobias Coutinho , Tiscoski Gabriela Pellegrini , Rosolen Talita , Ferrato da Silva Matheus Roquette , Abreu de Campos Ana Carolina , Sakamuto Douglas Aparecido
Published: May 2013

O presente artigo objetiva analisar as mudanças na cultura organizacional das organizações do terceiro setor (OTS) para atingir a sustentabilidade financeira, a partir da contextualização das OTS no Brasil e da apresentação do Estudo de Caso de duas organizações do terceiro setor, o INVAR e o Laboridade. A pesquisa baseou-se na visão construtivista, conforme propõe Stake (2005) e no método dedutivo no nível de análise organizacional, sendo a análise elaborada com base na abordagem contextualista, a fim de identificar e explorar padrões que podem ser recorrentes (FISCHER, 2002b; PETTIGREW, 2007), como a formação de parcerias e alianças interorganizacionais (FISCHER, 2002a). Observou-se que as organizações estudadas estão em processo de adaptação, mas ainda caminham de forma reativa às mudanças e transformações impostas pelo contexto. Presas a uma forma já ultrapassada de obtenção de recursos, as OTS enxergam a necessidade de mudanças, mas seu maior desafio é identificar as oportunidades.
Decay of Motor Memories in the Absence of Error
Authors: Vaswani Pavan A. , Shadmehr Reza
Published: May 2013

When motor commands are accompanied by an unexpected outcome, the resulting error induces changes in subsequent commands. However, when errors are artificially eliminated, changes in motor commands are not sustained but show decay. Why does the adaptation-induced change in motor output decay in the absence of error? A prominent idea is that decay reflects the stability of the memory. We show results that challenge this idea and instead suggest that motor output decays because the brain actively disengages a component of the memory. Humans adapted their reaching movements to a perturbation and were then introduced to a long period of trials in which errors were absent (error-clamp). We found that, in some subjects, motor output did not decay at the onset of the error-clamp block but a few trials later. We manipulated the kinematics of movements in the error-clamp block and found that, as movements became more similar to subjects' natural movements in the perturbation block, the lag to decay onset became longer and eventually reached hundreds of trials. Furthermore, when there was decay in the motor output, the endpoint of decay was not zero but a fraction of the motor memory that was last acquired. Therefore, adaptation to a perturbation installed two distinct kinds of memories: (1) one that was disengaged when the brain detected a change in the task and (2) one that persisted despite it. Motor memories showed little decay in the absence of error if the brain was prevented from detecting a change in task conditions.
Entrainment of the Intrinsic Dynamics of Single Isolated Neurons by Natural-Like Input
Authors: Gal Asaf , Marom Shimon
Published: May 2013

Neuronal dynamics is intrinsically unstable, producing activity fluctuations that are essentially scale free. Here we study single cortical neurons of newborn ratsin vitro, and show that while these scale-free fluctuations are independent of temporal input statistics, they can be entrained by input variation. Joint input–output statistics and spike train reproducibility in synaptically isolated cortical neurons were measured in response to various input regimes over extended timescales (many minutes). Response entrainment was found to be maximal when the input itself possesses natural-like, scale-free statistics. We conclude that preference for natural stimuli, often observed at the system level, exists already at the elementary, single neuron level.
The Cav3–Kv4 Complex Acts as a Calcium Sensor to Maintain Inhibitory Charge Transfer during Extracellular Calcium Fluctuations
Authors: Anderson Dustin , Engbers Jordan D. T. , Heath N. Colin , Bartoletti Theodore M. , Mehaffey W. Hamish , Zamponi Gerald W. , Turner Ray W.
Published: May 2013

Synaptic transmission and neuronal excitability depend on the concentration of extracellular calcium ([Ca]o), yet repetitive synaptic input is known to decrease [Ca]oin numerous brain regions. In the cerebellar molecular layer, synaptic input reduces [Ca]oby up to 0.4 mmin the vicinity of stellate cell interneurons and Purkinje cell dendrites. The mechanisms used to maintain network excitability and Purkinje cell output in the face of this rapid change in calcium gradient have remained an enigma. Here we use single and dual patch recordings in anin vitroslice preparation of Sprague Dawley rats to investigate the effects of physiological decreases in [Ca]oon the excitability of cerebellar stellate cells and their inhibitory regulation of Purkinje cells. We find that a Cav3–Kv4 ion channel complex expressed in stellate cells acts as a calcium sensor that responds to a decrease in [Ca]oby dynamically adjusting stellate cell output to maintain inhibitory charge transfer to Purkinje cells. The Cav3–Kv4 complex thus enables an adaptive regulation of inhibitory input to Purkinje cells during fluctuations in [Ca]o, providing a homeostatic control mechanism to regulate Purkinje cell excitability during repetitive afferent activity.
Altered Calcium Metabolism in Aging CA1 Hippocampal Pyramidal Neurons
Authors: Oh M. Matthew , Oliveira Fernando A. , Waters Jack , Disterhoft John F.
Published: May 2013

Altered neuronal calcium homeostasis is widely hypothesized to underlie cognitive deficits in normal aging subjects, but the mechanisms that underlie this change are unknown, possibly due to a paucity of direct measurements from aging neurons. Using CCD and two-photon calcium imaging techniques on CA1 pyramidal neurons from young and aged rats, we show that calcium influx across the plasma membrane increases with aging, and that this change is countered by increased intracellular calcium buffering. The additional buffer in aging neurons balances the increased calcium influx following a small number (<3) action potentials, but is overwhelmed during sustained or theta-like activity which leads to a greater rise in intracellular calcium concentration in aging than that in young neurons. Our results demonstrate that calcium overload occurs regularly in aging CA1 pyramidal neurons under physiological conditions. This overload may be a critical factor in age-related decline in hippocampus-dependent cognitive function.
Oscillatory Beta Activity Mediates Neuroplastic Effects of Motor Cortex Stimulation in Humans
Authors: McAllister Craig J. , Rönnqvist Kim C. , Stanford Ian M. , Woodhall Gavin L. , Furlong Paul L. , Hall Stephen D.
Published: May 2013

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibit human motor cortex (M1) excitability and impair movement for ≤1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15–35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function.