bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the Long‐term Effects of Epilepsy Surgery with Three Different Reference Groups
Authors: Bien Christian G. , Schulze‐Bonhage Andreas , Soeder Bettina M. , Schramm Johannes , Elger Christian E. , Tiemeier Henning
Published: October 2006

Summary:  Purpose: It is difficult to validly assess the long‐term effect of epilepsy surgery. Here, this is attempted by comparing the outcome of surgically treated pharmacoresistant epilepsy patients to three different nonoperated comparison groups regarding seizure control, antiepilepsy drug (AED) usage, and health related quality of life (QOL).

Methods: One hundred thirty‐one operated patients (group 1, mean follow‐up since presurgical assessment 6.9 years), 105 patients awaiting presurgical assessment (group 2, mean follow‐up after assignment to waiting list 0.8 years), 99 patients considered to be presurgical candidates who chose to withdraw from waiting for presurgical assessment (group 3, mean follow‐up after assignment to waiting list 5.5 years), and 49 patients who were not deemed to be eligible for surgery after comprehensive assessment (group 4, mean follow‐up since presurgical assessment 6.5 years) were studied. The patients completed a questionnaire on seizures, AED usage, and QOL (ESI‐55).

Results: The surgical patients had a better outcome than all three comparison groups regarding seizure frequency, seizure freedom rate, and number of AEDs used. They scored higher than groups 2, 3, and 4 on 7/11, 6/11, and 3/11 ESI‐55 domains, respectively.

Conclusions: The superior long‐term outcome of the operated patients was most marked if compared to the patients awaiting surgery. This is compatible with the assumption that patients present for presurgical candidacy selection and assessment at a “nadir” of their disease course. After several years, a regression to the mean occurs which reduces (but does not abolish) the differences between nonoperated and operated patients.
Patient Awareness of Complex Partial Seizures
Authors: Heo Kyoung , Han Sang‐Don , Lim Sung Ryoung , Kim Mi Ae , Lee Byung In
Published: October 2006

Summary:  Purpose: To assess self‐awareness of complex partial seizures (CPSs) in unselected epilepsy patients through a thorough interview.

Methods: The study comprised 134 patients at our epilepsy clinic, whose CPSs had been documented by the patient's family members. We investigated the proportion and characteristics of patients unaware of their CPSs compared to those who were, and we monitored the evolution of unawareness of CPSs during the follow‐up.

Results: Thirty‐one (23%) patients were assigned to the unawareness group (complete, 23; incomplete, 8) and 103 (67%) patients to the awareness group. Patients in the unawareness group were older and had a later age of onset than patients in the awareness group. Interictal epileptiform discharges (IEDs) localized primarily to the temporal region and were more frequently detected in the unawareness group (94%) than the awareness group (55%). Bilateral independent IEDs were found more frequently in the unawareness group than in the awareness group (48% vs. 13%). The bilateral presence of lesions was also more frequent in the unawareness group than the awareness group (16.1% vs. 4.9%). Six (26%) of 23 patients with complete unawareness of their CPSs had experienced awareness of CPSs during the follow‐up. Two of these patients even experienced the emergence of de novo aura.

Conclusions: Our results indicate that a significant number of epilepsy patients are not aware of their CPSs. Unawareness of CPSs may be related to bitemporal dysfunction and a rapid and complete loss of consciousness caused by rapid spread of ictal discharges to the contralateral hemisphere in association with bilateral independent IEDs and bilateral presence of lesions.
Lack of Efficacy and Potential Aggravation of Myoclonus with Lamotrigine in Unverricht‐Lundborg Disease
Authors: Genton Pierre , Gelisse Philippe , Crespel Arielle
Published: October 2006

Summary:  Purpose: Unverricht‐Lundborg disease (ULD) is a progressive myoclonus epilepsy with tonic–clonic seizures, action myoclonus, mild ataxia, without dementia. Persistence of invalidating action myoclonus is a major problem. Drugs like phenytoin can aggravate ULD. In this study, we retrospectively analyzed the effect of add‐on lamotrigine (LTG) in the five patients under our care who received LTG.

Method: Three men and two women, aged 20–50 years who had ULD confirmed by molecular biology, followed in two epilepsy centers, received add‐on LTG at 50–300 mg/d. All of them had valproate. The other drugs used in cotherapy were high‐dose piracetam, benzodiazepines phenobarbital, topiramate, and primidone. The assessment of LTG was based on detailed interview and clinical examination. Aggravation was diagnosed when myoclonic jerks (MJ) increased without irregular intake of medication, inappropriate lifestyle, encephalopathic or metabolic complications, or overdosage.

Results: In two patients, LTG exacerbated MJ in a dose‐dependent manner. In one patient, a delayed, severe exacerbation of myoclonus occurred that only ceased after LTG withdrawal and introduction of levetiracetam. These three patients had minor forms of ULD. In two patients with moderate to severe forms of ULD, LTG had no effect.

Conclusion: Although symptoms may fluctuate in ULD, it was possible to pinpoint lack of improvement (2/5), dose‐related exacerbation of myoclonus (2/5), and putative late‐onset aggravation (1/5) in five patients treated with adjunctive LTG. LTG does not appear to be a sensible treatment option in ULD.
A New Measure of Binge Drinking: Prevalence and Correlates in a Probability Sample of Undergraduates
Authors: Cranford James A. , McCabe Sean Esteban , Boyd Carol J.
Published: October 2006

Background: A standard measure defines binge drinking as the consumption of 5 or more drinks in a row for men (4 or more drinks for women) on at least 1 occasion during the past 2 weeks. A revised operational definition of binge drinking was developed by the National Institute on Alcohol Abuse and Alcoholism in 2004 and incorporated the duration of the drinking episode in addition to the quantity of alcohol consumed. This study compares the standard and new binge measures for overall and subgroup prevalence rates; associations with gender, race/ethnicity, and age of drinking onset; and associations with negative drinking consequences.

Methods: A probability sample of 4,580 randomly selected college students (50.3% female, M age=19.9, SD=2.0) at a large Midwestern university in the United States completed a Web‐based survey of alcohol and other drug use. Participants reported on past 2‐week binge drinking using the standard measure and past‐year binge drinking using the new measure.

Results: The longer past‐year time frame of the new measure yielded a higher prevalence estimate of binge drinking (63.6%) compared with the 2‐week standard measure (53.2%). Approximately 9.9% of those who were classified as binge drinkers using the 2‐week standard measure were classified as non–binge drinkers using the new measure specification of a 2‐hour duration for the drinking episode. The past‐year new binge measure was positively associated with negative drinking consequences even when the 2‐week measure was statistically controlled.

Conclusions: Using a longer time frame and incorporating the duration of the drinking episode, the new measure of binge drinking appears to capture an important element of risky alcohol involvement in college students that is not fully assessed by the standard measure.
Ethanol‐Induced Apoptosis in Polarized Hepatic Cells Possibly Through Regulation of the Fas Pathway
Authors: McVicker Benita L. , Tuma Dean J. , Kubik Jacy L. , Tuma Pamela L. , Casey Carol A.
Published: October 2006

Background: It has been noted that alcohol‐related liver diseases can be associated with an increase in apoptotic hepatocellular death. Moreover, the promotion of hepatocyte apoptosis may be linked to signals emanating from death receptors, particularly Fas [CD95/apoptosis‐inducing protein 1 (APO‐1)]. In the present study, we utilized an in vitro hepatic culture model [hybrid of human fibroblast (WI 38) and rat hepatoma (Fao) cells, WIF‐B cells] to study potential contributing mechanisms involved in hepatocellular apoptosis following ethanol administration.

Methods: WIF‐B cultures (differentiated hepatic cells that efficiently metabolize alcohol) were treated with or without ethanol and specific inhibitors of alcohol metabolism and cysteine protease activity, followed by morphological and biochemical examination of proapoptotic parameters.

Results: The results of this work demonstrated that ethanol administration leads to an increase (45%–60%) in caspase‐3 activity and that the induction of apoptosis was found to be linked to the metabolism of alcohol. Additionally, increases were observed in the activity of upstream initiator caspases (caspase‐2 and caspase‐8) that are directly related to membrane signaling events of death receptors such as Fas. Moreover, it was determined that the activation of caspase‐3 could be blocked by the presence of a specific caspase‐8 inhibitor, again linking death receptor‐associated proteases to downstream effector caspase activity in alcohol‐related death. Finally, ethanol administration was found to result in an increase in the amount of Fas protein present in the membrane fraction of the cell. The increase in membrane Fas protein indicates ligand‐independent membrane targeting of Fas in the alcohol‐treated cells that could potentially be a key signaling event in the induction of the proapoptotic caspase cascade.

Conclusions: The data presented here indicate that alcohol metabolism induces apoptosis in WIF‐B cells that occurs, in part, by mechanisms involving signals emanating from death receptors.
BHT Blocks NF‐κB activation and Ethanol‐Induced Brain Damage
Authors: Crews Fulton , Nixon Kimberly , Kim Daniel , Joseph James , Shukitt‐Hale Barbara , Qin Liya , Zou Jian
Published: October 2006

Background: Binge ethanol administration causes corticolimbic brain damage that models alcoholic neurodegeneration. The mechanism of binge ethanol‐induced degeneration is unknown, but is not simple glutamate–N‐methyl‐d‐aspartate (NMDA) excitotoxicity. To test the hypothesis that oxidative stress and inflammation are mechanisms of binge ethanol‐induced brain damage, we administered 4 antioxidants, e.g., butylated hydroxytoluene (BHT), ebselen (Eb), vitamin E (VE), and blueberry (BB) extract, during binge ethanol treatment and assessed various measures of neurodegeneration.

Methods: Adult Sprague–Dawley rats were treated with intragastric ethanol 3 times per day (8–12 g/kg/d) alone or in combination with antioxidants or isocaloric diet for 4 days. Animals were killed, and brains were perfused and extracted for histochemical silver stain determination of brain damage, markers of neurogenesis, or other immunohistochemistry. Some animals were used for determination of nuclear factor κ B (NF‐κB)–DNA binding by electrophoretic mobility shift assay (EMSA) or for reverse transcription–polymerase chain reaction (RT‐PCR) of cyclooxygenase 2 (COX2).

Results: Binge ethanol induced corticolimbic brain damage and reduced neurogenesis. Treatment with BHT reversed binge induced brain damage and blocked ethanol inhibition of neurogenesis in all regions studied. Interestingly, the other antioxidants studied, e.g., Eb, VE, and BB, did not protect against binge‐induced brain damage. Binge ethanol treatment also caused microglia activation, increased NF‐κB–DNA binding and COX2 expression. Butylated hydroxytoluene reduced binge‐induced NF‐κB–DNA binding and COX2 expression.

Conclusions: Binge‐induced brain damage and activation of NF‐κB–DNA binding are blocked by BHT. These studies support a neuroinflammatory mechanism of binge ethanol‐induced brain damage.
Wage Bargaining Under the National Labor Relations Act
Authors: Schwartz Jesse A. , Wen Quan
Published: October 2006

Sections 8(a)(3) and 8(a)(5) of the National Labor Relations Act (NLRA) prohibit the management of a firm from unilaterally increasing the wage during contract negotiations without the union's approval. We show how the management can strategically increase the wage during negotiations without violating the NLRA. Increasing the wage during negotiations will upset the union's incentive to strike and decrease the union's bargaining power, thereby shrinking the set of equilibrium contracts in the firm's favor. Indeed, as the union becomes more patient, the set of equilibrium wages converges to the best equilibrium outcome to the firm.
The case for a new approach for documenting platelet viability
Authors: Murphy Scott
Published: October 2006

Methods of radiolabeling platelets (PLTs) have been available since 1958 (51Cr) and 1979 (111In) and have been used to assess candidate PLT products for transfusion by infusion into autologous volunteers. No minimum criteria defining acceptable results for licensing have been agreed to, however. In vivo recoveries of fresh PLTs in normal volunteers vary from 40 to 80 percent, and individual volunteers tend to repeat a low or high recovery in subsequent studies. It has become standard to compare test and control products in individual donors at the same time with the two isotopes. The current procedure of use of a currently licensed product at the end of its licensed storage interval as the control has problems. It has been proposed to use fresh PLTs as the control and to express the test results relative to that control. It is also proposed to have the fresh control collected, labeled, and infused on the same day as the test product is infused. I have proposed that test PLT recovery be at least 66 percent of control and survival be at least 50 percent of control.
Fetal Mouse Imaging Using Echocardiography: A Review of Current Technology
Authors: Spurney Christopher F. , Lo Cecilia W. , Leatherbury Linda
Published: October 2006

Advances in genetic research have led to the need for phenotypic analysis of small animal models. However, often these genetic alterations, especially when affecting the cardiovascular system, can result in fetal or perinatal death. Noninvasive ultrasound imaging is an ideal method for detecting and studying such congenital malformations, as it allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies. Two platforms for fetal mouse echocardiography exist, the clinical systems with 15‐MHz phased array transducers and research systems with 20–55‐MHz mechanical transducers. The clinical ultrasound system has limited two‐dimensional (2D) resolution (axial resolution of 440 μm), but the availability of color and spectral Doppler allows quick interrogations of blood flows, facilitating the detection of structural abnormalities. M‐mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. In comparison, the research biomicroscope system has significantly improved 2D resolution (axial resolution of 28 μm). Spectral Doppler imaging is also available, but in the absence of color Doppler, imaging times are increased and the detection of flow abnormalities is more difficult. M‐mode imaging is available and equivalent to the clinical ultrasound system. Overall, the research system, given its higher 2D resolution, is best suited for in‐depth analysis of mouse fetal cardiovascular structure and function, while the clinical ultrasound systems, equipped with phase array transducers and color Doppler imaging, are ideal for high‐throughput fetal cardiovascular screens.
Tissue Doppler Assessment of Longitudinal Right and Left Ventricular Strain and Strain Rate in Pulmonary Artery Hypertension
Authors: Rajdev Sanjay , Nanda Navin C. , Patel Vinod , Singh Anurag , Mehmood Farhat , Vengala Srinivas , Fang Ligang , Dasan Velayudhan , Benza Raymond L. , Bourge Robert C.
Published: October 2006

Tissue Doppler imaging (TDI) in 38 adult patients with pulmonary artery hypertension of varied etiology and normal left ventricular systolic function by two‐dimensional transthoracic echocardiography showed significantly reduced peak systolic strain (SS) in all three segments of left ventricular free wall and ventricular septum and two of three segments of right ventricular free wall when compared to 29 adults with no clinical or echocardiographic evidence of heart disease and normal left and right ventricular systolic function. A similar reduction in peak diastolic strain (DS) was also noted in all three segments of left ventricular free wall and ventricular septum and one of three segments of right ventricular free wall. This reduction in strain indices in patients with pulmonary hypertension was noted irrespective of whether right ventricular systolic function was normal or reduced as assessed by two‐dimensional transthoracic echocardiography. SS and DS rates also showed reductions in patients with pulmonary artery hypertension. Our study shows the potential value of TDI indices in identifying reduced regional left ventricular systolic and diastolic longitudinal function in patients with pulmonary artery hypertension and normal left ventricular systolic function by two‐dimensional transthoracic echocardiography. This reduction in left ventricular function was noted in patients with both normal and reduced right ventricular systolic functions by two‐dimensional echocardiography.
Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding
Authors: Gupta Kamlesh K. , Bharne Shubhada S. , Rathinasamy Krishnan , Naik Nishigandha R. , Panda Dulal
Published: October 2006

Curcumin, a component of turmeric, has potent antitumor activity against several tumor types. However, its molecular target and mechanism of antiproliferative activity are not clear. Here, we identified curcumin as a novel antimicrotubule agent. We have examined the effects of curcumin on cellular microtubules and on reconstituted microtubules in vitro. Curcumin inhibited HeLa and MCF‐7 cell proliferation in a concentration‐dependent manner with IC50 of 13.8 ± 0.7 µm and 12 ± 0.6 µm, respectively. At higher inhibitory concentrations (> 10 µm), curcumin induced significant depolymerization of interphase microtubules and mitotic spindle microtubules of HeLa and MCF‐7 cells. However, at low inhibitory concentrations there were minimal effects on cellular microtubules. It disrupted microtubule assembly in vitro, reduced GTPase activity, and induced tubulin aggregation. Curcumin bound to tubulin at a single site with a dissociation constant of 2.4 ± 0.4 µm and the binding of curcumin to tubulin induced conformational changes in tubulin. Colchicine and podophyllotoxin partly inhibited the binding of curcumin to tubulin, while vinblastine had no effect on the curcumin–tubulin interactions. The data together suggested that curcumin may inhibit cancer cells proliferation by perturbing microtubule assembly dynamics and may be used to develop efficacious curcumin analogues for cancer chemotherapy.
Customs, Culture, and Tradition—What Role Do They Play in a Woman’s Sexuality?
Authors: Fourcroy Jean L.
Published: October 2006

Introduction

Sexual health is an assumed right for every individual, but we know little regarding customs, culture, or tradition and the role they play on the sexual experiences for a woman. A woman’s sexuality must be considered in the context of the environment in which she and her partner live. Culture, social customs of the community, and religion often determine the acceptance and achievement of sexual health for both men and women.

Aim

This is a review of the available literature on the impact of culture on a woman’s sexual satisfaction, with emphasis placed on information from cultures practicing female genital circumcision (FGC).

Results

FGC provides a spectrum of surgical excisions and outcomes. The spectrum of FGC surgical excisions can alter well-being, obstetrical outcomes, and sexual responses. The psychologic aspects of a painful procedure in a young child may also impact her future sexual responsiveness.

Conclusion

There is a paucity of information on which to base conclusions and the effect of culture on a woman’s sexual satisfaction. Preliminary data suggest the need for further research using markers specific to the culture and her satisfaction.
Vardenafil Improves Sexual Function and Treatment Satisfaction in Couples Affected by Erectile Dysfunction (ED): A Randomized, Double-Blind, Placebo-Controlled Trial in PDE5 Inhibitor-Naïve Men with ED and Their Partners
Authors: Edwards David , Hackett Geoff , Collins Owen , Curram John
Published: October 2006

Introduction

Erectile dysfunction (ED) is a common condition with diverse sequelae affecting men and their women partners.

Aim

The FINDER study aimed to evaluate the efficacy and tolerability of the phosphodiesterase type-5 (PDE5) inhibitor, vardenafil, in a broad population of PDE5-naïve men with ED of different etiologies and severity and included their partners’ assessments of treatment with vardenafil.

Methods

Men with ED (N = 260) were randomized to receive either vardenafil or placebo in a multicenter, flexible-dose study.

Main Outcome Measures

Primary efficacy variables were patients’ responses to the Global Assessment Question (GAQ), and Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3).

Results

Compared with placebo, vardenafil significantly improved rates of successful “Yes” responses to SEP3 (“Did your erection last long enough for you to have successful intercourse?”) (49% placebo vs. 78% vardenafil at last period carried forward [LPCF]; P < 0.0001), SEP2 (“Were you able to insert your penis into your partner’s vagina?”) (65% placebo vs. 85% vardenafil at LPCF; P < 0.0001), and GAQ (36% placebo vs. 83% vardenafil at last observation carried forward; P < 0.0001). In addition, patients’ and their partners’ Treatment Satisfaction Scale (TSS) scores were statistically significantly improved across each of the TSS domains (satisfaction with orgasm, ease with erection, confidence, pleasure, erectile function satisfaction, and satisfaction with medication) in the vardenafil group compared with the placebo group.

Conclusions

Vardenafil improved sexual function to the extent that both patients and their partners expressed a considerable and agreed level of satisfaction with treatment.
Health promotion for women with human immunodeficiency virus or acquired immunodeficiency syndrome
Authors: Abel Elizabeth , Hopson Laura , Delville Carol
Published: October 2006

Purpose: The purpose of this pilot study was twofold: first, to modify Stuifbergen’s health promotion intervention initially developed for women with multiple sclerosis for use among women with human immunodeficiency virus or acquired immunodeficiency syndrome (HIV/AIDS) and to evaluate the feasibility of the newly modified health promotion intervention named “Put Health Into Living” (PHIL). The pilot study was completed in two phases.

Data sources: In phase I, data were derived from a literature review, a focus group of women with HIV/AIDS (n= 7), a panel of experts who reviewed the intervention for content, and three female community workers who evaluated the intervention for the context of living with HIV/AIDS, cultural relevancy, and literacy. During phase II, a pretest/posttest one‐group design was used to determine the feasibility of the study methods, content, and format of the health promotion intervention among 10 women with HIV/AIDS.

Conclusions: The pilot study demonstrated the importance of a health promotion intervention for a vulnerable population. Participants verbalized the benefits of attending a health promotion program to gain knowledge and skills to promote their health. One woman said, “I have been positive for 20 years now and no one has talked to me just about my overall health.” Participants indicated the PHIL intervention offered a supportive group environment, an overall health focus, and an acceptable format.

Implications for practice: Health promotion is a desirable goal for persons living with a chronic disease, and the PHIL intervention has the potential to benefit persons living with HIV/AIDS if subsequent evidence is found in further testing of the intervention.
Computed tomography study of implantation corridors in canine vertebrae
Authors: Watine S. , Cabassu J. P. , Catheland S. , Brochier L. , Ivanoff S.
Published: October 2006

Objectives: To define the characteristics of optimum implantation corridors in vertebral bodies C2 to C7 and T10 to S1, using computed tomography examination.

Methods: Measurements were taken from 207 vertebrae from 35 different adult dogs.

Results: Implantation corridors of the cervical vertebrae are narrow. The width preserving the transverse hole is less than 2·5 mm in 68·6 per cent of the 86 vertebrae C2 to C6. Dorsal implantation corridors of the last four thoracic vertebrae are narrow, and major anatomical structures are very close to their emergence point. In 63 per cent of the 40 thoracic vertebrae, the right azygos vein is at a distance less than or equal to 1 mm from the vertebral body. The first six lumbar vertebrae have broader corridors. Furthermore, vascular structures are far from the emergence point. The last lumbar vertebra and the sacrum have a broad pedicle, which provides an alternative site for implant placement.

Clinical Significance: For the vertebrae L1 to S1, the dorsal implantation can be performed. For the cervical vertebrae, the risk of laceration of the vertebral artery is high. For the last four thoracic vertebrae, the dorsal implantation should not be used.
Perioperative management of oral anticoagulation
Authors: ICKX BRIGITTE E. , MOTTE SERGE
Published: October 2006

Many patients receiving regular oral anticoagulation will need to undergo surgery at some point. However, the optimal management of such patients is uncertain. Various approaches have been suggested, but the strategy adopted must take into account each patient’s risk factors for thromboembolism as well as the type and likely duration of the surgical procedure. The objective of this review is to summarize the possible approaches to the management of orally anticoagulated patients requiring surgery and, in so doing, to provide a practical perioperative anticoagulation management scheme that can be used in daily practice.
Response to Comment on "Preindustrial to Modern Interdecadal Variability in Coral Reef pH"
Authors: Pelejero Carles , Calvo Eva , McCulloch Malcolm T. , Marshall John F. , Gagan Michael K. , Lough Janice M. , Opdyke Bradley N.
Published: October 2006

Coral reefs are exceptional environments where changes in calcification, photosynthesis, and respiration induce large temporal variations of pH. We argue that boron isotopic variations in corals provide a robust proxy for paleo-pH which, together with the likely concomitant changes in the reconstructed partial pressure of CO
2
(
P

CO
2

) calculated by Matear and McNeil, fall within ranges that are typical of modern coral reef ecosystems.
Molecular Phylogeny and Evolution of Morphology in the Social Amoebas
Authors: Schaap Pauline , Winckler Thomas , Nelson Michaela , Alvarez-Curto Elisa , Elgie Barrie , Hagiwara Hiromitsu , Cavender James , Milano-Curto Alicia , Rozen Daniel E. , Dingermann Theodor , Mutzel Rupert , Baldauf Sandra L.
Published: October 2006

The social amoebas (Dictyostelia) display conditional multicellularity in a wide variety of forms. Despite widespread interest inDictyostelium discoideumas a model system, almost no molecular data exist from the rest of the group. We constructed the first molecular phylogeny of the Dictyostelia with parallel small subunit ribosomal RNA and a-tubulin data sets, and we found that dictyostelid taxonomy requires complete revision. A mapping of characters onto the phylogeny shows that the dominant trend in dictyostelid evolution is increased size and cell type specialization of fruiting structures, with some complex morphologies evolving several times independently. Thus, the latter may be controlled by only a few genes, making their underlying mechanisms relatively easy to unravel.
Thrice Out of Africa: Ancient and Recent Expansions of the Honey Bee,
Apis mellifera
Authors: Whitfield Charles W. , Behura Susanta K. , Berlocher Stewart H. , Clark Andrew G. , Johnston J. Spencer , Sheppard Walter S. , Smith Deborah R. , Suarez Andrew V. , Weaver Daniel , Tsutsui Neil D.
Published: October 2006

We characterized
Apis mellifera
in both native and introduced ranges using 1136 single-nucleotide polymorphisms genotyped in 341 individuals. Our results indicate that
A. mellifera
originated in Africa and expanded into Eurasia at least twice, resulting in populations in eastern and western Europe that are geographically close but genetically distant. A third expansion in the New World has involved the near-replacement of previously introduced “European” honey bees by descendants of more recently introduced
A. m. scutellata
(“African” or “killer” bees). Our analyses of spatial transects and temporal series in the New World revealed differential replacement of alleles derived from eastern versus western Europe, with admixture evident in all individuals.
Tibolone and breast cancer
Authors: Erel C Tamer , Senturk Levent M , Kaleli Semih
Published: October 2006

Tibolone is a relatively new drug for postmenopausal women, which is structurally related to 19-nortestosterone derivatives and exhibits weak oestrogenic, progestogenic and androgenic activities. The effect of tibolone on breast tissue is still obscure. In vitro studies have shown conflicting results regarding the effects of tibolone on breast cells. On the other hand, although epidemiological studies show an increase in the risk of breast cancer among women treated with tibolone, accumulation of data obtained from radiological studies presents promising results. However, the safety of tibolone with regard to breast tissue needs to be investigated further, especially through well-designed, large-scale, randomised-controlled trials.
Prevalence of hypogonadism in male patients with renal failure
Authors: Albaaj F , Sivalingham M , Haynes P , McKinnon G , Foley R N , Waldek S , O'Donoghue D J , Kalra P A
Published: October 2006

Background

Hypogonadism in men may be secondary to renal failure and is well recognised in patients with end-stage renal disease. It is thought to contribute to the sexual dysfunction and osteoporosis experienced by these patients. However, the association between hypogonadism and lesser degrees of renal dysfunction is not well characterised.

Methods

The gonadal status of 214 male patients (mean age 56 (SD 18) years) attending a renal centre was studied; 62 of them were receiving haemodialysis and 22 continuous ambulatory peritoneal dialysis for end-stage renal disease, whereas 34 patients had functioning renal transplants and 96 patients were in the low-clearance phase. Non-fasting plasma was analysed for testosterone, follicle-stimulating hormone, luteinising hormone, sex hormone-binding globulin, parathyroid hormone and haemoglobin. Creatinine clearance was estimated in patients not on dialysis, and Kt/V and urea reduction ratio were assessed in patients on dialysis. Testosterone concentrations were classified as normal (>14 nmol/l), low-normal (10–14 nmol/l) or low (<10 nmol/l).

Results

56 (26.2%) patients had significantly low testosterone levels and another 65 (30.3%) had low-normal levels. No significant changes were seen in sex hormone-binding globulin or gonadotrophin levels. Gonadal status was not correlated with haemoglobin level, parathyroid hormone level, creatinine clearance, or dialysis duration or adequacy.

Conclusion

Over half of patients with renal failure, even in the pre-dialysis phase, have low or low-normal levels of testosterone, which may be a potentially reversible risk factor for osteoporosis and sexual dysfunction. These patients may be candidates for testosterone-replacement therapy, which has been shown to improve bone mineral-density and libido in men with low and low-normal testosterone levels.
Leishmaniasis
Authors: Piscopo T V , Mallia A C
Published: October 2006

Epidemiology, disease patterns, immunology, diagnosis, treatment and control measures of leishmaniasis are described. Various issues relating to leishmaniasis are highlighted: the relative lack of importance given to this disease is compared with other infections, climate change and its possible effect on extension of endemicity of this infection, and new diagnostic tests that are helping better diagnosis, especially in resource-poor areas. Other important aspects discussed include the potential for newer oral treatment to change the way this disease is managed; leishmania–HIV coinfection and groups at risk; and the development of an effective vaccine.
What is the origin of ulcerative colitis? Still more questions than answers
Authors: Lukas Milan , Bortlik Martin , Maratka Zdenek
Published: October 2006

Despite more than a century of existence as a clinical entity, the true origin of ulcerative colitis still remains elusive. Several factors probably contribute to the development of this condition. Recently discovered technologies have clarified the role of bacterial species, which may account for intestinal dysbiosis, as a factor triggering ulcerative colitis. Genetic susceptibility together with abnormal innate immunoreactivity probably comprise the essential prerequisites for the initiation and perpetuation of ulcerative colitis. Although the genetic background has been more clearly recognised in patients with Crohn's disease than in those with ulcerative colitis, some candidate loci associated with ulcerative colitis have also been intensively studied. Additionally, environmental factors may interfere with inherent predispositions to ulcerative colitis, and either suppress or reinforce them. Whatever the origin, the search for the aetiology of ulcerative colitis must have the same goal: the improvement of treatment and the quality of life in patients with ulcerative colitis.
POWER ANALYSIS OF VLSI INTERCONNECT WITH RLC TREE MODELS AND MODEL REDUCTION
Authors: SHIN YOUNGSOO , LEE JUNGHYUP
Published: October 2006

The lumped capacitance model, which ignores the existence of wire resistance, has been traditionally used to estimate the charging and discharging power consumption of CMOS circuits. We show that this model is not correct by pointing out that MOSFETs consume only part of the energy supplied by the source. During this study, it was revealed that about 20% of the power is consumed in the wire resistance of the buffered global interconnect, when the interconnect is modeled with RC tree networks. The percentage goes up to 30 when RLC model is used indicating the importance of inductance in interconnect model for power estimation. For RLC networks, we propose a compact yet very accurate power estimation method based on a model reduction technique.
FUNDAMENTAL GROUPS AND PRESENTATIONS OF ALGEBRAS
Authors: BUSTAMANTE JUAN CARLOS , CASTONGUAY DIANE
Published: October 2006

In this note, we investigate how different fundamental groups of presentations of a fixed algebra A can be. For finitely many finitely presented groups Gi, we construct an algebra A such that all Gi appear as fundamental groups of presentations of A.
Voltage-Dependent Potassium Currents During Fast Spikes of Rat Cerebellar Purkinje Neurons: Inhibition by BDS-I Toxin
Authors: Martina Marco , Metz Alexia E. , Bean Bruce P.
Published: October 2006

We characterized the kinetics and pharmacological properties of voltage-activated potassium currents in rat cerebellar Purkinje neurons using recordings from nucleated patches, which allowed high resolution of activation and deactivation kinetics. Activation was exceptionally rapid, with 10–90% activation in about 400 μs at +30 mV, near the peak of the spike. Deactivation was also extremely rapid, with a decay time constant of about 300 μs near −80 mV. These rapid activation and deactivation kinetics are consistent with mediation by Kv3-family channels but are even faster than reported for Kv3-family channels in other neurons. The peptide toxin BDS-I had very little blocking effect on potassium currents elicited by 100-ms depolarizing steps, but the potassium current evoked by action potential waveforms was inhibited nearly completely. The mechanism of inhibition by BDS-I involves slowing of activation rather than total channel block, consistent with the effects described in cloned Kv3-family channels and this explains the dramatically different effects on currents evoked by short spikes versus voltage steps. As predicted from this mechanism, the effects of toxin on spike width were relatively modest (broadening by roughly 25%). These results show that BDS-I–sensitive channels with ultrafast activation and deactivation kinetics carry virtually all of the voltage-dependent potassium current underlying repolarization during normal Purkinje cell spikes.
Cellular Mechanisms of Suppressive Interactions Between Somatosensory Responses In Vivo
Authors: Higley Michael J. , Contreras Diego
Published: October 2006

The neural integration of afferent inputs evoked by spatiotemporally distributed sensory stimuli is a critical step in the formation of coherent and continuous perceptual representations. Integration mechanisms in various systems include linear and nonlinear summation of sensory responses. One well-known example in the rat barrel system is the suppressive interaction between responses to the consecutive deflection of neighboring whiskers. The mechanism underlying cross-whisker suppression has long been postulated to rely on intracortical postsynaptic inhibition, although this hypothesis has been challenged by recent reports. Here we show, using intracellular and extracellular recordings in vivo, that cross-whisker suppression occurs in the absence of cortical activity. Instead, suppression arises from local circuit operations at multiple levels of the subcortical afferent pathway and is amplified by the nonlinear transformation of synaptic input into spike output in both the thalamus and cortex. Because these cellular processes are common to neural circuits subserving visual and auditory modalities, we propose that the suppressive mechanisms elucidated here are a general property of thalamocortical sensory systems.
Neural Coupling Between the Arms and Legs During Rhythmic Locomotor-Like Cycling Movement
Authors: Balter Jaclyn E. , Zehr E. Paul
Published: October 2006

Neuronal coupling between the arms and legs allowing coordinated rhythmic movement during locomotion is poorly understood. We used the modulation of cutaneous reflexes to probe this neuronal coupling between the arms and legs using a cycling paradigm. Participants performed rhythmic cycling with arms, legs, or arms and legs together. We hypothesized that any contributions from the arms would be functionally linked to locomotion and would thus be phase-dependent. Reflexes were evoked by electrical stimulation of the superficial peroneal nerve at the ankle, and electromyography (EMG) was recorded from muscles in the arms and legs. The main finding was that the relative contribution from the arms and legs was linked to the functional state of the legs. For example, in tibialis anterior, the largest contribution from arm movement [57% variance accounted for (VAF), P < 0.05] was during the leg power phase, whereas the largest from leg movement (71% VAF, P < 0.05) was during leg cycling recovery. Thus the contribution from the arms was functionally gated throughout the locomotor cycle in a manner that appears to support the action of the legs. Additionally, the effect of arm cycling on reflexes in leg muscles when the legs were not moving was relatively minor; full expression of the effect of rhythmic arm movement was only observed when both the arms and legs were moving. Our findings provide experimental support for the interaction of rhythmic arm and leg movement during human locomotion.
Processing Complexity of Complex Predicates: A Case Study in Japanese
Authors: Nakatani Kentaro
Published: October 2006

Complex predicates, by definition, behave like representationally ‘‘reduced’’ predicates, as extensively discussed in the syntax literature. This article reports the results from an experimental study using a type of complex predicate in Japanese (the V-te V predicate), testing how people process this type of complex ‘‘restructured’’ predicate in real time. Because of the properties of the V-te V predicate, it was possible to compare restructured predicates with nonrestructured ones, keeping such factors as event composition, Case licensing, and lexical choice constant. The results of the experiment suggest that the tested restructured predicates involve a single array of predicate-argument association rather than two separate arrays, even though they contain two verbs. The results also revealed that syntactically complex ditransitive predicates are processed with the same ease as lexical ditransitives.
454 sequencing put to the test using the complex genome of barley
Authors: Wicker Thomas , Schlagenhauf Edith , Graner Andreas , Close Timothy J , Keller Beat , Stein Nils
Published: October 2006

Background

During the past decade, Sanger sequencing has been used to completely sequence hundreds of microbial and a few higher eukaryote genomes. In recent years, a number of alternative technologies became available, among them adaptations of the pyrosequencing procedure (i.e. "454 sequencing"), promising a ~100-fold increase in throughput over Sanger technology – an advancement which is needed to make large and complex genomes more amenable to full genome sequencing at affordable costs. Although several studies have demonstrated its potential usefulness for sequencing small and compact microbial genomes, it was unclear how the new technology would perform in large and highly repetitive genomes such as those of wheat or barley.

Results

To study its performance in complex genomes, we used 454 technology to sequence four barley Bacterial Artificial Chromosome (BAC) clones and compared the results to those from ABI-Sanger sequencing. All gene containing regions were covered efficiently and at high quality with 454 sequencing whereas repetitive sequences were more problematic with 454 sequencing than with ABI-Sanger sequencing. 454 sequencing provided a much more even coverage of the BAC clones than ABI-Sanger sequencing, resulting in almost complete assembly of all genic sequences even at only 9 to 10-fold coverage. To obtain highly advanced working draft sequences for the BACs, we developed a strategy to assemble large parts of the BAC sequences by combining comparative genomics, detailed repeat analysis and use of low-quality reads from 454 sequencing. Additionally, we describe an approach of including small numbers of ABI-Sanger sequences to produce hybrid assemblies to partly compensate the short read length of 454 sequences.

Conclusion

Our data indicate that 454 pyrosequencing allows rapid and cost-effective sequencing of the gene-containing portions of large and complex genomes and that its combination with ABI-Sanger sequencing and targeted sequence analysis can result in large regions of high-quality finished genomic sequences.
P5L mutation in Ank results in an increase in extracellular inorganic pyrophosphate during proliferation and nonmineralizing hypertrophy in stably transduced ATDC5 cells
Authors: Zaka Raihana , Stokes David , Dion Arnold S , Kusnierz Anna , Han Fei , Williams Charlene J
Published: October 2006

Ank is a multipass transmembrane protein that regulates the cellular transport of inorganic pyrophosphate. In the progressive ankylosis (ank) mouse, a premature termination mutation at glutamic acid 440 results in a phenotype characterized by inappropriate deposition of basic calcium phosphate crystals in skeletal tissues. Mutations in the amino terminus of ANKH, the human homolog of Ank, result in familial calcium pyrophosphate dihydrate deposition disease. It has been hypothesized that these mutations result in a gain-of-function with respect to the elaboration of extracellular inorganic pyrophosphate. To explore this issue in a mineralization-competent system, we stably transduced ATDC5 cells with wild-type Ank as well as with familial chondrocalcinosis-causing Ank mutations. We evaluated the elaboration of inorganic pyrophosphate, the activity of pyrophosphate-modulating enzymes, and the mineralization in the transduced cells. Expression of transduced protein was confirmed by quantitative real-time PCR and by ELISA. Levels of inorganic pyrophosphate were measured, as were the activities of nucleotide pyrophosphatase phosphodiesterase and alkaline phosphatase. We also evaluated the expression of markers of chondrocyte maturation and the nature of the mineralization phase elaborated by transduced cells. The cell line expressing the proline to leucine mutation at position 5 (P5L) consistently displayed higher levels of extracellular inorganic pyrophosphate and higher phosphodiesterase activity than the other transduced lines. During hypertrophy, however, extracellular inorganic pyrophosphate levels were modulated by alkaline phosphatase activity in this cell system, resulting in the deposition of basic calcium phosphate crystals only in all transduced cell lines. Cells overexpressing wild-type Ank displayed a higher level of expression of type X collagen than cells transduced with mutant Ank. Other markers of hypertrophy and terminal differentiation, such as alkaline phosphatase, osteopontin, and runx2, were not significantly different in cells expressing wild-type or mutant Ank in comparison with cells transduced with an empty vector or with untransduced cells. These results suggest that the P5L Ank mutant is capable of demonstrating a gain-of-function with respect to extracellular inorganic pyrophosphate elaboration, but this effect is modified by high levels of expression of alkaline phosphatase in ATDC5 cells during hypertrophy and terminal differentiation, resulting in the deposition of basic calcium phosphate crystals.
Global analysis of mRNA stability in the archaeon Sulfolobus
Authors: Andersson Anders F , Lundgren Magnus , Eriksson Stefan , Rosenlund Magnus , Bernander Rolf , Nilsson Peter
Published: October 2006

Background

Transcript half-lives differ between organisms, and between groups of genes within the same organism. The mechanisms underlying these differences are not clear, nor are the biochemical properties that determine the stability of a transcript. To address these issues, genome-wide mRNA decay studies have been conducted in eukaryotes and bacteria. In contrast, relatively little is known about RNA stability in the third domain of life, Archaea. Here, we present a microarray-based analysis of mRNA half-lives in the hyperthermophilic crenarchaea Sulfolobus solfataricus and Sulfolobus acidocaldarius, constituting the first genome-wide study of RNA decay in archaea.

Results

The two transcriptomes displayed similar half-life distributions, with medians of about five minutes. Growth-related genes, such as those involved in transcription, translation and energy production, were over-represented among unstable transcripts, whereas uncharacterized genes were over-represented among the most stable. Half-life was negatively correlated with transcript abundance and, unlike the situation in other organisms, also negatively correlated with transcript length.

Conclusion

The mRNA half-life distribution of Sulfolobus species is similar to those of much faster growing bacteria, contrasting with the earlier observation that median mRNA half-life is proportional to the minimal length of the cell cycle. Instead, short half-lives may be a general feature of prokaryotic transcriptomes, possibly related to the absence of a nucleus and/or more limited post-transcriptional regulatory mechanisms. The pattern of growth-related transcripts being among the least stable in Sulfolobus may also indicate that the short half-lives reflect a necessity to rapidly reprogram gene expression upon sudden changes in environmental conditions.