bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic activation of mouse ganglioside synthase genes: implications for neurogenesis
Authors: Tsai Yi‐Tzang , Yu Robert K.
Published: October 2013

The quantity and expression pattern of gangliosides in mammalian brain change drastically during development and are mainly regulated through stage‐specific expression of ganglioside synthase genes. Despite extensive investigations in the past, it remains largely unclear how the transcriptional activation of the genes encoding glycosyltransferases is regulated. Here, we show that in the neuronogenic cultures of mouse embryonic brain‐derived neuroepithelial cells, histone modifications including acetylated histone H3 and histone H4, but not histone H3 trimethylation at lysine 27 of two genes encoding two key regulatory GTs, namely, N‐acetylgalactosaminyltransferase I and sialyltransferase II, were extensively and gradually enhanced, respectively. As a consequence, the level of each GT mRNA was increased correspondingly. Hyperacetylation of histones on the GalNAcT promoter resulted in recruitment of the trans‐activation factors Sp2 and AP‐1 when cellular histone deacetylases 1 and 2 were knocked down with RNA interference or inhibited by treatment with valproic acid. Moreover, epigenetic activation of GalNAcT was also detected, as accompanied by a pronounced induction of neural differentiation in primary neuroepithelium culture responding to an exogenous supplement of ganglioside GM1, a downstream product of the gene's encoding enzyme. Our findings thus provide direct evidence of novel pathways for ganglioside expression via the epigenetic up‐regulation of ganglioside synthase genes during neural development.

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Perceived support from healthcare professionals, shock anxiety and post‐traumatic stress in implantable cardioverter defibrillator recipients
Authors: Morken Ingvild M , Bru Edvin , Norekvål Tone M , Larsen Alf I , Idsoe Thormod , Karlsen Bjørg
Published: October 2013

Aims and objectives

To investigate (1) the extent to which shock anxiety and perceived support from healthcare professionals are related to post‐traumatic stress disease (PTSD) symptoms and (2) the extent to which perceived support from healthcare professionals moderates the relationship between shock anxiety and PTSD symptoms in implantable cardioverter defibrillator recipients. An additional aim was to describe the level of PTSD symptoms and perceptions of support from healthcare professionals.

Background

Studies examining PTSD symptoms among implantable cardioverter defibrillator recipients are still sparse. In addition, little is known about how perceived support from healthcare professionals is related to PTSD symptoms.

Design

Cross‐sectional survey design.

Methods

Recipients (n = 167) with implantable cardioverter defibrillator attending an outpatient device clinic completed questionnaires assessing shock anxiety, PTSD symptoms and perceived support from healthcare professionals.

Results

The results indicated that between ten and 15% of the recipients experienced moderate to severe symptoms of PTSD. Although a majority perceived constructive support from healthcare professionals, 12% perceived nonconstructive support. Regression analysis demonstrated that shock anxiety and perceived nonconstructive support from healthcare professionals had a statistically significant (p < 0·01) association with PTSD symptoms. Moreover, the results suggest that associations between shock anxiety and PTSD symptoms were significantly (p < 0·01) moderated by perceived nonconstructive support from healthcare professionals. Young age, short time since implantation and secondary prevention indication were also significantly associated with PTSD symptoms.

Conclusions

The results indicate that nonconstructive support from healthcare professionals can increase the tendency to develop PTSD symptoms, particularly in those who experience shock anxiety.

Relevance to clinical practice

Healthcare professionals should pay more attention to the way in which they communicate information to the recipients during follow‐up visits. Clinically based strategies and interventions targeting shock anxiety and PTSD symptoms should be carried out.
Evaluating an holistic assessment tool for palliative care practice
Authors: McIlfatrick Sonja , Hasson Felicity
Published: October 2013

Aims and objectives

To evaluate a holistic assessment tool for palliative care practice. This included identifying patients' needs using the holistic tool and exploring the usability, applicability and barriers and facilitators towards implementation in practice.

Background

The delivery of effective holistic palliative care requires a careful assessment of the patients' needs and circumstances. Whilst holistic assessment of palliative care needs is advocated, questions exist around the appropriateness of tools to assist this process.

Design

Mixed‐method research design.

Methods

Data collection involved an analysis of piloted holistic assessments undertaken using the tool (n = 132) and two focus groups with healthcare professionals (n = 10).

Results

The tool enabled health professionals to identify and gain an understanding of the needs of the patients, specifically in relation to the physical healthcare needs. Differences, however, between the analysis of the tool documentation and focus group responses were identified in particular areas. For example, 59 (68·8%) respondents had discussed preferred priorities of care with the patient; however, focus group comments revealed participants had concerns around this. Similarly, whilst over half of responses (n = 50; 57·5%) had considered a prognostic clinical indicator for the patient as an action, focus group results indicated questions around healthcare professionals' knowledge and perceived usefulness of such indicators. Positive aspects of the tool were that it was easy to understand and captured the needs of individuals. Negative aspects of the tool were that it was repetitive and the experience of assessors required consideration.

Conclusion

The tool evaluation identified questions regarding holistic assessment in palliative care practice and the importance of communication.

Relevance to clinical practice

A holistic assessment tool can support patient assessment and identification of patients' needs in the ‘real world’ of palliative care practice, but the ‘tool' is merely an aid to assist professionals to discuss difficult and sensitive aspects of care.
Nurse‐sensitive indicators suitable to reflect nursing care quality: a review and discussion of issues
Authors: Burston Sarah , Chaboyer Wendy , Gillespie Brigid
Published: October 2013

Aims and objectives

To review nurse‐sensitive indicators that may be suitable to assess nursing care quality.

Background

Patient safety concerns, fiscal pressures and patient expectation create a demand that healthcare providers demonstrate the quality of nursing care delivered. As a result, nurse managers are increasingly encouraged to provide evidence of nursing care quality. Nurse‐sensitive indicators are being proposed as a means of meeting this need.

Design

Literature review.

Methods

A review of the literature was conducted using CINAHL and MEDLINE from 2002–2011. Key search terms were nurs* and sensitive indicators, outcome measures, indicators, metrics and patient outcomes.

Results

Most of the research has examined the relationship between nursing structural variables and patient outcomes in acute care settings and have explored potential indicators for specific patient groups and nursing roles. When using nurse‐sensitive indicators, issues concerning the selection, reporting and sustained use are important for nurse managers to consider.

Conclusion

Evidence for the nurse‐sensitivity of some commonly used indicators is inconsistent due to the disparity in definitions used, data collection and analysis methods. Further research on the application and implementation of these indicators is required to assist nurse managers in attempting to quantify the quality of nursing care. Nurses need to continue to strive to achieve agreement on the definitions of indicators, gather strong consistent evidence of nurse‐sensitivity, resolve issues of regular data collection and consider selection, reporting and sustainment when implementing nurse‐sensitive indicators.

Relevance to clinical practice

Once identified, nurse‐sensitive indicators can be applied for quality improvement purposes, but consensus is required to fully realise their potential. Nurse managers need to be aware of the factors that can influence the use of indicators at unit level. Strategies need to be implemented to promote these indicators becoming integrated with routine nursing care.
Diabetes mellitus and abnormalities in semen analysis
Authors: Bhattacharya Sudhindra Mohan , Ghosh Mainak , Nandi Nupur
Published: October 2013

Aim

The aim of this study was to compare the semen parameters of diabetic husbands of infertile couples with those of non‐diabetic husbands of proven fertility.

Material and Methods

Assuming a 5% fall in DNA integrity of sperms would affect fertility, the required sample size calculated was 103, with 80% power and 5% level of significance. During the study period (January 2010 to May 2012), 52 husbands were found to have diabetes mellitus, by 2‐h/post 75 g of glucose load (≥200 mg %). Glycosylated hemoglobin level in each case was found to be more than 6.5% (study group). During the same period, six couples with infertility conceived spontaneously while undergoing evaluations, 60 couples conceived following treatment of ovulatory disorders in wives and all had ongoing pregnancies (more than 12 weeks). Husbands of these 66 couples were found to be non‐diabetic (control group). Conventional semen analysis (World Health Organization criteria), hypo‐osmotic swelling test and DNA integrity test (Acridine Orange test) were done in all cases. Body mass index was measured in each case.

Results

There were no differences in the mean age and body mass index between the two groups but significant differences were found in the following parameters: volume of the ejaculate (P = 0.004); total cells per ejaculate (P = 0.01); percent motility (P = 0.0001); total motile cells per ejaculate (P = 0.0001); percent of rapid progressive motility (P = 0.0001); percent normal morphology (P = 0.02); percent hypo‐osmotic swelling test (0.0001); and percent normal DNA integrity (P = 0.0001).

Conclusion

Diabetes mellitus can affect spermatogenesis at various levels, which can cause male‐factor infertility.
Change of childbirth preference after delivery among nulliparous Chinese women and their partners
Authors: Li Wen‐Ying , Liabsuetrakul Tippawan , Stray‐Pedersen Babill
Published: October 2013

Aim

The aim of the present study was to assess the effect of childbirth preference among nulliparous Chinese women and their partners on actual mode of delivery, and to assess women's change in preference from vaginal delivery to cesarean and the factors associated with this change.

Methods

A cohort study was conducted from July to October 2011 in the First Hospital of Tsinghua University, Beijing. Nulliparous women at the gestational age of 36–40 weeks and their partners were included. Their childbirth preference was recorded twice: once in pregnancy and again 2 or 3 days post‐partum.

Results

Women preferring cesarean during pregnancy had a 3.9‐fold higher chance of undergoing a cesarean than those preferring vaginal delivery (P = 0.004), while the partner's preference had no effect (P = 0.35). Preference for cesarean in the post‐partum period increased significantly compared to that during pregnancy both among women, whose preference increased from 10.1% to 28.0%, and among their partners, whose preference increased from 7.8% to 16.7% (P < 0.001 for both). The rate of change in women's preference from vaginal delivery to cesarean was 26.0%. Women having high couple's monthly income, who were feeling depressed, whose partner preferred cesarean during pregnancy or who delivered by cesarean were more likely to experience this change due to fear of labor pain and perineal cutting and a greater perceived safety of cesarean.

Conclusion

Women's cesarean preference during pregnancy was associated with actual cesarean delivery. Inadequate quality of care in labor and delivery and overestimation of cesarean safety underlie post‐partum women's increased preference for cesarean.
Role of ultrasound in diagnosing isolated torsion of fallopian tube
Authors: Sun Li‐tao , Ning Chun‐ping , Guo Xi‐juan , Li Xiao‐ying , Liu Wei , Tian Jia‐wei
Published: October 2013

Aim

To summarize the ultrasonic features of isolated fallopian tube torsion (IFTT) by retrospectively analyzing cases presenting at our hospital.

Methods

This analysis was approved by the ethical committee of our hospital. Medical records of surgically proven IFTT patients admitted to our hospital since 2002 were collected. Clinical features and preoperative diagnoses of the patients were analyzed retrospectively. Ultrasonic images were reviewed and characteristics, including location, size, shape, echo and vascularity of the fallopian tube, were summarized.

Results

Eleven patients with IFTT were studied. No obvious association was found between the torsion and menstruation cycle. Only four accurate diagnoses were made before the operation. Degrees of torsion ranged 360–2160°. Most of them (9/11, 81.8%) were greater than 720°. Sonograms of the 11 patients could be classified into four types: cystic masses, tube‐like structures, heterogeneous masses and whirlpool signs. Cystic masses were the most commonly seen type (4/11, 36.4%), followed by tubular structures (3/11, 27.3%). Whirlpool sign was believed to be the most specific sign in diagnosing IFTT.

Conclusion

Through review of the authors' experiences, it is possible to diagnose IFTT preoperatively by ultrasound. Sonograms of the IFTT could be divided into four types while clinical significance of this classification requires further confirmation.
Recurrence of ovarian endometrioma after laparoscopic excision: Risk factors and prevention
Authors: Ouchi Nozomi , Akira Shigeo , Mine Katsuya , Ichikawa Masao , Takeshita Toshiyuki
Published: October 2013

Aim

The aim of this study was to assess the cut‐off age of the risk factors for postoperative recurrence of ovarian endometriomas and to evaluate the end‐points of follow‐up after laparoscopic excision of ovarian endometriomas.

Material and Methods

We retrospectively reviewed 167 patients who underwent laparoscopic excision of ovarian endometriomas at our hospital between 2000 and 2009, and followed up the patients until 2010. Following surgery, patients chose to receive gonadotrophin‐releasing hormone agonist, oral contraceptive pills (OCP), dienogest, or no medication and underwent regular ultrasonographic examinations. Potential risk factors for recurrence, including age at surgery, were assessed in the patients receiving no medication. Postoperative recurrence, defined as re‐appearance of an ovarian endometrioma > 2 cm in size, was assessed for each treatment group.

Results

Age at surgery was the only significant risk factor for recurrence, at a cut‐off of 32 years, obtained through receiver–operator curve analysis. In patients not receiving medication, the recurrence rate gradually increased up to 50% over 5 years; there was no recurrence 5 years after surgery. Although no recurrence was seen in patients during continuous treatment with OCP or dienogest, the disease recurred in 55.5% of patients after discontinuing OCP.

Conclusions

Although adjuvant therapy for all patients may represent overtreatment, the findings of the present study suggest that, in the interest of fertility preservation, continuous postoperative hormonal treatment should be administered, at least to patients younger than 32 years. In patients who decline hormonal treatment, we recommend that they undergo follow‐up for recurrence until 5 years after surgery.
Cervical column posture and airway dimensions in clinical bruxist adults: a preliminary study
Authors: Restrepo C. C. , Álvarez C. P , Jaimes J. , Gómez A. F.
Published: October 2013

The aim of this study was to compare the cervical column posture and the upper airway dimensions between sleep bruxist and non‐bruxist young adults. Twenty‐three sleep‐grinders and 22 asymptomatic subjects, selected according to the American Academy of Sleep Medicine (AASM) criteria (report by a sleep partner and the presence of dental wear, according to Wetselaar et al.), were evaluated. The mean age was 23·8 years (range 18–30). All the subjects had complete permanent dentition and skeletal and occlusal class I. A digital cephalometric radiograph with natural head posture was performed for each subject. The craniocervical posture was traced and evaluated according to Solow and Tallgren, and the airway dimensions of the oropharynx and nasopharynx were evaluated in agreement with Sayinsu. The data were analysed with independent‐samples t‐tests and Mann–Whitney U‐test. Significance was set at P < 0·05. Sleep bruxist young adults presented more forwarded cervical column posture and narrower measures of the oropharynx, when compared with controls (P < 0·05). As in children, anterior cervical column posture was found to be associated with sleep bruxism.
Resistance to Asparagus virus 1 in the Wild Relative Asparagus amarus
Authors: Nothnagel Thomas , Budahn Holger , Krämer Ilona , Schliephake Edgar , Schreyer Lutz , Krämer Reiner
Published: October 2013

Five asparagus cultivars, three breeding lines and the wild relative Asparagus amarus were tested for natural infection by Asparagus virus 1 (AV‐1) in experimental fields at two locations over 3 and 4 years, respectively. In the first year after re‐planting the annual crowns in the field, more than 90% of tested plants of cultivars were infected by AV‐1. In the third and fourth year, 100% of tested plants of cultivars were AV‐1 infected. In comparison, all plants of the wild relative A. amarus were completely free of AV‐1, suggesting a high level of resistance. Additionally, 1‐year‐old glasshouse‐cultivated plants of A. officinalis and A. amarus were placed in an AV‐1 provocation cabin under field conditions. Seven months later, 100% of the A. officinalis plants showed a high virus concentration in ELISA, whereas no AV‐1 was detectable in the A. amarus plants. This result was confirmed by highly sensitive AV‐1‐specific RT‐PCR. To exclude vector resistance, the feeding behaviour of green peach aphid Myzus persicae was tested over 12 h using the electrical penetration graph method. Both asparagus genotypes were accepted by the aphids as potential hosts, but the feeding time was significantly longer on A. amarus. A genetic distance analysis of the various cultivars of Asparagus officinalis and selected wild relatives of the JKI collection was carried out, resulting in a clear discrimination of cultivars and wild relatives, especially A. amarus. The potential breeding value of the putative resistance carrier is discussed.
Inhibition of c-Met promoted apoptosis, autophagy and loss of the mitochondrial transmembrane potential in oridonin-induced A549 lung cancer cells
Authors: Liu Ying , Liu Jian-Hong , Chai Kuan , Tashiro Shin-Ichi , Onodera Satoshi , Ikejima Takashi
Published: October 2013

Objective

Herein, inhibition of hepatocyte growth factor receptor, c-Met, significantly increased cytochrome c release and Bax/Bcl-2 ratio, indicating that c-Met played an anti-apoptotic role. The following experiments are to elucidate this anti-apoptotic mechanism, then the effect of c-Met on autophagy has also been discussed.

Methods

Investigated was the influence of c-Met on apoptosis, autophagy and loss of mitochondrial transmembrane potential (Δψm), and the relevant proteins were examined.

Key findings

First, we found that activation of extracellular signal-regulated kinase (ERK), p53 was promoted by c-Met interference. Subsequent studies indicated that ERK was the upstream effector of p53, and this ERK-p53 pathway mediated release of cytochrome c and up-regulation of Bax/Bcl-2 ratio. Secondly, the inhibition of c-Met augmented oridonin-induced loss of mitochondrial transmembrane potential (Δψm), resulting apoptosis. Finally, the inhibition of c-Met increased oridonin-induced A549 cell autophagy accompanied by Beclin-1 activation and conversion from microtubule-associated protein light chain 3 (LC3)-I to LC3-II. Activation of ERK-p53 was also detected in autophagy process and could be augmented by inhibition of c-Met. Moreover, suppression of autophagy by 3-methyladenine (3-MA) or small interfering RNA against Beclin-1 or Atg5 decreased oridonin-induced apoptosis. Inhibition of apoptosis by pan-caspase inhibitor (z-VAD-fmk) decreased oridonin-induced autophagy as well and Loss of Δψm also occurred during autophagic process.

Conclusion

Thus, inhibiting c-Met enhanced oridonin-induced apoptosis, autophagy and loss of Δψm in A549 cells.
Subcellular localization of dinoflagellate polyketide synthases and fatty acid synthase activity
Authors: Van Dolah Frances M. , Zippay Mackenzie L. , Pezzolesi Laura , Rein Kathleen S. , Johnson Jillian G. , Morey Jeanine S. , Wang Zhihong , Pistocchi Rossella
Published: October 2013

Dinoflagellates are prolific producers of polyketide secondary metabolites. Dinoflagellate polyketide synthases (PKSs) have sequence similarity to Type I PKSs, megasynthases that encode all catalytic domains on a single polypeptide. However, in dinoflagellate PKSs identified to date, each catalytic domain resides on a separate transcript, suggesting multiprotein complexes similar to Type II PKSs. Here, we provide evidence through coimmunoprecipitation that single‐domain ketosynthase and ketoreductase proteins interact, suggesting a predicted multiprotein complex. In Karenia brevis (C.C. Davis) Gert Hansen & Ø. Moestrup, previously observed chloroplast localization of PKSs suggested that brevetoxin biosynthesis may take place in the chloroplast. Here, we report that PKSs are present in both cytosol and chloroplast. Furthermore, brevetoxin is not present in isolated chloroplasts, raising the question of what chloroplast‐localized PKS enzymes might be doing. Antibodies to K. brevis PKSs recognize cytosolic and chloroplast proteins in Ostreopsis cf. ovata Fukuyo, and Coolia monotis Meunier, which produce different suites of polyketide toxins, suggesting that these PKSs may share common pathways. Since PKSs are closely related to fatty acid synthases (FAS), we sought to determine if fatty acid biosynthesis colocalizes with either chloroplast or cytosolic PKSs. [3H]acetate labeling showed fatty acids are synthesized in the cytosol, with little incorporation in chloroplasts, consistent with a Type I FAS system. However, although 29 sequences in a K. brevis expressed sequence tag database have similarity (BLASTx e‐value <10−10) to PKSs, no transcripts for either Type I (cytosolic) or Type II (chloroplast) FAS are present. Further characterization of the FAS complexes may help to elucidate the functions of the PKS enzymes identified in dinoflagellates.
Quantitative trait loci for growth and body size in the nine‐spined sticklebackPungitius pungitiusL.
Authors: Laine Veronika N. , Shikano Takahito , Herczeg Gábor , Vilkki Johanna , Merilä Juha
Published: October 2013

Body size is an ecologically important trait shown to be genetically variable both within and among different animal populations as revealed by quantitative genetic studies. However, few studies have looked into underlying genetic architecture of body size variability in the wild using genetic mapping methods. With the aid of quantitative trait loci (QTL) analyses based on 226 microsatellite markers, we mapped body size and growth rate traits in the nine‐spined stickleback (Pungitius pungitius) using anF2‐intercross (n = 283 offspring) between size‐divergent populations. In total, 17QTLlocations were detected. The proportion of phenotypic variation explained by individual body size‐relatedQTLranged from 3% to 12% and those related to growth parameters and increments from 3% to 10%. Several of the detectedQTLaffected either early or late growth. These results provide a solid starting point for more in depth investigations of structure and function of genomic regions involved in determination of body size in this popular model of ecological and evolutionary research.
Angiotensin II Regulates Islet Microcirculation and Insulin Secretion in Mice
Authors: Ihoriya Chieko , Satoh Minoru , Kuwabara Atsunori , Sasaki Tamaki , Kashihara Naoki
Published: October 2013

Objective

Angiotensin II causes potent increases in systemic and local pressure through its vasoconstrictive effect. Despite the importance of angiotensin II for local blood flow regulation, whether angiotensin II regulates the pancreatic islet microcirculation remains incompletely understood. We hypothesized that angiotensin II directly regulates the pancreatic islet microcirculation and thereby regulates insulin secretion. The aims of this study were to develop a new technique to visualize pancreatic islet hemodynamic changes in vivo and to analyze changes in islet circulation induced by angiotensin II or an angiotensin type 1 receptor blocker.

Methods

Using an in vivo imaging method, we observed the pancreatic islet microcirculation. Various doses of angiotensin II or an angiotensin type 1 receptor blocker were injected intravenously, and changes in islet microcirculation were observed. Glucose‐stimulated insulin secretion from the pancreas was measured from the hepatic portal vein.

Results

We identified islet microcirculation using a fluorescent dye. Angiotensin II significantly induced blood vessel contraction in the islets in a dose‐dependent manner. In contrast, the angiotensin type 1 receptor blocker induced vasodilation. Glucose‐stimulated insulin secretion was decreased by angiotensin II infusion.

Conclusions

These results show that angiotensin II is involved in the regulation of pancreatic islet microcirculation and insulin secretion.
ePAD: Earthquake Probability‐Based Automated Decision‐Making Framework for Earthquake Early Warning
Authors: Wu Stephen , Beck James L. , Heaton Thomas H.
Published: October 2013

The benefits and feasibility of earthquake early warning (EEW) are becoming more appreciated throughout the world. An EEW system detects an earthquake initiation based on a seismic sensor network and broadcasts a warning of the predicted location and magnitude shortly before an earthquake hits a site. The typical range of this lead time is very short, for example, from a few seconds up to a minute in California, which is a huge challenge for applications taking advantage of EEW. As a result, a robust automated decision process about whether to initiate a mitigation action is essential. Recent approaches based on cost–benefit analyses to properly treat the trade‐off between false alarms and missed alarms still face challenges in practical use, such as the exclusion of an important factor, lead time, in the real‐time decision process. In this study, we lay out an earthquake probability‐based automated decision‐making (ePAD) framework to give a general decision criterion based on basic decision theory and an existing cost–benefit analysis procedure. The concepts of decision function, decision contour, and surrogate model are utilized to achieve fast computation and to allow comparison between various decision criteria. A value of information model is developed to handle the lead time of EEW and its uncertainty to reduce the “false response rate” in the cost–benefit trade‐off. An illustrative example is presented to demonstrate how this framework allows more flexibility for users to adapt ePAD to correspond to their desired rational decision behavior.
Nuclear and nucleoid localization are independently conserved functions in bacteriophage terminal proteins
Authors: Redrejo‐Rodríguez Modesto , Muñoz‐Espín Daniel , Holguera Isabel , Mencía Mario , Salas Margarita
Published: October 2013

Bacteriophage terminal proteins (TPs) prime DNA replication and become covalently linked to the DNA 5′‐ends. In addition, they are DNA‐binding proteins that direct early organization of phage DNA replication at the bacterial nucleoid and, unexpectedly, contain nuclear localization signals (NLSs), which localize them to the nucleus when expressed in mammalian cells. In spite of the lack of sequence homology among the phage TPs, these three properties share some common features, suggesting a possible evolutionary common origin of TPs. We show here that NLSs of three different phage TPs, Φ29, PRD1 and Cp‐1, are mapped within the protein region required for nucleoid targeting in bacteria, in agreement with a previously proposed common origin of DNA‐binding domains and NLSs. Furthermore, previously reported point mutants of Φ29 TP with no nuclear localization still can target the bacterial nucleoid, and Cp‐1 TP contains two independent NLSs, only one of them required for nucleoid localization. Altogether, our results show that nucleoid and nucleus localization sequence requirements partially overlap, but they can be uncoupled, suggesting that conservation of both features could have a common origin but, at the same time, they have been independently conserved during evolution.
Analysis of Tomato spotted wilt virus NSs protein indicates the importance of the N‐terminal domain for avirulence and RNA silencing suppression
Authors: de Ronde Dryas , Pasquier Adrien , Ying Su , Butterbach Patrick , Lohuis Dick , Kormelink Richard
Published: October 2013

Recently, Tomato spotted wilt virus (TSWV) nonstructural protein NSs has been identified unambiguously as an avirulence (Avr) determinant for Tomato spotted wilt (Tsw)‐based resistance. The observation that NSs from two natural resistance‐breaking isolates had lost RNA silencing suppressor (RSS) activity and Avr suggested a link between the two functions. To test this, a large set of NSs mutants was generated by alanine substitutions in NSs from resistance‐inducing wild‐type strains (NSsRI), amino acid reversions in NSs from resistance‐breaking strains (NSsRB), domain deletions and swapping. Testing these mutants for their ability to suppress green fluorescent protein (GFP) silencing and to trigger a Tsw‐mediated hypersensitive response (HR) revealed that the two functions can be separated. Changes in the N‐terminal domain were found to be detrimental for both activities and indicated the importance of this domain, additionally supported by domain swapping between NSsRI and NSsRB. Swapping domains between the closely related Tospovirus Groundnut ringspot virus (GRSV) NSs and TSWV NSsRI showed that Avr functionality could not simply be transferred between species. Although deletion of the C‐terminal domain rendered NSs completely dysfunctional, only a few single‐amino‐acid mutations in the C‐terminus affected both functions. Mutation of a GW/WG motif (position 17/18) rendered NSs completely dysfunctional for RSS and Avr activity, and indicated a putative interaction between NSs and Argonaute 1 (AGO1), and its importance in TSWV virulence and viral counter defence against RNA interference.
Nurse qualifications and perceptions of patient safety and quality of care in South Africa
Authors: Blignaut Alwiena J. , Coetzee Siedine K. , Klopper Hester C.
Published: October 2013

A plethora of research links professional nurses' qualifications to patient outcomes. Also, research has shown that reports by nurses on the quality of care correspond with process or outcome measures of quality in a hospital. New to the debate is whether professional nurses' qualifications impact on their perceptions of patient safety and quality of care. This research aims to investigate professional nurses' perceptions of patient safety and quality of care in South Africa, and the relationship between these perceptions and professional nurses' qualifications. A cross‐sectional survey of 1117 professional nurses from medical and surgical units of 55 private and 7 public hospitals was conducted. Significant problems with regard to nurse‐perceived patient safety and quality of care were identified, while adverse incidents in patients and professional nurses were underreported. Qualifications had no correlation with perceptions of patient safety and quality of care, although perceptions may serve as a valid indicator of patient outcomes. Creating an organizational culture that is committed to patient safety and encourages the sharing of adverse incidents will contribute to patient safety and quality of care in hospitals.
Inhibition of cadmium ion uptake in rice (Oryza sativa) cells by a wall‐bound form of silicon
Authors: Liu Jian , Ma Jie , He Congwu , Li Xiuli , Zhang Wenjun , Xu Fangsen , Lin Yongjun , Wang Lijun
Published: October 2013

The stresses acting on plants that are alleviated by silicon (Si) range from biotic to abiotic stresses, such as heavy metal toxicity. However, the mechanism of stress alleviation by Si at the single‐cell level is poorly understood.

We cultivated suspended rice (Oryza sativa) cells and protoplasts and investigated them using a combination of plant nutritional and physical techniques including inductively coupled plasma mass spectrometry (ICP‐MS), the scanning ion‐selective electrode technique (SIET) and X‐ray photoelectron spectroscopy (XPS).

We found that most Si accumulated in the cell walls in a wall‐bound organosilicon compound. Total cadmium (Cd) concentrations in protoplasts from Si‐accumulating (+Si) cells were significantly reduced at moderate concentrations of Cd in the culture medium compared with those from Si‐limiting (−Si) cells. In situ measurement of cellular fluxes of the cadmium ion (Cd2+) in suspension cells and root cells of rice exposed to Cd2+ and/or Si treatments showed that +Si cells significantly inhibited the net Cd2+ influx, compared with that in −Si cells. Furthermore, a net negative charge (charge density) within the +Si cell walls could be neutralized by an increase in the Cd2+ concentration in the measuring solution.

A mechanism of co‐deposition of Si and Cd in the cell walls via a [Si‐wall matrix]Cd co‐complexation may explain the inhibition of Cd ion uptake, and may offer a plausible explanation for the in vivo detoxification of Cd in rice.
The Arabidopsis RAD51 paralogs RAD51B,RAD51D and XRCC2 play partially redundant roles in somatic DNA repair and gene regulation
Authors: Wang Yingxiang , Xiao Rong , Wang Haifeng , Cheng Zhihao , Li Wuxing , Zhu Genfeng , Wang Ying , Ma Hong
Published: October 2013

The eukaryotic RAD51 gene family has seven ancient paralogs conserved between plants and animals. Among these, RAD51, DMC1, RAD51C and XRCC3 are important for homologous recombination and/or DNA repair, whereas single mutants in RAD51B, RAD51D or XRCC2 show normal meiosis, and the lineages they represent diverged from each other evolutionarily later than the other four paralogs, suggesting possible functional redundancy.

The function of Arabidopsis RAD51B, RAD51D and XRCC2 genes in mitotic DNA repair and meiosis was analyzed using molecular genetic, cytological and transcriptomic approaches.

The relevant double and triple mutants displayed normal vegetative and reproductive growth. However, the triple mutant showed greater sensitivity than single or double mutants to DNA damage by bleomycin. RNA‐Seq transcriptome analysis supported the idea that the triple mutant showed DNA damage similar to that caused by bleomycin. On bleomycin treatment, many genes were altered in the wild‐type but not in the triple mutant, suggesting that the RAD51 paralogs have roles in the regulation of gene transcription, providing an explanation for the hypersensitive phenotype of the triple mutant to bleomycin.

Our results provide strong evidence that Arabidopsis XRCC2, RAD51B and RAD51D have complex functions in somatic DNA repair and gene regulation, arguing for further studies of these ancient genes that have been maintained in both plants and animals during their long evolutionary history.
Leptin levels and risk of type 2 diabetes: gender‐specific meta‐analysis
Authors: Chen G.‐C. , Qin L.‐Q. , Ye J.‐K.
Published: October 2013

This meta‐analysis aimed to assess the gender‐specific differences in the relationship between circulating leptin levels and risk of type 2 diabetes. Published prospective studies that reported the association of leptin levels with risk of type 2 diabetes for a certain gender or those that reported gender‐specific associations were considered. Dose‐response relationships were assessed by the generalized least squares trend estimation and summary relative risks (RRs) with 95% confidence interval (CI) were computed with the random‐effects model. Stratified and sensitivity analyses were also performed to investigate potential sources of heterogeneity. Overall, 11 prospective studies were identified. The summary RR for an increment in leptin levels of 1‐log ng mL−1 was 1.37 (95% CI, 1.13–1.66) for men and 0.96 (95% CI, 0.90–1.03) for women. The differences between genders were statistically significant (P for interaction = 0.006). Subgroup and sensitivity analyses generally confirmed the robustness of these findings. Furthermore, the increased risk in men appeared non‐linear, with a tendency to plateau at high levels (P for non‐linearity = 0.03). Little evidence of publication bias was found. Collectively, higher leptin levels were found to be associated with elevated risk of type 2 diabetes in men but not in women.
Variations of pupil centration and their effects on video eye tracking
Authors: Wildenmann Ulrich , Schaeffel Frank
Published: October 2013

Purpose

To evaluate measurement errors that are introduced in video eye tracking when pupil centration changes with pupil size.

Methods

Software was developed under Visual C++ to track both pupil centre and corneal centre at 87 Hz sampling rate at baseline pupil sizes of 4.75 mm (800 lux room illuminance) and while pupil constrictions were elicited by a flashlight. Corneal centres were determined by a circle fit through the pixels detected at the corneal margin by an edge detection algorithm. Standard deviations for repeated measurements were ±0.04 mm for horizontal pupil centre position and ±0.04 mm for horizontal corneal centre positions and ±0.03 mm for vertical pupil centre position and ±0.05 mm for vertical corneal centre position. Ten subjects were tested (five female, five male, age 25–58 years).

Results

At 4 mm pupil sizes, the pupils were nasally decentred relative to the corneal centre by 0.18 ± 0.19 mm in the right eyes and −0.14 ± 0.22 mm in the left eyes. Vertical decentrations were 0.30 ± 0.30 mm and 0.27 ± 0.29 mm, respectively, always in a superior direction. At baseline pupil sizes (the natural pupil sizes at 800 lux) of 4.75 ± 0.52 mm, the decentrations became less (right and left eyes: horizontal 0.17 ± 0.20 mm and −0.12 ± 0.22 mm, and vertical 0.26 ± 0.28 mm and 0.20 ± 0.25 mm). While pupil decentration changed minimally in eight of the subjects, it shifted considerably in two others. Averaged over all subjects, the shift of the pupil centre position per millimetre pupil constriction was not significant (right and left eyes: −0.03 ± 0.07 mm and 0.03 ± 0.04 mm nasally per mm pupil size change, respectively, and −0.04 ± 0.06 mm and −0.05 ± 0.12 mm superiorly). Direction and magnitude of the changes in pupil centration could not be predicted from the initial decentration at baseline pupil sizes.

Conclusions

In line with data in the literature, the pupil centre was significantly decentred relative to the corneal centre in the nasal and superior direction. Pupil decentration changed significantly with pupil size by 0.05 mm on average for 1 mm of constriction. Assuming a Hirschberg ratio of 12° mm−1, a shift of 0.05 mm is equivalent to a measurement error in a Purkinje image‐based eye tracker of 0.6°. However, the induced measurement error could also exceed 1.5° in some subjects for only a 1 mm change in pupil size.
Benefits and limits of anticholinergic use in schizophrenia: Focusing on its effect on cognitive function
Authors: Ogino Shin , Miyamoto Seiya , Miyake Nobumi , Yamaguchi Noboru
Published: October 2013

All currently available antipsychotic drugs are the dopamine D2 receptor antagonists and are capable of producing extrapyramidal side‐effects (EPS). Anticholinergic drugs are primarily used to treat EPS or prevent EPS induced by antipsychotics in the treatment of psychosis and schizophrenia. However, they can cause a variety of distressing peripheral side‐effects (e.g. dry mouth, urinary disturbances, and constipation) and central adverse effects (e.g. cognitive impairment, worsening of tardive dyskinesia, and delirium). Disturbances in cognitive abilities are cardinal features of schizophrenia from its earliest phases and account for much of the functional disability associated with the illness. It is likely that long‐term concomitant administration of anticholinergics exacerbates the underlying cognitive impairment in patients with schizophrenia and subsequently affects patients' quality of life. Thus, current treatment guidelines for schizophrenia generally do not recommend the prophylactic and long‐term use of anticholinergics. However, the high use of long‐term anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in several countries. To assess the benefits and limits of anticholinergic use in psychosis and schizophrenia, this article will provide a brief review of the pharmacology and clinical profiles of anticholinergic drugs and will focus on their effects on cognitive function in schizophrenia, particularly during the course of the early phase of the illness. In addition, we will address the effects of discontinuation of anticholinergics on cognitive function in patients with schizophrenia and provide a strategy for adjunctive anticholinergic use in patients treated with long‐acting injectable antipsychotics.
UVA and UVB‐Induced 8‐Methoxypsoralen Photoadducts and a Novel Method for their Detection by Surface‐Enhanced Laser Desorption Ionization Time‐of‐Flight Mass Spectrometry (SELDI‐TOF MS)
Authors: Buhimschi Alexandru D. , Gasparro Francis P.
Published: October 2013

UVA‐activated psoralens are used to treat hyperproliferative skin conditions due to their ability to form DNA photoadducts, which impair cellular processes and may lead to cell death. Although UVA (320–400 nm) is more commonly used clinically, studies have shown that UVB (280–320 nm) activation of psoralen can also be effective. However, there has been no characterization of UVB‐induced adduct formation in DNA alone. As psoralen derivatives have a greater extinction coefficient in the UVB region (11 800 cm−1 M−1 at 300 nm) compared with the UVA region (2016 cm−1 M−1 at 365 nm), a greater extent of adduct formation is expected. SELDI‐TOF, a proteomic technique that combines chromatography with mass spectrometry, was used to detect photoadduct formation in an alternating A–T oligonucleotide. 8‐Methoxypsoralen (8‐MOP) and DNA solutions were irradiated with either UVA or UVB. An adduct peak was obtained with SELDI‐TOF. For UVB‐activated 8‐MOP, the extent of adducts was three times greater than for UVA. HPLC ESI‐MS analysis showed that UVB irradiation yielded high levels of 3,4‐monoadducts (78% of total adducts). UVA was more effective than UVB at conversion of 4′,5′‐monoadducts to crosslinks (17% vs 4%, respectively). This report presents a method for comparing DNA binding efficiencies of interstrand crosslink inducing agents.
Neutrophils have a protective role during early stages of Leishmania amazonensis infection in BALB/c mice
Authors: Sousa L. M. A. , Carneiro M. B. H. , Resende M. E. , Martins L. S. , dos Santos L. M. , Vaz L. G. , Mello P. S. , Mosser D. M. , Oliveira M. A. P. , Vieira L. Q.
Published: October 2013

Neutrophils are involved in the early stages of immune responses to pathogens. Here, we investigated the role of neutrophils during the establishment of Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an accumulation of neutrophils between 6 and 24 h post‐infection, followed by a reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior to infection using RB6‐8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion development, increased parasite numbers and higher arginase activity during the first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased susceptibility was accompanied by augmented levels of anti‐L. amazonensis IgG and increased production of IL‐10 and IL‐17. Because IL‐10 is a mediator of susceptibility to Leishmania infection, we blocked IL‐10 signalling in neutrophil‐depleted mice using anti‐IL‐10R. Interestingly, inhibition of IL‐10 signalling abrogated the increase in parasite loads observed in neutrophil‐depleted mice, suggesting that parasite proliferation is at least partially mediated by IL‐10. Additionally, we tested the effect of IL‐17 in inflammatory macrophages and observed that IL‐17 increased arginase activity and favoured parasite growth. Taken together, our data indicate that neutrophils control parasite numbers and limit lesion development during the first week of infection in BALB/c mice.
Maternal Liver Damage Delays Meiotic Resumption in Bovine Oocytes through Impairment of Signalling Cascades Originated from Low p38MAPK Activity in Cumulus Cells
Authors: Tanaka H , Takeo S , Monji Y , Kuwayama T , Iwata H
Published: October 2013

Contents

The main objective of the present study is to investigate the molecular mechanism underlying the delay in progression of nuclear maturation in oocytes derived from cows with damaged livers (DL cows), which was previously reported. In present study, delayed progression of nuclear maturation of oocytes derived from DL cows relative to oocytes derived from cows with healthy livers (HL cows) was accompanied by low maturation promoting factor (MPF) activity (0.43 fold, p < 0.05). When cumulus cells were removed from cumulus‐oocyte complexes and the denuded oocytes were cultured, there was no difference in the progression of nuclear maturation between the two liver conditions. In addition, gap junctional communication (GJC) between the oocyte and cumulus cells was higher in DL cows than in HL cows at 3 and 7 h of in vitro maturation (IVM) (p < 0.05). Supplementation of IVM medium with epidermal growth factor (EGF) increased the ratio of germinal vesicle breakdown (GVBD) of oocytes derived from DL cows to the level seen in oocytes derived from HL cows. Additionally, the level of p38MAPK phosphorylation at 0 h of IVM was significantly lower in cumulus cells derived from DL cows than in cumulus cells derived from HL cows (HL cows, 53.5%; DL cows, 28.9%; p < 0.05). Thus, a low level of p38MAPK phosphorylation in cumulus cells induced slow GJC closure between oocyte and cumulus cells, which resulted in slow meiotic maturation of oocytes derived from DL cows.