bluuebunny/crossref_metadata_2025 huggingface dataset:
Botulinum Toxin to Treat Upper-Limb Spasticity in Hemiparetic Patients: Analysis of Function and Kinematics of Reaching Movements
Authors: Bensmail Djamel , Robertson Johanna V. G. , Fermanian Christophe , Roby-Brami Agnès
Published: January 2010

Background. Poor control of reaching in spastic hemiparetic patients could be because of a combination of poor individuation of joints, weakness, spasticity, and/or sensory loss. Objective. To assess the effect of botulinum toxin injections (BTIs) on spasticity, upper-limb function, and kinematics of reaching movements in patients with spastic hemiparesis caused by brain injury. Methods. Fifteen patients with spastic hemiparesis and 9 healthy controls were included in this single-site, open-labeled study. The trajectories of reaching movements were recorded, and kinematic variables were computed. A clinical evaluation included the Motor Activity Log, the Action Research Arm Test (ARAT), and the Box and Block Test (BBT). Patients were assessed before (M0), 1 month after a first (M1), and 1 month after a second BTI (M4, at 4 months) in proximal and distal muscles. Results. Significant differences were found between hemiparetic patients and healthy participants for all kinematic parameters. All parameters tended to improve after BTI. This effect was significant for velocity and smoothness. Functional scores also tended to improve. Improvements were greater at M4 than at M1, although the differences were not significant. Conclusions. Kinematic parameters improved following BTI, without significant changes in clinical outcomes such as ARAT and BBT. The decrease in spasticity alone does not seem to explain the results, which may be a result of adaptation to the decrease in hypertonicity leading to increased use of the arm and possibly an increase in antagonist muscle strength.
The Real Weighty Issue: Losing Is Just the Beginning
Authors: Gerweck Catherine , Curran Celentano Joanne
Published: January 2010

There are numerous strategies, including bariatric surgery, for obese and super-obese patients to achieve weight loss, but weight regain and attrition are well documented, and long-term success rates for maintaining weight loss are not favorable. Many patients have unrealistic expectations for weight loss and may either be unaware or may minimize the effort required to maintain their weight loss. The skilled nutrition professional, the registered dietitian, can help optimize patient success by teaching the patient the necessary new eating and drinking behaviors and coaching him or her in “mindful eating” techniques.
Degrees of Emotion: Judicial Responses to Victim Impact Statements
Authors: Schuster Mary Lay , Propen Amy
Published: January 2010

Emotional standards and hierarchies in the courtroom may affect judicial reactions to victim impact statements. Based on judicial conversations and courtroom observations in two judicial districts in Minnesota, we suggest that judges contrast emotion with reason in order to maintain control of their courtrooms; when faced with emotional expressions in victim impact statements, judges appreciate expressions of compassion and tolerate expressions of grief but are uncomfortable with expressions of anger. These judicial responses to emotional expression, however, must be contextualized; for example, the judges we spoke with often articulated different reactions to impact statements given by victims of sexual assault, those who are strangers to the perpetrator, and impact statements given by victims of domestic violence, those who are in a relationship with the perpetrator.
Review: Hepatitis C virus replication and potential targets for direct-acting agents
Authors: O'Leary Jacqueline G. , Davis Gary L.
Published: January 2010

We finally stand at the brink of novel, oral, direct-acting antivirals for the treatment of hepatitis C virus (HCV) infection. Basic science research has lead to a greater understanding of the viral life cycle and identified numerous potential targets for therapy. Early compounds were plagued by inconsistent in vivo activity and side effects that led to discontinuation of investigational efforts. However, several agents have now progressed to phase 2 human studies and two protease inhibitors have completed enrolment for their phase 3 clinical trials and look promising. Thus, while it appears that protease inhibitors will likely be the next available drugs for the treatment of HCV infection, the quest for additional therapeutic agents will continue. The future of HCV therapy lies in multidrug cocktails of several agents targeted against a variety of targets. In the near future these agents will be added to the current standard therapy consisting of pegylated interferon and ribavirin; however, the ultimate and probably realistic goal will be to develop multidrug oral regiments to replace the need for interferon.
Review: Immunomodulators for all patients with inflammatory bowel disease?
Authors: Ardizzone Sandro , Cassinotti Andrea , Manes Gianpiero , Bianchi Porro Gabriele
Published: January 2010

Recent insight into the pathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC) have led to the development of new treatment options, with a progressive shift to more evidence-based strategies based on sound pathophysiological rationales. A better understanding of inflammatory bowel disease (IBD) pathophysiology has progressively resulted in a more frequent use of immunomodulators. We review the recommended or suggested use of conventional immunomodulators such as azathioprine, 6-mercaptopurine, methotrexate in the treatment of IBD. Moreover, an effort is made to explore some critical areas in which early and more diffuse use of these agents may be advocated.
A Prospective Study Comparing Attempted Weight Bearing in Fiberglass Below-Knee Casts and Prefabricated Pneumatic Braces
Authors: Mason Lyndon W. , Dodds Alex
Published: January 2010

Partial weight bearing is commonly advised after fracture of the lower extremity. Research has determined this to be inaccurate both in its instruction and its reproducibility. Many trauma departments are commonly using alternatives to plaster in the splintage of fractures, such as fiberglass and the prefabricated pneumatic braces. This study’s null hypothesis is that there is no difference between partial weight bearing through a fiberglass cast as compared with a pneumatic walker. A prospective study was conducted in our department including all patients who had metatarsal or ankle fractures and could partially weight bear. Patients were excluded if they were not allowed to bear weight, had received operative fixation of their fracture, or were younger than age 16 years. The patients’ total weight was measured first, and then they were trained to place 50% of their weight through the splinted limb. Three measurements were taken of their attempted weight bearing at 50%, and they were blinded to the results. Over a 16-month period, 117 patients were enrolled for this study: 72 in the pneumatic walker group and 45 in the fiberglass group. There was no significant difference in sex, age, or fracture type. There was a significant difference in percentage of weight placed through the splinted limb, with the pneumatic brace group placing much greater force than the fiberglass group. This may have been caused by altered proprioception from the walker. It is important to realize this when prescribing partial weight bearing in a particular splint as this may result in avoidable complications.
Genome-wide cloning and sequence analysis of leucine-rich repeat receptor-like protein kinase genes in Arabidopsis thaliana
Authors: Gou Xiaoping , He Kai , Yang Hui , Yuan Tong , Lin Honghui , Clouse Steven D , Li Jia
Published: January 2010

Background

Transmembrane receptor kinases play critical roles in both animal and plant signaling pathways regulating growth, development, differentiation, cell death, and pathogenic defense responses. InArabidopsis thaliana, there are at least 223 Leucine-rich repeat receptor-like kinases (LRR-RLKs), representing one of the largest protein families. Although functional roles for a handful of LRR-RLKs have been revealed, the functions of the majority of members in this protein family have not been elucidated.

Results

As a resource for the in-depth analysis of this important protein family, the complementary DNA sequences (cDNAs) of 194 LRR-RLKs were cloned into the GatewayRdonor vector pDONR/ZeoRand analyzed by DNA sequencing. Among them, 157 clones showed sequences identical to the predictions in the Arabidopsis sequence resource, TAIR8. The other 37 cDNAs showed gene structures distinct from the predictions of TAIR8, which was mainly caused by alternative splicing of pre-mRNA. Most of the genes have been further cloned into GatewayRdestination vectors with GFP or FLAG epitope tags and have been transformed into Arabidopsis forin plantafunctional analysis. All clones from this study have been submitted to the Arabidopsis Biological Resource Center (ABRC) at Ohio State University for full accessibility by the Arabidopsis research community.

Conclusions

Most of the Arabidopsis LRR-RLK genes have been isolated and the sequence analysis showed a number of alternatively spliced variants. The generated resources, including cDNA entry clones, expression constructs and transgenic plants, will facilitate further functional analysis of the members of this important gene family.
Acetylation of p65 at lysine 314 is important for late NF-κB-dependent gene expression
Authors: Rothgiesser Karin M , Fey Monika , Hottiger Michael O
Published: January 2010

Background

NF-κB regulates the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation and survival. We have earlier reported that p65, a subunit of NF-κB, is acetylated in vitro and in vivo at three different lysines (K310, K314 and K315) by the histone acetyltransferase p300.

Results

In this study, we describe that site-specific mutation of p65 at lysines 314 and 315 enhances gene expression of a subset of NF-κB target genes including Mmp10 and Mmp13. Increased gene expression was mainly observed three hours after TNFα stimulation. Chromatin immunoprecipitation (ChIP) experiments with an antibody raised against acetylated lysine 314 revealed that chromatin-bound p65 is indeed acetylated at lysine 314.

Conclusions

Together, our results establish acetylation of K314 as an important regulatory modification of p65 and subsequently of NF-κB-dependent gene expression.
The capsule of Porphyromonas gingivalis reduces the immune response of human gingival fibroblasts
Authors: Brunner Jorg , Scheres Nina , El Idrissi Nawal B , Deng Dong M , Laine Marja L , van Winkelhoff Arie J , Crielaard Wim
Published: January 2010

Background

Periodontitis is a bacterial infection of the periodontal tissues. The Gram-negative anaerobic bacterium Porphyromonas gingivalis is considered a major causative agent. One of the virulence factors of P. gingivalis is capsular polysaccharide (CPS). Non-encapsulated strains have been shown to be less virulent in mouse models than encapsulated strains.

Results

To examine the role of the CPS in host-pathogen interactions we constructed an insertional isogenic P. gingivalis knockout in the epimerase-coding gene epsC that is located at the end of the CPS biosynthesis locus. This mutant was subsequently shown to be non-encapsulated. K1 capsule biosynthesis could be restored by in trans expression of an intact epsC gene. We used the epsC mutant, the W83 wild type strain and the complemented mutant to challenge human gingival fibroblasts to examine the immune response by quantification of IL-1β, IL-6 and IL-8 transcription levels. For each of the cytokines significantly higher expression levels were found when fibroblasts were challenged with the epsC mutant compared to those challenged with the W83 wild type, ranging from two times higher for IL-1β to five times higher for IL-8.

Conclusions

These experiments provide the first evidence that P. gingivalis CPS acts as an interface between the pathogen and the host that may reduce the host's pro-inflammatory immune response. The higher virulence of encapsulated strains may be caused by this phenomenon which enables the bacteria to evade the immune system.
Protection against Pseudomonas aeruginosa lung infection in mice by recombinant OprF-pulsed dendritic cell immunization
Authors: Peluso Lucia , de Luca Cristiana , Bozza Silvia , Leonardi Antonio , Giovannini Gloria , Lavorgna Alfonso , De Rosa Gaetano , Mascolo Massimo , De Luna Loredana Ortega , Catania Maria Rosaria , Romani Luigina , Rossano Fabio
Published: January 2010

Background

The Pseudomonas aeruginosa major constitutive outer membrane porin protein F (OprF) has been shown to be a protective antigen and was previously used to activate an immunological response in a mouse model of lung pneumonia. The purpose of our study was to demonstrate the ability of mouse dendritic cells pulsed with purified or recombinant OprF to protect mice against P. aeruginosa infection and inflammation.

Both native (n-OprF), isolated and purified from PAO1 bacterial strain, and recombinant (histidin-conjugated) OprF (His-OprF), obtained by cloning of the oprF gene into the pET28a expression vector, were used to stimulate dendritic cells in vitro before adoptive transfer into prospective recipient mice with P. aeruginosa pulmonary infection.

Results

Similar to n-OprF, His-OprF activated dendritic cells in vitro, inducing the costimulatory molecule expression as well as cytokine production. Upon adoptive transfer in vivo, porin-pulsed dendritic cells (DCs) induced Th1-mediated resistance to infection and associated inflammatory pathology caused by either the PAO1 strain or a clinically-isolated mucoid strain.

Conclusions

This study highlights the pivotal contribution of DCs to vaccine-induced protection against P. aeruginosa infection and associated inflammation.
Study of the outcome of suicide attempts: characteristics of hospitalization in a psychiatric ward group, critical care center group, and non-hospitalized group
Authors: Kudo Kaoru , Otsuka Kotaro , Endo Jin , Yoshida Tomoyuki , Isono Hisayasu , Yambe Takehito , Nakamura Hikaru , Kawamura Sachiyo , Koeda Atsuhiko , Yagi Junko , Kemuyama Nobuo , Harada Hisako , Chida Fuminori , Endo Shigeatsu , Sakai Akio
Published: January 2010

Background

The allocation of outcome of suicide attempters is extremely important in emergency situations. Following categorization of suicidal attempters who visited the emergency room by outcome, we aimed to identify the characteristics and potential needs of each group.

Methods

The outcomes of 1348 individuals who attempted suicide and visited the critical care center or the psychiatry emergency department of the hospital were categorized into 3 groups, "hospitalization in the critical care center (HICCC)", "hospitalization in the psychiatry ward (HIPW)", or "non-hospitalization (NH)", and the physical, mental, and social characteristics of these groups were compared. In addition, multiple logistic analysis was used to extract factors related to outcome.

Results

The male-to-female ratio was 1:2. The hospitalized groups, particularly the HICCC group, were found to have biopsychosocially serious findings with regard to disturbance of consciousness (JCS), general health performance (GAS), psychiatric symptoms (BPRS), and life events (LCU), while most subjects in the NH group were women who tended to repeat suicide-related behaviors induced by relatively light stress. The HIPW group had the highest number of cases, and their symptoms were psychologically serious but physically mild. On multiple logistic analysis, outcome was found to be closely correlated with physical severity, risk factor of suicide, assessment of emergent medical intervention, and overall care.

Conclusion

There are different potential needs for each group. The HICCC group needs psychiatrists on a full-time basis and also social workers and clinical psychotherapists to immediately initiate comprehensive care by a medical team composed of multiple professionals. The HIPW group needs psychological education to prevent repetition of suicide attempts, and high-quality physical treatment and management skill of the staff in the psychiatric ward. The NH group subjects need a support system to convince them of the risks of attempting suicide and to take a problem-solving approach to specific issues.
Consumption of fruit and vegetables among elderly people: a cross sectional study from Iran
Authors: Salehi Leili , Eftekhar Hassan , Mohammad Kazem , Tavafian Sedigheh Sadat , Jazayery Abolghasem , Montazeri Ali
Published: January 2010

Background

There is substantial evidence that low consumption of fruit and vegetables (FV) is a major risk factor for many chronic diseases. The aim of this study was to assess FV consumption and the variables that influence it among elderly individuals in Iran aged 60 and over.

Methods

This was a cross-sectional study to investigate FV intake by a randomly-selected sample of members of elderly centers in Tehran, Iran. A multidimensional questionnaire was used to collect data on demographic characteristics, daily consumption of FV, knowledge, self-efficacy, social support, perceived benefits, and barriers against FV. Data were analyzed using t-tests, one way analysis of variance, Pearson correlation, and logistic regression.

Results

In total, 400 elderly individuals took part in the study. The mean age of the participants was 64.07 (SD = 4.49) years, and most were female (74.5%). The mean number of FV servings per day was 1.76 (SD = 1.15). Ninety-seven percent of participants (n = 388) did not know the recommended intake was at least five servings of FV per day. Similarly, 88.3% (n = 353) did not know the size of a single serving. The most frequent perceived benefits of and barriers against FV consumption were availability and expense, respectively. Knowledge (OR = 0.59, 95% CI = 0.39-0.88), perceived benefits (OR = 0.92, 95% CI = 0.88-0.96) and barriers (OR = 1.08, 95% CI = 1.04-1.14), self-efficacy (OR = 0.89, 95% CI = 0.83-0.95) and family support (OR = 0.91, 95% CI = 0.83-0.99) were significantly associated with fruit and vegetable consumption.

Conclusion

The findings of this study indicate that FV intake among elderly individuals in Iran was lower than the recommended minimum of five daily servings and varied greatly with age, marital status, educational attainment, and income level. The results also indicated that low perceived benefits, low self-efficacy, and perceived barriers could lead to lower consumption of FV. It seems that in order to improve FV consumption among elderly individuals in Iran, raising awareness, improving perception of benefits and enhancing self-efficacy regarding FV consumption should receive more attention. Indeed, it is essential to plan health education programs and nutritional interventions for this group of the population.
Changes in the proteomes of the hemocytes and fat bodies of the flesh fly Sarcophaga bullata larvae after infection by Escherichia coli
Authors: Masova Alice , Sanda Miloslav , Jiracek Jiri , Selicharova Irena
Published: January 2010

Background

Insects have an efficient self-defense system that is based on innate immunity. Recent findings have disclosed many parallels between human and insect innate immunity, and simultaneously fine differences in the processes between various species have been revealed. Studies on the immune systems of various insect species may uncover the differences in their host defense strategies.

Results

We analyzed the proteomes of the hemocytes and fat bodies ofSarcophaga bullatalarvae after infection byEscherichia coli. The 2-DE gels of the hemocytes and fat bodies of infected larvae were compared with those of aseptically injured larvae. Our analysis included the construction of protein maps of the hemocyte cells and cells from fat bodies, the identification of the changed proteins, in response to infection, using LC-MS/MS, and the estimation of the trends in expression of these proteins at three time points (30 min, 6 hours and 22 hours) after infection. In total, seven changed spots were found in the hemocytes, and four changed spots were found in the fat bodies. Three types of trends in protein expression were observed. Cofilin and transgelin were undetectable at 30 min after infection but were continuously up-regulated in the induced larvae after 22 hours. A prophenoloxidase isoform and lectin subunit α were slightly up-regulated at 30 min after infection, and their protein levels reached the highest points after 6 hours but decreased after 22 hours. T-Complex subunit α, GST, ferritin-like protein and an anterior fat body protein (regucalcin homologue) were down-regulated at 22 hours after infection.

Conclusions

Many proteins identified in our study corresponded to the proteins identified in other insects. Compared to the former studies performed in insects, we presented 2-D protein maps of the hemocytes and fat bodies and showed the trends in expression of the immune-elicited proteins.
A quantitative real time PCR method to analyze T cell receptor Vβ subgroup expansion by staphylococcal superantigens
Authors: Seo Keun Seok , Park Joo Youn , Terman David S , Bohach Gregory A
Published: January 2010

Background

Staphylococcal enterotoxins (SEs), SE-like (SEl) toxins, and toxic shock syndrome toxin-1 (TSST-1), produced byStaphylococcus aureus, belong to the subgroup of microbial superantigens (SAgs). SAgs induce clonal proliferation of T cells bearing specific variable regions of the T cell receptor β chain (Vβ). Quantitative real time PCR (qRT-PCR) has become widely accepted for rapid and reproducible mRNA quantification. Although the quantification of Vβ subgroups using qRT-PCR has been reported, qRT-PCR using both primers annealing to selected Vβ nucleotide sequences and SYBR Green I reporter has not been applied to assess Vβ-dependent expansion of T cells by SAgs.

Methods

Human peripheral blood mononuclear cells were stimulated with various SAgs or a monoclonal antibody specific to human CD3. Highly specific expansion of Vβ subgroups was assessed by qRT-PCR using SYBR Green I reporter and primers corresponding to selected Vβ nucleotide sequences.

Results

qRT-PCR specificities were confirmed by sequencing amplified PCR products and melting curve analysis. To assess qRT-PCR efficiencies, standard curves were generated for each primer set. The average slope and R2of standard curves were -3.3764 ± 0.0245 and 0.99856 ± 0.000478, respectively, demonstrating that the qRT-PCR established in this study is highly efficient. With some exceptions, SAg Vβ specificities observed in this study were similar to those reported in previous studies.

Conclusions

The qRT-PCR method established in this study produced an accurate and reproducible assessment of Vβ-dependent expansion of human T cells by staphylococcal SAgs. This method could be a useful tool in the characterization T cell proliferation by newly discovered SAg and in the investigation of biological effects of SAgs linked to pathogenesis.
An evaluation of inflammatory gene polymorphisms in sibships discordant for premature coronary artery disease: the GRACE-IMMUNE study
Authors: Brown Benjamin D , Nsengimana Jérémie , Barrett Jennifer H , Lawrence Richard A , Steiner Lori , Cheng Suzanne , Bishop D Timothy , Samani Nilesh J , Ball Stephen G , Balmforth Anthony J , Hall Alistair S
Published: January 2010

Background

Inflammatory cytokines play a crucial role in coronary artery disease (CAD). We investigated the association between 48 coding and three non-coding single nucleotide polymorphisms (SNPs) from 35 inflammatory genes and the development of CAD, using a large discordant sibship collection (2699 individuals in 891 families).

Methods

Family-based association tests (FBAT) and conditional logistic regression (CLR) were applied to single SNPs and haplotypes and, in CLR, traditional risk factors of CAD were adjusted for.

Results

An association was observed between CAD and a common three-locus haplotype in the interleukin one (IL-1) cluster with P = 0.006 in all CAD cases, P = 0.01 in myocardial infarction (MI) cases and P = 0.0002 in young onset CAD cases (<50 years). The estimated odds ratio (OR) per copy of this haplotype is 1.21 (95% confidence interval [95CI] = 1.04 - 1.40) for CAD; 1.30 (95CI = 1.09 - 1.56) for MI and 1.50 (95CI = 1.22 - 1.86) for young onset CAD. When sex, smoking, hypertension and hypercholesterolaemia were adjusted for, the haplotype effect remained nominally significant (P = 0.05) in young onset CAD cases, more so (P = 0.002) when hypercholesterolaemia was excluded. As many as 82% of individuals affected by CAD had hypercholesterolaemia compared to only 29% of those unaffected, making the two phenotypes difficult to separate.

Conclusion

Despite the multiple hypotheses tested, the robustness of family design to population confoundings and the consistency with previous findings increase the likelihood of true association. Further investigation using larger data sets is needed in order for this to be confirmed.

See the related commentary by Keavney: http://www.biomedcentral.com/1741-7015/8/6
A high protein moderate carbohydrate diet fed at discrete meals reduces early progression of N-methyl-N-nitrosourea-induced breast tumorigenesis in rats
Authors: Moulton Christopher J , Valentine Rudy J , Layman Donald K , Devkota Suzanne , Singletary Keith W , Wallig Matthew A , Donovan Sharon M
Published: January 2010

Breast cancer is the most prevalent cancer in American women. Dietary factors are thought to have a strong influence on breast cancer incidence. This study utilized a meal-feeding protocol with female Sprague-Dawley rats to evaluate effects of two ratios of carbohydrate:protein on promotion and early progression of breast tissue carcinomas. Mammary tumors were induced by N-methyl-N-nitrosourea (MNU) at 52 d of age. Post-induction, animals were assigned to consume either a low protein high carbohydrate diet (LPHC; 15% and 60% of energy, respectively) or a high protein moderate carbohydrate diet (HPMC; 35% and 40% of energy, respectively) for 10 wk. Animals were fed 3 meals/day to mimic human absorption and metabolism patterns. The rate of palpable tumor incidence was reduced in HPMC relative to LPHC (12.9 ± 1.4%/wk vs. 18.2 ± 1.3%/wk). At 3 wk, post-prandial serum insulin was larger in the LPHC relative to HPMC (+136.4 ± 33.1 pmol/L vs. +38.1 ± 23.4 pmol/L), while at 10 wk there was a trend for post-prandial IGF-I to be increased in HPMC (P= 0.055). There were no differences in tumor latency, tumor surface area, or cumulative tumor mass between diet groups. The present study provides evidence that reducing the dietary carbohydrate:protein ratio attenuates the development of mammary tumors. These findings are consistent with reduced post-prandial insulin release potentially diminishing the proliferative environment required for breast cancer tumors to progress.
ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain
Authors: Beyer Nancy , Coulson David TR , Heggarty Shirley , Ravid Rivka , Irvine G Brent , Hellemans Jan , Johnston Janet A
Published: January 2010

Background

ZnT3 is a membrane Zn2+ transporter that is responsible for concentrating Zn2+ into neuronal presynaptic vesicles. Zn2+ homeostasis in the brain is relevant to Alzheimer's disease (AD) because Zn2+ released during neurotransmission may bind to Aβ peptides, accelerating the assembly of Aβ into oligomers which have been shown to impair synaptic function.

Results

We quantified ZnT3 mRNA levels in Braak-staged human post mortem (pm) brain tissue from medial temporal gyrus, superior occipital gyrus, superior parietal gyrus, superior frontal gyrus and cerebellum from individuals with AD (n = 28), and matched controls (n = 5) using quantitative real-time PCR. ZnT3 mRNA levels were significantly decreased in all four cortical regions examined in the AD patients, to 45-60% of control levels. This reduction was already apparent at Braak stage 4 in most cortical regions examined. Quantification of neuronal and glial-specific markers in the same samples (neuron-specific enolase, NSE; and glial fibrillary acidic protein, GFAP) indicated that loss of cortical ZnT3 expression was more pronounced, and occurred prior to, significant loss of NSE expression in the tissue. Significant increases in cortical GFAP expression were apparent as the disease progressed. No gene expression changes were observed in the cerebellum, which is relatively spared of AD neuropathology.

Conclusions

This first study to quantify ZnT3 mRNA levels in human pm brain tissue from individuals with AD and controls has revealed a significant loss of ZnT3 expression in cortical regions, suggesting that neuronal cells in particular show reduced expression of ZnT3 mRNA in the disease. This suggests that altered neuronal Zn2+ handling may be an early event in AD pathogenesis.
Correlation of pain relief with physical function in hand osteoarthritis: randomized controlled trial post hocanalysis
Authors: Barthel H Richard , Peniston John H , Clark Michael B , Gold Morris S , Altman Roy D
Published: January 2010

Introduction

Nonsteroidal anti-inflammatory drugs are recommended for the relief of pain associated with hand osteoarthritis (OA) but do not alter the underlying structural changes that contribute to impaired physical function. The current analysis examined the relationship of pain relief with measures of function and global rating of disease in patients with hand OA.

Methods

This was a combined analysis of 2 prospective, randomized, double-blind, 8-week, multicenter, parallel-group studies comparing diclofenac sodium 1% gel with placebo gel (vehicle) in patients with radiographically confirmed mild to moderate hand OA. Patients (n = 783) aged ≥ 40 years applied diclofenac sodium 1% gel (2 g) or vehicle to each hand 4 times daily for 8 weeks. Outcome measures included pain intensity assessed on a 100-mm Visual Analog Scale (VAS); the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) subscales for pain, stiffness, and physical function (100-mm VAS); and a global rating of disease (100-mm VAS). Change in VAS pain intensity from baseline to week 8 was categorized (<0%, 0%-<15%, 15%-<30%, 30%-<50%, 50%-<70%, and ≥ 70%) without regard to treatment and compared in each category with the mean change from baseline in each AUSCAN subindex and the global rating of disease. Pearson correlations between changes in outcome measures from baseline to week 8 were calculated.

Results

Changes in VAS pain intensity were accompanied by similar changes in AUSCAN scores and global rating of disease. Pearson correlations confirmed significant associations (P < 0.001) between change in VAS pain intensity and changes in AUSCAN pain (correlation coefficient [r] = 0.81), AUSCAN function (r = 0.75), AUSCAN stiffness (r = 0.66), and global rating of disease (r = 0.76).

Conclusions

Pain relief correlated with improvements in physical function, stiffness, and global rating of disease in patients with hand OA, irrespective of treatment. This suggests that pain or anticipation of pain inhibits physical function and influences patient perception of disease severity in hand OA. These results also suggest that any intervention to relieve the pain of hand OA may improve function and patient perception of disease severity, despite the absence of a disease-modifying mechanism of action.

Trial registration

Clinicaltrials.gov NCT00171652, NCT00171665.
Disruption of the Single Copy Gonadotropin-Releasing Hormone Receptor in Mice by Gene Trap: Severe Reduction of Reproductive Organs and Functions in Developing and Adult Mice
Authors: Wu Sheng , Wilson Michael D. , Busby Ellen R. , Isaac Emma R. , Sherwood Nancy M.
Published: January 2010

Mutations in the GnRH receptor gene (GNRHR) can result in hypogonadotropic hypogonadism in humans. Unlike most mammals, mice lack a second form of GnRH (GnRH2) and a type 2 GnRH receptor. To determine whether the GnRH receptor is critical at all stages of reproduction and whether this receptor has additional physiological functions in developing and adult mice, we have generated mice from an embryonic stem cell line containing a retroviral vector with multiple stop codons inserted into intron 1 of the Gnrhr gene. This gene trap insertion resulted in the disruption of exon 2 and exon 3 of the Gnrhr gene. The insertion also contained a lacZ gene that was used as a reporter for GnRH receptor expression in these mice. This model has a similar phenotype to the clinical syndrome of hypogonadotropic hypogonadism. Null Gnrhr mice had small sexual organs, low levels of FSH, LH, and steroid hormones, failure of sexual maturation, infertility, and inability to respond to exogenous GnRH. However, the defective GnRH receptor did not prevent morula/blastocyst development, implantation, masculinization of fetal male mice, or maintenance of early pregnancy. The phenotype of this null Gnrhr mouse was more severe than models in the literature, including the N-ethyl-N-nitrosourea-induced Gnrhr mutant, the kisspeptin (Kiss1) knockout, and the kisspeptin receptor (Gpr54) knockout. In terms of gonadal morphology, adult gene trap-Gnrhr null mice demonstrate a complete cessation of reproduction and serve as an important model for understanding GnRH/GnRHR physiology.
Nonmuscle Myosin IIA (Myosin Heavy Polypeptide 9): A Novel Class of Signal Transducer Mediating the Activation of Gαh/Phospholipase C-δ1 Pathway
Authors: Lin Yuan-Feng , Yeh Tien-Shun , Chen Sung-Fang , Tsai Yu-Hui , Chou Chih-Ming , Yang Yi-Yuan , Huang Haw-Ming
Published: January 2010

The dimeric Gh protein is comprised of α (tissue transglutaminase) and β (Calreticulin) subunits and known to be associated with FSH-, oxytocin-, or epinephrine-receptors/functions in their respective target cells. After establishing the FSH-induced activation of Gαh/phospholipase C (PLC)-δ1 pathway in rat Sertoli cells (SCs), we have attempted to identify a possible Gαh-coupled novel FSH receptor (FSH-R). Remarkably, a protein with approximately 240-kDa molecular mass was coimmunoprecipitated with Gαh in the fractionated membrane proteins of rat SCs. The protein was identified as myosin heavy polypeptide 9 (MyH9) by mass spectrometric analysis and immunoblotting. In addition, immunoprecipitation analysis reveals that MyH9 is constitutively associated with classical Gs-coupled FSH-R and inactive GDP-bound Gαh at resting state of rat SCs, but did not interact with FSH directly as judged by Far-Western analysis. Upon the stimulation of higher levels of extracellular FSH (>1000 IU/liter), classical FSH-R induces the phosphorylation of MyH9, the dissociation of active GTP-bound Gαh from FSH-R:MyH9 complexes, and the elicitation of Gαh/PLC-δ1 pathway-dependent Ca2+-influx in rat SCs. Furthermore, the specific inhibition of MyH9 ATPase activity with Blebbistatin dose-dependently suppressed FSH-induced Gαh/PLC-δ1 signaling and Ca2+-influx, but not intracellular cAMP accumulation in rat SCs, implying that MyH9 mediates FSH-induced activation of Gαh/PLC-δ1/IP3/Ca2+-influx pathway in rat SCs. This is the first to demonstrate that the filament protein MyH9 constitutively forms a ternary complex with FSH-R and inactive GDP-bound Gαh. At higher FSH levels, this ternary complex executes an alternative signaling of classical Gs-coupled FSH-R through activating a Gs/cAMP-independent, Gαh/PLC-δ1 pathway in rat SCs.
Gene Expression Profiling Identifies Key Estradiol Targets in the Frontal Cortex of the Rat
Authors: Sárvári Miklós , Hrabovszky Erik , Kalló Imre , Galamb Orsolya , Solymosi Norbert , Likó István , Molnár Béla , Tihanyi Károly , Szombathelyi Zsolt , Liposits Zsolt
Published: January 2010

Estradiol modulates a wide range of neural functions in the frontal cerebral cortex where subsets of neurons express estrogen receptor-α and -β. Through these receptors, estradiol contributes to the maintenance of normal operation of the frontal cortex. During the decline of gonadal hormones, the frequency of neurological and psychiatric disorders increases. To shed light on the etiology of disorders related to declining levels of estrogens, we studied the genomic responses to estradiol. Ovariectomized rats were treated with a sc injection of estradiol. Twenty-four hours later, samples from the frontal cortices were dissected, and their mRNA content was analyzed. One hundred thirty-six estradiol-regulated transcripts were identified on Rat 230 2.0 Expression Array. Of the 136 estrogen-regulated genes, 26 and 36 genes encoded proteins involved in the regulation of transcription and signal transduction, respectively. Thirteen genes were related to the calcium signaling pathway. They comprised five genes coding for neurotransmitter receptors. Transcription of three neuropeptides, including cocaine- and amphetamine-regulated transcript, were up-regulated. Fifty-two genes were selected for validation, and 12 transcriptional changes were confirmed. These results provided evidence that estradiol evokes broad transcriptional response in the cortex. Modulation of key components of the calcium signaling pathway, dopaminergic, serotonergic, and glutamatergic neurotransmission, may explain the influence of estrogens on cognitive function and behavior. Up-regulation of cocaine- and amphetamine-regulated transcript contributes to the neuroprotective effects of estradiol. Identification of estradiol-regulated genes in the frontal cortex helps to understand the pathomechanism of neurological and psychiatric disorders associated with altered levels of estrogens.
Food Politics and Consumption in Peronist Argentina
Authors: Milanesio Natalia
Published: January 2010

From the beginning of Juan Domingo Perón’s administration, food consumption was both a significant object of state policy and a central component of official propaganda. This essay resists the analytical separation between politics and imaginaries in order to expand our understanding of Peronism in new directions. First, it shows the economic, political, and iconographic centrality of food for state planning, commercial culture, public health, and definitions of social, national, and physical well-being. Second, the essay reinterprets nationalism and social entitlement—concepts that researchers have identified as key in Peronist ideology—through a new focus on food. An increase in per capita beef consumption, beyond serving as a symbol of popular well-being, undermined the images of Argentina as an export economy subservient to foreign capitalism. By favoring internal consumers over external markets, Peronist beef politics created an empowering ideology of economic sovereignty. This ideology reinforced the commitment of the state to benefit the local population in the distribution of national wealth. Between 1946 and 1949, the government popularized the rise in beef intake as the new entitlement of the working classes to what had previously been a “luxury food.” Finally, the analysis demonstrates that Peronism collected and instrumentally continued or redefined key arguments circulating in Argentine popular culture and medical and leftist discourses, including the relation of beef consumption to nationalism, luxury, rights, and health; the intervention of the state in nutritional issues; the dietary education of the masses; and the connection between nationalism, tradition, and culinary culture.
Functional characterization of protein-sorting machineries at the trans-Golgi network in Drosophila melanogaster
Authors: Kametaka Satoshi , Sawada Naoki , Bonifacino Juan S. , Waguri Satoshi
Published: January 2010

Targeting of proteins to their final destination is a prerequisite for living cells to maintain their homeostasis. Clathrin functions as a coat that forms transport carriers called clathrin-coated vesicles (CCVs) at the plasma membrane and post-Golgi compartments. In this study, we established an experimental system using Schneider S2 cells derived from the fruit fly, Drosophila melanogaster, as a model system to study the physiological roles of clathrin adaptors, and to dissect the processes of CCV formation. We found that a clathrin adaptor Drosophila GGA (dGGA), a homolog of mammalian GGA proteins, localizes to the trans-Golgi network (TGN) and is capable of recruiting clathrin from the cytosol onto TGN membranes. dGGA itself is recruited from the cytosol to the TGN in an ARF1 small GTPase (dARF79F)-dependent manner. dGGA recognizes the cytoplasmic acidic-cluster-dileucine (ACLL) sorting signal of Lerp (lysosomal enzyme receptor protein), a homolog of mammalian mannose 6-phosphate receptors. Moreover, both dGGA and another type of TGN-localized clathrin adaptor, AP-1 (adaptor protein-1 complex), are shown to be involved in the trafficking of Lerp from the TGN to endosomes and/or lysosomes. Taken together, our findings indicate that the protein-sorting machinery in fly cells is well conserved relative to that in mammals, enabling the use of fly cells to dissect CCV biogenesis and clathrin-dependent protein trafficking at the TGN of higher eukaryotes.
FAK-mediated extracellular signals are essential for interkinetic nuclear migration and planar divisions in the neuroepithelium
Authors: Tsuda Sachiko , Kitagawa Tadao , Takashima Shigeo , Asakawa Shuichi , Shimizu Nobuyoshi , Mitani Hiroshi , Shima Akihiro , Tsutsumi Makiko , Hori Hiroshi , Naruse Kiyoshi , Ishikawa Yuji , Takeda Hiroyuki
Published: January 2010

During the development of the vertebrate nervous system, mitosis of neural progenitor cells takes place near the lumen, the apical side of the neural tube, through a characteristic movement of nuclei known as interkinetic nuclear migration (INM). Furthermore, during the proliferative period, neural progenitor cells exhibit planar cell divisions to produce equivalent daughter cells. Here, we examine the potential role of extracellular signals in INM and planar divisions using the medaka mutant tacobo (tab). This tab mutant shows pleiotropic phenotypes, including neurogenesis, and positional cloning identified tab as laminin γ1 (lamc1), providing a unique framework to study the role of extracelluar signals in neurogenesis. In tab mutant neural tubes, a number of nuclei exhibit abnormal patterns of migration leading to basally mislocalized mitosis. Furthermore, the orientation of cell division near the apical surface is randomized. Probably because of these defects, neurogenesis is accelerated in the tab neural tube. Detailed analyses demonstrate that extracellular signals mediated by the FAK pathway regulate INM and planar divisions in the neuroepithelium, possibly through interaction with the intracellular dynein-motor system.
Cytoskeletal coherence requires myosin-IIA contractility
Authors: Cai Yunfei , Rossier Olivier , Gauthier Nils C. , Biais Nicolas , Fardin Marc-Antoine , Zhang Xian , Miller Lawrence W. , Ladoux Benoit , Cornish Virginia W. , Sheetz Michael P.
Published: January 2010

Maintaining a physical connection across cytoplasm is crucial for many biological processes such as matrix force generation, cell motility, cell shape and tissue development. However, in the absence of stress fibers, the coherent structure that transmits force across the cytoplasm is not understood. We find that nonmuscle myosin-II (NMII) contraction of cytoplasmic actin filaments establishes a coherent cytoskeletal network irrespective of the nature of adhesive contacts. When NMII activity is inhibited during cell spreading by Rho kinase inhibition, blebbistatin, caldesmon overexpression or NMIIA RNAi, the symmetric traction forces are lost and cell spreading persists, causing cytoplasm fragmentation by membrane tension that results in ‘C’ or dendritic shapes. Moreover, local inactivation of NMII by chromophore-assisted laser inactivation causes local loss of coherence. Actin filament polymerization is also required for cytoplasmic coherence, but microtubules and intermediate filaments are dispensable. Loss of cytoplasmic coherence is accompanied by loss of circumferential actin bundles. We suggest that NMIIA creates a coherent actin network through the formation of circumferential actin bundles that mechanically link elements of the peripheral actin cytoskeleton where much of the force is generated during spreading.
Digestive-vacuole genesis and endocytic processes in the early intraerythrocytic stages ofPlasmodium falciparum
Authors: Bakar Nurhidanatasha Abu , Klonis Nectarios , Hanssen Eric , Chan Cherrine , Tilley Leann
Published: January 2010

The digestive vacuole of the malaria parasite Plasmodium falciparum is the site of haemoglobin digestion and haem detoxification, and is the target of chloroquine and other antimalarials. The mechanisms for genesis of the digestive vacuole and transfer of haemoglobin from the host cytoplasm are still debated. Here, we use live-cell imaging and photobleaching to monitor the uptake of the pH-sensitive fluorescent tracer SNARF-1-dextran from the erythrocyte cytoplasm in ring-stage and trophozoite-stage parasites. We compare these results with electron tomography of serial sections of parasites at different stages of growth. We show that uptake of erythrocyte cytoplasm is initiated in mid-ring-stage parasites. The host cytoplasm is internalised via cytostome-derived invaginations and concentrated into several acidified peripheral structures. Haemoglobin digestion and haemozoin formation take place in these vesicles. The ring-stage parasites can adopt a deeply invaginated cup shape but do not take up haemoglobin via macropinocytosis. As the parasite matures, the haemozoin-containing compartments coalesce to form a single acidic digestive vacuole that is fed by haemoglobin-containing vesicles. There is also evidence for haemoglobin degradation in compartments outside the digestive vacuole. The work has implications for the stage specificity of quinoline and endoperoxide antimalarials.
Boundary element method analysis of assembled plate structures undergoing large deflection
Authors: Di Pisa C , Aliabadi M H , Young A
Published: January 2010

The boundary element method (BEM) for large deflection of shear deformable plates is reformulated to the case of multi-section assembled plate structures. Each plate section is modelled as a BEM region under membrane and bending loads, with force, moments, displacements, and rotations represented by generalized traction and displacement nodal variables on the boundary. Non-linear terms in the boundary integral formulation for each section that arises owing to large deflection are treated as effective body forces, and the associated domain integrals are transformed into boundary integrals using the dual reciprocity method. Derivatives of stresses and deflection on the boundary arise in the non-linear terms, and are evaluated by exploring their values at interior domain points using radial basis functions. Plate sections are joined along their edges using compatibility and equilibrium conditions involving the generalized traction and displacement nodal variables. The resulting non-linear equation system is solved numerically using an incremental load approach. An illustrative example of the method is presented for a transversely loaded plate reinforced with Z-stringers.