bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient satisfaction and barriers to initiating real‐time continuous glucose monitoring in early pregnancy in women with diabetes
Authors: Secher A. L. , Madsen A. B. , Ringholm L. , Barfred C. , Stage E. , Andersen H. U. , Damm P. , Mathiesen E. R.
Published: September 2011

Diabet. Med. 29, 272–277 (2012)

Aim  To evaluate self‐reported satisfaction and barriers to initiating real‐time continuous glucose monitoring in early pregnancy among women with pregestational diabetes.

Methods  Fifty‐four women with Type 1 diabetes and 14 women with Type 2 diabetes were offered continuous glucose monitoring for 6 days at median 9 (range 6–14) gestational weeks and were asked to answer a semi‐structured questionnaire on patient satisfaction.

Results  Median HbA1c was 49 (range 34–86) mmol/mol) [6.6 (5.3–10.0) %] and duration of diabetes was 12 (0.5–37) years. Continuous glucose monitoring was used for 6 (0.5–7) days, with 43 (65%) women using continuous glucose monitoring for at least 5 days. The women experienced 2.7 (0–12) alarms per 24 h, of which approximately one third was technical alarms and one third disturbed their sleep. Sixteen women (24%) reported discomfort with continuous glucose monitoring during daytime and twelve (18%) during sleep. Many women reported improved diabetes understanding (52%) and would recommend continuous glucose monitoring to others (83%). Twenty‐four patients (36%) had continuous glucose monitoring removed earlier than planned ( before the intended 6 days of initial monitoring). Ten women (15%) did not wish to use continuous glucose monitoring again in pregnancy. Main causes behind early removal of continuous glucose monitoring were self‐reported skin irritation, technical problems and continuous glucose monitoring inaccuracy. No differences were found in continuous glucose monitoring use, inconvenience or compliance with respect to diabetes type.

Conclusions  The majority of pregnant women with diabetes found real‐time continuous glucose monitoring useful and the intervention was equally tolerated regardless of diabetes type. Nevertheless, continuous glucose monitoring was frequently removed earlier than planned, primarily because of skin irritation, technical problems and inaccuracy.
Ethnic Stigma, Academic Anxiety, and Intrinsic Motivation in Middle Childhood
Authors: Gillen‐O’Neel Cari , Ruble Diane N. , Fuligni Andrew J.
Published: September 2011

Previous research addressing the dynamics of stigma and academics has focused on African American adolescents and adults. The present study examined stigma awareness, academic anxiety, and intrinsic motivation among 451 young (ages 6–11) and diverse (African American, Chinese, Dominican, Russian, and European American) students. Results indicated that ethnic‐minority children reported higher stigma awareness than European American children. For all children, stigma awareness was associated with higher academic anxiety and lower intrinsic motivation. Despite these associations, ethnic‐minority children reported higher levels of intrinsic motivation than their European American peers. A significant portion of the higher intrinsic motivation among Dominican students was associated with their higher levels of school belonging, suggesting that supportive school environments may be important sources of intrinsic motivation among some ethnic‐minority children.
The Roles of Structured Input Activities in Processing Instruction and the Kinds of Knowledge They Promote
Authors: Marsden Emma , Chen Hsin‐Ying
Published: September 2011

This study aimed to isolate the effects of the two input activities in Processing Instruction: referential activities, which force learners to focus on a form and its meaning, and affective activities, which contain exemplars of the target form and require learners to process sentence meaning. One hundred and twenty 12‐year‐old Taiwanese learners of English as a foreign language were assigned to one of four groups: Referential + Affective, Referential only, Affective only, or Control. The treatments were computer‐based. Pretests, posttests, and delayed posttests, including a timed grammaticality judgment, a written gap‐fill, an oral picture narration, and a short semistructured conversation, measured learning of the –ed past tense verb inflection. Findings suggested that referential activities were responsible for the learning gains observed, that affective activities did not provide additional benefits in terms of learning –ed, and that the gains observed displayed some broadly defined characteristics of explicit knowledge.
New Rice for Africa (NERICA) cultivars exhibit different levels of post‐attachment resistance against the parasitic weeds Striga hermonthica and Striga asiatica
Authors: Cissoko Mamadou , Boisnard Arnaud , Rodenburg Jonne , Press Malcolm C. , Scholes Julie D.
Published: September 2011

See also the Commentary by John A. Pickett
Pre‐attachment Striga hermonthica resistance of New Rice for Africa (NERICA) cultivars based on low strigolactone production
Authors: Jamil Muhammad , Rodenburg Jonne , Charnikhova Tatsiana , Bouwmeester Harro J.
Published: September 2011

See also the Commentary by John A. Pickett
Dysregulated phosphorylation of Ca2+/calmodulin‐dependent protein kinase II‐α in the hippocampus of subjects with mild cognitive impairment and Alzheimer’s disease
Authors: Reese Lindsay C. , Laezza Fernanda , Woltjer Randall , Taglialatela Giulio
Published: September 2011

J. Neurochem.(2011)119, 791–804.

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder and the most prevalent senile dementia. The early symptom of memory dysfunction involves synaptic loss, thought to be mediated by soluble amyloid‐beta (Aβ) oligomers. These aggregate species target excitatory synapses and their levels correlate with disease severity. Studies in cell culture and rodents have shown that oligomers increase intracellular calcium (Ca2+), impairing synaptic plasticity. Yet, the molecular mechanism mediating Aβ oligomers’ toxicity in the aged brain remains unclear. Here, we apply quantitative immunofluorescence in human brain tissue from clinically diagnosed mild cognitive impaired (MCI) and AD patients to investigate the distribution of phosphorylated (active) Ca2+/calmodulin‐dependent protein kinase‐α (p(Thr286)CaMKII), a critical enzyme for activity‐dependent synaptic remodeling associated with cognitive function. We show that p(Thr286)CaMKII immunoreactivity is redistributed from dendritic arborizations to neural perikarya of both MCI and AD hippocampi. This finding correlates with cognitive assessment scores, suggesting that it may be a molecular read‐out of the functional deficits in early AD. Treatment with oligomeric Aβ replicated the observed phenotype in mice and resulted in a loss of p(Thr286)CaMKII from synaptic spines of primary hippocampal neurons. Both outcomes were prevented by inhibiting the phosphatase calcineurin (CaN). Collectively, our results support a model in which the synaptotoxicity of Aβ oligomers in human brain involves the CaN‐dependent subcellular redistribution of p(Thr286)CaMKII. Therapies designed to normalize the homeostatic imbalance of neuronal phosphatases and downstream dephosphorylation of synaptic p(Thr286)CaMKII should be considered to prevent and treat early AD.
The use of deep oral swabs as a surrogate for transoral tracheal wash to obtain bacterial cultures in dogs with pneumonia
Authors: Sumner Catherine M. , Rozanski Elizabeth A. , Sharp Claire R. , Shaw Scott P.
Published: September 2011

Objective

To determine agreement in bacterial culture and susceptibility (BC&S) between deep oral swab (DOS) and routine transoral tracheal wash (TOTW) in dogs with pneumonia.

Design

Prospective study, performed between 2008 and 2010 with no follow‐up period.

Setting

University teaching hospital.

Animals

Five puppies and 5 adult dogs with community or hospital‐acquired pneumonia.

Measurements and Main Results

ADOSwas collected from each patient; dogs were then briefly anesthetized with propofolafor a routineTOTW. Routine microbiology techniques were used for culture. Positive culture results were obtained from all 20 swabs. Results ofBC&Swere compared between the 2 sites. In all puppies, there was no agreement betweenDOSandTOTW. In adult dogs, 2 patients with hospital‐acquired infection (HAI) had complete agreement between theBC&Sresults fromDOSandTOTW. Two adult dogs had some similarity inBC&Sresults, and the final dog had no relationship between cultures.

Conclusions

DOSis not an appropriate alternative toTOTWto obtain samples forBC&Sin puppies with pneumonia. In adult dogs, traditionalTOTWremains the gold standard, butDOSmay be considered in dogs with suspectedHAI. Further work is needed to confirm this preliminary finding.
A β‐amyloid oligomer directly modulates P/Q‐type calcium currents in Xenopus oocytes
Authors: Mezler M , Barghorn S , Schoemaker H , Gross G , Nimmrich V
Published: September 2011

BACKGROUND AND PURPOSE β‐amyloid (Aβ) oligomers have been implicated in the early pathophysiology of Alzheimer's disease (AD). While the precise nature of the molecular target has not been fully revealed, a number of studies have indicated that Aβ oligomers modulate neuron‐specific ion channels. We recently provided evidence that Aβ oligomers suppress isolated P/Q‐type calcium currents in cultured nerve cells. Using a heterologous expression system, we aimed to prove a direct effect on the membrane channel mediating such current.

EXPERIMENTAL APPROACH The effects of a synthetically generated Aβ oligomer, Aβ globulomer, were investigated on P/Q‐type currents recorded from Xenopus laevis oocytes expressing the full P/Q‐type calcium channel or the pore‐forming subunit only. We also examined the effects of Aβ globulomer on recombinant NMDA receptor currents. Finally, we compared the modulation by Aβ globulomer with that induced by a synthetic monomeric Aβ.

KEY RESULTS Aβ globulomer directly and dose‐dependently modulated P/Q‐type calcium channels. A leftward shift of the current‐voltage curve indicated that the threshold for channel opening was reduced. The effect of Aβ globulomer was also present when only the α1A subunit of the normally tripartite channel was expressed. In contrast, the monomeric Aβ had no effect on P/Q current. Also globulomer Aβ had no effect on glutamate‐induced NMDA currents.

CONCLUSIONS AND IMPLICATIONS The α1A subunit of the P/Q‐type calcium channel is directly modulated by oligomeric Aβ. Threshold reduction as well as an increase in current at synaptic terminals may facilitate vesicle release and could trigger excitotoxic events in the brains of patients with AD.
Mortality and cancer risk related to primary sclerosing cholangitis in a Swedish population‐based cohort
Authors: de Valle Maria Benito , Björnsson Einar , Lindkvist Björn
Published: September 2011

Background

Population‐based studies on the epidemiology of primary sclerosing cholangitis (PSC) are sparse.

Aims

To investigate mortality and risk of cancer, and to identify risk factors for hepatobiliary cancer and the combined end‐point liver related death or liver transplantation (OLT) in a population‐based PSC cohort in Västra Götaland, Sweden.

Methods

Primary sclerosing cholangitis cases were identified in diagnostic registries. Case validation and follow up was provided through individual review of case files and linkage to the Swedish Cancer and Cause of Death registries. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) for cancer were calculated in relation to the background population. Cox's proportional hazards analysis was used to calculate crude and adjusted relative risks (RRs).

Results

A total of 199 PSC patients were identified between 1992 and 2005. SMR in the PSC cohort was 4.20 (95% confidence interval (CI), 3.01–5.69). SIR for hepatobiliary cancer, cholangiocarcinoma and colorectal cancer were 177 (110–271), 868 (505–1390) and 2.87 (0.33–10.4) respectively. Age (RR=1.25 (1.01–1.53) per decade), female gender (RR=2.01 (1.09–3.72)), cholangitis (RR=2.56 (1.20–5.64)) and bilirubin (RR=3.95 (1.96–10.75) highest vs lowest quartile) were associated with the risk of liver related death or OLT. Age was associated with the risk of hepatobiliary cancer (RR 1.40 (1.01–1.95) per decade).

Conclusions

Primary sclerosing cholangitis was associated with a four‐fold increase in mortality in this population‐based study. In accordance with previous studies, the risk of hepatobiliary cancer was dramatically increased. However, the increased risk of colorectal cancer reported in previous studies could not be confirmed.
Pretreatment of wool/polyester blended fabrics to enhance titanium dioxide nanoparticle adsorption and self‐cleaning properties
Authors: Montazer Majid , Seifollahzadeh Samira
Published: September 2011

This research aims to enhance the self‐cleaning properties of fibre‐blended fabric using surface pretreatment prior to the application of titanium dioxide nanoparticles. To this end, the polyester/wool fabric was modified, in that the wool fibres were oxidised with potassium permanganate and the polyester fibres were hydrolysed with lipase before nano processing. Butane tetracarboxylic acid was also used to enhance the adsorption of the nanoparticles and also to stabilise them on the fabric surface. The self‐cleaning properties of the fabric were examined through staining of the fabric with CI Basic Blue 9 and then discolouring by exposing to ultraviolet and daylight irradiation. Some other properties of the treated fabrics, such as water drop absorption, crease recovery angle and bending were investigated and are discussed in detail. The colour changes of different samples indicated an appropriate discoloration on the titanium dioxide‐treated fabrics after ultraviolet and daylight irradiation. Overall, the surface pretreatment of the wool and polyester fibres improved the self‐cleaning properties of the fabric significantly.
Plasma Klotho and Cardiovascular Disease in Adults
Authors: Semba Richard D. , Cappola Anne R. , Sun Kai , Bandinelli Stefania , Dalal Mansi , Crasto Candace , Guralnik Jack M. , Ferrucci Luigi
Published: September 2011

OBJECTIVES: To determine whether plasma klotho, a recently discovered hormone that has been implicated in atherosclerosis, is related to prevalent cardiovascular disease (CVD) in adults.

DESIGN: Cross‐sectional.

SETTING: Population‐based sample of adults residing in Tuscany, Italy.

PARTICIPANTS: One thousand twenty‐three men and women aged 24 to 102 participating in the Invecchiare in Chianti (InCHIANTI) study.

MEASUREMENTS: Anthropometric measures, plasma klotho, fasting plasma total, high‐density lipoprotein cholesterol (HDL‐C), triglycerides, glucose, creatinine, C‐reactive protein (CRP). Clinical measures: medical assessment, diabetes mellitus, hypertension, coronary heart disease, heart failure, stroke, peripheral artery disease, cancer, chronic kidney disease. Logistic regression models were used to examine the relationship between plasma klotho and prevalent CVD.

RESULTS: Of 1,023 participants, 259 (25.3%) had CVD. Median (25th, 75th percentile) plasma klotho concentrations were 676 pg/mL (530, 819 pg/mL). Plasma klotho was correlated with age (correlation coefficient (r)=−0.14, P<.001), HDL‐C (r=0.11, P<.001), and CRP (r=−0.10, P<.001) but not systolic blood pressure, fasting plasma glucose, or renal function. Plasma klotho age‐adjusted geometric means were 626 pg/mL (95% confidence interval (CI)=601–658 pg/mL) in participants with CVD and 671 pg/mL (95% CI=652–692 pg/mL) in those without CVD (P=.001). Adjusting for traditional cardiovascular risk factors (age, sex, smoking, total cholesterol, HDL‐C, systolic blood pressure, and diabetes mellitus), log plasma klotho was associated with prevalent CVD (odds ratio per 1 standard deviation increase=0.85, 95% CI=0.72–0.99).

CONCLUSION: In community‐dwelling adults, higher plasma klotho concentrations are independently associated with a lower likelihood of having CVD.
Impaired Frontal Executive Function and Predialytic Chronic Kidney Disease
Authors: Lee Jung Jae , Chin Ho Jun , Byun Min‐Soo , Choe Jin Yeong , Park Joon Hyuk , Lee Seok Bum , Choi Eun Ae , Chae Dong Wan , Kim Ki Woong
Published: September 2011

OBJECTIVES: To investigate the nature of frontal dysfunction associated with chronic kidney disease (CKD) in people without stroke or depressive disorders.

DESIGN: Cross‐sectional.

SETTING: Community based.

PARTICIPANTS: Five hundred twenty‐nine community‐dwelling participants.

MEASUREMENTS: Participants with CKD were classified into one of three diagnostic groups based on their estimated glomerular filtration rate (eGFR): normal (≥60.0 mL/min per 1.73 m2), mild CKD (45.0–59.9 mL/min per 1.73 m2), or moderate to severe CKD (<45.0 mL/min per 1.73 m2). Cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery, lexical fluency, digit span test, and the 64‐card Wisconsin Card Sorting Test.

RESULTS: Perseverative responses and perseverative errors were significantly more prevalent in the group with moderate to severe CKD than in those without CKD and those with mild CKD. The mean number of perseverative responses was 28.6±16.9 in participants with moderate to severe CKD, 19.0±11.4 in those with mild CKD, and 17.1±10.6 in those without CKD (P<.001, ANCOVA). The mean number of perseverative errors was 23.1±12.3 in participants with moderate to severe CKD, 16.2±8.3 in those with mild CKD, and 14.8±7.8 in those without CKD (P<.001, analysis of covariance). The odds ratios in the fully adjusted model for the presence of moderate to severe CKD for perseverative responses and perseverative errors were 4.82 (95% confidence interval (CI)=2.14–10.85, P<.001) and 5.01 (95% CI=2.22–11.28, P<.001), respectively.

CONCLUSION: Frontal dysfunction, particularly perseverative errors and responses, was associated with moderate to severe CKD in the population studied.
Genetic variations in multiple myeloma I: effect on risk of multiple myeloma
Authors: Vangsted Annette , Klausen Tobias W. , Vogel Ulla
Published: September 2011

Few risk factors have been established for the plasma cell disorder multiple myeloma, but some of these like African American ethnicity and a family history of B‐cell lymphoproliferative diseases suggest a genetic component for the disease. Genetic variation represents the genetic basis of variability in a population. The complex interplay between environment and genes for the development of cancer may therefore be influenced by genetic variations. A genetic variation may change the function of the gene, and if the genetic variation is associated with the risk of disease, that particular gene may be involved in the pathogenesis of disease. Genes of interest are genes involved in the normal development and function of the plasma cell and genes that protect us against exposures from the environment, for example, genes involved in the metabolism of xenobiotics, metabolism of folate and methionine, as well as genes involved in inflammation and DNA repair. Identification of genes with potential influence on cancer risk may help us to establish relevant laboratory studies on exposure and dose–response assessment and may help us to test the hypothesis in epidemiological studies. Knowledge of individual at high risk of cancer may offer promising insight for the prevention of cancer.
Analysis of human perception of facial skin radiance by means of image histogram parameters of surface and subsurface reflections from the skin
Authors: Matsubara Akira , Liang Zhiwu , Sato Yuji , Uchikawa Keiji
Published: September 2011

Background

The appearance of the skin is the result of complicated light–skin interactions involving surface and subsurface reflections. Radiant skin is a complicated attribute but is important for skin beauty. The aim of the present study was to achieve an understanding of the association between human perceptions of skin radiance and image histogram parameters from technically recorded images of surface and subsurface reflections.

Methods

Facial images of 45 subjects were evaluated visually by 30 respondents and were also computer analyzed in terms of their image histogram parameters. A partial least squares regression model was created to explain visual perceptions in terms of the image histogram parameters.

Results

Visual perceptions of subsurface reflections can be explained in terms of the mean from the subsurface reflection image histogram, and visual perceptions of surface reflections can be explained in terms of the standard deviation (SD) and skewness from the surface reflection image histogram. Skin radiance can be explained in terms of the mean from the subsurface reflection and the SD from the surface reflection.

Conclusion

To acquire skin radiance, a surface reflection component that makes the skin look shiny and a subsurface reflection component that is in line with skin fairness are both needed. A balance of these features provides the origin of skin radiance.
Hotspots Organize Clathrin‐Mediated Endocytosis by Efficient Recruitment and Retention of Nucleating Resources
Authors: Nunez Daniel , Antonescu Costin , Mettlen Marcel , Liu Allen , Schmid Sandra L. , Loerke Dinah , Danuser Gaudenz
Published: September 2011

The formation of clathrin‐coated pits (CCPs) at the plasma membrane has been reported to sometimes occur repeatedly at predefined sites. However, defining such CCP ‘hotspots’ structurally and mechanistically has been difficult due to the dynamic and heterogeneous nature of CCPs. Here, we explore the molecular requirements for hotspots using a global assay of CCP dynamics. Our data confirmed that a subset of CCPs is nucleated at spatially distinct sites. The degree of clustering of nucleation events at these sites is dependent on the integrity of cortical actin, and the availability of certain resources, including the adaptor protein AP‐2 and the phospholipid PI(4,5)P2. We observe that modulation in the expression level of FCHo1 and 2, which have been reported to initiate CCPs, affects only the number of nucleations. Modulation in the expression levels of other accessory proteins, such as SNX9, affects the spatial clustering of CCPs but not the number of nucleations. On the basis of these findings, we distinguish two classes of accessory proteins in clathrin‐mediated endocytosis (CME): nucleation factors and nucleation organizers. Finally, we observe that clustering of transferrin receptors spatially randomizes pit nucleation and thus reduces the role of hotspots. On the basis of these data, we propose that hotspots are specialized cortical actin patches that organize CCP nucleations from within the cell by more efficient recruitment and/or retention of the resources required for CCP nucleation partially due to the action of nucleation organizers.
Selenodiglutathione uptake by the Saccharomyces cerevisiae vacuolar ATP‐binding cassette transporter Ycf1p
Authors: Lazard Myriam , Ha‐Duong Nguyet‐Thanh , Mounié Stéphanie , Perrin Romary , Plateau Pierre , Blanquet Sylvain
Published: September 2011

The Saccharomyces cerevisiae vacuolar ATP‐binding cassette transporter Ycf1p is involved in heavy metal detoxification by mediating the ATP‐dependent transport of glutathione–metal conjugates to the vacuole. In the case of selenite toxicity, deletion of YCF1 was shown to confer increased resistance, rather than sensitivity, to selenite exposure [Pinson B, Sagot I & Daignan‐Fornier B (2000) Mol Microbiol36, 679–687]. Here, we show that when Ycf1p is expressed from a multicopy plasmid, the toxicity of selenite is exacerbated. Using secretory vesicles isolated from a sec6‐4 mutant transformed either with the plasmid harbouring YCF1 or the control plasmid, we establish that the glutathione‐conjugate selenodigluthatione is a high‐affinity substrate of this ATP‐binding cassette transporter and that oxidized glutathione is also efficiently transported. Finally, we show that the presence of Ycf1p impairs the glutathione/oxidized glutathione ratio of cells subjected to a selenite stress. Possible mechanisms by which Ycf1p‐mediated vacuolar uptake of selenodiglutathione and oxidized glutathione enhances selenite toxicity are discussed.
INVESTIGATION OF TEST PERFORMANCE OVER REPEATED SESSIONS USING SIGNAL DETECTION THEORY: COMPARISON OF THREE NONATTRIBUTE‐SPECIFIED DIFFERENCE TESTS 2‐AFCR, A‐NOT A AND 2‐AFC
Authors: VAN HOUT DANIELLE , HAUTUS MICHAEL J. , LEE HYE‐SEONG
Published: September 2011

To investigate more flexible methods for measuring overall sensory differences, the performance of three nonattribute‐specified difference test methods was compared using Signal Detection Theory. A‐Not A, 2‐AFC, and 2‐AFCR tests were performed with experienced subjects over repeated sessions. Learning effects were investigated to determine how much training would be needed before subjects could perform these tests consistently. Results in d′ showed that in early sessions, the 2‐AFC and 2‐AFCR performed better (higher d′) than A‐Not A and that after two sessions, the test performance stabilized on that level. Learning effects for the A‐Not A test were poorer in the earlier sessions, with performance levels increasing, even after six sessions. In business situations where the tested products frequently vary, the use of 2‐AFC and 2‐AFCR would be recommended because they are more sensitive in the earlier sessions, requiring less training time than A‐Not A.

PRACTICAL APPLICATIONS

Sensory difference tests are important tools for business decision making. Food companies may save a lot of money by employing more effective methodologies. For sensory difference tests to be used accurately and efficiently, test performances need to be investigated with consideration for food discrimination constraints and objectives. This article explored the performance of nonattribute‐specified 2‐AFC and 2‐AFCR tests over several sessions in comparison to the results of a standard signal detection measure, A‐Not A, to use the differences between these methods as a basis for inference concerning the cognitive strategies and relative test effectiveness of nonattribute‐specified 2‐AFC and 2‐AFCR for food discrimination, in practical situations when both the reference product and test product(s) change frequently. This article suggested the applicability of a nonattribute‐specified 2‐AFCR procedure for discriminating small differences without much prior training.
Glass and Glass‐Ceramic Technologies to Transform the World
Authors: Hench Larry L.
Published: September 2011

This presentation is an overview of the findings from June 21 to 22, 2010 American Ceramic Society Leadership Summit and a personal perspective on the economic issues and technical feasibility of achieving breakthrough technologies in the business segments of Energy and Healthcare. The top 10 rankings from an extensive listing of 100 potentially important ceramic, glass and glass–ceramic technologies were all in the Energy and Healthcare Sectors of business. Innovative technologies that have the potential for being world‐changing are discussed, including Transforming Technology for Energy No. 1: Innovative Energy Storage Devices; Transforming Technology for Healthcare No. 1: Bioactive Materials for Regeneration of Tissues; No. 2: Localized Therapies for Cancer and Autoimmune Diseases; No. 3: Tissue Engineering of Soft Tissues; No. 4: Stem Cell Engineering; No. 5: Preventative Medicine.
Undesired behaviour in horses: A review of their development, prevention, management and association with welfare
Authors: Hothersall B. , Casey R.
Published: September 2011

Undesired behaviours are a common problem amongst leisure and sporting horses in the UK and have a significant impact on the work of equine practitioners. In most cases, behaviours considered aberrant by owners are normal responses for their horses. Behaviours perceived as ‘naughtiness’ may in fact signify direct actions to avoid pain‐ or fear‐inducing stimuli. Examples that practitioners might deal with include trailer loading problems, avoidance of having saddlery equipment applied or reluctance to leave the yard. Even where no evidence of physical problems or pain can be detected, avoidance behaviours may reflect learnt responses that previously led to success in evading unpleasant consequences. Because owners often misunderstand the reason for such behaviours to develop in their horses, attempts at resolution often involve suppression or punishment based approaches. Although repeated subjugation of undesirable responses may ultimately appear to resolve the overt behavioural problem in some cases, in many others it can lead to a worsening of the problem, the development of alternative avoidance strategies or the horse learning that escaping the source of its pain or anxiety is impossible and ceasing to respond. Some horses develop abnormal or repetitive behaviours, which are not in the ‘normal’ behavioural repertoire. These stereotypic behaviours, sometimes termed ‘vices’, can indicate strategies to cope with a suboptimal environment. Indeed, their performance may serve to improve the situation for the animal. Attempts to suppress or prevent horses showing stereotypies, therefore, will generally exacerbate the underlying welfare problem. When dealing with either stereotypies or avoidance behaviours, it is important to recognise the role of learning in their development and maintenance. Resolution involves both understanding the underlying motivation for showing the behaviour and how it has become reinforced and established over time, for each individual case. The use of environmental change and/or behavioural modification techniques that are both successful and welfare compatible, are important in dealing with undesired behaviour in horses and selection of suitable professionals for referral an important responsibility for the equine practitioner.
Bottom-Up Synthetic Biology: Engineering in a Tinkerer’s World
Authors: Schwille Petra
Published: September 2011

How synthetic can “synthetic biology” be? A literal interpretation of the name of this new life science discipline invokes expectations of the systematic construction of biological systems with cells being built module by module—from the bottom up. But can this possibly be achieved, taking into account the enormous complexity and redundancy of living systems, which distinguish them quite remarkably from design features that characterize human inventions? There are several recent developments in biology, in tight conjunction with quantitative disciplines, that may bring this literal perspective into the realm of the possible. However, such bottom-up engineering requires tools that were originally designed by nature’s greatest tinkerer: evolution.
Food and Biodiversity
Authors: Godfray H. Charles J.
Published: September 2011

Density-yield curves help evaluate whether land sharing or land sparing most benefits biodiversity.
A Computational Model to Predict the Effects of Class I Anti-Arrhythmic Drugs on Ventricular Rhythms
Authors: Moreno Jonathan D. , Zhu Z. Iris , Yang Pei-Chi , Bankston John R. , Jeng Mao-Tsuen , Kang Chaoyi , Wang Lianguo , Bayer Jason D. , Christini David J. , Trayanova Natalia A. , Ripplinger Crystal M. , Kass Robert S. , Clancy Colleen E.
Published: September 2011

Two- and three-dimensional models of cardiac excitability based on sodium channel kinetics can predict the adverse effects of class I anti-arrhythmic drugs.
Experimental Model of Tuberculosis in the Domestic Goat after Endobronchial Infection with Mycobacterium caprae
Authors: Pérez de Val Bernat , López-Soria Sergio , Nofrarías Miquel , Martín Maite , Vordermeier H. Martin , Villarreal-Ramos Bernardo , Romera Nadine , Escobar Manel , Solanes David , Cardona Pere-Joan , Domingo Mariano
Published: September 2011

Caprine tuberculosis (TB) has increased in recent years, highlighting the need to address the problem the infection poses in goats. Moreover, goats may represent a cheaper alternative for testing of prototype vaccines in large ruminants and humans. With this aim, a
Mycobacterium caprae
infection model has been developed in goats. Eleven 6-month-old goats were infected by the endobronchial route with 1.5 × 10
3
CFU, and two other goats were kept as noninfected controls. The animals were monitored for clinical and immunological parameters throughout the experiment. After 14 weeks, the goats were euthanized, and detailed postmortem analysis of lung lesions was performed by multidetector computed tomography (MDCT) and direct observation. The respiratory lymph nodes were also evaluated and cultured for bacteriological analysis. All infected animals were positive in a single intradermal comparative cervical tuberculin (SICCT) test at 12 weeks postinfection (p.i.). Gamma interferon (IFN-γ) antigen-specific responses were detected from 4 weeks p.i. until the end of the experiment. The humoral response to MPB83 was especially strong at 14 weeks p.i. (13 days after SICCT boost). All infected animals presented severe TB lesions in the lungs and associated lymph nodes.
M. caprae
was recovered from pulmonary lymph nodes in all inoculated goats. MDCT allowed a precise quantitative measure of TB lesions. Lesions in goats induced by
M. caprae
appeared to be more severe than those induced in cattle by
M. bovis
over a similar period of time. The present work proposes a reliable new experimental animal model for a better understanding of caprine tuberculosis and future development of vaccine trials in this and other species.
Characterization of Bacterial Communities in Venous Insufficiency Wounds by Use of Conventional Culture and Molecular Diagnostic Methods
Authors: Tuttle Marie S. , Mostow Eliot , Mukherjee Pranab , Hu Fen Z. , Melton-Kreft Rachael , Ehrlich Garth D. , Dowd Scot E. , Ghannoum Mahmoud A.
Published: September 2011

Microbial infections delay wound healing, but the effect of the composition of the wound microbiome on healing parameters is unknown. To better understand bacterial communities in chronic wounds, we analyzed debridement samples from lower-extremity venous insufficiency ulcers using the following: conventional anaerobic and aerobic bacterial cultures; the Ibis T5000 universal biosensor (Abbott Molecular); and 16S 454 FLX titanium series pyrosequencing (Roche). Wound debridement samples were obtained from 10 patients monitored clinically for at least 6 months, at which point 5 of the 10 sampled wounds had healed. Pyrosequencing data revealed significantly higher bacterial abundance and diversity in wounds that had not healed at 6 months. Additionally,
Actinomycetales
was increased in wounds that had not healed, and
Pseudomonadaceae
was increased in wounds that had healed by the 6-month follow-up. Baseline wound surface area, duration, or analysis by Ibis or conventional culture did not reveal significant differences between wounds that healed after 6 months and those that did not. Thus, pyrosequencing identified distinctive baseline characteristics of wounds that did not heal by the 6-month follow-up, furthering our understanding of potentially unique microbiome characteristics of chronic wounds.
Comparative Utility of Cytokine Levels and Quantitative RD-1-Specific T Cell Responses for Rapid Immunodiagnosis of Tuberculous Meningitis
Authors: Patel Vinod B. , Singh Ravesh , Connolly Cathy , Kasprowicz Victoria , Ndung'u Thumbi , Dheda Keertan
Published: September 2011

The rapid diagnosis of tuberculous meningitis (TBM) is problematic. We found in 150 patients with suspected TBM that, similar to RD-1-specific quantitative cerebrospinal fluid (CSF) T-cell responses, unstimulated CSF gamma interferon (IFN-γ) levels when used together with other rapid confirmatory tests (Gram stain and cryptococcal latex agglutination test) may allow the accurate and rapid diagnosis of TBM in a setting in which tuberculosis (TB) and HIV are endemic. In resource-poor settings, a clinical prediction rule (CPR) may be useful to clinicians, and thus the IFN-γ assay may potentially need to be used only when the clinical score is below a prespecified threshold. These preliminary findings will need to be confirmed in further studies.
Prevalence and Density-Related Concordance of Three Diagnostic Tests for Malaria in a Region of Tanzania with Hypoendemic Malaria
Authors: Schachterle Stephen E. , Mtove George , Levens Joshua P. , Clemens Emily G. , Shi Lirong , Raj Amirita , Munoz Beatrice , Reller Megan E. , West Sheila , Dumler J. Stephen , Sullivan David ,   and the PRET Project Team
Published: September 2011

Accurate malaria diagnosis has dual roles in identification of symptomatic persons for effective malaria treatment and also enumeration of asymptomatic persons who contribute to the epidemiologic determinants of transmission. Three currently used diagnostic tests, microscopy, rapid diagnostic tests (RDTs), and real-time PCR, all have different sensitivities and specificities, which are parasite density dependent. Here, we compare their concordance among 451 febrile episodes in a cohort of 2,058 children and adults followed over 6 months in a region in central Tanzania with hypoendemic malaria. Microscopy, a histidine-rich protein-based RDT, and two different real-time PCR gene probes detected
Plasmodium falciparum
in 20, 54, 41, and 78 episodes of fever, respectively. They had complete concordance in only 9 episodes. Real-time PCR with an 18S probe was more sensitive than with a mitochondrial probe for cytochrome
b
despite higher copy numbers of mitochondrial DNA. Both PCR yields were increased 4-fold by glycogen/acetate precipitation with low-speed centrifugation. Duplicate PCR increases low-density malaria detection. RDT had the highest number of unique positives, presumably from persistent antigen despite the absence of parasites, although RDT did not detect 3 parasitemias with over 1,000 parasites/μl. In a latent class analysis, real-time PCR had significantly higher sensitivity than did microscopy or RDT. Agreement between real-time PCR, RDT, and microscopy was highest in March and April, when both the
P. falciparum
parasite rate and parasite densities are highest. Real-time PCR is more sensitive and specific than RDT and microscopy in low-prevalence, low-parasite-density settings.
Novel IS
711
Chromosomal Location Useful for Identification of Marine Mammal Brucella Genotype ST27, Which Is Associated with Zoonotic Infection
Authors: Cloeckaert Axel , Bernardet Nelly , Koylass Mark S. , Whatmore Adrian M. , Zygmunt Michel S.
Published: September 2011

We report a novel IS
711
chromosomal location that is specific for the
Brucella
genotype ST27 previously associated with Pacific marine mammals and human zoonotic infection in New Zealand and Peru. Our data support the previous observation that this peculiar genotype is distinct from those commonly isolated from the Atlantic and currently classified within the species
B. ceti
and
B. pinnipedialis
.
Lassa Virus Nucleoprotein Mutants Generated by Reverse Genetics Induce a Robust Type I Interferon Response in Human Dendritic Cells and Macrophages
Authors: Carnec Xavier , Baize Sylvain , Reynard Stéphanie , Diancourt Laure , Caro Valérie , Tordo Noel , Bouloy Michèle
Published: September 2011

Lassa virus (LASV;
Arenaviridae
) is responsible for severe hemorrhagic fevers in Africa. LASV nucleoprotein (NP) plays important roles in regulating viral transcription and replication and in inhibiting type I interferon (IFN) production. The NP C-terminal domain contains a 3′-to-5′ exonuclease activity involved in suppressing IFN induction. We have established a murine polymerase (Pol) I reverse genetics system for LASV, showing that residues D389 and G392 of NP were critical for LASV viability, while the D389A/G392A and D389T/392A double mutants were severely altered in the ability to suppress IFN in macrophages and dendritic cells. Assessing their attenuation
in vivo
may open new perspectives in vaccinology.
Adaptive and Innate Transforming Growth Factor β Signaling Impact Herpes Simplex Virus 1 Latency and Reactivation
Authors: Allen Sariah J. , Mott Kevin R. , Wechsler Steven L. , Flavell Richard A. , Town Terrence , Ghiasi Homayon
Published: September 2011

Innate and adaptive immunity play important protective roles by combating herpes simplex virus 1 (HSV-1) infection. Transforming growth factor β (TGF-β) is a key negative cytokine regulator of both innate and adaptive immune responses. Yet, it is unknown whether TGF-β signaling in either immune compartment impacts HSV-1 replication and latency. We undertook genetic approaches to address these issues by infecting two different dominant negative TGF-β receptor type II transgenic mouse lines. These mice have specific TGF-β signaling blockades in either T cells or innate cells. Mice were ocularly infected with HSV-1 to evaluate the effects of restricted innate or adaptive TGF-β signaling during acute and latent infections. Limiting innate cell but not T cell TGF-β signaling reduced virus replication in the eyes of infected mice. On the other hand, blocking TGF-β signaling in either innate cells or T cells resulted in decreased latency in the trigeminal ganglia of infected mice. Furthermore, inhibiting TGF-β signaling in T cells reduced cell lysis and leukocyte infiltration in corneas and trigeminal ganglia during primary HSV-1 infection of mice. These findings strongly suggest that TGF-β signaling, which generally functions to dampen immune responses, results in increased HSV-1 latency.
A Common Evolutionary Origin for Tailed-Bacteriophage Functional Modules and Bacterial Machineries
Authors: Veesler David , Cambillau Christian
Published: September 2011

Bacteriophages belonging to the order
Caudovirales
possess a tail acting as a molecular nanomachine used during infection to recognize the host cell wall, attach to it, pierce it, and ensure the high-efficiency delivery of the genomic DNA to the host cytoplasm. In this review, we provide a comprehensive analysis of the various proteins constituting tailed bacteriophages from a structural viewpoint. To this end, we had in mind to pinpoint the resemblances within and between functional modules such as capsid/tail connectors, the tails themselves, or the tail distal host recognition devices, termed baseplates. This comparison has been extended to bacterial machineries embedded in the cell wall, for which shared molecular homology with phages has been recently revealed. This is the case for the type VI secretion system (T6SS), an inverted phage tail at the bacterial surface, or bacteriocins. Gathering all these data, we propose that a unique ancestral protein fold may have given rise to a large number of bacteriophage modules as well as to some related bacterial machinery components.
Three-dimensional numerical modelling of discrete piles used to stabilize landslides
Authors: Kanagasabai S. , Smethurst J. A. , Powrie W.
Published: September 2011

Three-dimensional finite difference analyses have been carried out to investigate the behaviour of a single pile used to stabilize a slipping mass of soil by embedment into a stable stratum. Analyses were initially carried out to determine the reduction in the limiting pile–soil lateral force per metre length, pu, close to the unconfined ground surface. The analyses then explore the failure mechanisms for landslide stabilizing piles categorized by Viggiani. The effects of varying the strength of the slip plane interface between the sliding and stable strata, and of a sloping ground surface on the behaviour of the pile are then investigated. The results from numerical models with a rigid pile, a distinct plane of sliding, and a horizontal ground surface, as assumed by Viggiani, agree well with his theoretical mechanisms. Lower values of puclose to the ground surface and adjacent to the sliding plane are found to reduce the maximum shear resistance that piles can provide to the slipping mass when compared with Viggiani’s theoretical solutions. Further analyses show that the strength of the slip plane interface has a considerable influence on pile behaviour, and that the slope of the ground surface is only significant above a certain angle.
TGF-β1mediates sirolimus and cyclosporine A-induced alteration of barrier function in renal epithelial cells via a noncanonical ERK1/2 signaling pathway
Authors: Martin-Martin Natalia , Slattery Craig , McMorrow Tara , Ryan Michael P.
Published: September 2011

The immunosuppressant drugs cyclosporine A (CsA) and sirolimus (SRL) used in combination demonstrated beneficial effects in organ transplantation, but this combination can also result in increased adverse effects. We previously showed that not only CsA treatment but also its combination with SRL decreased paracellular permeability in renal proximal tubular cells by modification of the tight junction proteins, claudins, through ERK1/2 signaling pathway. In this present study, evidence is presented that not only CsA but also the combination of CsA/SRL may have adverse effects on the barrier function of renal proximal cells, at least in part, through the expression of the cytokine transforming growth factor (TGF)-β1. CsA treatment upregulated TGF-β1gene expression and this upregulation was enhanced when CsA and SRL were applied together. Addition of TGF-β1(5 ng/ml) altered the barrier function with increased transepithelial electrical resistance (TER) and claudin-1 expression. Use of a TGF-β1-blocking antibody or blockage of TGF-β1receptor kinase activity with SD208 prevented the CsA- and CsA/SRL-induced increase in TER. No evidence was found in the present studies to indicate that CsA or CsA/SRL treatment activated the TGF-β1Smad canonical signaling pathway, whereas addition of TGF-β1(5 ng/ml) did activate the Smad pathway. Addition of the ERK1/2 signaling inhibitor U0126 was able to prevent the TGF-β1-mediated increase in TER and claudin expression. It is most likely that the CsA- and CsA/SRL-induced increases in TGF-β1expression may not be sufficient to trigger the Smad pathway but however may trigger other TGF-β1receptor-mediated signaling including the ERK1/2 signaling pathway.
Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABAA receptors
Authors: Ji Guangchen , Neugebauer Volker
Published: September 2011

Pain-related hyperactivity in the amygdala leads to deactivation of the medial prefrontal cortex (mPFC) and decision-making deficits. The mechanisms of pain-related inhibition of the mPFC are not yet known. Here, we used extracellular single-unit recordings of prelimbic mPFC neurons to determine the role of GABAA receptors and metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5, in pain-related activity changes of mPFC neurons. Background and evoked activity of mPFC neurons decreased after arthritis induction. To determine pain-related changes, the same neuron was recorded continuously before and after induction of arthritis in one knee joint by intra-articular injection of kaolin/carrageenan. Stereotaxic administration of a GABAA receptor antagonist {[ R-( R*, S*)]-5-(6,8-dihydro-8-oxofuro[3,4- e]-1,3-benzodioxol-6-yl)-5,6,7,8-tetrahydro-6,6-dimethyl-1,3-dioxolo[4,5- g]isoquinolinium iodide (bicuculline)} into the mPFC by microdialysis reversed pain-related inhibition, whereas offsite injections into the adjacent anterior cingulate cortex had no or opposite effects on prelimbic mPFC neurons. A selective mGluR1/5 agonist [(S)-3,5-dihydroxyphenylglycine (DHPG)] inhibited background and evoked activity under normal conditions through a GABAergic mechanism, because the inhibitory effect was blocked with bicuculline. In the arthritis pain state, DHPG, alone or in the presence of bicuculline, had no effect. Consistent with the involvement of mGluR1 in pain-related inhibition of the mPFC, a selective mGluR1 antagonist [( S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid] reversed the pain-related decrease of background and evoked activity of mPFC neurons in arthritis, whereas a selective mGluR5 antagonist [2-methyl-6-(phenylethynyl)pyridine hydrochloride] had no effect. The mGluR antagonists had no effect under normal conditions. We interpret our data to suggest that pain-related inhibition of mPFC neurons in the arthritis model depends on mGluR1-mediated endogenous activation of GABAA receptors. Exogenous activation of mGluR1/5 produces GABAergic inhibition under normal conditions. Restoring normal activity in the mPFC may be a therapeutic strategy to improve cognitive deficits associated with persistent pain.