bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Francisella tularensis AcpB Acid Phosphatase Substrate Preferences
Authors: Crowe Evan , Valladares Ricardo , Vu Clara , Kuznetsova Ekaterina , Gonzalez Claudio F.
Published: October 2010

The Francisella speciesencode 4 main acid phosphatases (Acp) that are potentially involved in pathogenesis through currently unknown mechanisms. Only 2 of these enzymes, AcpA and AcpC, have been biochemically characterized to date. In this work we describe the catalytic properties of Francisella tularensis AcpB utilizing an array of 120 phosphorylated substrates. In contrast to most acid phosphatases, the purified enzyme showed a narrow range of substrate preferences, with the highest affinity towards thiamine phosphate (Km = 150 µM). Francisella species do not possess a thiamine biosynthetic pathway even though vitamin B1 is indispensable in numerous cellular functions. Consequently, thiamine should be incorporated from the environment, in this case, from the host cell. Our results suggested that AcpB could provide the hydrolytic activity necessary to transform the nontransportable phosphorylated vitamin B1 present in tissues to a form that can be absorbed by the intracellular pathogen.
Proinflammatory and Proadhesive Activation of Lymphocytes and Macrophages in Sudden Sensorineural Hearing Loss
Authors: Kassner Stefan S. , Schöttler Sarah , Bonaterra Gabriel A. , Stern-Sträter Jens , Sommer Ulrich , Hormann Karl , Kinscherf Ralf , Gössler Ulrich R.
Published: October 2010

Even though sudden sensorineural hearing loss (SHL) is a quite frequent disease, the pathogenetic processes leading to it are widely unknown. There is increasing evidence that immunomodulatory cells, especially T lymphocytes, might be involved. Twelve patients with acute SHL and 12 healthy, age-matched individuals were included in this study. In addition to routine blood parameters, plasma levels of tumor necrosis factor alpha (TNF-α), soluble CD40 (sCD40) and sCD40 ligand (sCD40L) were determined by ELISA. Moreover, peripheral blood mononuclear cells were isolated by Ficoll density gradient. Afterwards, in subpopulations – identified by CD14 (monocytes), CD68 (macrophages), CD3 (T lymphocytes) or CD19 (B lymphocytes) immunoreactivity – proinflammatory (CD40, TNF-α or cyclooxygenase-2) and proadhesive (CD38) proteins were measured by 2-color fluorescence-activated cell sorter analyses. In comparison with healthy individuals, patients with acute SHL revealed elevated plasma levels of sCD40 and sCD40L and a significantly decreased percentage (36%) of lymphocytes, especially of T lymphocytes (28%). Additionally, in patients with acute SHL the percentage of proinflammatory CD40, TNF-α, cyclooxygenase-2 or CD38-positive T or B lymphocytes was significantly increased. Our data suggest an enhanced extravasation of proadhesive and proinflammatory lymphocytes from the peripheral circulation, which may contribute to SHL disease induction as well as progression and, thus, may be suggested as a novel therapeutical target.
Everything You Always Wanted to Know about Sex ... in Flies
Authors: Arbeitman M.N. , Kopp A. , Siegal M.L. , Van Doren M.
Published: October 2010

‘Everything you always wanted to know about sex’ is a workshop organized as part of the annual Drosophila Research Conference of the Genetics Society of America. This workshop provides an intellectual venue for interaction among research groups that study sexual dimorphism from the molecular, evolutionary, genomic, and behavioral perspectives. The speakers summarize the key ideas behind their research for people working in other fields, outline unsolved questions, and offer their opinions about future directions. The 2010 workshop highlighted the power of the Drosophila model for understanding sexual dimorphism at levels ranging from cell biology and gene regulation to population genetics and genome evolution, and demonstrated the importance of cross-disciplinary interactions in the study of sex. In this respect, Drosophila sets a good example for research in other organisms, including humans and their mammalian relatives.
Membrane Topology Analysis of the Escherichia coli Aromatic Amino Acid Efflux Protein YddG
Authors: Airich Larisa G. , Tsyrenzhapova Irina S. , Vorontsova Olga V. , Feofanov Alexey V. , Doroshenko Vera G. , Mashko Sergey V.
Published: October 2010

YddG is an inner membrane protein (IMP) that exports aromatic amino acids in Escherichia coli. Topology models of YddG produced by sequence-based analysis in silico have predicted the presence of 9 or 10 potential transmembrane segments. To experimentally analyze the membrane topology of YddG, we used randomly created fusions to β-lactamase (BlaM) as a reporter. The selection of such fusions under 50 µg/ml of ampicillin had to fit with the periplasmic location of the BlaM domain. Five periplasmic loops of YddG predicted by the 10-transmembrane (TM) helices model were identified via the characterization of 12 unique in-frame fusions distributed along the yddG coding region. To confirm the 10-TM helices model further, cytoplasmic regions of YddG were identified with the help of ZsGreen fluorescent protein as a reporter. The presence of four cytoplasmic regions and the cytoplasmic localization of the C-terminus were revealed. Therefore, a 10-TM helices topology with cytoplasmic locations of the N- and C-termini is supported. The present data confirm the ‘positive-inside rule’ for IMPs and the early results of other workers regarding the cytoplasmic location of the C-terminus of YddG. The pole-specific localization of YddG-ZsGreen in E. coli cells was detected by fluorescence microscopy.
Pitfalls and Technical Aspects during the Research of Intestinal Anastomotic Healing in Rats
Authors: Marjanovic G. , Holzner P. , Kulemann B. , Kuesters S. , Karcz W.K. , Timme S. , zur Hausen A. , Baumann T. , Hopt U.T. , Obermaier R. , Hoeppner J.
Published: October 2010

Background: Fundamental experimental research into intestinal anastomotic healing in rodent models will gain increasing interest in the future. Methods: The aim of this study was to describe our 5-year experience with a standardized experimental setup of small and large bowel anastomoses in a rodent model and present a basic set of assessment tools investigating anastomotic healing. Anastomotic technique, perioperative complications such as anastomotic insufficiency (AI) and obstructive ileus were in the focus. Results: During different studies with varying study patterns, 167 rat small bowel anastomoses and 120 colonic anastomoses were performed. Overall mortality was 3.6% in small bowel and 2.5% in colonic anastomoses, AI occurred in 2.9 and 4%, respectively. A postoperative obstructive ileus was seen in 3/167 small bowel anastomoses and none in the colonic group. Conclusion: When performing experimental intestinal anastomoses in a standardized operative setting and critically considering special perioperative issues, the incidence of relevant complications can be maintained at an adequately low level.
Intradermal Running Suture versus 3M™ Vetbond™ Tissue Adhesive for Wound Closure in Rodents: A Biomechanical and Histological Study
Authors: Sabol F. , Vasilenko T. , Novotný M. , Tomori Z. , Bobrov N. , Živčák J. , Hudák R. , Gál P.
Published: October 2010

Background: Although tissue adhesives and traditional sutures were compared in numerous studies during the early stages of healing, it has to be clarified, from the histological and biomechanical point of view, how the differences develop during the later phases. Methods: Twenty-four male Sprague-Dawley rats were used and divided into 2 groups: the IRS (intradermal running suture) and G (glue) groups. Two parallel full-thickness skin incisions were made on the back of each rat. Wounds in the IRS group were closed by an IRS, whereas wounds in the G group were closed using tissue adhesive (n-butylcyanoacrylate). Rats were sacrificed 7 and 22 days after surgery. Results: Similar wound tensile strengths of glued and sutured wounds were measured on days 7 (IRS = 10.3 ± 1.7 g/mm2 vs. G = 12.9 ± 4.0 g/mm2, p = 0.9612) and 22 (IRS = 95.6 ± 15.7 g/mm2 vs. G = 85.6 ± 16.4 g/mm2, p = 0.2502) after surgery. Histology revealed a significantly increased amount of granulation tissue formation in glued wounds on day 7. The difference in granulation tissue formation was reduced until day 22. Conclusions: Tissue adhesive based on n-butylcyanoacrylate presents a fair alternative to traditional suture wound closure techniques.
In vitro and in vivo Inhibitory Effects of Glycyrrhetinic Acid on Cytochrome P450 3A Activity
Authors: Li Hai Yun , Xu Wen , Su Juan , Zhang Xi , Hu Li Wei , Zhang Wei Dong
Published: October 2010

The liquorice plant has long been used in both Eastern and Western cultures. Glycyrrhizin is the major triterpenoid saponin in liquorice root, and glycyrrhetinic acid (GA) is its predominant metabolite and a pharmacologically active form of glycyrrhizin. We have assessed the ability of GA to inhibit the enzyme cytochrome P450 3A (CYP3A). A Lineweaver-Burk plot showed that GA was a mixed inhibitor of CYP3A, with an IC50 of 7.25 µmol/l, a Km of 4.3 µmol/l and a Ki of 6.4 µmol/l by non-linear regression analysis. CYP3A activity was also affected by intragastric administration of GA, which resulted in increases in area under the plasma concentration-time curve (AUC)0–t and in apparent elimination half-time (t1/2) and significant decreases in body clearance, as well as in the formation of 1-hydroxy-midazolam after intragastric or intravenous administration of midazolam (p < 0.05). An increase in Cmax after intragastric administration (p < 0.05) was also observed. These results suggest the likelihood of an interaction between GA and CYP3A-metabolised drugs in humans and indicate that liquorice root should be used with caution when taken concomitantly with other drugs that interact with CYP3A.
An XY Agonadal Oldenburg Warmblood Horse Exhibiting a Male Phenotype
Authors: Kuiper H. , Blum N. , Distl O.
Published: October 2010

In a 1.5-year-old Oldenburg horse, a clitoris-like structure instead of a penis was identified in the prepuce. The external genital organs did not show any abnormalities at visual inspection except that exteriorization of the penis was not possible, not even under general anesthesia. The horse’s owner observed a continuous dripping of urine and a tendency to mild colics beginning 2 weeks after birth. Testosterone concentration was 0.01 ng/ml and therefore under the threshold for geldings, and the horse did not respond to the application of gonadotropin-releasing hormone (GnRH). The inner genital consisted of a male urinary tract. Gonads and accessory male glands were missing. Residual structures of a female genital tract were not observed. Abnormalities of the mesentery could be found which might explain the recurrent colics of this horse. A cytogenetic examination revealed a 2n = 64,XY-karyotype and a positive result for the SRY-PCR. This is the first report on an agonadal horse with a male karyotype and a pseudohermaphrodite phenotype.
An Introduction to Instrumental Variables – Part 2: Mendelian Randomisation
Authors: Bennett Derrick A.
Published: October 2010

In the first part of this series, it was highlighted how even though randomised controlled trials can provide robust evidence for therapeutic interventions, for many types of exposure it may not be either practical or ethical to randomise patients to such studies (see part 1). Instrumental variables (IV) analyses have been increasingly employed in recent times in epidemiology to investigate the potential causal effects of an exposure. An IV is a variable that can realistically mimic the treatment allocation process in a randomised study and is assumed to be not directly related to outcome, except through the direct effect of treatment and not related to outcome through either measured or unmeasured confounders. As discussed in the first article, IV analyses can be useful in estimating direct treatment effects provided that the chosen instrument is strong. A particular type of IV analysis where a specific genetic variant has been used as the instrument known as ‘Mendelian randomisation’ has become increasingly common. The aim of the second part of this statistical primer is to outline the approach to Mendelian randomisation and some of the advantages and disadvantages of this approach.
Interventions Aiming at Balance Confidence Improvement in Older Adults: An Updated Review
Authors: Büla Christophe J. , Monod Stéfanie , Hoskovec Constanze , Rochat Stéphane
Published: October 2010

Background: Loss of balance confidence is a frequent condition that affects 20–75% of community-dwelling older persons. Although a recent fall is a common trigger, loss of balance confidence also appears independent of previous experience with falls. Maintaining or improving balance confidence is important to avoid unnecessary, self-imposed restrictions of activity and subsequent disability. Holding another person’s hand or using an assistive device while walking are simple interventions that are used naturally to address poor balance confidence in daily life. However, more complex interventions have also been developed and tested to achieve more sustained improvement in balance confidence. Objectives: This review describes interventions that have been tested to improve balance confidence in older community-dwelling persons. Methods: Based on 2 recent systematic reviews, an additional search for literature was performed to update current information on interventions aiming at balance confidence improvement. Interventions were classified as those directly aimed at increasing balance confidence or not, and further stratified into those using monofactorial or multifactorial approaches. Results: A total of 46 randomized controlled trials were identified. Five of the 8 interventions that directly targeted balance confidence showed benefits. Among those, multicomponent behavioral group interventions provided the most robust evidence of benefits in improving balance confidence and in decreasing activity avoidance. Among interventions not directly aiming at balance confidence improvement (11/21 studies with benefits), exercise (including tai chi) appears as the most promising monofactorial intervention. Nine of the 17 multifactorial fall prevention programs showed an effect on balance confidence, exercise being a main component in 7 of these 9 studies. Interventions that targeted elderly persons reporting poor balance confidence and/or those at risk for falls seemed more likely to be beneficial. Conclusions: Positive and sometimes sustained improvement in balance confidence can be achieved by various interventions among community-dwelling elderly persons. The effect of these interventions on activity restriction associated with poor balance confidence have been less well studied, but some studies also suggest potential benefits.
Cellular and Molecular Changes Associated With Inhibitory Effect of Pioglitazone on Neointimal Growth in Patients With Type 2 Diabetes After Zotarolimus-Eluting Stent Implantation
Authors: Hong Soon Jun , Kim Sung Tae , Kim Tae-Jin , Kim Eun-Ok , Ahn Chul-Min , Park Jae Hyoung , Kim Je Sang , Lee Kyung-Mi , Lim Do-Sun
Published: October 2010

Objective—

To investigate the mechanistic basis underlying antirestenosis and the antiatherogenic effect of pioglitazone in patients with type 2 diabetes mellitus who were undergoing zotarolimus-eluting stent implantation.

Methods and Results—

Recent studies highlight the beneficial effect of pioglitazone in attenuating neointimal growth after stent implantation. Patients with coronary artery diseases were randomly assigned to pioglitazone (n=47) or placebo (n=47) after stent implantation. Pioglitazone significantly reduced neointimal hyperplasia within the stented lesion and attenuated total plaque burden in the in-segment regions of the stent, as assessed by intravascular ultrasonography at the 8-month follow-up. These changes were preceded by reduced circulating natural killer (NK) cells, diminished interleukin 6 and monocyte chemoattractant protein-1 levels, and downregulation of chemokine receptor 2 at 2 days after stent implantation; and an elevated interleukin 10 level at 10 days after implantation. Furthermore, the proliferation and migration of vascular smooth muscle cells were inhibited in the presence of pioglitazone-treated patient serum, demonstrating that the antiproliferative effects of pioglitazone occurred concurrently with its antiinflammatory action.

Conclusion—

Our data present early cellular and immunologic changes by pioglitazone that might have been associated with antirestenotic and antiatherogenic effects in diabetic patients. Inhibiting proinflammatory responses while promoting antiinflammatory circuits, together with an antiproliferative action, may, in part, account for the antirestenotic effect of pioglitazone by altering vascular remodeling processes in the early phase.
Macrophage Adipose Triglyceride Lipase Deficiency Attenuates Atherosclerotic Lesion Development in Low-Density Lipoprotein Receptor Knockout Mice
Authors: Lammers Bart , Chandak Prakash G. , Aflaki Elma , Van Puijvelde Gijs H.M. , Radovic Branislav , Hildebrand Reeni B. , Meurs Illiana , Out Ruud , Kuiper Johan , Van Berkel Theo J.C. , Kolb Dagmar , Haemmerle Guenter , Zechner Rudolf , Levak-Frank Sanja , Van Eck Miranda , Kratky Dagmar
Published: October 2010

Objective—

The consequences of macrophage triglyceride (TG) accumulation on atherosclerosis have not been studied in detail so far. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for the initial step in TG hydrolysis. Because ATGL knockout (KO) mice exhibit massive TG accumulation in macrophages, we used ATGL KO mice to study the effects of macrophage TG accumulation on atherogenesis.

Methods and Results—

Low-density lipoprotein receptor (LDLr) KO mice were transplanted with bone marrow from ATGL KO (ATGL KO→LDLr KO) or wild-type (WT→LDLr KO) mice and challenged with a Western-type diet for 9 weeks. Despite TG accumulation in ATGL KO macrophages, atherosclerosis in ATGL KO→LDLr KO mice was 43% reduced associated with decreased plasma monocyte chemoattractant protein-1 (MCP-1) and macrophage interleukin-6 concentrations. This coincided with a reduced amount of macrophages, possibly because of a 39% increase in intraplaque apoptosis and a decreased migratory capacity of ATGL KO macrophages. The reduced number of white blood cells might be due to a 36% decreased Lin
−
Sca-1
+
cKit
+
hematopoietic stem cell population.

Conclusion—

We conclude that the attenuation of atherogenesis in ATGL KO→LDLr KO mice is due to decreased infiltration of less inflammatory macrophages into the arterial wall and increased macrophage apoptosis.
RISC RNA Sequencing for Context-Specific Identification of In Vivo MicroRNA Targets
Authors: Matkovich Scot J. , Van Booven Derek J. , Eschenbacher William H. , Dorn Gerald W.
Published: October 2010

Rationale:

MicroRNAs (miRs) are expanding our understanding of cardiac disease and have the potential to transform cardiovascular therapeutics. One miR can target hundreds of individual mRNAs, but existing methodologies are not sufficient to accurately and comprehensively identify these mRNA targets in vivo.

Objective:

To develop methods permitting identification of in vivo miR targets in an unbiased manner, using massively parallel sequencing of mouse cardiac transcriptomes in combination with sequencing of mRNA associated with mouse cardiac RNA-induced silencing complexes (RISCs).

Methods and Results:

We optimized techniques for expression profiling small amounts of RNA without introducing amplification bias and applied this to anti–Argonaute 2 immunoprecipitated RISCs (RISC-Seq) from mouse hearts. By comparing RNA-sequencing results of cardiac RISC and transcriptome from the same individual hearts, we defined 1645 mRNAs consistently targeted to mouse cardiac RISCs. We used this approach in hearts overexpressing miRs from
Myh6
promoter-driven precursors (programmed RISC-Seq) to identify 209 in vivo targets of miR-133a and 81 in vivo targets of miR-499. Consistent with the fact that miR-133a and miR-499 have widely differing “seed” sequences and belong to different miR families, only 6 targets were common to miR-133a– and miR-499–programmed hearts.

Conclusions:

RISC-sequencing is a highly sensitive method for general RISC profiling and individual miR target identification in biological context and is applicable to any tissue and any disease state.
Asymptomatic Hemorrhagic Transformation of Infarction and Its Relationship With Functional Outcome and Stroke Subtype
Authors: England Timothy J. , Bath Philip M.W. , Sare Gillian M. , Geeganage Chamila , Moulin Thierry , O'Neill Desmond , Woimant France , Christensen Hanne , De Deyn Peter , Leys Didier , Ringelstein E. Bernd
Published: October 2010

Background and Purpose—

Asymptomatic hemorrhagic transformation of infarction (AHTI) is common, but its risk factors and relationship with functional outcome are poorly defined.

Methods—

The analyses used data from the Tinzapararin in Acute Ischaemic Stroke Trial, a randomized controlled trial assessing tinzaparin (low molecular weight heparin) versus aspirin in 1484 patients with acute ischemic stroke. CT head scans (baseline, day 10) were adjudicated for the presence of hemorrhagic transformation. Stroke subtype was classified according to modified Trial of Org 10172 in Acute Stroke Treatment (small vessel, large vessel, cardioembolic) and the Oxfordshire Community Stroke Project (total anterior, partial anterior, lacunar, and posterior circulatory syndromes). Modified Rankin scale and Barthel Index were measured at 3 and 6 months. Analyses were adjusted for age, sex, severity, blood pressure, infarct volume, and treatment. Symptomatic hemorrhage was excluded.

Results—

At day 10, AHTI did not differ between aspirin (300 mg; 32.8%) and medium-dose (100 IU/kg; 36.0%) and high-dose (175 IU/kg; 31.4%) tinzaparin groups (
P
=0.44). Relative to lacunar stroke, AHTI on follow-up CT was significantly increased in total anterior circulation syndrome (odds ratio, 11.5; 95% CI, 7.1 to 18.7) and partial anterior circulation syndrome (odds ratio, 7.2; 95% CI, 4.5 to 11.4) stroke. Similarly, relative to small vessel disease, AHTI was increased in large vessel (odds ratio, 15.1; 95% CI, 9.4 to 24.3) and cardioembolic (odds ratio, 14.1; 95% CI, 8.5 to 23.5) stroke. After adjustment for infarct volume, the presence of AHTI was not associated with outcome at 3 or 6 months as measured by the modified Rankin Scale and Barthel Index.

Conclusions—

AHTI is increased in ischemic stroke with cortical syndromes and of large vessel or cardioembolic etiology. Heparin does not increase AHTI. AHTI is not associated with functional outcome.
Influence of Age on Outcome From Thrombolysis in Acute Stroke
Authors: Mishra Nishant Kumar , Diener Hans-Christoph , Lyden Patrick D. , Bluhmki Erich , Lees Kennedy R.
Published: October 2010

Background and Purpose—

Thrombolysis for acute ischemic stroke in patients aged >80 years is not approved in some countries due to limited trial data in the very elderly. We compared outcomes between thrombolysed and nonthrombolysed (control) patients from neuroprotection trials to assess any influence of age on response.

Method—

Among patients with ischemic stroke of known age, pretreatment severity (baseline National Institutes of Health Scale Score), and 90-day outcome (modified Rankin Scale score; National Institutes of Health Scale score), we compared the distribution of modified Rankin score in thrombolysed patients with control subjects by Cochran-Mantel-Haenszel test and then logistic regression after adjustment for age and baseline National Institutes of Health Scale score. We examined patients ≤80 and ≥81 years separately and then each age decile.

Results—

Rankin data were available for 5817 patients, 1585 thrombolysed and 4232 control subjects; 20.5% were aged >80 years (mean±SD, 85.1±3.4 years). Baseline severity was higher among thrombolysed than control subjects (median National Institutes of Health Scale score 14 versus 13,
P
<0.05). The distribution of modified Rankin Scale scores was better among thrombolysed patients (
P
<0.0001; OR, 1.39; 95% CI, 1.26 to 1.54). The association occurred independently with similar magnitude among young (
P
<0.0001; OR, 1.42; 95% CI, 1.26 to 1.59) and elderly (
P
=0.002; OR, 1.34; 95% CI, 1.05 to 1.70) patients. ORs were consistent across all age deciles >30 years; outcomes assessed by National Institutes of Health Scale score gave supporting significant findings, and dichotomized modified Rankin Scale score outcomes were also consistent.

Conclusions—

Outcome after thrombolysis for acute ischemic stroke was significantly better than in control subjects. Despite the expected poorer outcomes among elderly compared with young patients that is independent of any treatment effect, the association between thrombolysis treatment and improved outcome is maintained in the very elderly. Age alone should not be a barrier to treatment.
Influence of Prophylactic, Endovascularly Based Normothermia on Inflammation in Patients With Severe Cerebrovascular Disease
Authors: Broessner Gregor , Lackner Peter , Fischer Marlene , Beer Ronny , Helbok Raimund , Pfausler Bettina , Schneider Dietmar , Schmutzhard Erich
Published: October 2010

Background and Purpose—

We analyzed the impact of long-term endovascularly based prophylactic normothermia versus conventional temperature management on inflammatory parameters in patients with severe cerebrovascular disease.

Methods—

This was a prospective, randomized, controlled trial comparing the course of inflammatory parameters between the 2 treatment arms: (1) prophylactically endovascular long-term normothermia; and (2) conventional, stepwise fever management with antiinflammatory drugs and surface cooling. Inclusion criteria were (1) spontaneous subarachnoid hemorrhage with Hunt–Hess grade between 3 and 5; (2) spontaneous intracerebral hemorrhage with a Glasgow Coma Scale score of ≤10; or (3) complicated cerebral infarction requiring intensive care unit treatment with a NIH Stroke Scale score of ≥15. Treatment period was 336 hours in subarachnoid hemorrhage patients and 168 hours in patients with complicated stroke or intracerebral hemorrhage patients.

Results—

A total of 102 patients (56 female) were enrolled during a 3.5-year period. Overall median total fever burden during the course of treatment was 0.0°C hour and 4.3°C hours in the catheter and conventional group, respectively (
P
<0.0001). C-reactive protein and interleukin-6 were significantly elevated in the endovascular group (
P
<0.05). Nonsteroidal antiinflammatory drugs, used as additional treatment of fever, significantly reduced mean C-reactive protein in endovascular treated patients (
P
<0.01).

Conclusions—

The proinflammatory cytokines C-reactive protein and interleukin-6 were significantly elevated in patients receiving prophylactic endovascularly based long-term normothermia. Nonsteroidal antiinflammatory drugs significantly affected the course of proinflammatory parameters; thus, future trials should investigate the role of nonsteroidal antiinflammatory drugs in severe cerebrovascular disease patients and their interaction with temperature management.

Clinical Trial Registration—

Trial not registered; enrollment began before July 2005.
Cerebral Microbleeds in the Elderly
Authors: Fisher Mark , French Samuel , Ji Ping , Kim Ronald C.
Published: October 2010

Background and Purpose—

Cerebral microbleeds in the elderly are routinely identified by brain MRI. The purpose of this study was to better characterize the pathological basis of microbleeds.

Methods—

We studied postmortem brain specimens of 33 individuals with no clinical history of stroke and with an age range of 71 to 105 years. Cerebral microbleeds were identified by presence of hemosiderin (iron), identified by routine histochemistry and Prussian blue stain. Cellular localization of iron (in macrophages and pericytes) was studied by immunohistochemistry for smooth muscle actin, CD68, and, in selected cases, electron microscopy. Presence of β-amyloid was analyzed using immunohistochemistry for epitope 6E10.

Results—

Cerebral microbleeds were present in 22 cases and occurred at capillary, small artery, and arteriolar levels. Presence of microbleeds occurred independent of amyloid deposition at site of microbleeds. Although most subjects had hypertension, microbleeds were present with and without hypertension. Putamen was the site of microbleeds in all but 1 case; 1 microbleed was in subcortical white matter of occipital lobe. Most capillary microbleeds involved macrophages, but the 2 microbleeds studied by electron microscopy demonstrated pericyte involvement.

Conclusions—

These findings indicate that cerebral microbleeds are common in elderly brain and can occur at the capillary level.
Hypertension and Cerebral Diffusion Tensor Imaging in Small Vessel Disease
Authors: Gons Rob A.R. , de Laat Karlijn F. , van Norden Anouk G.W. , van Oudheusden Lucas J.B. , van Uden Inge W.M. , Norris David G. , Zwiers Marcel P. , de Leeuw Frank-Erik
Published: October 2010

Background and Purpose—

Hypertension is a risk factor for cerebral small vessel disease, which includes white matter lesions (WML) and lacunar infarcts. These lesions are frequently observed on MRI scans of elderly people and play a role in cognitive decline. Preferably, one would like to evaluate the effect of hypertension before fluid-attenuated inversion recovery visible macrostructural lesions occur, possibly by investigating its effect on the microstructural integrity of the white matter. Diffusion tensor imaging provides measures of structural integrity.

Methods—

In 503 patients with small vessel disease, aged between 50 and 85 years, we cross-sectionally studied the relation between blood pressure, hypertension, and hypertension treatment status and diffusion tensor imaging parameters in both normal-appearing white matter (NAWM) and WMLs. All of the subjects underwent 1.5-T MRI and diffusion tensor imaging scanning. Fractional anisotropy and mean diffusivity were calculated in both NAWM and WMLs.

Results—

Increased blood pressure and hypertension were significantly related to lower fractional anisotropy in both NAWM and WMLs and to higher mean diffusivity in WMLs. For hypertensives, odds ratios for the risk of impaired microstructural integrity (fractional anisotropy) were 3.1 (95% CI: 1.8 to 5.7) and 2.1 (95% CI: 1.2 to 3.5) in NAWM and WMLs, respectively, compared with normotensives. Fractional anisotropy odds ratios for treated uncontrolled subjects were 6.5 (95% CI: 3.3 to 12.7) and 2.7 (95% CI: 1.5 to 5.1) in NAWM and WMLs, respectively, compared with normotensives.

Conclusions—

Our data show that diffusion tensor imaging may be an appropriate tool to monitor the effect of blood pressure and the response to treatment on white matter integrity, probably even before the development of WMLs on fluid-attenuated inversion recovery.
Stochastic Parameterization Schemes for Use in Realistic Climate Models
Authors: Culina Joel , Kravtsov Sergey , Monahan Adam H.
Published: October 2010

Stochastic parameterizations of fast-evolving, subgrid-scale processes are increasingly being used in a range of models from conceptual models to general circulation models. However, stochastic terms are generally included in an ad hoc fashion. In this study, a systematic method—“Hasselmann’s method”—of stochastic parameterization is developed through the direct application of rigorously justified limit theorems that predict the effective slow dynamics in systems with coupled slow and fast variables. The multiple Hasselmann models form a hierarchy of models ordered by the time scales over which they are expected to provide good approximations to the slowly evolving variables. Adaptable, efficient algorithms for integrating these reduced models are developed that require minimal changes to the unreduced model.

Hasselmann’s method is tested on an O(10 000)-dimensional (planetary and synoptic scale) quasigeostrophic model of atmospheric low-frequency variability. Low-dimensional deterministic and stochastic models in the planetary-scale modes alone are derived, which accurately generate the statistics of the corresponding modes of the unreduced model, including the statistical signatures of jet regime behavior. It is shown that deterministic nonlinearity through slow forcing averaged with respect to the fast modes distribution dominates over multiplicative noise in generating the regime behavior.
Ice–Ice Collisions: An Ice Multiplication Process in Atmospheric Clouds
Authors: Yano J.-I. , Phillips V. T. J.
Published: October 2010

Ice in atmospheric clouds undergoes complex physical processes, interacting especially with radiation, which leads to serious impacts on global climate. After their primary production, atmospheric ice crystals multiply extensively by secondary processes. Here, it is shown that a mostly overlooked process of mechanical breakup of ice particles by ice–ice collisions contributes to such observed multiplication. A regime for explosive multiplication is identified in its phase space of ice multiplication efficiency and number concentration of ice particles. Many natural mixed-phase clouds, if they have copious millimeter-sized graupel, fall into this explosive regime. The usual Hallett–Mossop (H–M) process of ice multiplication is shown to dominate the overall ice multiplication when active, as it starts sooner, compared to the breakup ice multiplication process. However, for deep clouds with a cold base temperature where the usual H–M process is inactive, the ice breakup mechanism should play a critical role. Supercooled rain, which may freeze to form graupel directly in only a few minutes, is shown to hasten such ice multiplication by mechanical breakup, with an ice enhancement ratio exceeding 104 approximately 20 min after small graupel first appear. The ascent-dependent onset of subsaturation with respect to liquid water during explosive ice multiplication is predicted to determine the eventual ice concentrations.
The Quasi-Biennial Oscillation in a Double CO2 Climate
Authors: Kawatani Yoshio , Hamilton Kevin , Watanabe Shingo
Published: October 2010

The effects of anticipated twenty-first-century global climate change on the stratospheric quasi-biennial oscillation (QBO) have been studied using a high-resolution version of the Model for Interdisciplinary Research on Climate (MIROC) atmospheric GCM. This version of the model is notable for being able to simulate a fairly realistic QBO for present-day conditions including only explicitly resolved nonstationary waves. A long control integration of the model was run with observed climatological sea surface temperatures (SSTs) appropriate for the late twentieth century, followed by another integration with increased atmospheric CO2 concentration and SSTs incremented by the projected twenty-first-century warming in a multimodel ensemble of coupled ocean–atmosphere runs that were forced by the Special Report on Emissions Scenarios (SRES) A1B scenario of future atmospheric composition. In the experiment for late twenty-first-century conditions the QBO period becomes longer and QBO amplitude weaker than in the late twentieth-century simulation. The downward penetration of the QBO into the lowermost stratosphere is also curtailed in the late twenty-first-century run. These changes are driven by a significant (30%–40%) increase of the mean upwelling in the equatorial stratosphere, and the effect of this enhanced mean circulation overwhelms counteracting influences from strengthened wave fluxes in the warmer climate. The momentum fluxes associated with waves propagating upward into the equatorial stratosphere do strengthen overall by ∼(10%–15%) in the warm simulation, but the increases are almost entirely in zonal phase speed ranges that have little effect on the stratospheric QBO but that would be expected to have important influences in the mesosphere and lower thermosphere.
A New Extratropical Tracer Describing the Role of the Western Pacific in the Onset of El Niño: Implications for ENSO Understanding and Forecasting
Authors: Ballester Joan , Rodríguez-Arias Miquel Àngel , Rodó Xavier
Published: October 2010

A complex empirical orthogonal function analysis was applied to sea surface temperature data in the southern high-latitude Pacific to identify and isolate primary processes related to the onset of El Niño (EN) events. Results were compared to those of a lead–lag composite analysis of a new tracer of EN events in the southern high-latitude Pacific, the Ross–Bellingshausen (RB) dipole. Both techniques successfully isolate the main low-frequency features in the interaction among the tropical and southern extratropical Pacific during the onset of recent eastward-propagating EN events. Particularly, positive RB peaks were followed by EN events around 9 months later, on average. In turn, RB maxima were anticipated by local warm anomalies in the western tropical Pacific a year in advance, which enhance local convection and upper-troposphere divergence and generate an anomalous wave train extending eastward and poleward in the southern extratropics. In addition, circulation changes lead to a warm SST region in the central tropical Pacific, which is then strengthened by suppressed equatorial easterlies. Convection thus starts to move to the central Pacific and so the Walker circulation weakens, activating the positive Bjerknes feedback that ultimately leads to the development of an EN event. These results highlight the enormous potential of the interaction between the tropics and this high-latitude region in the Southern Hemisphere to increase El Niño–Southern Oscillation understanding and to improve the long-lead prediction skill of EN phenomenon.
Intraseasonal Modulation of the North Pacific Storm Track by Tropical Convection in Boreal Winter
Authors: Deng Yi , Jiang Tianyu
Published: October 2010

The modulation of the North Pacific storm track by tropical convection on intraseasonal time scales (30–90 days) in boreal winter (December–March) is investigated using the NCEP–NCAR reanalysis and NOAA satellite outgoing longwave radiation (OLR) data. Multivariate empirical orthogonal function (MEOF) analysis and case compositing based upon the principal components (PCs) of the EOFs reveal substantial changes in the structure and intensity of the Pacific storm track quantified by vertically (925–200 mb) averaged synoptic eddy kinetic energy (SEKE) during the course of a typical Madden–Julian oscillation (MJO) event. The storm-track response is characterized by an amplitude-varying dipole propagating northeastward as the center of the anomalous tropical convection moves eastward across the eastern Indian Ocean and the western-central Pacific. A diagnosis of the SEKE budget indicates that the storm-track anomaly is induced primarily by changes in the convergence of energy flux, baroclinic conversion, and energy generation due to the interaction between synoptic eddies and intraseasonal flow anomalies. This demonstrates the important roles played by eddy–mean flow interaction and eddy–eddy interaction in the development of the extratropical response to MJO variability. The feedback of synoptic eddy to intraseasonal flow anomalies is pronounced: when the center of the enhanced tropical convection is located over the Maritime Continent (western Pacific), the anomalous synoptic eddy forcing partly drives an upper-tropospheric anticyclonic (cyclonic) and, to its south, a cyclonic (anticyclonic) circulation anomaly over the North Pacific. Associated with the storm-track anomaly, a three-band (dry–wet–dry) anomaly in both precipitable water and surface precipitation propagates poleward over the eastern North Pacific and induces intraseasonal variations in the winter hydroclimate over western North America.
El Niño–Southern Oscillation’s Impact on Atlantic Basin Hurricanes and U.S. Landfalls
Authors: Klotzbach Philip J.
Published: October 2010

El Niño–Southern Oscillation (ENSO) has been shown in many previous papers to impact seasonal levels of Atlantic basin tropical cyclone activity. This paper revisits this relationship by examining a longer period (1900–2009) than has been examined in earlier analyses. Alterations in large-scale climate parameters, especially vertical wind shear, are shown to be the primary reasons why tropical cyclone activity in the Atlantic is reduced in El Niño years. Climate signals are found to be somewhat stronger in the Caribbean than for the remainder of the tropical Atlantic. The focus of the paper then shifts to U.S. landfalls, confirming previous research that U.S. landfalls are reduced in El Niño years. The reduction in landfall frequency is greater along the Florida peninsula and East Coast than it is along the Gulf Coast, especially for major hurricanes. The probability of each state being impacted by a hurricane and major hurricane is given for El Niño, La Niña, and neutral years. The most dramatic probability differences between warm and cold ENSO events lie along the East Coast and, in particular, the state of North Carolina. The relationship between ENSO and the Atlantic multidecadal oscillation (AMO) is also examined. In general, the negative phase of the AMO is characterized by a stronger ENSO modulation signal than a positive phase of the AMO.
Self-Leadership: A Multilevel Review
Authors: Stewart Greg L. , Courtright Stephen H. , Manz Charles C.
Published: October 2010

Over the past 30 years substantial research has focused on the concept of self-leadership. The authors adopt a multilevel perspective to review this research at both individual and team levels of analysis. At the individual level, studies consistently show that increased self-leadership corresponds with better affective responses and improved work performance. Findings are not as consistent at the team level. Relationships between team-level self-leadership and both affective and performance outcomes appear to be moderated by contextual factors. The authors also identify internal and external forces that influence self-leadership. Among these forces, external leadership is particularly important, as self-leadership is not a complete substitute for external leadership. Specifically, external leadership in the forms of empowering leadership and shared leadership facilitate self-leadership of individuals and teams. The authors also identify a number of cross-level research questions that illustrate how future research can benefit from exploring ways that self-leadership at the individual level interacts with self-leadership at the team level.
Control at Work, Control at Home, and Planning Behavior
Authors: Lapierre Laurent M. , Allen Tammy D.
Published: October 2010

This study offers a cross-domain perspective on both individual and situational factors relating to work–family conflict. Individuals’ control at work and control at home were examined in relation to work interference with family (WIF) and to family interference with work (FIW). The authors also tested whether employees’ use of planning behavior moderated these relationships. Results suggest that control at work was more strongly related to reductions in WIF among employees who used more rather than less planning behavior. Control at home was related to FIW, but this relationship did not vary with employee’s use of planning behavior. Unexpectedly, control at home was also related to reductions in WIF.
Inclusion and Diversity in Work Groups: A Review and Model for Future Research
Authors: Shore Lynn M. , Randel Amy E. , Chung Beth G. , Dean Michelle A. , Holcombe Ehrhart Karen , Singh Gangaram
Published: October 2010

A great deal of research has focused on work group diversity, but management scholars have only recently focused on inclusion. As a result, the inclusion literature is still under development, with limited agreement on the conceptual underpinnings of this construct. In this article, the authors first use Brewer’s optimal distinctiveness theory to develop a definition of employee inclusion in the work group as involving the satisfaction of the needs of both belongingness and uniqueness. Building on their definition, the authors then present a framework of inclusion. Their framework is subsequently used as a basis for reviewing the inclusion and diversity literature. Potential contextual factors and outcomes associated with inclusion are suggested in order to guide future research.
Decreases in Binding Capacity of the Mitochondrial 18 kDa Translocator Protein Accompany Oxidative Stress and Pathological Signs in Rat Liver After DMBA Exposure
Authors: Dimitrova-Shumkovska Jasmina , Veenman Leo , Ristoski Trpe , Leschiner Svetlana , Gavish Moshe
Published: October 2010

7,12-Dimethylbenz[ a]anthracene (DMBA) presents a pollutant implicated in various toxicological effects. The aim of this experiment was to study the effects of DMBA administration on oxidative stress, histopathological signs, and 18 kDa translocator protein (TSPO) binding characteristics in rat liver. We also studied the effects of dose stoichiometry, dose frequency, and duration of protocol of DMBA administration. In this study, rats surviving eighteen weeks after DMBA exposure showed mild to moderate histopathological changes in the liver, mainly characterized by glossy appearance of hepatocytes, heterochromatic nuclei, and glycogen overload in the midzonal region of the hepatic lobe. These changes were accompanied by significant rises in oxidant levels, along with declines in nonenzymic antioxidants, indicating that DMBA induced oxidative stress in the liver. This finding correlated well with decreases in TSPO binding capacity in the liver of the rats in our study. Other studies have shown that TSPO can be affected by oxidative stress, as well as contribute to oxidative stress at mitochondrial levels. Further studies are needed to assay whether the decreases in TSPO density in the liver are part of the damaging effects caused by DMBA or a compensatory response to the oxidative stress induced by DMBA.
Design-based Stereology
Authors: Boyce Rogely Waite , Dorph-Petersen Karl-Anton , Lyck Lise , Gundersen Hans Jørgen G.
Published: October 2010

In regulatory toxicology studies, qualitative histopathological evaluation is the reference standard for assessment of test article–related morphological changes. In certain cases, quantitative analysis may be required to detect more subtle morphological changes, such as small changes in cell number. When the detection of subtle test article–related morphological changes is critical to the decision-making process, sensitive quantitative methods are needed. Design-based stereology provides the tools for obtaining accurate, precise quantitative structural data from tissue sections. These tools have the sensitivity necessary to detect small changes by combining statistical sampling principles with geometric analysis of the tissue microstructure. It differs from other morphometric methods based on tissue section analysis by providing estimates that are statistically valid, truly three-dimensional, and referent to the entire organ. Further, because the precision of the stereological analysis procedure can be predicted, studies can be designed and powered to detect subtle, potentially toxicologically significant changes. Although stereological methods have not been widely applied in toxicologic pathology, recent advances have made it feasible to implement these methods in a regulatory toxicology setting, particularly methods for estimation of total cell number.