bluuebunny/crossref_metadata_2025 huggingface dataset:
Biolistic co‐transformation of the nuclear and plastid genomes
Authors: Elghabi Zouhair , Ruf Stephanie , Bock Ralph
Published: May 2011

Particle gun‐mediated (so‐called ‘biolistic’) transformation represents a universal genetic transformation technology that is widely applied in nearly all groups of organisms. The mechanism of how accelerated DNA‐coated particles, after their entry into the cell, deliver the foreign DNA to the target compartment is not known. Here we have studied this process in plants by performing co‐transformation experiments with vectors targeted to two different cellular compartments, the nucleus and the plastids (chloroplasts). We find that coating of particles with both plastid and nuclear transformation vectors can result in co‐transformation of chloroplasts and the nucleus. In contrast, mixing of particles coated individually with the vectors does not produce co‐transformed plants. Our data suggest that a single DNA‐coated particle can transform more than one compartment of the plant cell, opening up the possibility to generate doubly transgenic plants in one step. Importantly, co‐transformation can also be obtained in the absence of selection, thus providing a method to produce marker‐free transgenic genomes. In addition, our findings raise the possibility of occasional inadvertent co‐transformation of two genomes and, therefore, have important implications for the molecular characterization and regulation of transgenic plants.
A novel homozygous missense mutation in WNT10B in familial split‐hand/foot malformation
Authors: Khan S , Basit S , Zimri F K , Ali N , Ali G , Ansar M , Ahmad W
Published: May 2011

Khan S, Basit S, Zimri FK, Ali N, Ali G, Ansar M, Ahmad W. A novel homozygous missense mutation in WNT10B in familial split‐hand/foot malformation.

Split‐hand/foot malformation (SHFM) is a rare limb developmental malformation, characterized by variable degree of median clefts of hands and feet due to the absence of central rays of extremities. To date, six different forms of SHFM have been described. Four of these SHFM1, SHFM3, SHFM4 and SHFM5 show autosomal dominant, SHFM6 autosomal recessive and SHFM2 X‐linked pattern of inheritance. In this study a large consanguineous Pakistani family, with autosomal recessive SHFM, appeared in the last two generations, was investigated. In total 15 individuals including 9 males and 6 females were affected with the syndrome. Affected members of the family exhibited SHFM phenotype with involvement of hands and feet. Most of the affected members showed syndactyly/polydactyly in hands and feet, dysplastic hand, aplasia of radial ray of hand and cleft foot. Investigating linkage to known autosomal SHFM loci mapped the family to SHFM6 locus on chromosome 12p11.1‐q13.13. Mutation screening of the gene WNT10B revealed a novel sequence variant (c.986C>G, p.Thr329Arg) in all affected individuals who were studied. This is the third mutation reported in gene WNT10B causing autosomal recessive SHFM syndrome.
Identification of kallikrein and FXIa as impurities in therapeutic immunoglobulins: implications for the safety and control of intravenous blood products
Authors: Etscheid M. , Breitner‐Ruddock S. , Gross S. , Hunfeld A. , Seitz R. , Dodt J.
Published: May 2011

Background and Objectives  The occurrence of thromboembolic events (TEEs) with intravenous immunoglobulin lots (IVIGs) raised the question of the causative agent for these adverse events. We investigated the predominant plasma proteases in 19 IVIG lots from five manufacturers including three lots associated with adverse events.

Material and Methods  The inhibitor profile of the amidolytic activity in IVIG lots was investigated with substrates S‐2302 and S‐2288. In immunocapture assays, prekallikrein and FXI antigen and respective active proteases were quantified. Non‐activated partial thromboplastin time (NAPTT) and a modified FXIa PTT served as global and FXIa‐specific clotting assays, respectively.

Results  Kallikrein was identified as one major contaminant activity in IVIGs. A second activity was seen in some IVIGs with substrate S‐2288, but not with S‐2302. Inhibition studies excluded FXIIa, thrombin or plasmin as contaminant activity. FXI antigen was seen in all 19 IVIG lots, and FXIa activity was found as second major impurity in some IVIGs, including all lots involved in TEEs. FXIa highly correlated with a short clotting time in NAPTT.

Conclusions  Kallikrein and FXIa are the major contaminants in IVIGs. FXIa was highly procoagulant, with highest level in TEE‐associated IVIGs. Since the NAPTT unambiguously identified FXIa procoagulant activity in IVIGs, its implementation as a release test would improve the safety of IVIGs.
The cactus effect: an alternative to the lupin effect for increasing ovulation rate in sheep reared in semi‐arid regions?
Authors: Rekik M. , Gonzalez‐Bulnes A. , Lassoued N. , Ben Salem H. , Tounsi A. , Ben Salem I.
Published: May 2011

The present study evaluated the effects of supplementation with cactus cladodes on follicular dynamics and ovulatory response of sheep reared in semi‐arid areas. A total of 76 ewes were distributed into two equal groups supplemented with either concentrated feed or cactus cladodes. After 30 days of supplementation, no differences were found between feeding regimens on the final live weight (LW; 41.5 ± 0.6 and 42.1 ± 0.7 kg in the Concentrate and Cactus groups respectively) and body condition score (BCS; 1.8 ± 0.3 and 1.8 ± 0.4 for Concentrate and Cactus group respectively). Moreover, no differences were found between the initial and the final values of both LW and BCS; thus, there were no effects of supplementation on any of both parameters. Analysis of follicular population showed that, during the follicular phase induced by ram effect, the number of follicles reaching ovulatory size increased in both groups. However, the number was always higher in Cactus ewes and, at oestrus, Cactus ewes had 1.6 ± 0.2 and Concentrate sheep had 1.2 ± 0.2 large follicles (p < 0.05). Thereafter, ovulation rate was affected by duration of supplementation; being higher in sheep fed with cactus for 6–10 days (1.7 ± 0.1) than in ewes supplied with cactus for more than 11 days (1.3 ± 0.1; p < 0.05), in sheep fed with concentrate for 6–10 days (1.2 ± 0.1; p < 0.01) and even than in individuals subjected to classical flushing with concentrate (1.3 ± 0.1; p < 0.05).
Screening for diabetes using Japanese monitoring guidance in schizophrenia patients treated with second‐generation antipsychotics: A cross‐sectional study using baseline data
Authors: Kusumi Ichiro , Ito Koki , Honda Minoru , Hayashishita Tadayuki , Uemura Keiichi , Hashimoto Naoki , Murasaki Mitsukuni , Atsumi Yoshihito , Kadowaki Takashi , Koyama Tsukasa
Published: May 2011

Aim:  The Japanese blood glucose monitoring guidance for patients receiving second‐generation antipsychotics has been newly developed. We aimed to report a cross‐sectional study using the baseline data of the Japanese monitoring guidance to find undiagnosed hyperglycemia systematically as a routine clinical practice and to quantify the frequency of glucose abnormalities in schizophrenia patients treated with second‐generation antipsychotics.

Methods:  Data for 537 patients with schizophrenia, who had not been diagnosed as having diabetes prior to baseline screening and started the monitoring between June 2008 and January 2009, were collected from medical records in 25 hospitals. Blood glucose (fasting or casual), hemoglobinA1c, serum lipids, height/weight, clinical diabetic symptoms, and family history of diabetes were assessed. Patients were classified into normal, pre‐diabetic or probable diabetic type based on their values of blood glucose or hemoglobinA1c, and various background characteristics and serum lipid values were compared among the three types.

Results:  Out of 537 patients, 13 (2.4%) met criteria for probable diabetic type, 51 (9.5%) for pre‐diabetic type, and 473 (88.1%) for normal type. Individuals categorized as probable diabetic type had a higher body mass index and higher frequency of family history of diabetes mellitus than those with normal type.

Conclusion:  Glucose abnormalities were newly detected in 11.9% of schizophrenia patients treated with second‐generation antipsychotics by the baseline monitoring. To assess the detective power and usefulness of the guidance, longitudinal investigations are necessary.
Hemifield effects of spatial attention in early human visual cortex
Authors: Kraft Antje , Kehrer Stefanie , Hagendorf Herbert , Brandt Stephan A.
Published: May 2011

Early visual areas (V1, V2, V3/VP, V4v) contain representations of the contralateral hemifield within each hemisphere. Little is known about the role of the visual hemifields along the visuo‐spatial attention processing hierarchy. It is hypothesized that attentional information processing is more efficient across the hemifields (known as bilateral field advantage) and that the integration of information is greater within one hemifield as compared with across the hemifields. Using functional magnetic resonance imaging we examined the effect of distance and hemifield on parallel attentional processing in the early visual areas (V1–V4v) at individually mapped retinotopic locations aligned adjacently or separately within or across the hemifields. We found that the bilateral field advantage in parallel attentional processing over separated attended locations can be assigned, at least partly, to differences in distractor position integration in early visual areas. These results provide evidence for a greater integration of locations between two attended locations within one hemifield than across both hemifields. This nicely correlates with behavioral findings of a bilateral field advantage in parallel attentional processing (when distractors in between cannot be excluded) and a unilateral field advantage if attention has to be shifted across separated locations (when locations in between were integrated).
Safety and feasibility of the prostatic urethral lift: a novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH)
Authors: Woo Henry H. , Chin Peter T. , McNicholas Thomas A. , Gill Harcharan S. , Plante Mark K. , Bruskewitz Reginald C. , Roehrborn Claus G.
Published: May 2011

Study Type – Therapy (case series)  Level of Evidence 4

What’s known on the subject? and What does the study add?

Most surgical treatments for benign prostatic hyperplasia procedural involve the removal or destruction of prostate tissue and these approaches are commonly associated with treatment related morbidity. Unlike the other therapies, the prostatic urethral lift mechanically opens the prostatic urethra using tensioned sutures that compress prostate tissue between the urethra and prostate capsule. This is the first publication on this technology. This manuscript reports and confirms its safety and feasibility as a minimally invasive surgical treatment for symptomatic benign prostatic hyperplasia to justify further clinical evaluation.

OBJECTIVES

• To investigate the Prostatic Urethral Lift (PUL) procedure, a novel, minimally invasive treatment for symptomatic benign prostatic hyperplasia (BPH), which aims to mechanically open the prostatic urethra without ablation or resection.

• To demonstrate the safety and feasibility of this procedure and to make an initial assessment of effectiveness.

PATIENTS AND METHODS

• The PULprocedure was performed on 19 men in Australia.

• Small suture‐based implants were implanted transurethrally under cystoscopic visualisation to separate encroaching lateral prostatic lobes.

• Patients were evaluated at 2 weeks and 3, 6, and 12 months after PUL.

RESULTS

• All cases were successfully completed with no serious or unexpected adverse events (AEs).

• Between two and five sutures were delivered in each patient and the prostatic urethral lumen was visually increased in all patients.

• Reported postoperative AEs were typically mild and transient and included dysuria and haematuria.

• Follow‐up cystoscopy at 6 months in a subset of patients showed no calcification. Histological findings from two of three patients who progressed to transurethral resection of the prostate for return of symptoms showed no evidence of inflammation related to the implanted materials.

• The mean International Prostate Symptom Score was reduced by 37% at 2 weeks and 39% at 1 year after PUL as compared with baseline.

CONCLUSIONS

• We demonstrated in this initial experience that the PUL procedure is safe and feasible.

• The safety profile of the PUL procedure appears favourable; most patients reported sustained symptom relief to 12 months with minimal morbidity

• PUL therefore warrants further study as a new option for the many patients who seek an alternative to current therapies.
Obesity surgery and the management of excess: exploring the body multiple
Authors: Throsby Karen
Published: May 2011

Drawing on ethnographic data gathered through observations and interviews at a surgical weight management clinic in a large hospital, this article argues that while the core values governing the provision of obesity surgery (obesity = ill health; obesity surgery = weight loss; weight loss = improved health and cost savings) can be seen as governing the clinical encounter, the singularity of these collective equations reflects neither the complexity of the patient experience of obesity surgery nor the extent to which the ‘war on obesity’ itself does not adhere strictly to those principles. Drawing on Annemarie Mol’s concept of the body multiple, and focusing on three different forms of excess (excess weight, excess consumption and excess skin) that emerged in the course of the study, this article argues that the rationalised singularity of obesity that is enacted in the obesity surgery clinic risks obscuring the uncertainties inherent to those practices and the moral judgements and values that are ultimately inextricable from them.
Contribution of ultrasound in the assessment of nerve diseases
Authors: Padua L. , Liotta G. , Di Pasquale A. , Granata G. , Pazzaglia C. , Caliandro P. , Martinoli C.
Published: May 2011

Background and purpose:  Recently, ultrasound (US) has been used to assess the peripheral nervous system; however, there is no real study about its possible significant role in routine practice. Our study aims to assess the contribution of US as a routine tool in a neurophysiological laboratory.

Methods:  The study assesses 130 patients who presented clinical suspicion of peripheral nerve diseases, excluding motor neuron disease, radiculopathy, hereditary and acquired polyneuropathy. All patients were clinically, neurophysiologically and sonographically assessed in the same session by the same neurologist/neurophysiologist. To avoid interpretation bias, two independent and blinded clinicians, different than the examiners performing electrodiagnosis and US, reviewed clinical, neurophysiological and US findings (also data about follow‐up, when available) and classified the contribution of US as follows: Contributive (US had influence on the diagnostic and therapeutic strategies), Confirming (US confirmed the clinical and neurophysiological diagnosis), Non‐Confirming (US findings were normal) and Incorrect (US findings led to incorrect diagnosis).

Results:  US impacted, namely modified the diagnostic and therapeutic path in 42.3% of cases (55 patients); US had a confirmatory role in 40% (52 patients); US did not confirm clinical and neurophysiological diagnosis in 17.7% (23 cases); no incorrect US findings were observed.

Conclusion:  US complements neurophysiological assessment even in routine practice, and this confirms the increasing interest in US for a multidimensional evaluation of peripheral nerve system diseases.
Diversification and Performance in Developed and Emerging Market Contexts: A Review of the Literature*
Authors: Purkayastha Saptarshi , Manolova Tatiana S. , Edelman Linda F.
Published: May 2011

The link between diversification and performance has become an important topic for research in diverse fields such as strategic management, industrial organization and financial management. However, a synthesis of the research done in developed and emerging markets is missing. This paper attempts such a synthesis by comparing and contrasting the past cumulative empirical research evidence on the relationship between diversification and firm performance in the context of developed economies to the more recent work in the emerging economies. The empirical literature has been divided into three broad perspectives, and the paper highlights the considerable diversity in its findings in developed and emerging markets across each of these perspectives. Based on this study, it is proposed that related diversification is preferable in developed economies and should be based on specific resources, whereas unrelated diversification is appropriate in emerging economies and should be based on generic resources. Although agency problems exist in both contexts, it is argued that the type of problem differs in developed and emerging markets. The paper concludes by identifying three directions for future research. First, the relationship between diversification and performance should be examined across each industry separately and not in aggregate. Secondly, future research needs to examine the organizational mechanisms required to make diversification successful. Finally, the relationship needs to be examined under unstable and dynamic situations such as the current global economic downturn.
Virological response to darunavir in patients infected with HIV is linked to darunavir resistance–associated mutations corrected by the count of mutations with positive impact and is not associated with pharmacological and combined virological/pharmacological parameters
Authors: Dailly Eric , Rodallec Audrey , Allavena Clotilde , Deslandes Guillaume , Garnier Elisabeth , Billaud Eric , Ferré Virginie , Reliquet Véronique , Bouquié Régis , Raffi François , Jolliet Pascale
Published: May 2011

The relationships between virological (darunavir resistance–associated mutations), pharmacological (darunavir trough plasma concentration), combined virological/pharmacological [darunavir genotypic inhibitory quotient (GIQ)] parameters and virological response were evaluated in experienced patients infected with human immunodeficiency virus. In this retrospective study (48 patients), the relationship between these parameters and the virological response was investigated by multivariate logistic regression. Darunavir GIQ is defined as the ratio between darunavir trough plasma concentration and the count of darunavir resistance–associated mutations (V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, L89V) corrected or not corrected by the count of mutations with positive impact (V82A and E35D). The pharmacological and combined virological/pharmacological parameters failed to predict virological response. The count of darunavir resistance–associated mutations corrected by the count of V82A and E35D mutations was the single parameter significantly (P = 0.027) associated with virological response. This result suggests that both negative and positive impacts of mutations including V82A and E35D should be considered to predict virological response in experienced patients.
Hepatitis C viral protein translation: mechanisms and implications in developing antivirals
Authors: Hoffman Brett , Liu Qiang
Published: May 2011

Hepatitis C viral protein translation occurs in a cap‐independent manner through the use of an internal ribosomal entry site (IRES) present within the viral 5′‐untranslated region. The IRES is composed of highly conserved structural domains that directly recruit the 40S ribosomal subunit to the viral genomic RNA. This frees the virus from relying on a large number of translation initiation factors that are required for cap‐dependent translation, conferring a selective advantage to the virus especially in times when the availability of such factors is low. Although the mechanism of translation initiation on the Hepatitis C virus (HCV) IRES is well established, modulation of the HCV IRES activity by both cellular and viral factors is not well understood. As the IRES is essential in the HCV life cycle and as such remains well conserved in an otherwise highly heterogenic virus, the process of HCV protein translation represents an attractive target in the development of novel antivirals. This review will focus on the mechanisms of HCV protein translation and how this process is postulated to be modulated by cis‐acting viral factors, as well as trans‐acting viral and cellular factors. Numerous therapeutic approaches investigated in targeting HCV protein translation for the development of novel antivirals will also be discussed.
The Role of Future‐Market Focus in the Early Stages of NPD across Varying Levels of Innovativeness
Authors: Lindgren Lisa M. , O'Connor Gina Colarelli
Published: May 2011

The concept of future‐market focus (FMF) arose out of the debate about firm size and incumbency in the face of radical or disruptive innovations, and has been demonstrated to have a positive correlation with radical innovation (RI) success. This study examines the relationship between FMF and the processes used in the early stages of NPD for four types of innovation projects: incremental innovations, technological breakthroughs, market breakthroughs, and radical innovations. We found that the future‐market focus of a project team can influence the early stage processes used in a new product innovation project, and does so differentially across levels of innovativeness. In particular, the concept generation process, understanding of market needs, and screening decision criteria are different for low‐ versus high‐FMF projects and there are differences based on the level of innovation. In addition, we found that radical innovation projects rated low in FMF are markedly different than the radical innovation projects described in prior studies.
Applying Industrial Design and Cost Engineering to New Product Development in Early‐Stage Firms
Authors: Marion Tucker J. , Meyer Marc H.
Published: May 2011

For early‐stage firms, successful commercialization of each new product is critically important, given the shortage of financial resources, the limited product portfolio, and small staffs typical of such firms. This paper investigates two key contributing factors for new product success in entrepreneurial firms: designing products that are appealing to target users in both form and function and designing products that can be manufactured at an attractive margin so that the new enterprise can generate much needed positive cash flow. These two practices—industrial design and cost engineering—are well studied in the context of larger, established corporations but have not been explored in the context of new ventures. This study focuses on the intensity of individual and combined adoption of design and cost engineering as measured by product development efficiency and effectiveness. The study was conducted on a homogeneous sample of early‐stage firms that develop physical, assembled products where design plays a role. The data collection focused only on the first product developed by each firm respectively. The results show that when implemented together, industrial design and cost engineering enhance both the effectiveness and efficiency of new product development in early‐stage firms, to greater effect than each does individually. Intensive individual adoption of practices had a negative impact on development efficiency measures such as development cost and duration. Only cost engineering individually had a beneficial impact on development effectiveness as measured by product margins. When combined, these two practices had a beneficial impact on both development duration and cost for the company's first commercial product, thereby reducing time‐to‐market and precious cash expenditures while maximizing project breakeven timing. The most successful firms in the study achieved a balance between creative innovation and cost discipline in the NPD process with third‐party design and manufacturing resources. It was found that integrating third‐party design firms into the development process can challenge, simplify, and add additional creative resources to the core entrepreneurial team, maximizing the ability to catalyze beneficial tension between creativity and cost discipline.
Networks and the Decision to Persist with Underperforming R&D Projects
Authors: Patzelt Holger , Lechner Christian , Klaukien Anja
Published: May 2011

Drawing on aspiration level theory and the networks literature, this paper develops a model toward decision makers' persistence with underperforming R&D projects based on the perceived properties of their personal network. The assumption is that positive feedback from network partners motivates persistence, and that this effect is multiplied when the decision makers' network is larger and denser, when network ties are predominantly strong, and when communication frequency within the network is high. The model is tested by a field experiment and conjoint methodology. Analysis of 1632 persistence decisions nested within 51 scientists responsible for R&D projects reveals that more positive feedback enhances persistence of underperforming R&D projects, and that this effect becomes stronger with increasing network size, network density, and communication frequency. These findings extend the project management literature by focusing on the social environment of the decision maker as one so far neglected factor in empirical studies on persistence decisions. Moreover, this study is among the first to investigate contingency relationships between feedback received from network partners and network structure. Finally, while most studies have emphasized that individuals and organizations can profit from their engagements in social networks, this paper suggests a potential dark side of networks by showing that networks can encourage decision makers to persist with their investment in an underperforming—and potentially failing—project. These results can help project managers involved in networking activities to better understand the effects of these activities on their decision policies, and thus draw better and more accurate decisions. Second, this study provides insights into how organizational strategy with respect to dissemination of R&D results and involvement of the organization's R&D managers in the scientific community influences the persistence of underperforming R&D projects, and thereby the organization's R&D expenditures. This can assist top managers to design financial controls and allocate financial resources to managers of underperforming R&D projects in line with the organization's networking strategy.
In situ Measurement of the Electrical Potential Across the Lysosomal Membrane Using FRET
Authors: Koivusalo Mirkka , Steinberg Benjamin E. , Mason David , Grinstein Sergio
Published: May 2011

The progressive acidification of the endocytic pathway is generated by H+ pumping of electrogenic vacuolar‐type ATPases (V‐ATPases) on the endosomal/lysosomal membrane. The determinants of pH during endosome maturation are not completely understood, but the permeability to ions that neutralize the electrogenic effect of the V‐ATPase has been proposed to play a central role. If counter‐ion conductance becomes limiting, the generation of a large membrane potential would dominate the proton‐motive force (pmf), diminishing the pH gradient proportionally. Validation of this notion requires direct measurement of the electrical potential that develops across the endosomal/lysosomal membrane. To date, the measurement of lysosomal membrane potential (ψφ) in situ has been hampered by the inability to access endosomes by electrophysiological means and the fact that individual organelles cannot be discerned when using potentiometric fluorescent dyes. Here, we describe a noninvasive procedure to estimate ψφ in intact cells, based on fluorescence resonance energy transfer (FRET). At steady state, ψφ averaged 19 mV (lumen positive) and was only partially dissipated by inhibition of the V‐ATPase with concanamycin A (CcA). ψφ was considerably increased by alkalinization of the lysosome lumen by NH4Cl, implying that at steady state the V‐ATPase operates at submaximal rates and that the contribution of ψφ to pmf is relatively small. Our method should enable systematic studies of endosomal/lysosomal potential.
Rab27a Targeting to Melanosomes Requires Nucleotide Exchange but Not Effector Binding
Authors: Tarafder Abul K. , Wasmeier Christina , Figueiredo Ana C. , Booth Antonia E. G. , Orihara Asumi , Ramalho Jose S. , Hume Alistair N. , Seabra Miguel C.
Published: May 2011

Rab GTPases are important determinants of organelle identity and regulators of vesicular transport pathways. Consequently, each Rab occupies a highly specific subcellular localization. However, the precise mechanisms governing Rab targeting remain unclear. Guanine nucleotide exchange factors (GEFs), putative membrane‐resident targeting factors and effector binding have all been implicated as critical regulators of Rab targeting. Here, we address these issues using Rab27a targeting to melanosomes as a model system. Rab27a regulates motility of lysosome‐related organelles and secretory granules. Its effectors have been characterized extensively, and we have identified Rab3GEP as the non‐redundant Rab27a GEF in melanocytes (Figueiredo AC et al. Rab3GEP is the non‐redundant guanine nucleotide exchange factor for Rab27a in melanocytes. J Biol Chem 2008;283:23209–23216). Using Rab27a mutants that show impaired binding to representatives of all four Rab27a effector subgroups, we present evidence that effector binding is not essential for targeting of Rab27a to melanosomes. In contrast, we observed that knockdown of Rab3GEP resulted in mis‐targeting of Rab27a, suggesting that Rab3GEP activity is required for correct targeting of Rab27a. However, the identification of Rab27a mutants that undergo efficient GDP/GTP exchange in the presence of Rab3GEP in vitro but are mis‐targeted in a cellular context indicates that nucleotide loading is not the sole determinant of subcellular targeting of Rab27a. Our data support a model in which exchange activity, but not effector binding, represents one essential factor that contributes to membrane targeting of Rab proteins.
Suicide mortality trends in young people aged 15 to 19 years in Lithuania
Authors: Strukcinskiene B , Andersson R , Janson S
Published: May 2011

Aim:  This paper considers the suicide mortality trends from 1990–2009 in young people aged 15 to 19 years in Lithuania.

Methods:  Suicide and injury mortality data, plus mortality data from all causes, were used to compare the trend lines.

Results:  Suicide mortality rate in young people aged 15–19 years and in all population showed a rising trend from 1990, and then a decreasing trend from 2002 year. This trend was significant exclusively in boys. When comparing suicide deaths as a percentage of injury deaths and of all deaths in the age group 15–19 years, rising trends for boys were evident, whilst in girls, there was no evidence of change.

Conclusions:  In Lithuania, from early 1990s, the frequency of suicide increased amongst adults and young people aged 15–19 years. After 2002, a decrease in deaths by suicide was observed both for the whole population and for young people aged 15–19 years. The rise and fall was obvious for boys. The reasons for different trends may have been influenced by the political and socioeconomic instability in the 1990–2002 period, and the socioeconomic stability, together with active preventive measures, from 2002. Although the consumption of modern Selective serotonin reuptake inhibitors (SSRIs) increased during the same time, suicide mortality was again high during the economic crisis in 2008–2009.
Modelling effective thermal climate for mountain forests in the Bavarian Alps: Which is the best model?
Authors: Reger Birgit , Kölling Christian , Ewald Jörg
Published: May 2011

Question: Which thermal climate model performs best in predicting the combined effects of temperature and radiation on forest vegetation in the Bavarian Alps?

Location: Bavarian Alps, Germany.

Methods: In order to find the best model for effective thermal climate for the Bavarian Alps, we analysed models using the following predictors derived from climate data and/or a digital elevation model: (a) temperature variables only, (b) temperature plus slope aspect and inclination, and (c) temperature plus potential global solar radiation. Models were tested by linear regression against four response variables based on average Ellenberg indicator values for temperature (cover weighted/unweighted, with/without bryophytes), which were computed for 2280 georeferenced relevés from the vegetation database BERGWALD. We optimized (b) by empirically searching for thermally most favourable slope aspect and inclination.

Results: Closest model fit was achieved for unweighted temperature values based on vascular plants without bryophytes. Model fit (adj. R2) increased from using temperature alone to temperature–radiation, to temperature–aspect–inclination as predictors. The best spatially explicit model for predicting temperature values (adj. R2=0.57) was based on the variable combination mean temperature in the growing season (May to September), slope aspect (optimal aspect 195°) and inclination (optimal slope 30°).

Conclusion: Combining mean temperatures and relief variables in GIS allows creation of predictive maps of mountain forest response to thermal climate. Applied to climate change scenarios, our model can forecast potential vegetation distribution in the future. The superiority of simple empirical relief factors over a widely used model of potential radiation casts doubt on the meaningfulness of the latter for vegetation studies.
Heterologous synthesis of cytochrome c′ by Escherichia coli is not dependent on the System I cytochrome c biogenesis machinery
Authors: Inoue Hiroki , Wakai Satoshi , Nishihara Hirofumi , Sambongi Yoshihiro
Published: May 2011

Hydrogenophilus thermoluteolus cytochrome c′ (PHCP) has typical spectral properties previously observed for other cytochromes c′, which comprise Ambler’s class II cytochromes c. The PHCP protein sequence (135 amino acids) deduced from the cloned gene is the most homologous (55% identity) to that of cytochrome c′ from Allochromatium vinosum (AVCP). These findings indicate that PHCP forms a four‐helix bundle structure, similar to AVCP. Strikingly, PHCP with a covalently bound heme was heterologously synthesized in the periplasm of Escherichia coli strains deficient in the DsbD protein, a component of the System I cytochrome c biogenesis machinery. The heterologous synthesis of PHCP by aerobically growing E. coli also occurred without a plasmid carrying the genes for Ccm proteins, other components of the System I machinery. Unlike Ambler’s class I general cytochromes c, the synthesis of PHCP is not dependent on the System I machinery and exhibits similarity to that of E. coli periplasmic cytochrome b562, a 106‐residue four‐helix bundle.

Database
 The sequence data reported here have been deposited in the DDBJ database under accession no. AB617519.
Vesicular traffic in cell navigation
Authors: Zylbersztejn Kathleen , Galli Thierry
Published: May 2011

Cell navigation is the process whereby cells or cytoplasmic extensions are guided from one point to another in multicellular organisms or, in the case of unicellular eukaryotic organisms, in the environment. Recent work has demonstrated that membrane trafficking plays an important role in this process. Here, we review the role of soluble N‐ethylmaleimide‐sensitive fusion attachment protein (SNAP) receptors (SNAREs), which constitute the core machinery for membrane fusion and are essential for intracellular vesicular trafficking. We discuss the important functions of several vesicular‐ and target‐SNAREs, in particular vesicular‐associated membrane proteins 1, 2, 3, 4 and 7; vti1a/b; SNAP23 and SNAP25; and syntaxins 1, 3, 6 and 13. We conclude that endosomal SNAREs are important for cell navigation, a concept that opens avenues for fundamental research. There are also possible therapeutic applications because some of these SNAREs are the targets of clostridial neurotoxins.
New Insights into the Pathophysiology of Sickle Cell Disease-Associated Priapism
Authors: Bivalacqua Trinity J. , Musicki Biljana , Kutlu Omer , Burnett Arthur L.
Published: May 2011

Introduction

Priapism is defined as an erectile disorder, in which erection persists uncontrollably without sexual purpose. The precise mechanisms involved in the development of sickle cell disease-associated priapism are ill defined.

Aim

To summarize the recent developments that increase our understanding of the molecular mechanisms of priapism.

Methods

This article reviews the literature (Medline search 2000–2010) that relates the key molecular signaling pathways that contribute to the development of priapism associated with sickle-cell disease. It focuses on basic science investigations using multiple animal models.

Main Outcome Measures

The reader will be informed of the most current research regarding the role of endothelial nitric oxide synthase, phosphodiesterase type 5 (PDE5), adenosine, RhoA/Rho-kinase (ROCK), and opiorphins in the pathophysiology of priapism.

Results

New concepts in the field of priapism research suggest that priapism often results from altered vascular homeostatic actions in the penis and is associated with deficient erection control mechanisms on a molecular level. A leading proposal in this regard is the notion of aberrant signaling of the endothelium-derived nitric oxide and PDE5 signal transduction pathway in the penis. Additionally, dysfunctional regulatory control of signal transduction systems which interact with this pathway such as adenosine and RhoA/Rho-kinase may contribute to the development of priapism. Recent investigations of opiorphins also demonstrate a role in regulating corporal smooth muscle tone and thereby dysregulation of erection physiology in priapism. These advances have paved the way for understanding this disorder as having a molecular pathogenesis.

Conclusions

As the science underlying priapism further emerges, increasingly effective therapeutics for sickle cell disease-associated priapism is certain to follow.
Overqualified Employees: Making the Best of a Potentially Bad Situation for Individuals and Organizations
Authors: Erdogan Berrin , Bauer Talya N. , Peiró José María , Truxillo Donald M.
Published: May 2011

One of the “truisms” of personnel selection is that overqualified applicants are likely to be a poor fit and thus experience low job satisfaction and performance and higher turnover. Recently, the issue of overqualification has come to the forefront because of the economic downturn, especially in some European Union countries where unemployment rates are extremely high. However, empirical research on overqualification in the industrial–organizational/organizational behavior literature is limited. In this article, we argue that although there may be drawbacks to overqualification for both organizations and employees, overqualification may also provide a number of positive outcomes for workers and employers alike. We review the limited research on overqualification, noting the positive and negative consequences of overqualification and the conditions under which overqualified employees may be a boon to organizations. We conclude by recommending some possible research streams to better understand the overqualification phenomenon and by making recommendations for organizational practices.
CandidaSpecies Isolated from Urban Bats of Londrina‐Paraná, Brazil and their Potential Virulence
Authors: Botelho N. S. , de Paula S. B. , Panagio L. A. , Pinge‐Filho P. , Yamauchi L. M. , Yamada‐Ogatta S. F.
Published: May 2011

The aim of this study was to isolate yeasts from the faeces of urban bats inhabiting the city of Londrina, Paraná, Brazil and to determine their potential virulence attributes. Seven (12.3%) of 57 bats screened in this study showed yeasts in their faeces. Five species of the genusCandidawere isolated:C. guilliermondii,C. krusei,C. lusitaniae,C. parapsilosis, andC. pelliculosa. No phospholipase activity was detected in the egg yolk plate assay; however, all isolates demonstrated protease secretion in skim milk agar. Yeasts isolated from bats produced biofilm on the surface of polystyrene plates and all were classified as intermediate biofilm producers. Minimal inhibitory concentration (MIC) values for fluconazole in the yeasts varied according to the species. Only one isolate (M34– C. lusitaniae) was considered susceptible dose‐dependent to fluconazole. The yeasts were injected intravenously into Swiss mice, and at 15 days post‐infection, the animals were killed and portions of their kidneys cultured on Sabouraud dextrose agar medium. All tissues analysed showed positive cultures ofCandidaspp. This is the first study evaluating the presence of fungi in the faeces of bats in an urban region, where the yeast species found were shown to be potentially pathogenic. As bats are commonly found in cities, these findings indicate the need for continuous surveillance concerning environmental contamination by their excreta.
Retrospective study on 30 horses with chronic proliferative pododermatitis (canker)
Authors: Oosterlinck M. , Deneut K. , Dumoulin M. , Gasthuys F. , Pille F.
Published: May 2011

The medical records of 30 horses (18 Warmbloods, 7 draught horses, 3 other breeds and 2 of unknown origin) with chronic proliferative pododermatitis (canker) were reviewed and long‐term outcome was obtained by telephone questionnaire. In 28/30 cases, the owner was the first to discover the problem. The disease was initially recognised as canker in only 5/28 cases, whereas in 10/28 cases a treatment for thrush had been continued for several months before referral. There was a similar prevalence in the fore (41) and hind (44) hooves; 13/30 horses had 4 hooves affected. Treatment consisted of surgical debridement and hoof care. Duration of hospitalisation was significantly decreased in horses receiving oral prednisolone for 3 weeks compared to those without this additional systemic treatment (mean ± s.d. 24 ± 5 days, n = 7 vs. 40 ± 19 days, n = 19, respectively). Long‐term follow‐up ranged from 3 months to 6 years (36 ± 22 months) and was available for 24 horses. No recurrence was reported in 10 horses. In 14 horses problems recurred within the first year, and 6 had been subjected to euthanasia for this reason specifically, whereas the others were managed by regular trimming. There was no significant association between recurrence and the number of affected hooves or the use of any systemic treatment. Horses with delayed referral because of preceding treatments had significantly more chance to develop recurrence, highlighting the need for prompt diagnosis and subsequent treatment.
Osseous metaplasia in the conjunctiva of a horse presenting with recurrent ulcerative keratitis
Authors: Donaldson D. , Matas M. , Stewart J.
Published: May 2011

A 13‐year‐old Thoroughbred gelding presented with a 6 month history of recurrent conjunctivitis, dacryocystitis and corneal ulceration affecting the left eye (OS). Treatment had included multiple topical antibiotic and anti‐inflammatory preparations, nasolacrimal system flushing and an injection of methylprednisolone acetate (MPA) (Depomedrone)1 administered subconjunctivally into the left lower eyelid. No mechanical cause for the ulcerative keratitis could be visualised but digital palpation revealed a firm linear structure in the central palpebral conjunctiva of the lower eyelid. An excisional biopsy was performed and histopathological examination revealed the lesion to be a region of osseous metaplasia. Following excision of the lesion, the corneal ulcer resolved and the eye remained disease free over a 4 year follow‐up period. A causal link between the osseous metaplasia and the recurrent ulcerative keratitis was therefore suspected. This report describes the management of this case and discusses the pathogenesis of osseous metaplasia and the use of subconjunctival corticosteroids.
Developing Data Mining-Based Prognostic Models for CF-18 Aircraft
Authors: Zaluski Marvin , Létourneau Sylvain , Bird Jeff , Yang Chunsheng
Published: May 2011

The CF-18 (CF denotes Canadian Forces) aircraft is a complex system for which a variety of data are systematically being recorded: flight data from sensors, built-in test equipment data, and maintenance data. Without proper analytical and statistical tools, these data resources are of limited use to the operating organization. Focusing on data mining-based modeling, this paper investigates the use of readily available CF-18 data to support the development of prognostics and health management systems. A generic data mining methodology has been developed to build prognostic models from operational and maintenance data. This paper introduces the methodology and elaborates on challenges specific to the use of CF-18 data from the Canadian Forces. A number of key data mining tasks are examined including data gathering, information fusion, data preprocessing, model building, and model evaluation. The solutions developed to address these tasks are described. A software tool developed to automate the model development process is also presented. Finally, this paper discusses preliminary results on the creation of models to predict F404 no. 4 bearing and main fuel control failures on the CF-18.
Phase change random access memory featuring silicide metal contact and high-κ interlayer for operation power reduction
Authors: Fang Lina Wei-Wei , Zhao Rong , Lim Kian-Guan , Yang Hongxin , Shi Luping , Chong Tow-Chong , Yeo Yee-Chia
Published: May 2011

A phase change memory device integrated with a nickel monosilicide (NiSi) bottom electrode and a dielectric (Ta2O5) interlayer was investigated. The presence of a low thermal conductivity thin film between the bottom electrode and phase change layer promotes heating efficiency in the device. Reset voltages down to 2.2 and 1.86 V could be achieved for memory device without and with the Ta2O5 interlayer, respectively. In addition, low reset current of 0.66 mA and SET current of 0.2 mA were obtained for devices with Ta2O5 interlayer having a contact dimension of ∼1 μm. Endurance of the devices was also studied.
Deciphering the Rhizosphere Microbiome for Disease-Suppressive Bacteria
Authors: Mendes Rodrigo , Kruijt Marco , de Bruijn Irene , Dekkers Ester , van der Voort Menno , Schneider Johannes H. M. , Piceno Yvette M. , DeSantis Todd Z. , Andersen Gary L. , Bakker Peter A. H. M. , Raaijmakers Jos M.
Published: May 2011

A common plant pathogen induces the growth of disease-suppressive microbes in local soil communities.
Climate Trends and Global Crop Production Since 1980
Authors: Lobell David B. , Schlenker Wolfram , Costa-Roberts Justin
Published: May 2011

Climate change has decreased global maize and wheat production, while soybean and rice production have remained stable.