bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitoxin DinJ influences the general stress response through transcript stabilizer CspE
Authors: Hu Ying , Benedik Michael J. , Wood Thomas K.
Published: October 2011

Antitoxins are becoming recognized as proteins that regulate more than their own synthesis; for example, we found previously that antitoxin MqsA of the Escherichia coli toxin/antitoxin (TA) pair MqsR/MqsA directly represses the gene encoding the stationary‐phase sigma factor RpoS. Here, we investigated the physiological role of antitoxin DinJ of the YafQ/DinJ TA pair and found DinJ also affects the general stress response by decreasing RpoS levels. Corroborating the reduced RpoS levels upon producing DinJ, the RpoS‐regulated phenotypes of catalase activity, cell adhesins and cyclic diguanylate decreased while swimming increased. Using a transcriptome search and DNA‐binding assays, we determined that the mechanism by which DinJ reduces RpoS is by repressing cspE at the LexA palindrome; cold‐shock protein CspE enhances translation of rpoS mRNA. Inactivation of CspE abolishes the ability of DinJ to influence RpoS. Hence, DinJ influences the general stress response indirectly by regulating cspE.
Gaze aversion as a cognitive load management strategy in autism spectrum disorder and Williams syndrome
Authors: Doherty‐Sneddon Gwyneth , Riby Deborah M. , Whittle Lisa
Published: October 2011

Background:  During face‐to‐face questioning, typically developing children and adults use gaze aversion (GA), away from their questioner, when thinking. GA increases with question difficulty and improves the accuracy of responses. This is the first study to investigate whether individuals with autism spectrum disorder (ASD; associated with reduced sociability and atypical face gaze) and Williams syndrome (WS; associated with hypersociability and atypical face gaze) use GA to manage cognitive load during face‐to‐face interactions.

Methods:  Two studies were conducted exploring the typicality of GA during face‐to‐face questioning in (a) ASD and (b) WS.

Results:  In Study 1, children with ASD increased their GA as question difficulty increased. In addition, they used most GA when thinking about their responses to questions, mirroring evidence from typically developing children. An important atypicality for participants with ASD was a significantly higher level of GA when listening to interlocutors. In Study 2, participants with WS showed typical patterns of GA in relation to question difficulty and across different points of the interaction.

Conclusions:  Two different neuro‐developmental disorders, both characterized by significant problems with executive control of attention and atypicalities of social interactions, exhibited generally typical patterns of GA. All groups used most GA while thinking about questions, and increased their GA as questions got harder. In addition, children with ASD showed elevated levels of GA while listening to questions, but not while thinking about or making their responses, suggesting that they sometimes fail to see the relevance of attending to visual cues rather than actively avoiding them. Results have important implications for how professionals interpret GA in these populations and for social skills training.
Root aeration via aerenchymatous phellem: three‐dimensional micro‐imaging and radial O2 profiles in Melilotus siculus
Authors: Verboven Pieter , Pedersen Ole , Herremans Els , Ho Quang Tri , Nicolaï Bart M. , Colmer Timothy David , Teakle Natasha
Published: October 2011

Internal root aeration enables waterlogging‐tolerant species to grow in anoxic soil. Secondary aerenchyma, in the form of aerenchymatous phellem, is of importance to root aeration in some dicotyledonous species. Little is known about this type of aerenchyma in comparison with primary aerenchyma.

Micro‐computed tomography was employed to visualize, in three dimensions, the microstructure of the aerenchymatous phellem in roots of Melilotus siculus. Tissue porosity and respiration were also measured for phellem and stelar tissues. A multiscale, three‐dimensional, diffusion–respiration model compared the predicted O2 profiles in roots with those measured using O2 microelectrodes.

Micro‐computed tomography confirmed the measured high porosity of aerenchymatous phellem (44–54%) and the low porosity of stele (2–5%) A network of connected gas spaces existed in the phellem, but not within the stele. O2 partial pressures were high in the phellem, but fell below the detection limit in the thicker upper part of the stele, consistent with the poorly connected low porosity and high respiratory demand.

The presented model integrates and validates micro‐computed tomography with measured radial O2 profiles for roots with aerenchymatous phellem, confirming the existence of near‐anoxic conditions at the centre of the stele in the basal parts of the root, coupled with only hypoxic conditions towards the apex.
The cytoprotective effects of oleoylethanolamide in insulin‐secreting cells do not require activation of GPR119
Authors: Stone Virginia M , Dhayal Shalinee , Smith David M , Lenaghan Carol , Brocklehurst Katy J , Morgan Noel G
Published: October 2011

BACKGROUND AND PURPOSE β‐cells express a range of fatty acid‐responsive G protein‐coupled receptors, including GPR119, which regulates insulin secretion and is seen as a potential therapeutic target in type 2 diabetes. The long‐chain unsaturated fatty acid derivative oleoylethanolamide (OEA) is an endogenous agonist of GPR119 and, under certain conditions, some long‐chain unsaturated fatty acids can promote β‐cell cytoprotection. It is not known, however, if OEA is cytoprotective in β‐cells. The present study has examined this and determined whether GPR119 is involved.

METHODS Clonal rat insulin‐secreting cell lines, BRIN‐BD11 or INS‐1E, were exposed to fatty acids complexed with BSA. cAMP levels, insulin release and cell viability were measured. Protein expression was studied by Western blotting and receptor expression by RT‐PCR.

KEY RESULTS GPR119 was expressed in both BRIN‐BD11 and INS‐1E cells and OEA was cytoprotective in these cells. However, cytoprotection was not reproduced by any of a range of selective, synthetic ligands of GPR119. The cytoprotective response to OEA was lost during exposure to inhibitors of fatty acid amide hydrolase (FAAH) suggesting that OEA per se is not the cytoprotective species but that release of free oleate is required. Similar data were obtained with anandamide, which was cytoprotective only under conditions favouring release of free arachidonate.

CONCLUSIONS AND IMPLICATIONS Activation of GPR119 is not required to mediate the cytoprotective actions of OEA in BRIN‐BD11 or INS‐1E cells. Rather, OEA is internalised and subjected to hydrolysis by FAAH to release free oleate, which then mediates the cytoprotection.
Unilateral and Bilateral Laparoscopic Ovariectomy in 157 Mares: A Retrospective Multicenter Study
Authors: Röcken Michael , Mosel Gesine , Seyrek‐Intas Kamil , Seyrek‐Intas Deniz , Litzke F. , Verver Jorrit , Rijkenhuizen Astrid B.M.
Published: October 2011

Objective

To evaluate surgical techniques, perioperative complications and outcome of laparoscopic surgery for unilateral and bilateral ovariectomy in mares.

Study Design

Retrospective multicenter case series.

Animals

Mares (n = 157).

Methods

Indications for surgery were neutering, fertility problems, elimination of hormone‐related abnormal behavior, ovarian tumors as well as nonregressive ovarian hematomas or cysts. Ovariectomy (n = 206) were performed by a standard laparoscopic procedure in 157 standing sedated mares. Dissection and hemostasis were achieved by using either (1) a linear stapling device, (2) bipolar electrosurgical instruments, with or without a modified Roeder knot, (3) a vessel‐sealing system, or (4) a diode‐laser with ligation. For some larger ovarian masses (>20 cm diameter), a 2‐step surgical procedure was used with standing flank laparoscopic ovariectomy followed by ovarian retrieval through a median celiotomy. Surgical techniques, outcome, and perioperative complications of each method were recorded and analyzed.

Results

Laparoscopic dissection of the ovary was accomplished in all mares. Because of the size of the ovarian tumor (n = 7) or in 1 mare with behavioral problems (n = 1), the dissected ovary was removed through a median celiotomy under general anesthesia. Seventeen mares (10.8%) developed postoperative complications (eg, incisional drainage, incisional infection, seroma formation, dehiscence, transient fever and mild abdominal discomfort). All mares with flank incisional problems had ovarian size >12 cm and in 15 (88%) of these mares electrosurgical instruments were used for mesovarial dissection.

Conclusions

Laparoscopic ovariectomy in standing sedated mares provides good surgical access and is associated with low morbidity.
Psychotic experience subtypes, poor mental health status and help‐seeking behaviour in a community sample of young adults
Authors: Armando Marco , Nelson Barnaby , Yung Alison R. , Saba Riccardo , Monducci Elena , Dario Claudia , Righetti Valentino , Birchwood Maximilian , Fiori Nastro Paolo , Girardi Paolo
Published: October 2011

Background: Different subtypes of psychotic experiences (PEs) have been identified in clinical and non‐clinical samples. Researchers have considered these PEs to either be variations of personality or expressions of vulnerability to psychotic disorder. This study aimed to determine which particular subtypes of PEs were more likely to be associated with poor mental health status and help‐seeking behaviour in a non‐clinical sample of young adults.

Methods: The study was conducted on a community sample of 997 young adults. The prevalence of PEs and distress was measured using the Community Assessment of Psychic Experiences (CAPE), depressive and anxiety symptoms were measured using Beck Depression Inventory‐II and Beck Anxiety Inventory, and general functioning was measured using the General Health Questionnaire‐12. Factorial analysis of the CAPE positive dimension was conducted and correlations between factors and clinical variables were analysed.

Results: Four PE subtypes were identified: perceptual abnormalities, persecutory ideas (PI), bizarre experiences, and magical thinking. At least one high frequency PI was endorsed by 60.8% (n = 606) of the sample and proved to be significantly associated both with poor mental health status and help‐seeking behaviour.

Conclusion: PEs subtypes are differentially associated with various markers of poor mental health status. PI seem to have stronger psychopathological significance than other subtypes of PEs. Further longitudinal studies are required to extend these findings.
Moving from the Laboratory Bench to Patients’ Bedside: Considerations for Effective Therapy with Stem Cells
Authors: Sherman Lauren S. , Munoz Jessian , Patel Shyam A. , Dave Meneka A. , Paige Ilani , Rameshwar Pranela
Published: October 2011

Although stem cell therapy is not a new field, the field was limited to transplantation of hematopoietic stem cells. Such transplantation has provided invaluable information for the emerging field with new stem cells. Mesenchymal stem cells (MSCs) are an attractive source for therapy; reduced ethical concern, ease in expansion, as off‐the‐shelf stem cells. MSCs exert immune suppressive properties, providing them with the potential for immune suppressive therapy such as autoimmunity, asthma, allergic rhinitis and graft versus host disease. In addition, MSCs, as well as other stem cells, can be applied for bone and cartilage repair, cardiovascular disease, and neural repair/protection. The data thus far with MSCs are mixed. This review discusses the immune‐enhancing properties of MSCs to explain the possible confounds of inflammatory microenvironment in the MSCs therapy. Although this review focuses on MSCs, the information can be extrapolated to other stem cells. The review summarizes the biology of MSCs, including multilineage differentiation potential, transdifferentiation capability, and immunological effects. We emphasize the key concepts that may predict the use of these cells in medicine, namely, the application of these cells from the bench to the bedside. Prospects on immunotherapy, neuroregeneration, and cardiovascular repair are used as examples of tissue repair. Clin Trans Sci 2011; Volume 4: 380–386
Advancing Knowledge and Research: Developing a Doctoral Program in Clinical and Translational Science
Authors: Moore Debra W. , Dilmore Terri Collin , Robinson Georgeanna F. W. B.
Published: October 2011

In an emerging field, such as clinical and translational science, questions of purpose and educational philosophy are crucial to consider as programs, competencies, and milestones are developed and become generally accepted as broad national standards. This article outlines issues to be taken into account as curricula are planned, implemented, and evaluated. It also discusses how philosophy, competencies, and assessments, including milestones, must be intertwined purposefully, with careful attention paid to the integration of knowledge, skills, and attitudes. Clin Trans Sci 2011; Volume 4: 359–362
Axon‐Like Basal Processes in Enteroendocrine Cells: Characteristics and Potential Targets
Authors: Bohórquez Diego V. , Liddle Rodger A.
Published: October 2011

Enteroendocrine cells (EECs) play a key role in nutrient digestion and absorption, and are essential for normal life. Recently, EEC function has received considerable attention because several gastrointestinal hormones modulate insulin secretion and food intake; and, gut hormone‐based therapies have been developed to treat diabetes mellitus. Despite these advances, the regulation of EECs remains poorly understood. The development of transgenic mouse models that express green fluorescent proteins (GFP) under specific hormone promoters (e.g., peptide YY‐GFP) is shedding light onto previously overlooked features of EECs. These cells have prominent cytoplasmic processes that extend underneath enterocytes, and in some EECs, such as the L cell of the distal ileum, the basal process can be over 50 μm long. These basal cytoplasmic processes resemble axons and end in synaptic‐like bouton. The location and anatomy of these processes suggest two functions: (1) to monitor absorbed nutrients at the base of enterocytes; and (2) to convey electrochemical information through cell–cell connections with subepithelial myofibroblasts and/or nerves located directly beneath in the lamina propria. Understanding how EECs communicate with cells in the lamina propria may provide novel ways to treat metabolic disorders such as obesity and diabetes. Clin Trans Sci 2011; Volume 4: 387–391
Genetic Risk Score Does Not Correlate with Body Mass Index of Latina Women in a Clinical Trial
Authors: Coenen Kimberly R. , Karp Sharon M. , Gesell Sabina B. , Dietrich Mary S. , Morgan Thomas M. , Barkin Shari L.
Published: October 2011

Obesity disproportionately affects Latina women. Common genetic variants are convincingly associated with body mass index (BMI) and may be used to create genetic risk scores (GRS) for obesity that could define genetically influenced forms of obesity and alter response to clinical trial interventions. The objective of this study was (1) to identify the frequency and effect size of common obesity genetic variants in Latina women; (2) to determine the clinical utility of a GRS for obesity with Latina women participating in a community‐based clinical trial. DNA from 85 Latina women was genotyped for eight genetic variants previously associated with BMI in Caucasians, but not yet assessed in Latina populations. The main outcome measure was the correlation of GRS (sum of eight risk alleles) with BMI, waist circumference, and percent body fat. A majority (83%) of participants had a BMI ≥25. Frequency of loci near FTO, MC4R, and GNPDA2 were lower in Latinas than Caucasians. Association of each locus with BMI was lower in Latinas compared to Caucasians with no significant correlations with BMI. We conclude that an eight locus GRS has no clinical utility for explaining obesity or predicting response to intervention in Latina women participating in a clinical trial. Clin Trans Sci 2011; Volume 4: 323–327
Patient Electronic Health Data–Driven Approach to Clinical Decision Support
Authors: Mane Ketan K. , Bizon Chris , Owen Phillips , Gersing Ken , Mostafa Javed , Schmitt Charles
Published: October 2011

This article presents a novel visual analytics (VA)‐based clinical decision support (CDS) tool prototype that was designed as a collaborative work between Renaissance Computing Institute and Duke University. Using Major Depressive Disorder data from MindLinc electronic health record system at Duke, the CDS tool shows an approach to leverage data from comparative population (patients with similar medical profile) to enhance a clinicians’ decision making process at the point of care. The initial work is being extended in collaboration with the University of North Carolina CTSA to address the key challenges of CDS, as well as to show the use of VA to derive insight from large volumes of Electronic Health Record patient data. Clin Trans Sci 2011; Volume 4: 369–371
Recommendations for Planning Pilot Studies in Clinical and Translational Research
Authors: Moore Charity G. , Carter Rickey E. , Nietert Paul J. , Stewart Paul W.
Published: October 2011

Advances in clinical and translation science are facilitated by building on prior knowledge gained through experimentation and observation. In the context of drug development, preclinical studies are followed by a progression of phase I through phase IV clinical trials. At each step, the study design and statistical strategies are framed around research questions that are prerequisites for the next phase. In other types of biomedical research, pilot studies are used for gathering preliminary support for the next research step. However, the phrase “pilot study” is liberally applied to projects with little or no funding, characteristic of studies with poorly developed research proposals, and usually conducted with no detailed thought of the subsequent study. In this article, we present a rigorous definition of a pilot study, offer recommendations for the design, analysis and sample size justification of pilot studies in clinical and translational research, and emphasize the important role that well‐designed pilot studies play in the advancement of science and scientific careers. Clin Trans Sci 2011; Volume 4: 332–337
Using Electronically Available Inpatient Hospital Data for Research
Authors: Apte Mandar , Neidell Matthew , Yoko Furuya E. , Caplan David , Glied Sherry , Larson Elaine
Published: October 2011

Despite a push to create electronic health records and a plethora of healthcare data from disparate sources, there are no data from a single electronic source that provide a full picture of a patient’s hospital course. This paper describes a process to utilize electronically available inpatient hospital data for research. We linked several different sources of extracted data, including clinical, procedural, administrative, and accounting data, using patients’ medical record numbers to compile a cohesive, comprehensive account of patient encounters. Challenges encountered included (1) interacting with distinct administrative units to locate data elements; (2) finding a secure, central location to house the data; (3) appropriately defining health measures of interest; (4) obtaining and linking these data to create a usable format for conducting research; and (5) dealing with missing data. Although the resulting data set is incredibly rich and likely to prove useful for a wide range of clinical and comparative effectiveness research questions, there are multiple challenges associated with linking hospital data to improve the quality of patient care. Clin Trans Sci 2011; Volume 4: 338–345
Children's event reports: Factors affecting responses to repeated questions in vignette scenarios and event recall interviews
Authors: Howie Pauline , Nash Laura , Kurukulasuriya Nadezhda , Bowman Alison
Published: October 2011

When adults repeat questions, children often give inconsistent answers. This study aimed to test the claim that these inconsistencies occur because children infer that their first answer was unsatisfactory, and that the adult expects them to change their answer. Children aged 4, 6, and 8 years (N= 134) were asked about vignettes in which an adult repeated a question, with manipulation of the adult's overt dissatisfaction (high vs. low pressure) and knowledge about the information sought. On a separate occasion, the children were given an unrelated event recall interview containing repeated questions. All age groups showed sensitivity to adult dissatisfaction, interpreting question repetition as an implicit request for answer change more frequently in the high than in the low‐pressure vignettes. Overall, however, these ‘change‐expected’ interpretations were least frequent in the younger children, who were the most prone to shifting. Also there was no evidence that these interpretations were associated with more frequent shifting in the recall interview. The results do not provide clear support for a simple conversational inference account of shifting, especially in younger children.
Effects of the magnetic field strength on the modulated pulsed power magnetron sputtering of metallic films
Authors: Lin Jianliang , Moore John J. , Sproul William D. , Lee S. L.
Published: October 2011

The influence of the magnetic field strength (B) on the deposition rate and plasma properties for Ta, Cr, Ti, Al, Cu materials using the modulated pulsed power (MPP) magnetron sputtering technique in a closed field unbalanced magnetron sputtering system was investigated. The MPP deposition rates were compared to those obtained from the films deposited by direct current magnetron sputtering (DCMS) under similar experimental conditions. The time averaged ion energy and mass distributions of positive ions in the MPP plasmas at different magnetic field strengths were compared, using a Hiden electrostatic quadrupole plasma mass spectrometer. The effects of the repetition frequency and pulse length on the MPP deposition rate were investigated. For a given target power, the MPP deposition rate increased when the repetition frequency was increased. It also increased as the pulse length was increased at a constant repetition frequency and target power. The MPP deposition rate is strongly material dependent. The MPP deposition rate increased as B decreased for a given target power. For a B of 550 G, the RMPP/RDCMS ratio for Cu was in a range of 0.81–1.02, for Al it was 0.84–1.01, for Cr it was 0.64–1.01, for Ti it was 0.52–0.89, and for Ta it was 0.47–0.84. For a B of 350 G, the RMPP/RDCMS ratio for Cu was increased to 1.03–1.07, for Al it was 0.94–1.04, for Cr it was 0.8–1.03, for Ti it was 0.79–0.94, and for Ta it was 0.72–0.88. However, a decrease in the ionization of metal and gas species was observed as B was decreased, which affected the microstructure and mechanical properties of the deposited Cr films.
Making a hybrid microfluidic platform compatible for in situ imaging by vacuum-based techniques
Authors: Yang Li , Yu Xiao-Ying , Zhu Zihua , Thevuthasan Theva , Cowin James P.
Published: October 2011

A self-contained microfluidic-based device was designed and fabricated for in situ imaging of aqueous surfaces using vacuum techniques. The device is a hybrid between a microfluidic poly(dimethyl siloxane) block and external accessories, all portable on a small platform (10 × 8 cm2). The key feature is that a small aperture with a diameter of 2-3 μm is opened to the vacuum, which serves as a detection window for in situ imaging of aqueous surfaces. Vacuum compatibility and temperature drop due to water vaporization are the two most important challenges in this invention. Theoretical calculations and fabrication strategies are presented from multiple design aspects. In addition, results from the time-of-flight secondary ion mass spectrometry and scanning electron microscopy of aqueous surfaces are presented.
Dosimetry of a new P‐32 ophthalmic applicator
Authors: Choi Chang Heon , Han Hyon Soo , Son Kwang‐Jae , Park Ul Jae , Lee Jun Sig , Wee Won Ryang , Ha Sung Whan , Kim Il Han , Ye Sung‐Joon
Published: October 2011

Purpose:

The potential of P‐32 ophthalmic applicator irradiation after pterygium excision has been demonstrated as an alternative to Sr/Y‐90 irradiation. This study aimed to provide the clinical dosimetry for this new applicator.

Methods:

The prototype of a cylindrical P‐32 applicator was fabricated according to the Monte Carlo (MC)‐based design study. At a nominal activity of 6 mCi (0.22 GBq), the absorbed dose rate at the front surface (i.e., reference dose rate) was measured by using an extrapolation ionization chamber (EC). The radiochromic film (RCF) was also used to measure the reference dose, axial depth dose distributions and transaxial dose profiles at various depths in water.

Results:

The reference dose rate was 3.89 ± 0.14 cGy/s for EC and 3.84 ± 0.25 cGy/s for RCF. The depth dose rate was reduced approximately by an order of magnitude for every 2 mm depth in water. Measured depth doses in depths of 0.5–2.5 mm agreed with Monte Carlo data within ±3%. Due to nonuniform absorption of P‐32 into an absorbent disk, the dose profiles were not symmetric and decreased more rapidly toward the periphery than those predicted by the MC. The authors confirmed no leakage of P‐32 activities and negligible exposure rate around the hand grip of the applicator.

Conclusions

: The P‐32 applicator can deliver therapeutic doses to the surface of the conjunctiva, while sparing the lens better than Sr/Y‐90 applicators. The doses at any points from the P‐32 applicator could be calculated by using the measured dosimetry data. They also confirmed no leakage of the source, reliable integrity of the applicator, and negligible exposure level around the hand grip of the applicator. However, due to a possibility of nonuniform distributions of P‐32 in an absorbent disk, measuring dose profiles as well as the reference dose rate for every new applicator would be recommended.
Automated 3‐dimensional segmentation of pelvic lymph nodes in magnetic resonance images
Authors: Debats O. A. , Litjens G. J. S. , Barentsz J. O. , Karssemeijer N. , Huisman H. J.
Published: October 2011

Purpose:

Computer aided diagnosis (CAD) of lymph node metastases may help reduce reading time and improve interpretation of the large amount of image data in a 3‐D pelvic MRI exam. The purpose of this study was to develop an algorithm for automated segmentation of pelvic lymph nodes from a single seed point, as part of a CAD system for the classification of normal vs metastatic lymph nodes, and to evaluate its performance compared to other algorithms.

Methods:

The authors' database consisted of pelvic MR images of 146 consecutive patients, acquired between January 2008 and April 2010. Each dataset included four different MR sequences, acquired after infusion of a lymph node specific contrast medium based on ultrasmall superparamagnetic particles of iron oxide. All data sets were analyzed by two expert readers who, reading in consensus, annotated and manually segmented the lymph nodes. The authors compared four segmentation algorithms: confidence connected region growing (CCRG), extended CCRG (ECC), graph cut segmentation (GCS), and a segmentation method based on a parametric shape and appearance model (PSAM). The methods were ranked based on spatial overlap with the manual segmentations, and based on diagnostic accuracy in a CAD system, with the experts' annotations as reference standard.

Results:

A total of 2347 manually annotated lymph nodes were included in the analysis, of which 566 contained a metastasis. The mean spatial overlap (Dice similarity coefficient) was: 0.35 (CCRG), 0.57 (ECC), 0.44 (GCS), and 0.46 (PSAM). When combined with the classification system, the area under the ROC curve was: 0.805 (CCRG), 0.890 (ECC), 0.807 (GCS), 0.891 (PSAM), and 0.935 (manual segmentation).

Conclusions:

We identified two segmentation methods, ECC and PSAM, that achieve a high diagnostic accuracy when used in conjunction with a CAD system for classification of normal vs metastatic lymph nodes. The manual segmentations still achieve the highest diagnostic accuracy.
The Impact of a Consortium of Fermented Milk Strains on the Gut Microbiome of Gnotobiotic Mice and Monozygotic Twins
Authors: McNulty Nathan P. , Yatsunenko Tanya , Hsiao Ansel , Faith Jeremiah J. , Muegge Brian D. , Goodman Andrew L. , Henrissat Bernard , Oozeer Raish , Cools-Portier Stéphanie , Gobert Guillaume , Chervaux Christian , Knights Dan , Lozupone Catherine A. , Knight Rob , Duncan Alexis E. , Bain James R. , Muehlbauer Michael J. , Newgard Christopher B. , Heath Andrew C. , Gordon Jeffrey I.
Published: October 2011

Metagenomic analyses of gnotobiotic mice and monozygotic twins reveal the effects of eating a popular fermented milk product on their microbiomes.
Tackling TIA
Authors: Boxer Rebecca S.
Published: October 2011

A 34-gene expression signature identifies patients who have suffered a transient ischemic attack with 100% sensitivity and 100% specificity.
With This Ring
Authors: Emadi Ashkan
Published: October 2011

Messenger RNA splicing mutations are frequent in myelodysplastic syndromes with ring sideroblasts and predict better prognosis and survival.
Bioterrorism: Lessons Learned Since the Anthrax Mailings
Authors: Imperiale Michael J. , Casadevall Arturo
Published: October 2011

In the fall of 2001,
Bacillus anthracis
spores were spread through letters mailed in the United States. Twenty-two people are known to have been infected, and five of these individuals died. Together with the  September 11 attacks, this resulted in a reevaluation of the risks and benefits of life science research with the potential for misuse. In this editorial, we review some of the results of these discussions and their implications for the future.
A decompositional analysis of the relative contribution of age, sex and methods of suicide to the changing patterns of suicide in Taipei City, 2004–2006
Authors: Yip Paul S F , Caine Eric D , Kwok Raymond C L , Chen Ying-Yeh
Published: October 2011

Background

Taipei has seen a substantial increase in suicide rates during the past decade, with a significant rise between 2004 and 2006, the time of this study period.

Methods

A decompositional analytic method was used to quantify the relative contributions of age, sex and case fatality of methods to attempts and suicides.

Results

From 2004 to 2006, the rate of fatal and non-fatal suicide attempts combined for population aged 15 years or above in Taipei increased by 37.3%, while the suicide rate increased by 29.2%. Three factors in these analyses contributed to the increase in suicide rates: (1) an increase in number of attempts, (2) a greater proportion of men among fatal and non-fatal attempts and (3) an increase in the use of a lethal method—burning of charcoal to produce carbon monoxide. The authors estimated that 74.5% and 25.6% among men and women, respectively, of the overall increased suicide mortality were attributable to increased ‘charcoal burning suicides.’

Conclusions

The rise in suicide rate reflected an increase in attempts and an influx of working-age men joining the pool of people attempting suicide. The much larger size of the attempter pool had the effect of reducing the case fatality even as the suicide rate climbed. The increase in the number of suicide attempts and the rise in the suicide rate were age-, sex-, and method-specific. These results strongly support the concept that reducing the total number of attempts is a central element to curbing suicides.
Effect of maternal age and growth on placental nutrient transport: potential mechanisms for teenagers' predisposition to small-for-gestational-age birth?
Authors: Hayward Christina E. , Greenwood Susan L. , Sibley Colin P. , Baker Philip N. , Challis John R. G. , Jones Rebecca L.
Published: October 2011

Teenagers have an increased risk of delivering small-for-gestational-age (SGA) infants. Young maternal age and continued skeletal growth have been implicated as causal factors. In growing adolescent sheep, impaired placental development and nutrient transfer cause reduced birth weight. In human pregnancies, SGA is associated with reduced placental amino acid transport. Maternal growth has no effect on placental morphology or cell turnover, but growing teenagers have higher birth weight:placental weight ratios than nongrowing teenagers. We hypothesized that placental nutrient transporter activity would be affected by maternal age and/or growth status. Placentas from teenagers and adults were collected. Teenagers were defined as growing or nongrowing based on knee height measurements. System A amino acid transporter activity was quantified as sodium-dependent uptake of [14C]methylaminoisobutyric acid into placental fragments. Teenagers had lower placental system A activity than adults ( P < 0.05). In adults, placental system A activity was lower in SGA infants than appropriate-for-gestational-age (AGA) infants ( P < 0.05). In teenagers, AGA and SGA infants had lower placental system A activity than AGA infants born to adults ( P < 0.05). Placental system A activity was higher in growing teenagers than in nongrowing teenagers ( P < 0.001). Placental mRNA expression of system A transporter isoforms SLC38A1 and -2 was lower in teenagers than in adults ( P < 0.05) but did not differ between growing and nongrowing teenagers. There was no difference in transporter protein expression/localization between cohorts. Teenagers have inherently reduced placental transport, which may underlie their susceptibility to delivering SGA infants. Growing teenagers appear to overcome this susceptibility by stimulating the activity, but not expression, of system A transporters.
Insulin resistance after a 72-h fast is associated with impaired AS160 phosphorylation and accumulation of lipid and glycogen in human skeletal muscle
Authors: Vendelbo M. H. , Clasen B. F. F. , Treebak J. T. , Møller L. , Krusenstjerna-Hafstrøm T. , Madsen M. , Nielsen T. S. , Stødkilde-Jørgensen H. , Pedersen S. B. , Jørgensen J. O. L. , Goodyear L. J. , Wojtaszewski J. F. P. , Møller N. , Jessen N.
Published: October 2011

During fasting, human skeletal muscle depends on lipid oxidation for its energy substrate metabolism. This is associated with the development of insulin resistance and a subsequent reduction of insulin-stimulated glucose uptake. The underlying mechanisms controlling insulin action on skeletal muscle under these conditions are unresolved. In a randomized design, we investigated eight healthy subjects after a 72-h fast compared with a 10-h overnight fast. Insulin action on skeletal muscle was assessed by a hyperinsulinemic euglycemic clamp and by determining insulin signaling to glucose transport. In addition, substrate oxidation, skeletal muscle lipid content, regulation of glycogen synthesis, and AMPK signaling were assessed. Skeletal muscle insulin sensitivity was reduced profoundly in response to a 72-h fast and substrate oxidation shifted to predominantly lipid oxidation. This was associated with accumulation of both lipid and glycogen in skeletal muscle. Intracellular insulin signaling to glucose transport was impaired by regulation of phosphorylation at specific sites on AS160 but not TBC1D1, both key regulators of glucose uptake. In contrast, fasting did not impact phosphorylation of AMPK or insulin regulation of Akt, both of which are established upstream kinases of AS160. These findings show that insulin resistance in muscles from healthy individuals is associated with suppression of site-specific phosphorylation of AS160, without Akt or AMPK being affected. This impairment of AS160 phosphorylation, in combination with glycogen accumulation and increased intramuscular lipid content, may provide the underlying mechanisms for resistance to insulin in skeletal muscle after a prolonged fast.
Catecholamine and insulin control of lipolysis in subcutaneous adipose tissue during long-term diet-induced weight loss in obese women
Authors: Koppo Katrien , Siklová-Vitková Michaela , Klimčáková Eva , Polák Jan , Marques Marie A. , Berlan Michel , Van de Voorde Johan , Bulow Jens , Langin Dominique , de Glisezinski Isabelle , Stich Vladimir
Published: October 2011

The aim of this study was to investigate the evolution of the adrenergic and insulin-mediated regulation of lipolysis during different phases of a 6-mo dietary intervention. Eight obese women underwent a 6-mo dietary intervention consisting of a 1-mo very low-calorie diet (VLCD) followed by a 2-mo low-calorie diet (LCD) and 3-mo weight maintenance (WM) diet. At each phase of the dietary intervention, microdialysis of subcutaneous adipose tissue (SCAT) was performed at rest and during a 3-h hyperinsulinemic euglycemic clamp. Responses of dialysate glycerol concentration (DGC) were determined at baseline and during local perfusions with adrenaline or adrenaline and phentolamine before and during the last 30 min of the clamp. Dietary intervention induced a body weight reduction and an improved insulin sensitivity. DGC progressively decreased during the clamp, and this decrease was similar during the different phases of the diet. The adrenaline-induced increase in DGC was higher at VLCD and LCD compared with baseline condition and returned to prediet levels at WM. In the probe with adrenaline and phentolamine, the increase in DGC was higher than that in the adrenaline probe at baseline and WM, but it was not different at VLCD and LCD. The results suggest that the responsiveness of SCAT to adrenaline-stimulated lipolysis increases during the calorie-restricted phases due to a reduction of the α2-adrenoceptor-mediated antilipolytic action of adrenaline. At WM, adrenaline-stimulated lipolysis returned to the prediet levels. Furthermore, no direct relationship between insulin sensitivity and the diet-induced changes in the regulation of lipolysis was found.
Testosterone regulates smooth muscle contractile pathways in the rat prostate: emphasis on PDE5 signaling
Authors: Zhang Xinhua , Zang Ning , Wei Yu , Yin Jin , Teng Ruobing , Seftel Allen , DiSanto Michael E.
Published: October 2011

Testosterone (T) plays a permissive role in the development of benign prostatic hyperplasia (BPH), and phosphodiesterase 5 inhibitors (PDE5is) have been found to be effective for BPH and lower urinary tract symptoms (LUTS) in clinical trials. This study investigated the effect of T on smooth muscle (SM) contractile and regulatory signaling pathways, including PDE5 expression and functional activity in prostate in male rats (sham-operated, surgically castrated, and castrated with T supplementation). In vitro organ bath studies, real-time RT-PCR, Western blot analysis, and immunohistochemistry were performed. Castration heavily attenuated contractility, including sensitivity to phenylephrine with SM myosin immunostaining revealing a disrupted SM cell arrangement in the stroma. PDE5 was immunolocalized exclusively in the prostate stroma, and orchiectomy signficantly reduced PDE5 immunopositivity, mRNA, and protein expression, along with nNOS and ROKβ mRNA, whereas it increased eNOS plus α1aand α1badrenoreceptor expression in castrated animals. The PDE5i zaprinast significantly increased prostate strip relaxation to the nitric oxide donor sodium nitroprusside (SNP) in control but not castrated rats. But SNP alone was more effective on castrated rats, comparable with sham treated with SNP plus zaprinast. T supplementation prevented or restored all above changes, including SNP and zaprinast in vitro responsiveness. In conclusion, our data show that T positively regulates PDE5 expression and functional activities in prostate, and T ablation not only suppresses prostate size but also reduces prostatic SM contractility, with several potential SM contraction/relaxation pathways implicated. Zaprinast findings strongly suggest a major role for PDE5/cGMP in this signaling cascade. PDE5 inhibition may represent a novel mechanism for treatment of BPH.
Activation of mTOR/p70S6 kinase by ANG II inhibits insulin-stimulated endothelial nitric oxide synthase and vasodilation
Authors: Kim Jeong-a , Jang Hyun-Ju , Martinez-Lemus Luis A. , Sowers James R.
Published: October 2011

Elevated tissue levels of angiotensin II (ANG II) are associated with impairment of insulin actions in metabolic and cardiovascular tissues. ANG II-stimulated activation of mammalian target of rapamycin (mTOR)/p70 S6 kinase (p70S6K) in cardiovascular tissues is implicated in cardiac hypertrophy and vascular remodeling. However, the role of ANG II-stimulated mTOR/p70S6K in vascular endothelium is poorly understood. In the present study, we observed that ANG II stimulated p70S6K in bovine aortic endothelial cells. ANG II increased phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser636/639and inhibited the insulin-stimulated phosphorylation of endothelial nitric oxide synthase (eNOS). An inhibitor of mTOR, rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 (Ser636/639) and blocked the ability of ANG II to impair insulin-stimulated phosphorylation of eNOS, nitric oxide production, and mesenteric-arteriole vasodilation. Moreover, point mutations of IRS-1 at Ser636/639to Ala prevented the ANG II-mediated inhibition of insulin signaling. From these results, we conclude that activation of mTOR/p70S6K by ANG II in vascular endothelium may contribute to impairment of insulin-stimulated vasodilation through phosphorylation of IRS-1 at Ser636/639. This ANG II-mediated impairment of vascular actions of insulin may help explain the role of ANG II as a link between insulin resistance and hypertension.
Dietary supplementation with vitamin E and C attenuates dexamethasone-induced glucose intolerance in rats
Authors: Williams Deon B. , Wan Zhongxiao , Frier Bruce C. , Bell Rhonda C. , Field Catherine J. , Wright David C.
Published: October 2011

Glucocorticoid excess induces marked insulin resistance and glucose intolerance. A recent study has shown that antioxidants prevent dexamethasone (DEX)-induced insulin resistance in cultured adipocytes. The purpose of this investigation was to examine the effects of dietary vitamin E and C (Vit E/C) supplementation on DEX-induced glucose intolerance in rats. We hypothesized that feeding rats a diet supplemented with Vit E/C would improve glucose tolerance and restore insulin signaling in skeletal muscle, adipose, and liver and prevent alterations in AMPK signaling in these tissues. Male Wistar rats received either a control or Vit E/C-supplemented diet (0.5 g/kg diet each of l-ascorbate and dl-all rac-alpha-tocopherol) for 9 days prior to, and during, 5 days of daily DEX treatment (subcutaneous injections 0.8 mg/g body wt). DEX treatment resulted in increases in the glucose and insulin area under the curve (AUC) during an intraperitoneal glucose tolerance test. The glucose, but not insulin, AUC was lowered with Vit E/C supplementation. Improvements in glucose tolerance occurred independent of a restoration of PKB phosphorylation in tissues of rats stimulated with an intraperitoneal injection of insulin but were associated with increases in AMPK signaling in muscle and reductions in AMPK signaling and the expression of fatty acid oxidation enzymes in liver. There were no differences in mitochondrial enzymes in triceps muscles between groups. This study is the first to report that dietary Vit E/C supplementation can partially prevent DEX-induced glucose intolerance in rats.
Differential modulation of neurons in the rostral ventromedial medulla by neurokinin-1 receptors
Authors: Brink Thaddeus S. , Pacharinsak Cholawat , Khasabov Sergey G. , Beitz Alvin J. , Simone Donald A.
Published: October 2011

The rostral ventromedial medulla (RVM) is part of descending circuitry that modulates nociceptive processing at the level of the spinal cord. RVM output can facilitate pain transmission under certain conditions such as inflammation, and thereby contribute to hyperalgesia. Evidence suggests that substance P and activation of neurokinin-1 (NK-1) receptors in the RVM are involved in descending facilitation of nociception. We showed previously that injection of NK-1 receptor antagonists into the RVM attenuated mechanical and heat hyperalgesia produced by intraplantar injection of capsaicin. Furthermore, intraplantar injection of capsaicin excited ON cells in the RVM and inhibited ongoing activity of OFF cells. In the present studies, we therefore examined changes in responses of RVM neurons to mechanical and heat stimuli after intraplantar injection of capsaicin and determined the role of NK-1 receptors by injecting a NK-1 receptor antagonist into the RVM prior to capsaicin. After capsaicin injection, excitatory responses of ON cells and inhibitory responses of OFF cells evoked by mechanical and heat stimuli applied to the injected, but not contralateral, paw were increased. Injection of the NK-1 antagonist L-733,060 did not alter evoked responses of ON or OFF cells but attenuated the capsaicin-evoked enhanced responses of ON cells to mechanical and heat stimuli with less of an effect on the enhanced inhibitory responses of OFF cells. These data support the notion that descending facilitation from RVM contributes to hyperalgesia and that NK-1 receptors, presumably located on ON cells, play an important role in initiating descending facilitation of nociceptive transmission.
Acute milk yield response to frequent milking during early lactation is mediated by genes transiently regulated by milk removal
Authors: Wall E. H. , Bond J. P. , McFadden T. B.
Published: October 2011

Milking dairy cows four times daily (4×) instead of twice daily (2×) during early lactation stimulates an increase in milk yield that partly persists through late lactation; however, the mechanisms behind this response are unknown. We hypothesized that the acute mammary response to regular milkings would be transient and would involve different genes from those that may be specifically regulated in response to 4×. Nine multiparous cows were assigned at parturition to unilateral frequent milking (UFM; 2× of the left udder half, 4× of the right udder half). Mammary biopsies were obtained from both rear quarters at 5 days in milk (DIM), immediately after 4× glands had been milked ( experiment 1, n = 4 cows), or 2.5 h after both udder halves had last been milked ( experiment 2, n = 5 cows). Affymetrix GeneChip Bovine Genome Arrays were used to measure gene expression. We found 855 genes were differentially expressed in mammary tissue between 2× vs. 4× glands of cows in experiment 1 (false discovery rate ≤ 0.05), whereas none were differentially expressed in experiment 2 using the same criterion. We conclude that there is an acute transcriptional response to milk removal, but 4× milking did not elicit differential expression of unique genes. Therefore, there does not appear to be a sustained transcriptional response to 4× milking on day 5 of lactation. Using a differential expression plot of data from both experiments, as well as qRT-PCR, we identified at least two genes (chitinase 3-like-1 and low-density lipoprotein-related protein-2 that may be responsive to both milk removal and to 4× milking. Therefore, the milk yield response to 4× milking may be mediated by genes that are acutely regulated by removal of milk from the mammary gland.