bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of calpain-1 in human carotid artery atherosclerotic lesions
Authors: Gonçalves Isabel , Nitulescu Mihaela , Saido Takaomi C , Dias Nuno , Pedro Luis M , e Fernandes José Fernandes , Ares Mikko PS , Pörn-Ares Isabella
Published: July 2009

Background

In a previous study, we observed that oxidized low-density lipoprotein-induced death of endothelial cells was calpain-1-dependent. The purpose of the present paper was to study the possible activation of calpain in human carotid plaques, and to compare calpain activity in the plaques from symptomatic patients with those obtained from patients without symptoms.

Methods

Human atherosclerotic carotid plaques (n = 29, 12 associated with symptoms) were removed by endarterectomy. Calpain activity and apoptosis were detected by performing immunohistochemical analysis and TUNEL assay on human carotid plaque sections. An antibody specific for calpain-proteolyzed α-fodrin was used on western blots.

Results

We found that calpain was activated in all the plaques and calpain activity colocalized with apoptotic cell death. Our observation of autoproteolytic cleavage of the 80 kDa subunit of calpain-1 provided further evidence for enzyme activity in the plaque samples. When calpain activity was quantified, we found that plaques from symptomatic patients displayed significantly lower calpain activity compared with asymptomatic plaques.

Conclusion

These novel results suggest that calpain-1 is commonly active in carotid artery atherosclerotic plaques, and that calpain activity is colocalized with cell death and inversely associated with symptoms.
DDEC: Dragon database of genes implicated in esophageal cancer
Authors: Essack Magbubah , Radovanovic Aleksandar , Schaefer Ulf , Schmeier Sebastian , Seshadri Sundararajan V , Christoffels Alan , Kaur Mandeep , Bajic Vladimir B
Published: July 2009

Background

Esophageal cancer ranks eighth in order of cancer occurrence. Its lethality primarily stems from inability to detect the disease during the early organ-confined stage and the lack of effective therapies for advanced-stage disease. Moreover, the understanding of molecular processes involved in esophageal cancer is not complete, hampering the development of efficient diagnostics and therapy. Efforts made by the scientific community to improve the survival rate of esophageal cancer have resulted in a wealth of scattered information that is difficult to find and not easily amendable to data-mining. To reduce this gap and to complement available cancer related bioinformatic resources, we have developed a comprehensive database (Dragon Database of Genes Implicated in Esophageal Cancer) with esophageal cancer related information, as an integrated knowledge database aimed at representing a gateway to esophageal cancer related data.

Description

Manually curated 529 genes differentially expressed in EC are contained in the database. We extracted and analyzed the promoter regions of these genes and complemented gene-related information with transcription factors that potentially control them. We further, precompiled text-mined and data-mined reports about each of these genes to allow for easy exploration of information about associations of EC-implicated genes with other human genes and proteins, metabolites and enzymes, toxins, chemicals with pharmacological effects, disease concepts and human anatomy. The resulting database, DDEC, has a useful feature to display potential associations that are rarely reported and thus difficult to identify. Moreover, DDEC enables inspection of potentially new 'association hypotheses' generated based on the precompiled reports.

Conclusion

We hope that this resource will serve as a useful complement to the existing public resources and as a good starting point for researchers and physicians interested in EC genetics. DDEC is freely accessible to academic and non-profit users at http://apps.sanbi.ac.za/ddec/. DDEC will be updated twice a year.
Prevalence of obsessive-compulsive disorder in Turkish university students and assessment of associated factors
Authors: Yoldascan Elcin , Ozenli Yarkin , Kutlu Oguz , Topal Kenan , Bozkurt Ali Ihsan
Published: July 2009

Background

Many students who begin university at risky periods for OCD development cannot meet the new challenges successfully. They often seek help and apply to the university health center for psychiatric distress. We aimed to determine the prevalence and associated factors of Obsessive Compulsive Disorder (OCD) at students of the Cukurova University in this cross sectional study.

Methods

This study was performed in the Cukurova University Faculty of Education with a population of 5500 students; the representative sample size for detecting the OCD prevalence was calculated to be 800. After collecting sociodemographic data, we questioned the students for associated factors of OCD. The General Health Questionnaire-12 (GHQ-12) and Composite International Diagnostic Interview (CIDI, Section K) were used for psychiatric evaluation. Logistic regression analysis was performed to evaluate the linkage between OCD and associated factors.

Results

A total of 804 university students were included in this study. The GHQ-12-positive students (241 students, 29.9%) were interviewed using Section K of the CIDI (222 students, 27.6%). OCD was diagnosed in 33 (4.2%) students. The Logistic regression analysis of the data showed significant associations between OCD and male gender (p:0.036), living on government dormitory (p: 0.003), living on students' house/parental house (p:0.006), having private room in the parental house (p:0.055) and verbal abuse in the family (p:0.006).

Conclusion

This study demonstrates a higher prevalence of OCD among a group of university students compared to other prevalence studies of OCD in Turkish society. Furthermore, our findings also suggest relationships between OCD and sociodemographic factors, as well as other environmental stress factors.
Coming home to die? the association between migration and mortality in rural South Africa
Authors: Welaga Paul , Hosegood Victoria , Weiner Renay , Hill Caterina , Herbst Kobus , Newell Marie-Louise
Published: July 2009

Background

Studies on migration often ignore the health and social impact of migrants returning to their rural communities. Several studies have shown migrants to be particularly susceptible to HIV infection. This paper investigates whether migrants to rural households have a higher risk of dying, especially from HIV, than non-migrants.

Methods

Using data from a large and ongoing Demographic Surveillance System, 41,517 adults, enumerated in bi-annual rounds between 2001 and 2005, and aged 18 to 60 years were categorized into four groups: external in-migrants, internal migrants, out-migrants and residents. The risk of dying by migration status was quantified by Cox proportional hazard regression. In a sub-group analysis of 1212 deaths which occurred in 2000 – 2001 and for which cause of death information was available, the relationship between migration status and dying from AIDS was examined in logistic regression.

Results

In all, 618 deaths were recorded among 7,867 external in-migrants, 255 among 4,403 internal migrants, 310 among 11,476 out-migrants and 1900 deaths were registered among 17,771 residents. External in-migrants were 28% more likely to die than residents [adjusted Hazard Ratio (aHR) = 1.28, P < 0.001, 95% Confidence Interval (CI) (1.16, 1.41)]. In the sub-group analysis, the odds of dying from AIDS was 1.79 [adjusted Odd ratio (aOR) = 1.79, P = 0.009, 95% CI (1.15, 2.78)] for external in-migrants compared to residents; there was no statistically significant difference in AIDS mortality between residents and out-migrants, [aOR = 1.25, P = 0.533, 95% CI (0.62–2.53)]. Independently, females were more likely to die from AIDS than males [aOR = 2.35, P < 0.001, 95% CI (1.79, 3.08)].

Conclusion

External in-migrants have a higher risk of dying, especially from HIV related causes, than residents, and in areas with substantial migration this needs to be taken into account in evaluating mortality statistics and planning health care services.
A randomized cross-over study of the quality of cardiopulmonary resuscitation among females performing 30:2 and hands-only cardiopulmonary resuscitation
Authors: Trowbridge Cynthia , Parekh Jesal N , Ricard Mark D , Potts Jerald , Patrickson W Clive , Cason Carolyn L
Published: July 2009

Background

Hands-Only cardiopulmonary resuscitation (CPR) is recommended for use on adult victims of witnessed out-of-hospital (OOH) sudden cardiac arrest or in instances where rescuers cannot perform ventilations while maintaining minimally interrupted quality compressions. Promotion of Hands-Only CPR should improve the incidence of bystander CPR and, subsequently, survival from OOH cardiac arrest; but, little is known about a rescuer's ability to deliver continuous chest compressions of adequate rate and depth for periods typical of emergency services response time. This study evaluated chest compression rate and depth as subjects performed Hands-Only CPR for 10 minutes. For comparison purposes, each also performed chest compressions with ventilations (30:2) CPR. It also evaluated fatigue and changes in body biomechanics associated with each type of CPR.

Methods

Twenty healthy female volunteers certified in basic life support performed Hands-Only CPR and 30:2 CPR on a manikin. A mixed model repeated measures cross-over design evaluated chest compression rate and depth, changes in fatigue (chest compression force, perceived exertion, and blood lactate level), and changes in electromyography and joint kinetics and kinematics.

Results

All subjects completed 10 minutes of 30:2 CPR; but, only 17 completed 10 minutes of Hands-Only CPR. Rate, average depth, percentage at least 38 millimeters deep, and force of compressions were significantly lower in Hands-Only CPR than in 30:2 CPR. Rates were maintained; but, compression depth and force declined significantly from beginning to end CPR with most decrement occurring in the first two minutes. Perceived effort and joint torque changes were significantly greater in Hands-Only CPR. Performance was not influenced by age.

Conclusion

Hands-Only CPR required greater effort and was harder to sustain than 30:2 CPR. It is not known whether the observed greater decrement in chest compression depth associated with Hands-Only CPR would offset the potential physiological benefit of having fewer interruptions in compressions during an actual resuscitation. The dramatic decrease in compression depth in the first two minutes reinforces current recommendations that rescuers take turns performing compressions, switching every two minutes or less. Further study is recommended to determine the impact of real-time feedback and dispatcher coaching on rescuer performance.
Anti-malarial activity of 6-(8'Z-pentadecenyl)-salicylic acid from Viola websteri in mice
Authors: Chung Ill-Min , Seo Su-Hyun , Kang Eun-Young , Park Won-Hwan , Moon Hyung-In
Published: July 2009

Background

Petroleum ether extracts of Viola websteri Hemsl (Violaceae) were reported to have anti-plasmodial activity against Plasmodium falciparum in vitro, with this activity being largely attributable to 6-(8'Z-pentadecenyl)-salicylic acid (6-SA).

Methods

The schizontocidal activity of 6-SA on early Plasmodium berghei infections was evaluated in a four-day test. The possible 'repository' activity of 6-SA was assessed using the method described by Peters. The median lethal dose (LD50) of 6-SA, when given intraperitoneally, was also determined using uninfected ICR mice and the method of Lorke.

Results

In the present study, 6-SA was found to have anti-malarial activity in vivo, when tested against P. berghei in mice. 6-SA at 5, 10 and 25 mg/kg·day exhibited a significant blood schizontocidal activity in four-day early infections, repository evaluations and established infections with a significant mean survival time comparable to that of the standard drug, chloroquine (5 mg/kg·day).

Conclusion

6-SA possesses a moderate anti-malarial activity that could be exploited for malaria therapy.
Oncolytic vaccinia therapy of squamous cell carcinoma
Authors: Yu Zhenkun , Li Sen , Brader Peter , Chen Nanhai , Yu Yong A , Zhang Qian , Szalay Aladar A , Fong Yuman , Wong Richard J
Published: July 2009

Background

Novel therapies are necessary to improve outcomes for patients with squamous cell carcinomas (SCC) of the head and neck. Historically, vaccinia virus was administered widely to humans as a vaccine and led to the eradication of smallpox. We examined the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68) as an oncolytic agent against a panel of six human head and neck SCC cell lines.

Results

All six cell lines supported viral transgene expression (β-galactosidase, green fluorescent protein, and luciferase) as early as 6 hours after viral exposure. Efficient transgene expression and viral replication (>150-fold titer increase over 72 hrs) were observed in four of the cell lines. At a multiplicity of infection (MOI) of 1, GLV-1h68 was highly cytotoxic to the four cell lines, resulting in ≥ 90% cytotoxicity over 6 days, and the remaining two cell lines exhibited >45% cytotoxicity. Even at a very low MOI of 0.01, three cell lines still demonstrated >60% cell death over 6 days. A single injection of GLV-1h68 (5 × 106 pfu) intratumorally into MSKQLL2 xenografts in mice exhibited localized intratumoral luciferase activity peaking at days 2–4, with gradual resolution over 10 days and no evidence of spread to normal organs. Treated animals exhibited near-complete tumor regression over a 24-day period without any observed toxicity, while control animals demonstrated rapid tumor progression.

Conclusion

These results demonstrate significant oncolytic efficacy by an attenuated vaccinia virus for infecting and lysing head and neck SCC both in vitro and in vivo, and support its continued investigation in future clinical trials.
Different gait tasks distinguish immediate vs. long-term effects of concussion on balance control
Authors: Catena Robert D , van Donkelaar Paul , Chou Li-Shan
Published: July 2009

The purpose of this study was to longitudinally compare the sensitivity of previously documented paradigms for measuring balance control during gait following a concussion. We hypothesized that gait with a concurrent cognitive task would be most sensitive to the effects of concussion on dynamic balance control. Individuals with concussion (n = 30) and matched controls (n = 30) performed a single task of level walking, attention divided walking, and an obstacle-crossing task at two heights. Testing occurred four times post-injury. Balance control during gait was assessed with whole-body center of mass and center of pressure motion. The single-task level walking task did not result in any significant differences in balance control between individuals with concussion and control subjects. Within 48 hours post-injury, individuals with concussion walked slower and allowed less motion of their center of mass in the sagittal plane when attention was divided during walking, but there were no group differences by day 6 for this task. Group differences in balance control during obstacle crossing was unremarkable during the first two testing sessions, but by day 14 individuals with concussion displayed less mediolateral motion of their center of mass. Attention divided gait is able to better distinguish gait adaptations immediately following a concussion, but obstacle crossing can be used further along in the recovery process to detect new gait adaptations.
Evidence for a Role of NTS2 Receptors in the Modulation of Tonic Pain Sensitivity
Authors: Roussy Geneviève , Dansereau Marc-André , Baudisson Stéphanie , Ezzoubaa Faouzi , Belleville Karine , Beaudet Nicolas , Martinez Jean , Richelson Elliott , Sarret Philippe
Published: July 2009

Background

Central neurotensin (NT) administration results in a naloxone-insensitive antinociceptive response in animal models of acute and persistent pain. Both NTS1 and NTS2 receptors were shown to be required for different aspects of NT-induced analgesia. We recently demonstrated that NTS2 receptors were extensively associated with ascending nociceptive pathways, both at the level of the dorsal root ganglia and of the spinal dorsal horn. Then, we found that spinally administered NTS2-selective agonists induced dose-dependent antinociceptive responses in the acute tail-flick test. In the present study, we therefore investigated whether activation of spinal NTS2 receptors suppressed the persistent inflammatory pain symptoms observed after intraplantar injection of formalin.

Results

We first demonstrated that spinally administered NT and NT69L agonists, which bind to both NTS1 and NTS2 receptors, significantly reduced pain-evoked responses during the inflammatory phase of the formalin test. Accordingly, pretreatment with the NTS2-selective analogs JMV-431 and levocabastine was effective in inhibiting the aversive behaviors induced by formalin. With resolution at the single-cell level, we also found that activation of spinal NTS2 receptors reduced formalin-induced c-fos expression in dorsal horn neurons. However, our results also suggest that NTS2-selective agonists and NTS1/NTS2 mixed compounds differently modulated the early (21–39 min) and late (40–60 min) tonic phase 2 and recruited endogenous pain inhibitory mechanisms integrated at different levels of the central nervous system. Indeed, while non-selective drugs suppressed pain-related behaviors activity in both part of phase 2, intrathecal injection of NTS2-selective agonists was only efficient in reducing pain during the late phase 2. Furthermore, assessment of the stereotypic pain behaviors of lifting, shaking, licking and biting to formalin also revealed that unlike non-discriminative NTS1/NTS2 analogs reversing all nociceptive endpoint behaviors, pure NTS2 agonists specifically inhibited paw lifting, supporting a role of NTS2 in spinal modulation of persistent nociception.

Conclusion

The present study provides the first demonstration that activation of NTS2 receptors produces analgesia in the persistent inflammatory pain model of formalin. The dichotomy between these two classes of compounds also indicates that both NTS1 and NTS2 receptors are involved in tonic pain inhibition and implies that these two NT receptors modulate the pain-induced behavioral responses by acting on distinct spinal and/or supraspinal neural circuits. In conclusion, development of NT agonists targeting both NTS1 and NTS2 receptors could be useful for chronic pain management.
Extraneural metastases from cranial meningioma: a case report
Authors: Abboud Mirna , Haddad George , Kattar Mireille , Aburiziq Ibrahim , Geara Fady B
Published: July 2009

Extracranial metastases from brain meningiomas is a rare, but well-documented entity. Metastases occur mostly in the lungs, pleura and liver, but may also affect lymph nodes and bones. We report here on a patient who was treated for an atypical brain meningioma with multiple surgeries and multiple sessions of stereotactic radiosurgery with good control of his brain disease. Thirteen years after diagnosis, he developed bilateral large sacroiliac and abdominal metastases.
EBV-positive diffuse large B-cell lymphoma in a human T-lymphotropic virus type 1 carrier
Authors: Beltran Brady , Salas Renzo , Quiñones Pilar , Morales Domingo , Hurtado Fernando , Cotrina Esther , Riva Luis , Castillo Jorge
Published: July 2009

The development of B-cell lymphomas has been seldom described in HTLV-1 carriers. We present the case of an elderly Peruvian HTLV-1 carrier who was diagnosed with EBV-positive diffuse large B-cell lymphoma. Despite an initial good response to therapy, patient died during treatment due to fatal Pneumocystis jirovecci pneumonia. EBV infection is characterized by B-cell lymphotropism and selective immunodeficiency. HTLV-1, on the other hand, induces T-cell dysfunction and B-cell proliferation. Finally, immunosenescence is characterized by T-cell dysregulation, decreased apoptosis and cytokine upregulation. In this elderly patient, the combination of EBV and HTLV-1 coinfection and immunosenescence may have played a role in the development of this aggressive diffuse large B-cell lymphoma. Furthermore, the immunodeficiency caused by the viral infections and chemotherapy may have played a role in developing life-threatening infectious complications.
HER-2 positive breast cancer: decreasing proportion but stable incidence in Finnish population from 1982 to 2005
Authors: Köninki Katri , Tanner Minna , Auvinen Anssi , Isola Jorma
Published: July 2009

Introduction

Classification of breast cancers according to the HER-2 oncogene status is of central importance in the selection of post-surgical therapies. A decrease in the proportion of HER-2-positive breast cancer has been suspected, but no data on the incidence trends at population level have been reported.

Methods

We studied the proportion of HER-2-positive breast cancers by chromogenic in situ hybridization (CISH) in three cohorts (years 1982 to 1986 (n = 310), 1989 to 1992 (n = 108), and 2004 to 2005 (n = 713)) in the population of the Pirkanmaa hospital district (approximately 220,000 women). Cancer incidence rates were age-adjusted to the world standard population.

Results

The proportion of HER-2-positive breast cancer declined from 21.6% (average in 1982 to 1986) to 13.6% (average in 2004 to 2005). However, during the same time period the age-adjusted incidence of all invasive breast cancers had increased by 40%. These opposite trends balanced each other and indicated that the incidence of HER-2-positive breast cancer has remained unchanged (Poisson regression coefficient for time trend 1.000; 95% CI = 0.989 to 1.012). In contrast, the incidence of HER-2-negative cancer showed 2% annual increase (Poisson regression coefficient 1.021, 95% CI = 1.016 to 1.026). Although HER-2-negative cancers were more likely to be diagnosed by mammography screening, the changes were more likely to be explained by etiological risk factors favoring HER-2-negative (and hormone receptor-positive) disease such as menopausal hormone therapy.

Conclusions

These results document a significant decrease in the proportion of HER-2-positive breast cancer. However, the incidence of HER-2-positive cancer at the population level was found to be unchanged.
Thoracic epidural anesthesia time-dependently modulates pulmonary endothelial dysfunction in septic rats
Authors: Lauer Stefan , Freise Hendrik , Westphal Martin , Zarbock Alexander , Fobker Manfred , Van Aken Hugo K , Sielenkämper Andreas W , Fischer Lars G
Published: July 2009

Introduction

Increasing evidence indicates that epidural anesthesia improves postoperative pulmonary function. The underlying mechanisms, however, remain to be determined. Because pulmonary nitric oxide has been identified to play a critical role in pulmonary dysfunction in sepsis, we hypothesized that thoracic epidural anesthesia (TEA) modulates endothelial dysfunction via a nitric oxide-dependent pathway.

Methods

Thirty-six Sprague-Dawley rats underwent sham laparotomy or induction of peritoneal sepsis caused by cecal ligation and puncture (CLP). Septic animals were then treated with either bupivacaine 0.5% or normal saline epidurally (15 μl/h-1) for 6 hours or 24 hours after injury. Previous experiments demonstrated that these time points correspond with a hyperdynamic (at 6 hours) and hypodynamic circulation (at 24 hours), respectively. In addition, two sham control groups received either bupivacaine 0.5% or normal saline epidurally (15 μl/h-1). Six and 24 hours after injury, hemodynamic measurements and arterial blood gas analyses were performed in awake, spontaneously breathing rats. Exhaled nitric oxide, bradykinin-induced pulmonary vasoconstriction (a surrogate marker of endothelial dysfunction), pulmonary wet/dry-weight ratio (an estimate of pulmonary edema), and myeloperoxidase activity (MPO, a surrogate marker of neutrophil infiltration into lung tisssue) were investigated at 6 and 24 hours by using an established model of isolated and perfused lungs.

Results

In hyperdynamic sepsis, treatment with TEA resulted in reduced bradykinin-induced pulmonary vasoconstriction (P < 0.05) and lower levels of exhaled NO as compared with those in untreated septic rats (P < 0.05). However, the development of pulmonary edema or MPO activity in the lungs was not alleviated by sympathetic blockade in this phase of sepsis. Conversely, TEA led to an increased bradykinin-induced pulmonary vasoconstriction and pulmonary edema despite reduced exNO levels and pulmonary MPO activity in hypodynamic sepsis (each P < 0.05 versus CLP 24 h). Pulmonary gas exchange was only marginally affected under the influence of TEA in hypodynamic sepsis. Mean arterial pressure and heart rate were not affected beyond the changes caused by sepsis itself.

Conclusions

The results of the present study suggest that TEA modulates the NO pathway and exerts positive effects on pulmonary endothelial integrity only in hyperdynamic sepsis. Whether the negative effects on endothelial function in hypodynamic sepsis have an impact on overall morbidity and mortality remains to be determined in future studies.
The relation between the incidence of hypernatremia and mortality in patients with severe traumatic brain injury
Authors: Maggiore Umberto , Picetti Edoardo , Antonucci Elio , Parenti Elisabetta , Regolisti Giuseppe , Mergoni Mario , Vezzani Antonella , Cabassi Aderville , Fiaccadori Enrico
Published: July 2009

Introduction

The study was aimed at verifying whether the occurrence of hypernatremia during the intensive care unit (ICU) stay increases the risk of death in patients with severe traumatic brain injury (TBI). We performed a retrospective study on a prospectively collected database including all patients consecutively admitted over a 3-year period with a diagnosis of TBI (post-resuscitation Glasgow Coma Score ≤ 8) to a general/neurotrauma ICU of a university hospital, providing critical care services in a catchment area of about 1,200,000 inhabitants.

Methods

Demographic, clinical, and ICU laboratory data were prospectively collected; serum sodium was assessed an average of three times per day. Hypernatremia was defined as two daily values of serum sodium above 145 mmol/l. The major outcome was death in the ICU after 14 days. Cox proportional-hazards regression models were used, with time-dependent variates designed to reflect exposure over time during the ICU stay: hypernatremia, desmopressin acetate (DDAVP) administration as a surrogate marker for the presence of central diabetes insipidus, and urinary output. The same models were adjusted for potential confounding factors.

Results

We included in the study 130 TBI patients (mean age 52 years (standard deviation 23); males 74%; median Glasgow Coma Score 3 (range 3 to 8); mean Simplified Acute Physiology Score II 50 (standard deviation 15)); all were mechanically ventilated; 35 (26.9%) died within 14 days after ICU admission. Hypernatremia was detected in 51.5% of the patients and in 15.9% of the 1,103 patient-day ICU follow-up. In most instances hypernatremia was mild (mean 150 mmol/l, interquartile range 148 to 152). The occurrence of hypernatremia was highest (P = 0.003) in patients with suspected central diabetes insipidus (25/130, 19.2%), a condition that was associated with increased severity of brain injury and ICU mortality. After adjustment for the baseline risk, the incidence of hypernatremia over the course of the ICU stay was significantly related with increased mortality (hazard ratio 3.00 (95% confidence interval: 1.34 to 6.51; P = 0.003)). However, DDAVP use modified this relation (P = 0.06), hypernatremia providing no additional prognostic information in the instances of suspected central diabetes insipidus.

Conclusions

Mild hypernatremia is associated with an increased risk of death in patients with severe TBI. In a proportion of the patients the association between hypernatremia and death is accounted for by the presence of central diabetes insipidus.
Insights into female sperm storage from the spermathecal fluid proteome of the honeybee Apis mellifera
Authors: Baer Boris , Eubel Holger , Taylor Nicolas L , O'Toole Nicholas , Millar A Harvey
Published: July 2009

Background

Female animals are often able to store sperm inside their body - in some species even for several decades. The molecular basis of how females keep non-own cells alive is largely unknown, but since sperm cells are reported to be transcriptionally silenced and, therefore, limited in their ability to maintain their own function, it is likely that females actively participate in sperm maintenance. Because female contributions are likely to be of central importance for sperm survival, molecular insights into the process offer opportunities to observe mechanisms through which females manipulate sperm.

Results

We used the honeybee, Apis mellifera, in which queens are highly polyandrous and able to maintain sperm viable for several years. We identified over a hundred proteins representing the major constituents of the spermathecal fluid, which females contribute to sperm in storage. We found that the gel profile of proteins from spermathecal fluid is very similar to the secretions of the spermathecal gland and concluded that the spermathecal glands are the main contributors to the spermathecal fluid proteome. A detailed analysis of the spermathecal fluid proteins indicate that they fall into a range of different functional groups, most notably enzymes of energy metabolism and antioxidant defense. A metabolic network analysis comparing the proteins detected in seminal fluid and spermathecal fluid showed a more integrated network is present in the spermathecal fluid that could facilitate long-term storage of sperm.

Conclusions

We present a large-scale identification of proteins in the spermathecal fluid of honeybee queens and provide insights into the molecular regulation of female sperm storage.
Secondary necrosis of apoptotic neutrophils induced by the human cathelicidin LL-37 is not proinflammatory to phagocytosing macrophages
Authors: Li Hsin-Ni , Barlow Peter G , Bylund Johan , Mackellar Annie , Björstad Åse , Conlon James , Hiemstra Pieter S , Haslett Chris , Gray Mohini , Simpson A John , Rossi Adriano G , Davidson Donald J
Published: July 2009

LL37-induced secondary necrosis of apoptotic neutrophils with release of granule contents potentiates the anti-inflammatory activity of apoptotic neutrophils on macrophages.

Cathelicidins are CHDP with essential roles in innate host defense but also more recently associated with the pathogenesis of certain chronic diseases. These peptides have microbicidal potential and the capacity to modulate innate immunity and inflammatory processes. PMN are key innate immune effector cells with pivotal roles in defense against infection. The appropriate regulation of PMN function, death, and clearance is critical to innate immunity, and dysregulation is implicated in disease pathogenesis. The efferocytosis of apoptotic PMN, in contrast to necrotic cells, is proposed to promote the resolution of inflammation. We demonstrate that the human cathelicidin LL-37 induced rapid secondary necrosis of apoptotic human PMN and identify an essential minimal region of LL-37 required for this activity. Using these LL-37-induced secondary necrotic PMN, we characterize the consequence for macrophage inflammatory responses. LL-37-induced secondary necrosis did not inhibit PMN ingestion by monocyte-derived macrophages and in contrast to expectation, was not proinflammatory. Furthermore, the anti-inflammatory effects of apoptotic PMN on activated macrophages were retained and even potentiated after LL-37-induced secondary necrosis. However, this process of secondary necrosis did induce the release of potentially harmful PMN granule contents. Thus, we suggest that LL-37 can be a potent inducer of PMN secondary necrosis during inflammation without promoting macrophage inflammation but may mediate host damage through PMN granule content release under chronic or dysregulated conditions.
Nucleophosmin may act as an alarmin: implications for severe sepsis
Authors: Nawa Yuko , Kawahara Ko-ichi , Tancharoen Salunya , Meng Xiaojie , Sameshima Hisayo , Ito Takashi , Masuda Yoshiki , Imaizumi Hitoshi , Hashiguchi Teruto , Maruyama Ikuro
Published: July 2009

Nucleophosmin exerts potent biological activities that contribute to systemic inflammation.

NPM is a major nucleolar multifunctional protein involved in ribosome biogenesis, centrosome duplication, cell-cycle progression, apoptosis, cell differentiation, and sensing cellular stress. Alarmins are endogenous molecules released from activated cells and/or dying cells, which activate the immune system and cause severe damage to cells and tissue organs. In the present work, stimulation of cells with the alarmin-inducible molecule endotoxin, for 16 h, resulted in NPM release into the culture supernatants of RAW264.7 cells, a murine macrophage cell line. Extracellular NPM was detected in the ascites of the CLP model. NPM was translocated into the cytoplasm from the nucleus in LPS -stimulated RAW264.7 cells; furthermore, NPM was detected in the cytosols of infiltrated macrophages in the CLP model. rNPM induced release of proinflammatory cytokines, TNF-α, IL-6, and MCP-1, from RAW264.7 cells and increased the expression level of ICAM-1 in HUVECs. NPM induced the phosphorylation of MAPKs in RAW264.7 cells. Our data indicate that NPM may have potent biological activities that contribute to systemic inflammation. Further investigations of the role of NPM may lead to new therapies for patients with septic shock or other inflammatory diseases.
Phase III, Randomized Study of Gemcitabine and Oxaliplatin Versus Gemcitabine (fixed-dose rate infusion) Compared With Gemcitabine (30-minute infusion) in Patients With Pancreatic Carcinoma E6201: A Trial of the Eastern Cooperative Oncology Group
Authors: Poplin Elizabeth , Feng Yang , Berlin Jordan , Rothenberg Mace L. , Hochster Howard , Mitchell Edith , Alberts Steven , O'Dwyer Peter , Haller Daniel , Catalano Paul , Cella David , Benson Al Bowen
Published: July 2009

Purpose

Single-agent gemcitabine (GEM) is standard treatment of metastatic pancreatic cancer. Fixed-dose rate (FDR) GEM and GEM plus oxaliplatin have shown promise in early clinical trials. E6201 was designed to compare overall survival (OS) of standard weekly GEM 1,000 mg/m2/30 minutes versus GEM FDR 1,500 mg/m2/150 minutes or GEM 1,000 mg/m2/100 minutes/day 1 plus oxaliplatin 100 mg/m2/day 2 every 14 days (GEMOX).

Methods

This trial included patients with metastatic or locally advanced pancreatic cancer, normal organ function, and performance status of 0 to 2. The study was designed to detect a 33% difference in median survival (hazard ratio [HR] ≤ 0.75 for either of the experimental arms) with 81% power while maintaining a significance level of 2.5% in a two-sided test for each of the two primary comparisons.

Results

Eight hundred thirty-two patients were enrolled. The median survival and 1-year survival were 4.9 months (95% CI, 4.5 to 5.6) and 16% for GEM, 6.2 months (95% CI, 5.4 to 6.9), and 21% for GEM FDR (HR, 0.83; stratified log-rank P = .04), and 5.7 months (95% CI, 4.9 to 6.5) and 21% for GEMOX (HR, 0.88; stratified log-rank P = .22). Neither of these differences met the prespecified criteria for significance. Survival was 9.2 months for patients with locally advanced disease, and 5.4 months for those with metastatic disease. Grade 3/4 neutropenia and thrombocytopenia were greatest with GEM FDR. GEMOX caused higher rates of nausea, vomiting, and neuropathy.

Conclusion

Neither GEM FDR nor GEMOX resulted in substantially improved survival or symptom benefit over standard GEM in patients with advanced pancreatic cancer.
Hypothalamic Leptin Signaling Regulates Hepatic Insulin Sensitivity via a Neurocircuit Involving the Vagus Nerve
Authors: German Jonathan , Kim Francis , Schwartz Gary J. , Havel Peter J. , Rhodes Christopher J. , Schwartz Michael W. , Morton Gregory J.
Published: July 2009

Recent evidence suggests that hormones such as insulin and leptin act in the hypothalamus to regulate energy balance and glucose metabolism. Here we show that in leptin receptor-deficient Koletsky (fak/fak) rats, adenovirally induced expression of leptin receptors in the area of the hypothalamic arcuate nucleus improved peripheral insulin sensitivity via enhanced suppression of hepatic glucose production, with no change of insulin-stimulated glucose uptake or disposal. This effect was associated with increased insulin signal transduction via phosphatidylinositol-3-OH kinase (as measured by pY-insulin receptor substrate-1 and pS-PKB/Akt) in liver, but not skeletal muscle, and with reduced hepatic expression of the gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate kinase. Moreover, the beneficial effects of hypothalamic leptin signaling on hepatic insulin sensitivity were blocked by selective hepatic vagotomy. We conclude that hypothalamic leptin action increases peripheral insulin sensitivity primarily via effects on the liver and that the mechanism underlying this effect is dependent on the hepatic branch of the vagus nerve.
Metformin Inhibits Aromatase via an Extracellular Signal-Regulated Kinase-Mediated Pathway
Authors: Rice Suman , Pellatt Laura , Ramanathan Kumaran , Whitehead Saffron Anne , Mason Helen Diane
Published: July 2009

Metformin treatment, now widely prescribed in polycystic ovary syndrome, is aimed at correcting the associated insulin resistance, but it has also been shown to directly inhibit ovarian steroidogenesis. The mechanisms, however, by which metformin inhibits estradiol production in human granulosa cells remains unknown. Granulosa luteal cells were incubted with metformin, insulin, or combined metformin and insulin treatment, and aromatase mRNA expression was quantified using real-time RT-PCR. Enzyme activity was assessed by the conversion of 3H-androstenedione to estrone and estradiol. Metformin’s effect on the expression of specific untranslated first exon aromatase promoters was analyzed using semiquantitative PCR. The involvement of MAPK kinase (MEK)/ERK pathway was investigated by immunoblotting for aromatase, phosphorylated, and total ERK-1,2 from cells cultured as above with/without the MEK inhibitor PD98059. Metformin significantly inhibited basal and insulin-stimulated aromatase mRNA expression, with parallel results from the aromatase activity assay and protein assessment. This suppression was via down-regulation of aromatase promoter II, I.3, and 1.4 expression and was reversed by the addition of PD98059. Involvement of the ERK signaling pathway was demonstrated by the significant increase in phosphorylated ERK-1,2 with the combined metformin and insulin treatment. We have shown for the first time in human granulosa cells that metformin signficantly attenuated basal and insulin-stimulated P450 aromatase mRNA expression and activity, via silencing of key promoters. This occurred by activation of MEK/ERK pathway, which negatively regulated aromatase production. This is an important consideration given metformin’s widespread use in polycystic ovary syndrome and may further support a possible therapeutic indication in estrogen-dependent breast tumors.
Strain hardening behaviour in sintered Fe—0.8%C—1.0%Si—0.8%Cu powder metallurgy preform during cold upsetting
Authors: Rajeshkannan A , Narayan S
Published: July 2009

Cold upsetting experiments were performed on sintered Fe—0.8%C—1.0%Si—0.8%Cu steel preforms in order to evaluate the strain hardening characteristics. Powder preforms of 86 per cent theoretical density and an initial aspect ratio of 0.4 were prepared using a suitable die and a 1 MN capacity hydraulic press. Sintering was carried out in an electric muffle furnace for a period of 90 min at 1150 °C. Each sintered compact was subjected to an incremental compressive loading of 0.04 MN until fractures appeared on the free surface. Experiments were performed with no lubricant and using graphite as a lubricant. The behaviour of the applied stress as a function of both strain and densification level exhibits a continuous enhancement over three different response modes. The first and third stage responses offer a high resistance to deformation, whereas the second stage shows virtually steady-state behaviour. The instantaneous strain hardening exponent ni and strength coefficient Ki of the steel preforms were calculated and found to continuously increase with an increase in the deformation and densification levels.
The Bees Algorithm: Modelling foraging behaviour to solve continuous optimization problems
Authors: Pham D T , Castellani M
Published: July 2009

The Bees Algorithm models the foraging behaviour of honeybees in order to solve optimization problems. The algorithm performs a kind of exploitative neighbourhood search combined with random explorative search. This article describes the Bees Algorithm in its basic formulation, and two recently introduced procedures that increase the speed and accuracy of the search. A critical review of the related swarm intelligence literature is presented. The effectiveness of the proposed method is compared to that of three state-of-the-art biologically inspired search methods. The four algorithms were tested on a range of well-known benchmark function optimization problems of different degrees of complexity. The experimental results proved the reliability of the bees foraging metaphor. The Bees Algorithm performed optimally, or near optimally, in almost all the tests. Compared to the three control algorithms, the Bees Algorithm was highly competitive in terms of learning accuracy and speed. The experimental tests helped also to shed further light on the search mechanisms of the Bees Algorithm and the three control methods, and to highlight their differences, strengths, and weaknesses.
An analytic approximation of wire coating analysis for third-grade magneto-hydrodynamic flow
Authors: Shafieenejad I , Moallemi Ni , Moallemi Na , Novinzadeh A B
Published: July 2009

In this article, homotopy perturbation method (HPM) is applied to solve non-linear problems for third-grade fluid. The fluid is electrically conducting in the presence of a uniform applied magnetic field, and wire coating by withdrawal from a bath of third-grade fluid is investigated. Although traditional HPM is divergent for higher-order approximation to obtain enough accuracy in this work, a new method on boundary conditions is proposed to solve this boundary value problem by HPM and convergence of the solution is clearly discussed. Results reveal that this method is very effective and simple to overcome the divergence of the HPM solution. The influence of the non-Newtonian parameter on the velocity, volume flowrate, radius of coated wire, shear stress at the surface of the wire, and the force required to pull the wire is seen and discussed.
Experimental and numerical investigation of the flow field in a high-pressure centrifugal compressor impeller near surge
Authors: Bulot N , Trébinjac I , Ottavy X , Kulisa P , Halter G , Paoletti B , Krikorian P
Published: July 2009

Numerical and experimental investigations were conducted in a transonic centrifugal compressor stage composed of a backswept splittered unshrouded impeller and a vaned diffuser. The present article focuses on the results obtained within the impeller, at an operating condition close to the surge of the compressor. The experimental results were obtained from a laser Doppler anemometry investigation. Unsteady numerical simulations of the compressor stage were performed using a three-dimensional Reynolds-averaged Navier—Stokes code with a phase-lagged technique, at both peak efficiency and close to surge operating conditions. A good agreement between the experiments and simulations were obtained, which justifies the use of the computational fluid dynamics results for the comparison of the flow field at both operating conditions (peak efficiency and near surge). Even if the change in flow field within the impeller from peak efficiency to near surge looked to be gradual, an overall rotation of the whole flow in the blade passages led to a non-homogeneous flow at the impeller exit in terms of angle and velocity level. Therefore, the vaned diffuser has to tolerate upstream flows, which are all the more distorted as the operating point moves towards surge.
Numerical and experimental investigation of a low-pressure steam turbine during windage
Authors: Sigg R , Heinz C , Casey M V , Sürken N
Published: July 2009

Modern steam power plants must operate safely at extremely low loads, known as windage, in which the low pressure (LP) turbine runs with decreased or even zero flow. Windage is characterized by a strongly unsteady three-dimensional (3D) flow field leading to possible aerodynamic excitations. Extensive flow field measurements were performed in an LP steam turbine test rig during windage, using pneumatic probes in the last stage and a diffuser. The flow field of the whole turbine was also calculated with steady 3D computational fluid dynamics (ANSYS CFX). Good agreement is found between the simulations and the measurements of the flow field, and the characteristic vortex structures behind the last rotor row are captured. The numerically predicted trends of power output, pressure ratio, and temperature of the last turbine blade row closely match the experimental data. The complex vortex flow in the stage is interpreted using both numerical and experimental results.
A class of adaptive sliding mode controller with proportional-integral sliding surface
Authors: Fei J , Batur C
Published: July 2009

This paper presents an adaptive sliding mode tracking controller with a proportional and integral switching surface. A novel adaptive sliding mode controller based on model reference adaptive state feedback control is proposed to deal with the tracking problem for a class of dynamic systems. First, a proportional and integral sliding surface instead of a conventional sliding surface is chosen and then a class of adaptive sliding mode controller with integral sliding term is developed. It is shown that the stability of the closed-loop system can be guaranteed with the proposed adaptive sliding mode control strategy. The numerical simulation of a triaxial gyroscope is investigated to show the effectiveness of the proposed adaptive sliding mode control scheme with proportional plus integral sliding mode action.
Improved robust stability criterion for delay systems
Authors: Mahmoud M S
Published: July 2009

This paper develops a novel robust stability criterion with guaranteed performance for a class of linear continuous time-delay systems with polytopic uncertainties. The state-delay is an unknown-but-bounded interval, differentiable time-varying function satisfying some known bounding. The criterion is derived based on the constructive use of a new Lyapunov-Krasovskii functional coupled with integral inequality. The sufficient stability condition is expressed in terms of a linear matrix inequality which manipulates fewer decision variables and requires reduced computational effort. Through a comparison with other existing stability methods, it is established that the developed method retains some useful terms that are frequently ignored and does not use any free-weighting matrices to avoid redundancy. All the developed results are tested on representative examples.