bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure of Stored Packed Erythrocytes to Nitric Oxide Prevents Transfusion-associated Pulmonary Hypertension
Authors: Muenster Stefan , Beloiartsev Arkadi , Yu Binglan , Du E , Abidi Sabia , Dao Ming , Fabry Gregor , Graw Jan A. , Wepler Martin , Malhotra Rajeev , Fernandez Bernadette O. , Feelisch Martin , Bloch Kenneth D. , Bloch Donald B. , Zapol Warren M.
Published: August 2016

Background

Transfusion of packed erythrocytes stored for a long duration is associated with increased pulmonary arterial pressure and vascular resistance. Prolonged storage decreases erythrocyte deformability, and older erythrocytes are rapidly removed from the circulation after transfusion. The authors studied whether treating stored packed ovine erythrocytes with NO before transfusion could prevent pulmonary vasoconstriction, enhance erythrocyte deformability, and prolong erythrocyte survival after transfusion.

Methods

Ovine leukoreduced packed erythrocytes were treated before transfusion with either NO gas or a short-lived NO donor. Sheep were transfused with autologous packed erythrocytes, which were stored at 4°C for either 2 (“fresh blood”) or 40 days (“stored blood”). Pulmonary and systemic hemodynamic parameters were monitored before, during, and after transfusion. Transfused erythrocytes were labeled with biotin to measure their circulating lifespan. Erythrocyte deformability was assessed before and after NO treatment using a microfluidic device.

Results

NO treatment improved the deformability of stored erythrocytes and increased the number of stored erythrocytes circulating at 1 and 24 h after transfusion. NO treatment prevented transfusion-associated pulmonary hypertension (mean pulmonary arterial pressure at 30 min of 21 ± 1 vs. 15 ± 1 mmHg in control and NO–treated packed erythrocytes, P < 0.0001). Washing stored packed erythrocytes before transfusion did not prevent pulmonary hypertension.

Conclusions

NO treatment of stored packed erythrocytes before transfusion oxidizes cell-free oxyhemoglobin to methemoglobin, prevents subsequent NO scavenging in the pulmonary vasculature, and limits pulmonary hypertension. NO treatment increases erythrocyte deformability and erythrocyte survival after transfusion. NO treatment might provide a promising therapeutic approach to prevent pulmonary hypertension and extend erythrocyte survival.
Development of Hermes, a New Person-Centered Assessment Tool in Nursing Rehabilitation, Through Action Research
Authors: Thórarinsdóttir Kristín , Björnsdóttir Kristín , Kristjánsson Kristján
Published: August 2016

In this article, an action-research project has been outlined, aimed at exploring ways for developing an assessment tool, underpinned by phenomenology, which would enhance a person-centered approach to the participation of patients in nursing assessment and care planning in rehabilitation. Participants were nurses in physical rehabilitation and a consultant. Data were collected by interviews and observation of the documentation on the tool. The tool, Hermes, was adopted in practice. Through its use, important person-centered assessment practices were enhanced and several aspects of its phenomenological grounding were supported. Hermes has potential for facilitating the transfusion of phenomenology into nursing practice.
What End-of-Life Care Needs Now
Authors: Rosa William , Estes Tarron
Published: August 2016

Conscious Dying Institute is paving a new path in the realm of end of life care; one emerging from awareness, humanity, dignity, caring consciousness, and a return to the sacred. The purpose herein is to discuss the emerging theoretical perspectives of Conscious Dying Institute and to address their implications for broadening the scope of nursing and end of life care. In educating nurses about their own authentic selves, they return to their personal-professional purpose, awaken to a heightened awareness of needs for self and other, and influence a global shift in how end of life care is viewed, addressed, and delivered.
An Analysis and Evaluation of the Theory of Unpleasant Symptoms
Authors: Lee Seung Eun , Vincent Catherine , Finnegan Lorna
Published: August 2016

The Theory of Unpleasant Symptoms was developed to enhance understanding of relationships among multiple symptoms and symptom experiences. Although the theory has been used to guide research, no formal critique of the theory has been published since 2000. This article comprehensively analyzes and evaluates the theory using Fawcett and DeSanto-Madeya's framework. Although its semantic clarity, semantic and structural consistency, and parsimony could be improved, the theory demonstrates good social and theoretical significance, testability, and empirical and pragmatic adequacy. Understanding multiple patient symptoms is essential, and the theory demonstrates that nurses should focus on multiple rather than individual symptoms.
The “As-If” World of Nursing Practice
Authors: Grundy Quinn , Malone Ruth E.
Published: August 2016

The “as-if” world of nursing is a well-constructed, institutionally preserved and defended myth that asserts clinicians who are “just nurses” do not make decisions in the absence of “doctor's orders.” Drawing on data from an ethnography exploring the interactions between nurses and industry, we explore the finding that many nurses did not identify as “decision makers” and were mystified by the attention of sales representatives. Many nurses experienced marketing as benign as there was no “decision” to sway. Nursing must deconstruct the “as-if” nondecisional myth by confronting conflicts of interest and owning fully its rightful clinical and advocacy roles. www.advancesinnursingscience.com
Efficacy of the Mantram Repetition Program for Insomnia in Veterans With Posttraumatic Stress Disorder
Authors: Beck Danielle , Cosco Holt Lindsay , Burkard Joseph , Andrews Taylor , Liu Lin , Heppner Pia , Bormann Jill E.
Published: August 2016

Statistics show that more than 80% of Veterans mention posttraumatic stress disorder (PTSD)-related symptoms when seeking treatment. Sleep disturbances and nightmares are among the top 3 presenting problems. Current PTSD trauma-focused therapies generally do not improve sleep disturbances. The mantram repetition program (MRP), a mind-body-spiritual intervention, teaches a portable set of cognitive-spiritual skills for symptom management. The aim of this study was to evaluate the efficacy of the MRP on insomnia in Veterans with PTSD in a naturalistic, clinical setting. Results show that participation in the MRP significantly reduced insomnia, as well as decreased self-reported and clinician-assessed PTSD symptom burden.
Clavicle Fractures are Associated With Arthritis of the Glenohumeral Joint in a Large Osteological Collection
Authors: Weinberg Douglas S. , Vallier Heather A. , Gaumer Gregory A. , Cooperman Daniel R. , Liu Raymond W.
Published: August 2016

Objectives:

Recent data has challenged the historical precedent of nonoperative care for many clavicle fractures; clinical and biomechanical studies have shown altered joint-contact forces occur in the glenohumeral joint (GHJ) after fracture and shortening of the clavicle. However, to date, there have been no analyses documenting the long-term effects of these altered shoulder girdle mechanics on the GHJ.

Methods:

The clavicles of 2899 cadaveric skeletons were manually inspected for evidence of fracture. Shortening, fracture location, and laterality were recorded along with demographic information. Degenerative joint disease of the GHJ was graded. Correlations between the presence of a clavicle fracture and ipsilateral GHJ osteoarthritis were evaluated with multiple regression analysis using an age-, gender-, race-, and laterality-matched control group of 1154 GHJs.

Results:

One hundred three specimens had 104 clavicle fractures, a prevalence of 3.6% (103/2899) in this collection. There was a strong correlation between the presence of an ipsilateral clavicle fracture (standardized beta 0.108, P < 0.001), age (standardized beta 0.332, P < 0.001), male gender (standardized beta −0.069, P = 0.009), and laterality (right sided, standardized beta 0.056, P = 0.032) on the development of GHJ arthritis. There was a trend toward increased GHJ arthritis in specimens with shortening >20 mm (standardized beta 0.156, P = 0.109), although this subanalysis may have been underpowered.

Conclusions:

This is the first study to report long-term consequences of clavicle fracture on the development of ipsilateral GHJ osteoarthritis; clavicle fractures were shown to have a higher degree of GHJ osteoarthritis. Future clinical studies are needed to confirm these relationships.
Cardiac N-methyl d-aspartate Receptors as a Pharmacological Target
Authors: Makhro Asya , Tian Qinghai , Kaestner Lars , Kosenkov Dmitry , Faggian Giuseppe , Gassmann Max , Schwarzwald Colin , Bogdanova Anna
Published: August 2016

This study focuses on characterization of the cardiac N-methyl d-aspartate receptors (NMDARs) as a target for endogenous and synthetic agonists and antagonists. Using isolated perfused rat hearts, we have shown that intracoronary administration of the NMDAR agonists and antagonists has a pronounced effect on autonomous heart function. Perfusion of rat hearts with autologous blood supplemented with NMDAR agonists was associated with induction of tachycardia, sinus arrhythmia, and ischemia occurring within physiological plasma concentration range for glutamate and glycine. Intracoronary administration of the NMDAR antagonists exerted an antiarrhythmic effect and resulted in bradycardia and improvement of capillary perfusion. Action of antagonists eliprodil, Ro25-6981, memantine, ketamine, and MK-801 on autonomous heart function diverged strikingly from that of L-type Ca2+ channel blockers. Cardiac NMDAR subunit composition differed from that of neuronal receptors and was age specific and chamber specific. Transcripts of the GluN3A and GluN2D were found in all heart chambers, whereas expression of GluN1 and GluN2A and 2C was restricted to the atria. Expression of the GluN2B protein in ventricles increased markedly with age of the animals. The obtained data reveal that NMDARs are expressed in rat heart contributing to the autonomic heart rate regulation and the function of the cardiac conduction system.
What's new in the functional anatomy of pelvic organ prolapse?
Authors: DeLancey John O.L.
Published: August 2016

Purpose of review

Provide an evidence-based review of pelvic floor functional anatomy related to pelvic organ prolapse.

Recent findings

Pelvic organ support depends on interactions between the levator ani muscle and pelvic connective tissues. Muscle failure exposes the vaginal wall to a pressure differential producing abnormal tension on the attachments of the pelvic organs to the pelvic sidewall. Birth-induced injury to the pubococcygeal portion of the levator ani muscle is seen in 55% of women with prolapse and 16% of women with normal support. Failure of the lateral connective tissue attachments between the uterus and vagina to the pelvic wall (cardinal, uterosacral, and paravaginal) are strongly related with prolapse (effect sizes ∼2.5) and are also highly correlated with one another (r ∼ 0.85). Small differences exist with prolapse in factors involving the vaginal wall length and width (effect sizes ∼1). The primary difference in ligament properties between women with and without prolapse is found in ligament length. Only minor differences in ligament stiffness are seen.

Pelvic organ prolapse occurs because of injury to the levator ani muscles and failure of the lateral connections between the pelvic organs to the pelvic sidewall. Abnormalities of the vaginal wall fascial tissues may play a minor role.
Botulinum Toxin A: Dose-dependent Effect on Reepithelialization and Angiogenesis
Authors: Gugerell Alfred , Kober Johanna , Schmid Melanie , Buchberger Elisabeth , Kamolz Lars-Peter , Keck Maike
Published: August 2016

Background:

Botulinum (neuro)toxin A (BoNT) is widely used in the field of plastic and reconstructive surgery. Among treatment of pain, hyperhidrosis, or aesthetic purposes, it is also used to enhance wound healing and prevent excessive scar formation. Some clinical data already exist, but only little is known on a cellular level. The aim of this study was to evaluate the effect of BoNT on cells essential for wound healing in vitro. Therefore, primary human keratinocytes and endothelial cells were treated with different concentrations of BoNT and tested on proliferation, migration, and angiogenic behavior.

Methods:

BoNT was exposed to human keratinocytes and endothelial cells in a low (1 IU/mL), medium (10 IU/mL), and high (20 IU/mL) concentrations in cell culture. Proliferation and migration of the 2 cell types were observed and also the angiogenic potential of endothelial cells in vitro.

Results:

BoNT 20 IU/mL negatively influenced proliferation and migration of keratinocytes but not those of endothelial cells. Angiogenesis in vitro was less effective with the highest BoNT concentrations tested. Low concentrations of BoNT supported sprouting of endothelial cells.

Conclusions:

High concentrations of botulinum toxin interfered with wound closure as keratinocytes’ proliferation and migration were deteriorated. Furthermore, BoNT concentrations of 20 IU/mL constrain in vitro vessel formation but do not influence proliferation or migration of endothelial cells.
Utility of preclinical assays to assess stored platelet function
Authors: Francis Richard O.
Published: August 2016

Purpose of review

Increased use of platelets and the brief shelf life allowed by storage at 22 °C are promoting exploration of new methods to store platelets. As storage may affect the hemostatic efficacy of platelets, it is very important to assess their in-vivo hemostatic efficacy. The potential usefulness of preclinical models in evaluating methods for storing platelets will be discussed.

Recent findings

The use of new technologies to examine the in-vitro characteristics of stored platelet products continues to evolve. Although in-vitro evaluation, coupled with posttransfusion recovery in healthy volunteers and studies in thrombocytopenic patients, are mainstays of evaluating new platelet products, the inclusion of preclinical animal models for the systematic evaluation of the in-vivo hemostatic function of these products would enhance the information gained from these studies.

The application of novel integrated platforms will be key in realizing advancements in the field of platelet storage. These preclinical models can be applied to rapidly assess the effect of new additive solutions and storage methods on platelet hemostatic function prior to performing human clinical trials.
Matched sibling donor hematopoietic stem cell transplantation for thalassemia
Authors: Issaragrisil Surapol , Kunacheewa Chutima
Published: August 2016

Purpose of review

Bone marrow transplantation is the only curative treatment for severe thalassemia. Since its successful first report in 1981, more than 4000 patients with this disease worldwide underwent bone marrow transplantation. The purpose of this review is to update the most recent reports of matched sibling donor hematopoietic stem cell transplantation in thalassemia.

Recent findings

Advanced and improved transplant techniques result in the improved outcomes in those transplants from a matched sibling donor with transplant-related mortality less than 5%. Class 3 patients aged at least 7 years and liver enlargement at least 5 cm have a very high risk of graft rejection and regimen-related toxicity. This subset of patients require innovative approaches to overcome the morbidity and mortality. Those include the addition of hydroxyurea, azathioprine, and fludarabine as preconditioning to busulfan, thiotepa, and cyclophosphamide. Novel conditioning consisting of pretransplant immunosuppression with two cycles of fludarabine and dexamethasone followed by reduced intensity conditioning with fludarabine, busulfan, and thymoglobulin has been developed.

Bone marrow transplantation in young low-risk (class 1 and 2) patients should be performed as soon as possible. For class 3 severe thalassemia, novel conditioning regimens have been developed to overcome graft rejection and regimen-related toxicity. Hematopoietic stem cell transplantation in adults who have been well chelated should be offered with clinical trials.
Loss of a Candidate Biliary Atresia Susceptibility Gene, add3a, Causes Biliary Developmental Defects in Zebrafish
Authors: Tang Vivian , Cofer Zenobia C. , Cui Shuang , Sapp Valerie , Loomes Kathleen M. , Matthews Randolph P.
Published: August 2016

Objectives:

Biliary atresia (BA) is a progressive fibroinflammatory cholangiopathy affecting the bile ducts of neonates. Although BA is the leading indication for pediatric liver transplantation, the etiology remains elusive. Adducin 3 (ADD3) and X‐prolyl aminopeptidase 1 (XPNPEP1) are 2 genes previously identified in genome‐wide association studies as potential BA susceptibility genes. Using zebrafish, we investigated the importance of ADD3 and XPNPEP1 in functional studies.

Methods:

To determine whether loss of either gene leads to biliary defects, we performed morpholino antisense oligonucleotide (MO) knockdown studies targeting add3a and xpnpep1 in zebrafish. Individuals were assessed for decreases in biliary function and the presence of biliary defects. Quantitative polymerase chain reaction was performed on pooled 5 days postfertilization larvae to assess variations in transcriptional expression of genes of interest.

Results:

Although both xpnpep1 and add3a are expressed in the developing zebrafish liver, only knockdown of add3a produced intrahepatic defects and decreased biliary function. Similar results were observed in homozygous add3a mutants. MO‐mediated knockdown of add3a also showed higher mRNA expression of hedgehog (Hh) targets. Inhibition of Hh signaling rescued biliary defects caused by add3a knockdown. Combined knockdown of add3a and glypican‐1 (gpc1), another mediator of Hh activity that is also a BA susceptibility gene, resulted in more severe biliary defects than knockdown of either alone.

Conclusions:

Our results support previous studies identifying ADD3 as a putative genetic risk factor for BA susceptibility. Our results also provide evidence that add3a may be affecting the Hh pathway, an important factor in BA pathogenesis.
PAX7 Expression in Rhabdomyosarcoma, Related Soft Tissue Tumors, and Small Round Blue Cell Neoplasms
Authors: Charville Gregory W. , Varma Sushama , Forgó Erna , Dumont Sarah N. , Zambrano Eduardo , Trent Jonathan C. , Lazar Alexander J. , van de Rijn Matt
Published: August 2016

Rhabdomyosarcoma, the most common soft tissue malignancy of childhood, is a morphologically variable tumor defined by its phenotype of skeletal muscle differentiation. The diagnosis of rhabdomyosarcoma often relies in part on the identification of myogenic gene expression using immunohistochemical or molecular techniques. However, these techniques show imperfect sensitivity and specificity, particularly in scant tissue biopsies. Here, we expand the toolkit for rhabdomyosarcoma diagnosis by studying the expression of PAX7, a transcriptional regulator of mammalian muscle progenitor cells implicated in the pathogenesis of rhabdomyosarcoma. Immunohistochemical analysis of tissue microarrays using a monoclonal anti-PAX7 antibody was used to characterize PAX7 expression in 25 non-neoplastic tissues, 109 rhabdomyosarcomas, and 697 small round blue cell or other soft tissue tumors. Among non-neoplastic tissues, PAX7 was specifically expressed in adult muscle progenitor cells (satellite cells). In embryonal rhabdomyosarcoma, PAX7 expression was positive in 52 of 63 cases (83%), negative in 9 of 63 cases (14%), and focal in 2 of 63 cases (3%). PAX7-positive embryonal rhabdomyosarcoma cases included several showing focal or negative myogenin expression. PAX7 expression in alveolar rhabdomyosarcoma was positive in 6 of 31 cases (19%), negative in 14 of 31 cases (45%), and focal in 11 of 31 cases (36%). In addition, PAX7 was expressed in 5 of 7 pleomorphic rhabdomyosarcomas (71%) and 6 of 8 spindle cell rhabdomyosarcomas (75%). Among histologic mimics, only Ewing sarcoma showed PAX7 expression (7/7 cases, 100%). In contrast, expression of PAX7 was not seen in the large majority (688/690, 99.7%) of examined cases of other soft tissue tumors, small round blue cell neoplasms, and leukemias/lymphomas. In summary, immunohistochemical analysis of PAX7 expression may be a useful diagnostic tool in the assessment of skeletal muscle differentiation in human tumors.
Translating Neurodevelopmental Care Policies Into Practice: The Experience of Neonatal ICUs in France—The EPIPAGE-2 Cohort Study
Authors: Pierrat Veronique , Coquelin Anaëlle , Cuttini Marina , Khoshnood Babak , Glorieux Isabelle , Claris Olivier , Durox Mélanie , Kaminski Monique , Ancel Pierre-Yves , Arnaud Catherine
Published: August 2016

Objectives:

To describe the implementation of neurodevelopmental care for newborn preterm infants in neonatal ICUs in France in 2011, analyze changes since 2004, and investigate factors associated with practice.

Design:

Prospective national cohort study of all births before 32 weeks of gestation.

Setting:

Twenty-five French regions.

Participants:

All neonatal ICUs (n = 66); neonates surviving at discharge (n = 3,005).

Interventions:

None.

Measurements and Main Results:

Neurodevelopmental care policies and practices were assessed by structured questionnaires. Proportions of neonates initiating kangaroo care during the first week of life and those whose mothers expressed breast milk were measured as neurodevelopmental care practices. Multilevel logistic regression analyses were used to investigate relationships between kangaroo care or breast-feeding practices and unit policies, taking into account potential confounders. Free visiting policies, bed availability for parents, and kangaroo care encouragement significantly improved between 2004 and 2011 but with large variabilities between units. Kangaroo care initiation varied from 39% for neonates in the most restrictive units to 68% in less restrictive ones (p < 0.001). Individual factors associated with kangaroo care initiation were gestational age (odds ratio, 5.79; 95% CI, 4.49–7.48 for babies born at 27–31 wk compared with babies born at 23–26 wk) and, to a lesser extent, single pregnancy, birthweight above the 10th centile, and mother’s employment before pregnancy. At unit level, policies and training in neurodevelopmental care significantly influenced kangaroo care initiation (odds ratio, 3.5; 95% CI, 1.8–7.0 for Newborn Individualized Developmental Care and Assessment Program implementation compared with no training). Breast milk expression by mothers was greater in units with full-time availability professionals trained for breast-feeding support (60% vs 73%; p < 0.0001).

Conclusions:

Dissemination of neurodevelopmental practices occurred between 2004 and 2011, but large variabilities between units persist. Practices increased in units with supportive policies. Specific neurodevelopmental care training with multifaceted interventions strengthened the implementation of policies.
Donor Characteristics of Pancreas Transplantation in Australia and New Zealand: A Cohort Study 1984-2014
Authors: Peng Xi (Alex) , Kelly Patrick J. , Mulley William R. , Pleass Henry , Pilmore Helen , Webster Angela C.
Published: August 2016

Background

The aim of this study was to audit the characteristics of pancreas donors over time in Australia and New Zealand. Pancreas transplantation was introduced in Australian and New Zealand in 1984.

Methods

We analyzed data from the Australia and New Zealand Islet and Pancreas Transplant Registry, 1984 to 2014. We investigated the variation of donor characteristics of sex, age, body mass index, smoking status, blood group, multiple organ donation, cytomegalovirus status, terminal creatinine, hypertension, and cause of death for pancreas transplantation over time. We used χ2 test (Fisher test when necessary) or analysis of variance to test difference for categorical or continuous characteristics, respectively.

Results

There were 628 pancreas donors from 1984 to 2014. Donor body mass index (from 21.9 to 24.0, P < 0.001) and age (from 23.9 to 28.5, P = 0.02) have both increased while terminal creatinine has decreased (86.3 to 73.3, P = 0.01) from 1995 to 2014. In the meantime, the proportions of donors with hypertension (from 19% to 1%, P < 0.001) and who were smokers (from 54% to 15%, P < 0.001) have decreased. Profile of cause of donor death has also changed over time (P = 0.06) with increase in cerebral hypoxia/ischemia (from 3% to 17%) and reductions in intracranial hemorrhage (27% to 13%).

Conclusions

Many donor characteristics have changed over time. The most significant changes appear to reflect changes in the general population, rather than changes in donor selection.
Dissection of molecular assembly dynamics by tracking orientation and position of single molecules in live cells
Authors: Mehta Shalin B. , McQuilken Molly , Riviere Patrick La , Occhipinti Patricia , Verma Amitabh , Oldenbourg Rudolf , Gladfelter Amy S. , Tani Tomomi
Published: August 2016

Regulation of order, such as orientation and conformation, drives the function of most molecular assemblies in living cells, yet remains difficult to measure accurately through space and time. We built an instantaneous fluorescence polarization microscope, which simultaneously images position and orientation of fluorophores in living cells with single-molecule sensitivity and a time resolution of 100ms. We developed image acquisition and analysis methods to track single particles that interact with higher-order assemblies of molecules. We tracked the fluctuations in position and orientation of molecules from the level of an ensemble of fluorophores down to single fluorophores. We tested our systemin vitrousing fluorescently labeled DNA and F-actin in which the ensemble orientation of polarized fluorescence is known. We then tracked the orientation of sparsely labeled F-actin network at the leading edge of migrating human keratinocytes, revealing the anisotropic distribution of actin filaments relative to the local retrograde flow of the F-actin network. Additionally, we analyzed the position and orientation of septin-GFP molecules incorporated in septin bundles in growing hyphae of a filamentous fungus. Our data indicate that septin-GFP molecules undergo positional fluctuations within, ∼350nm of the binding site and angular fluctuations within ∼30°of the central orientation of the bundle. By reporting position and orientation of molecules while they form dynamic higher-order structures, our approach can provide new insights into how micron-scale ordered assemblies emerge from nanoscale molecules in living cells.

Significance Statement

In living cells, the 3D architecture of molecular assemblies such as chromosomes, lipid bilayers, and the cytoskeleton is regulated through the interaction among their component molecules. Monitoring the position and orientation of constituent molecules is important for understanding the mechanisms that govern the structure and function of these assemblies. We have developed an instantaneous fluorescence polarization microscope to track the position and orientation of fluorescently labeled particles, including single molecules, which form micron-scale macromolecular assemblies in living cells. Our imaging approach is broadly applicable to the study of dynamic molecular interactions that underpin the function of micron-scale assemblies in living cells.
Cleavage modification did not alter early blastomere fates during bryozoan evolution
Authors: Vellutini Bruno C. , Martín-Durán José M. , Hejnol Andreas
Published: August 2016

Stereotypic cleavage patterns play a crucial role in cell fate determination by precisely positioning early embryonic blastomeres. Although misplaced cell divisions can alter blastomere fates and cause embryonic defects, cleavage patterns have changed several times during animal evolution. Here, we analyze the evolutionary transition from spiral cleavage – a stereotypic pattern remarkably conserved in many protostomes – to the biradial cleavage of bryozoans. We characterize the cell lineage, MAPK signaling and expression of several developmental genes in the bryozoanMembranipora membranacea, and found that the fate and the genes expressed in the early bryozoan blastomeres are similar to their putative homologous blastomeres in spiral-cleaving embryos. The data indicate that cleavage geometry evolved independent from other developmental traits during the transition from spiral to biradial cleavage in the bryozoan lineage, revealing that stereotypic cleavage patterns can be evolutionarily modified without major changes to the molecular identity and fate of embryonic blastomeres.
Investigations of human myosin VI targeting using optogenetically-controlled cargo loading
Authors: French Alexander R. , Sosnick Tobin R. , Rock Ronald S.
Published: August 2016

Myosins play countless critical roles in the cell, each requiring it to be activated at a specific location and time. To control myosin VI with this specificity, we created a novel optogenetic tool for activating myosin VI by fusing the light-sensitiveAvena sativaphototropin1 LOV2 domain to a peptide from Dab2 (LOVDab), a myosin VI cargo protein. Our approach harnesses the native targeting and activation mechanism of myosin VI, allowing direct inferences on myosin VI function. LOVDab robustly recruits human full length myosin VI to various organellesin vivoand hinders peroxisome motion in a light-controllable manner. LOVDab also activates myosin VI in anin vitrogliding filament assay. Our data suggest that protein and lipid cargoes cooperate to activate myosin VI, allowing myosin VI to integrate Ca2+, lipid, and protein cargo signals in the cell to deploy in a site-specific manner.

Significance Statement

Myosins are a broad class of motor proteins that generate force on actin filaments and fulfill contractile, transport, and anchoring roles. Myosin VI, the only myosin to walk toward the pointed end of actin filaments, is implicated in cancer metastasis and deafness. Intriguingly, myosin VI may play both transport and anchoring roles, depending upon where it is activated in the cell. Here we develop an optogenetic tool for studying myosin VI activation with high spatial and temporal resolution. Our approach photoactivates unmodified myosin VI through its native cargo pathway, enabling investigation of motor function and activation partners with minimal perturbation. This approach allows us to detect how and where myosin VI integrates multiple protein and second messenger signals to activate.
Dopaminergic drugs decrease loss aversion in Parkinson’s disease with but not without depression
Authors: Timmer Monique H.M. , Sescousse Guillaume , Esselink Rianne A.J. , Piray Payam , Cools Roshan
Published: August 2016

Depression, a common non-motor symptom of Parkinson’s disease (PD), is accompanied by impaired decision making and an enhanced response to aversive outcomes. Current strategies to treat depression in PD include dopaminergic medication. However, their use can be accompanied by detrimental side effects, such as enhanced risky choice. The mechanisms underlying dopamine-induced increases in risky choice are unclear. In the current study we adopt a clinical-neuroeconomic approach to investigate the effects of dopaminergic medication on loss aversion during risky choice in depressed and non-depressed PD. Twenty-three healthy controls, 21 depressed and 22 non-depressed PD patients were assessed using a well-established gambling task measuring loss aversion during risky choice. Patients were tested on two occasions, after taking their normal dopaminergic medication (ON) and after withdrawal of their medication (OFF). Dopaminergic medication decreased loss aversion to a greater extent in depressed than non-depressed PD patients. Moreover, we show that the degree to which dopaminergic medication decreases loss aversion correlated with current depression severity and with drug effects on depression scores. These findings demonstrate that dopamine-induced changes in loss aversion depend on the presence of depressive symptoms in PD.

Significance statement

Dopaminergic medication that is used to treat motor and non-motor symptoms in patients with Parkinson’s disease is known to contribute to risky decision-making. The underlying mechanisms are unclear. The present study demonstrates that dopaminergic medication in Parkinson’s disease decreases loss aversion during risky choice, but only in depressed and not in non-depressed patients with Parkinson’s disease. These results advance our understanding of the mechanisms underlying dopamine-induced risky choice, while also identifying depression as an important factor that confers vulnerability to such dopamine-induced risky choice.

Conflict of Interest

The authors declare no competing financial interests.
Analysis of intrapatient heterogeneity uncovers the microevolution of Middle East respiratory syndrome coronavirus
Authors: Park Donghyun , Huh Hee Jae , Kim Yeon Jeong , Son Dae-Soon , Jeon Hyo-Jeong , Im Eu-Hyun , Kim Jong-Won , Lee Nam Yong , Kang Eun-Suk , Kang Cheol In , Chung Doo Ryeon , Ahn Jin-Hyun , Peck Kyong Ran , Choi Sun Shim , Kim Yae-Jean , Ki Chang-Seok , Park Woong-Yang
Published: August 2016

Genome sequence analysis of Middle East respiratory syndrome coronavirus (MERS-CoV) variants from patient specimens has revealed the evolutionary dynamics and mechanisms of pathogenesis of the virus. However, most studies have analyzed the consensus sequences of MERS-CoVs, precluding an investigation of intrapatient heterogeneity. Here, we analyzed non–consensus sequences to characterize intrapatient heterogeneity in cases associated with the 2015 outbreak of MERS in South Korea. Deep-sequencing analysis of MERS-CoV genomes performed on specimens from eight patients revealed significant intrapatient variation; therefore, sequence heterogeneity was further analyzed using targeted deep sequencing. A total of 35 specimens from 24 patients (including a super-spreader) were sequenced to detect and analyze variants displaying intrapatient heterogeneity. Based on the analysis of non–consensus sequences, we demonstrated the intrapatient heterogeneity of MERS-CoVs, with the highest level in the super-spreader specimen. The heterogeneity could be transmitted in a close association with variation in the consensus sequences, suggesting the occurrence of multiple MERS-CoV infections. Analysis of intrapatient heterogeneity revealed a relationship between D510G and I529T mutations in the receptor-binding domain (RBD) of the viral spike glycoprotein. These two mutations have been reported to reduce the affinity of the RBD for human CD26. Notably, although the frequency of both D510G and I529T varied greatly among specimens, the combined frequency of the single mutants was consistently high (87.7% ± 1.9% on average). Concurrently, the frequency of occurrence of the wild type at the two positions was only 6.5% ± 1.7% on average, supporting the hypothesis that selection pressure exerted by the host immune response played a critical role in shaping genetic variants and their interaction in human MERS-CoVs during the outbreak.
Two forms of (naphthalen-1-yl)boronic acid
Authors: Bemisderfer Kayleigh , Nazarenko Alexander Y.
Published: August 2016

Two polymorphs of the title compound, C10H9BO2, were prepared by recystallization from different solvents at room temperature. Both forms demonstrate nearly identical molecular structures with all naphthalene group atoms located in one plane and all boronic acid atoms in another: the dihedral angles between these planes are 39.88 (5) and 40.15 (5)° for the two asymmetric molecules of the orthorhombic form and 40.60 (3)° for the single asymmetric molecule in the monoclinic form. In each extended structure, molecules form dimers, connected via two O—H...O hydrogen bonds. The dimers are connected by further O—H...O hydrogen bonds, forming layered networks in the (001) plane and the (100) plane in the orthorhombic and monoclinic forms, respectively. The resulting layers are practically identical in both forms. However, these layers are shifted along the [010] axis in the two forms, resulting in a slightly more effective packing for monoclinic structure (packing index = 0.692) compared to the orthorhombic form (0.688).
2-Amino-4-methylpyridinium 2-(4-nitrophenyl)acetate
Authors: Sivakumar P. , Sudhahar S. , Israel S. , Chakkaravarthi G.
Published: August 2016

In the title molecular salt, C6H9N2+·C8H6NO4−, the cation is protonated at its pyridine N atom. In the crystal, the anions are connected by a pair of C—H...O contacts into [100] chains, which generateR22(11) loops and these chains are linkedviaanother C—H...O contact which encloses anR24(10) loop. Adjacent anions and cations are connected through N—H... O hydrogen bonds, generating anR22(8) loop. Two pairs of anions and cations are linked by N—H...O hydrogen bonds, forming a tetramer with anR22(8) loop motif. The packing also features weak C—H...π and π–π [centroid-to-centroid distances = 3.8972 (11) and 3.9549 (10) Å] interactions, which result in a three-dimensional network.
Tetrakis(dimethoxyboryl)methane
Authors: Liu Sumeng , Girolami Gregory S.
Published: August 2016

The title compound, tetrakis(dimethoxyboryl)methane (systematic name: octamethyl methanetetrayltetraboronate), C9H24B4O8or C[B(OMe)2]4, is a useful synthetic intermediate. Crystals of this compound at 102 K conform to the orthorhombic space groupPbcn. The molecules, which reside on sites of crystallographic twofold symmetry, have idealized -4 point symmetry like most other CX4molecules in which eachXgroup bears two non-H substituents at the 1-position. The central C atom has a slightly distorted tetrahedral coordination geometry, with C—B bond lengths of 1.5876 (16) and 1.5905 (16) Å. One of the methoxy groups is disordered over two sets of sites; the major component has an occupancy factor of 0.676 (8).
1,1′-Biphenyl-2,2′,5,5′-tetracarboxylic acid
Authors: Li Yan-Hong , Lu Li-Ping
Published: August 2016

In the title compound, C16H10O8or H4bptc, the dihedral angle between the planes of the phenyl rings is 51.90 (4)°. The asymmetric unit contains one half-molecule; complete molecules are generated by a twofold rotation axis. In the crystal, O—H...O and C—H...O hydrogen-bonding generate a two-dimensional supramolecular network. In addition, weak π–π interactions are also observed.
Development of vaccines against pertussis caused by Bordetella holmesii using a mouse intranasal challenge model
Authors: Saito Momoko , Odanaka Keita , Otsuka Nao , Kamachi Kazunari , Watanabe Mineo
Published: August 2016

Bordetella holmesii is recognized as the third causative agent of pertussis (whooping cough) in addition to Bordetella pertussis and Bordetella parapertussis. Pertussis caused by B. holmesii is not rare around the world. However, to date, there is no effective vaccine against B. holmesii. We examined the protective potency of pertussis vaccines available in Japan and vaccines prepared from B. holmesii. A murine model of respiratory infection was exploited to evaluate protective potency. No Japanese commercial pertussis vaccines were effective against B. holmesii. In contrast, a wBH vaccine and an aBH vaccine prepared from B. holmesii were both protective. Passive immunization with sera from mice immunized with aBH vaccine established protection against B. holmesii, indicating that B. holmesii‐specific serum antibodies might play an important role in protection. Immuno‐proteomic analysis with sera from mice immunized with aBH vaccine revealed that the sera recognized a BipA‐like protein of B. holmesii. An aBH vaccine prepared from a BipA‐like protein‐deficient mutant strain did not have a protective effect against B. holmesii. Taken together, our results suggest that the BipA‐like protein plays an important role in the protective efficacy of aBH vaccine.
A Contingency Analysis of Precarious Organizational Temporariness
Authors: Karmowska Joanna , Child John , James Philip
Published: August 2016

This paper extends current understanding of organizational temporariness. The life of a temporary British trade union branch established to recruit Eastern European migrant workers reveals ‘precarious temporariness’, which is less predictable than the ‘planned temporariness’ typically portrayed in the literature. This different type of temporariness was associated with four key contingencies affecting the branch: dispersed governance; bottom‐up initiatives; uncertain resourcing; and an effectuation logic. Analysis of the case extends existing understanding of organizational temporariness and points to an extension of existing theorizing by highlighting the contingent nature of temporariness. The broader managerial implication of the findings is that, for projects facing contingencies of the kind studied, the conventional linear approach of target setting and performance management will be less effective than an ongoing process of communication and consultation.
Rare tumour mimicking meninigioma: A case of primary intracranial amelanotic malignant melanoma with negative staining of S100 and HMB‐45
Authors: Yuen Ming‐Him , Kwok Ngai‐Fung , Chiu Hok‐Ming , Ho Luen‐Cheung
Published: August 2016

Primary intracranial malignant melanoma is a rare disease, and the imaging findings usually mimic meningioma. Diagnosis is based on histology. Here, we report a case of primary intracranial malignant melanoma in a Chinese patient. A 27‐year‐old man presented with a 1‐month history of headache. Magnetic resonance imaging findings resembled features of a meningioma. Craniotomy with tumour excision was done and confirmed to be S100 and human melanoma black 45‐negative primary intracranial malignant melanoma. There was no extracranial involvement. The 9‐month follow up was reported. To our knowledge, this is the first reported S100 and human melanoma black 45‐negative primary intracranial amelanotic malignant melanoma.
Day‐surgery approach for incision and drainage of an abscess
Authors: Balakumar Ramkishan , Samuel Nehemiah , Jackson Andrew , Butterworth Joanne , Shiwani Muhammad H.
Published: August 2016

Aim

The treatment for an abscess is usually incision and drainage in the emergency theatre. These cases are considered a low priority, and therefore, their procedure is often delayed, resulting in longer inpatient stay. Recent guidelines have recommended a day‐surgery approach for these cases.

Patients and Methods

An abscess pathway was created to allow patients to go home and return the following morning to be operated first on the emergency list and subsequently discharged by nurses. The process was audited before (retrospectively) and after (prospectively) the introduction of the pathway. It looked at clinically‐well adults presenting with a superficial uncomplicated abscess.

Results

A total of 40 and 35 patients were included for the preliminary and subsequent audit cycle, respectively. The introduction of the pathway reduced the mean inpatient stay from 29.3 to 13.8 h, reduced the preoperative waiting times from 12.5 to 4.3 h and resulted in only 26 per cent of patients waiting more than 6 h compared with 68 per cent prior to its introduction. Inpatient hospital costs per patient (calculated at £250/bed/day for non‐clinical services) were mean cost to £312.50 and £27.78 per patient, respectively, saving £284.72 per patient.

Conclusion

The abscess pathway has reduced preoperative waiting times and total inpatient stay significantly, without compromising patient safety.
Rapid Identification and Comparison of Compounds with Antioxidant Activity in Coreopsis tinctoria Herbal Tea by High‐Performance Thin‐Layer Chromatography Coupled with DPPH Bioautography and Densitometry
Authors: Lam Shing‐Chung , Lam Sio‐Fong , Zhao Jing , Li Shao‐Ping
Published: August 2016

A simple and efficient method based on high‐performance thin‐layer chromatography coupled with 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) bioautography (HPTLC‐DPPH) was established for the screening and comparison of antioxidants in different parts of Coreopsis tinctoria herbal tea from different origins and other related herbal tea materials, which used Chrysanthemum morifolium cv. “Gongju” and “Hangju” in this study. Scanning densitometry after DPPH derivatization was applied for the determination of antioxidant capacities of isolated compounds in each sample. It is considered that ethanol extracts of C. tinctoria had stronger antioxidant activity and more characteristic bands than those of 2 compared samples, C. morifolium cv. “Gongju” and “Hangju.” Chemometric analysis results showed that the combination of hierarchical clustering analysis and principal component analysis based on determined antioxidant capacities could be used for the discrimination of different parts of C. tinctoria and C. morifolium. Results showed that 7 compounds made up the major contributions of antioxidant activity in C. tinctoria, including okanin, isookanin, marein, flavanomarein, 5,7,3′,5′‐tetrahydroxyflavanone‐7‐O‐glucoside, 3,5‐dicaffeoylquinic acid, and chlorogenic acid. Therefore, 7 compounds were identified as major antioxidant biomarkers for quality control of C. tinctoria. Results demonstrated that the established method could be applied for the identification of C. tinctoria, and were beneficial for the bioactivity‐based quality control of C. tinctoria.
Yeasts from macroalgae and lichens that inhabit the South Shetland Islands, Antarctica
Authors: Duarte Alysson Wagner Fernandes , Passarini Michel Rodrigo Zambrano , Delforno Tiago Palladino , Pellizzari Franciane Maria , Cipro Caio Vinicius Zecchin , Montone Rosalinda Carmela , Petry Maria Virginia , Putzke Jair , Rosa Luiz Henrique , Sette Lara Durães
Published: August 2016

Antarctic terrestrial ecosystems are largely dominated by lichens, while shallow coastal environments are mainly covered by macroalgae. The aim of this study was to isolate and to evaluate the diversity of yeasts in different species of macroalgae and lichens collected in South Shetland Islands, Antarctica. A total of 405 yeasts were recovered (205 from macroalgae and 200 from lichens). The yeast community from macroalgae was most diversity than the yeast community from lichen. The dominance index was similar for both substrates. A total of 24 taxa from macroalgae and 18 from lichens were identified, and only 5 were common to both substrates. Metschnikowia australis, Mrakia sp., Rhodotorula glacialis and Glaciozyma litorale were the most abundant yeasts in macroalgae and Cryptococcus victoriae, Rhodotorula laryngis, Rhodotorula arctica, Trichosporon sp. 1 and Mrakia sp. were the most abundant in lichens. Based on molecular and phylogenetic analyses, four yeast from macroalgae and six from lichens were considered potential new species. This is the first study to report the yeast communities from the Antarctic macroalgae Himantothallus grandifolius and lichen Ramalina terebrata. Results suggest that Antarctic phyco and lichensphere represent a huge substrate for cold‐adapted yeasts and enhanced the knowledge of the microbiota from extreme environments.
Financial Reporting Quality and External Debt Financing Constraints: The Case of Privately Held Firms
Authors: Ding Shujun , Liu Mingzhi , Wu Zhenyu
Published: August 2016

Using a sample consisting of 1,160,801 observations of privately held firms, we explore the relationship between earnings quality and privately held firms’ debt financing, access to debt, and cost of debt, as well as the moderating effects of provincial‐level economic development on this relationship. Our findings indicate that better earnings quality increases private firms’ access to debt financing and lowers their cost of debt. The empirical results also show that these effects are more pronounced in less developed provinces.