bluuebunny/crossref_metadata_2025 huggingface dataset:
Host responses influence on the induction of lambda prophage
Authors: Rokney Assaf , Kobiler Oren , Amir Amnon , Court Donald L. , Stavans Joel , Adhya Sankar , Oppenheim Amos B.
Published: February 2008

Inactivation of bacteriophage lambda CI repressor leads almost exclusively to lytic development. Prophage induction can be initiated either by DNA damage or by heat treatment of a temperature‐sensitive repressor. These two treatments also cause a concurrent activation of either the host SOS or heat‐shock stress responses respectively. We studied the effects of these two methods of induction on the lytic pathway by monitoring the activation of different lambda promoters, and found that the lambda genetic network co‐ordinates information from the host stress response networks. Our results show that the function of the CII transcriptional activator, which facilitates the lysogenic developmental pathway, is not observed following either method of induction. Mutations in the cro gene restore the CII function irrespective of the induction method. Deletion of the heat‐shock protease gene ftsH can also restore CII function following heat induction but not following SOS induction. Our findings highlight the importance of the elimination of CII function during induction as a way to ensure an efficient lytic outcome. We also show that, despite the common inhibitory effect on CII function, there are significant differences in the heat‐ and SOS‐induced pathways leading to the lytic cascade.
Unintended pregnancy rates among a US military population
Authors: Custer Michael , Waller Kim , Vernon Sally , O'Rourke Kathleen
Published: February 2008

Unintended pregnancy among military women influences their lives and has implications for troop readiness and deployment. The purpose of this study was to identify the prevalence of unintended pregnancy in the US Army and assess the variables associated with unintended pregnancy. Using a cross‐sectional design, 212 female soldiers who delivered viable infants at Darnall Army Community Hospital, Fort Hood, Texas from 1 June 1998 to 6 October 1998 completed a self‐administered survey on pregnancy intention and sociodemographic factors. Approximately 35% of the infants were intended, 51% were unintended and 14% were ambivalent, resulting in 65% not intended, a rate consistent with the upper level of civilian communities. Factors associated univariably with unintended pregnancy included being unmarried, being in the lower enlisted rank, having less than a college degree, and living in the barracks. This study shows the importance of developing programmes and policies that address pregnancy among military personnel.
Flow transformations in slumps: a case study from the Waitemata Basin, New Zealand
Authors: STRACHAN L. J.
Published: February 2008

The process by which slumps transform into other flow types is an understudied phenomenon; generally, sedimentologists have assumed that this is how many debris flows and turbidity currents form, yet there is a paucity of information relating to the specific processes involved. This paper aims to redress this imbalance and investigates the processes of slump flow transformation using a well‐exposed example, where the precursor slump and flows to which it was transforming have been preserved in the outcrop. A detailed field investigation of the Lower Miocene, Little Manly Slump, located within the Waitemata Basin, New Zealand, reveals a complex bi‐partite deposit, comprised of a lower slump‐debrite unit and an upper turbidite unit, separated from one another by an impersistent contact. Reconstruction of slump evolution, from preserved strain indicators, shows that slump motion was unsteady and non‐uniform, and that the slump arrested rapidly. Flow transformation is directly linked to slump evolution and progressed through the multiple processes of body transformation, fluidization transformation and surface transformation. The resultant flow comprised a very dense lower unit with slump and debris flow phases overlain by a turbidity current. This study shows that flow transformation did not result in en masse transformation to a debris flow by a single process, but rather it was characterized by partial transformation of the slump to generate a three‐phase flow. Density is thought to be the key parameter in controlling flow transformation efficiency, which appears to have varied rapidly as a function of slump unsteadiness and non‐uniformity.
Maternal employment in child‐care institutions and the risk of infant wheeze and atopic dermatitis in the offspring
Authors: Hersoug Lars‐Georg , Benn Christine S. , Simonsen Jacob B. , Kamper‐Jørgensen Mads , Linneberg Allan
Published: February 2008

It has been proposed that exposure to infections and microbes protects against atopic diseases, but epidemiological data has so far been conflicting. We hypothesized that maternal exposure to infections and microbes before or during pregnancy would be of particular importance. To test this hypothesis, we studied the incidence of wheezing and atopic dermatitis (AD) in infants of mothers employed in child‐care institutions – and thus presumably being highly exposed to infections and microbes – compared with infants of mothers not so employed. A total of 31471 mother‐child pairs enroled in the Danish National Birth Cohort were followed prospectively. Information on wheezing episodes, AD, maternal employment, and other variables were collected by interview at 12 and 30 wk of gestation, and 6 and 18 months of age, and by linkage to the Danish Medical Birth Register and the Child‐care Database. The relative risk was estimated in Cox proportional hazard models. Analyses were stratified by sibling status (first born or not), as older siblings are likely to be a significant source of infectious agents. The adjusted relative risks of wheeze, recurrent wheeze and AD was 1.14 (95% CI: 0.96–1.37), 1.37 (95% CI: 1.05–1.77), and 1.03 (95% CI: 0.81–1.31), respectively, for first‐born infants of mothers employed in child‐care institutions compared with infants of mothers not so employed. There was no effect of maternal employment in child‐care institutions among infants with older siblings. In conclusion, the results did not support the hypothesis that maternal microbial exposure before or during pregnancy as reflected by maternal employment in child‐care institutions protects the offspring against infant wheeze and AD.
Expressed sequence tag analysis of the response of apple (Malus x domestica‘Royal Gala’) to low temperature and water deficit
Authors: Wisniewski Michael , Bassett Carole , Norelli John , Macarisin Dumitru , Artlip Timothy , Gasic Ksenija , Korban Schuyler
Published: February 2008

Leaf, bark, xylem and root tissues were used to make nine cDNA libraries from non‐stressed (control) ‘Royal Gala’ apple trees, and from ‘Royal Gala’ trees exposed to either low temperature (5°C for 24 h) or water deficit (45% of saturated pot mass for 2 weeks). Over 22 600 clones from the nine libraries were subjected to 5′ single‐pass sequencing, clustered and annotated using blastx. The number of clusters in the libraries ranged from 170 to 1430. Regarding annotation of the sequences, blastx analysis indicated that within the libraries 65–72% of the clones had a high similarity to known function genes, 6–15% had no functional assignment and 15–26% were completely novel. The expressed sequence tags were combined into three classes (control, low‐temperature and water deficit) and the annotated genes in each class were placed into 1 of 10 different functional categories. The percentage of genes falling into each category was then calculated. This analysis indicated a distinct downregulation of genes involved in general metabolism and photosynthesis, while a significant increase in defense/stress‐related genes, protein metabolism and energy was observed. In particular, there was a three‐fold increase in the number of stress genes observed in the water deficit libraries indicating a major shift in gene expression in response to a chronic stress. The number of stress genes in response to low temperature, although elevated, was much less than the water deficit libraries perhaps reflecting the shorter (24 h) exposure to stress. Genes with greater than five clones in any specific library were identified and, based on the number of clones obtained, the fold increase or decrease in expression in the libraries was calculated and verified by semiquantitative polymerase chain reaction. Genes, of particular note, that code for the following proteins were overexpressed in the low‐temperature libraries: dehydrin and metallothionein‐like proteins, ubiquitin proteins, a dormancy‐associated protein, a plasma membrane intrinsic protein and an RNA‐binding protein. Genes that were upregulated in the water deficit libraries fell mainly into the functional categories of stress (heat shock proteins, dehydrins) and photosynthesis. With few exceptions, the overall differences in downregulated genes were nominal compared with differences in upregulated genes. The results of this apple study are similar to other global studies of plant response to stress but offer a more detailed analysis of specific tissue response (bark vs xylem vs leaf vs root) and a comparison between an acute stress (24‐h exposure to low temperature) and a chronic stress (2 weeks of water deficit).
Effects of Monochromatic Light on Proliferation Response of Splencyte in Broilers
Authors: Xie D. , Wang Z. , Cao J. , Dong Y. , Chen Y.
Published: February 2008

To investigate the effects of various monochromatic lights on splenocyte proliferation responses, a total of 260 Arbor Acre male broilers on P1 (post‐hatching day 1) were exposed to blue light (BL), green light (GL), red light (RL) and white light treatments by light emitting diode system for 7 weeks, respectively. All light sources were equalized on the intensity of 15 lx and light period of 23 h daily. Morphological change of spleen and response of splenocyte proliferation were assessed by using histochemistry staining and colorimetric test in cultures of purified splenic cells. The results were as follows: (1) At P21, GL increased significantly the spleen weight by 163.6% and spleen index by 118.8% compared with RL (P < 0.05). Until P49, BL enhanced significantly the spleen weights by 42.2% compared with RL (P < 0.05), but no significant difference was found in the spleen index among four light‐treated groups (P > 0.05). (2) Compared with RL, GL increased significantly the diameter of splenic nodule and area of periarterial lymphatic sheath at P21 by 87.2 and 58.1%, respectively (P < 0.05); BL increased significantly the diameter of splenic nodule and area of periarterial lymphatic sheath at P49 by 64.4 and 50.5%, respectively (P < 0.05). (3) At P21, GL enhanced spleen lymphocytes proliferation in response to concanavalin A compared with RL by 50.0% (P < 0.05). Until P49, the mitogenic response in BL was significantly higher (29.4%) than that of RL (P < 0.05). (4) The interleukin‐2 (IL‐2) bioactivity was significantly increased to 34.3% in GL than in RL at P21 (P < 0.05). Until P49, the IL‐2 bioactivity in BL was significantly higher (62.2%) than that of RL (P < 0.05). (5) There was no significant difference in the nitric oxide (NO) concentration of splenocyte among RL, GL and BL groups at P21 (P > 0.05), but the concentration in RL group at P49 was significantly increased, 59.0 and 63.7% compared to that of GL and BL groups, respectively (P < 0.05). These results suggested that the monochromatic light affected splenocyte proliferation mainly because of alterations in IL‐2 bioactivity and NO production in splenocyte of broiler. In early stage of broiler growth, the action of GL was obvious, while the response of BL was stronger in later stage.
Distribution and Heterogeneity of Mast Cells in Female Reproductive Tract and Ovary on Different Days of the Oestrus Cycle in Angora Goats
Authors: Karaca T , Arikan S , Kalender H , Yoruk M
Published: February 2008

Contents

The physiological distribution of mast cells (MCs) in the reproductive tract and ovary of 12 Angora goats was determined using light microscopic histochemical techniques. Uterus (corpus uteri and cornu uteri), uterine cervix, uterine tubes (isthmus and ampulla) and ovary samples were obtained by laparatomy from groups of animals during metoestrus, dioestrus and proestrus (days 5, 10 and 16 of the oestrous cycle). Tissues were fixed in Mota's fixative (basic lead acetate) for 48 h and embedded in paraffin. Six‐micrometre‐thick sections were stained with toluidine blue in 1% aqueous solution at pH 1.0 for 5 min and alcian blue‐Safranin at pH 1.0 for 30 min. MCs were generally associated with blood vessels in all reproductive organs. In the uterus, they were concentrated mainly in the close of the uterine gland and deep stroma in the endometrium. Higher MC numbers were observed by toluidine blue staining in the uterus, uterine cervix and uterine tubes on days 10 (corpus uterine: 4.7 ± 3.8 and cornu uterine: 4.9 ± 3.5) and 16 (corpus uterine: 5.9 ± 4.5 and cornu uterine: 5.4 ± 2.4) of the oestrous cycle compared with day 5 (p < 0.05). Mast cells were not observed in the follicles, the corpus luteum and the underside of the surface epithelium of the ovarian cortex, but were observed in the interstitial cortical stroma and the ovarian medulla. In the ovary, MC numbers were significantly higher on day 16 of the oestrous cycle (cortex: 3.4 ± 2.4 and medulla: 5.7 ± 4.5, p < 0.05). Safranin‐positive connective tissue MCs were not observed in the uterine tube on any occasion. These results indicate oestrous cycle‐related changes in the number and location of MCs in goat reproductive organs.
Prevalence of chronic prostatitis symptoms in a randomly surveyed adult population of urban‐community‐dwelling Nigerian males
Authors: Ejike Chukwunonso ECC , Ezeanyika Lawrence US
Published: February 2008

Objectives:  Chronic prostatitis is a debilitating disease of the prostate gland that is characterized by chronic pelvic pain. Unlike the developed world, the prevalence of chronic prostatitis and its impact on the quality of life (QOL) of the sufferer is not known in Nigeria. This work was carried out to fill this vacuum.

Methods:  A random cross‐sectional survey of apparently normal men of ages 20–70 years, living in Nsukka, a university town in South‐eastern Nigeria, using the National Institute of Health Chronic Prostatitis Symptom Index (NIH‐CPSI) was carried out. The self reported pain and QOL scores were used to identify subjects with chronic prostatitis symptoms and the subjects' QOL status, respectively.

Results:  Of the 1507 men studied, 12.21% had symptoms suggestive of chronic prostatitis. Subjects with chronic prostatitis symptoms (CPS) (mean relative age 40.98 ± 12.51 years) had higher mean pain and voiding scores (5.65 ± 1.99 and 2.61 ± 2.23, respectively) compared with subjects without CPS (0.44 ± 0.73 and 1.29 ± 1.70 for pain and voiding scores, respectively; mean relative age 41.99 ± 12.99 years). A total of 39.62% of the population had pain in at least one location, while 22.69% of the population had impaired QOL.

Conclusion:  Chronic prostatitis symptoms are as common in Nigeria as they are in the developed world, and so are their effects on the QOL of the sufferer.
Landscape effects on crop pollination services: are there general patterns?
Authors: Ricketts Taylor H. , Regetz James , Steffan‐Dewenter Ingolf , Cunningham Saul A. , Kremen Claire , Bogdanski Anne , Gemmill‐Herren Barbara , Greenleaf Sarah S. , Klein Alexandra M. , Mayfield Margaret M. , Morandin Lora A. , Ochieng’ Alfred , Viana Blande F.
Published: February 2008

Pollination by bees and other animals increases the size, quality, or stability of harvests for 70% of leading global crops. Because native species pollinate many of these crops effectively, conserving habitats for wild pollinators within agricultural landscapes can help maintain pollination services. Using hierarchical Bayesian techniques, we synthesize the results of 23 studies – representing 16 crops on five continents – to estimate the general relationship between pollination services and distance from natural or semi‐natural habitats. We find strong exponential declines in both pollinator richness and native visitation rate. Visitation rate declines more steeply, dropping to half of its maximum at 0.6 km from natural habitat, compared to 1.5 km for richness. Evidence of general decline in fruit and seed set – variables that directly affect yields – is less clear. Visitation rate drops more steeply in tropical compared with temperate regions, and slightly more steeply for social compared with solitary bees. Tropical crops pollinated primarily by social bees may therefore be most susceptible to pollination failure from habitat loss. Quantifying these general relationships can help predict consequences of land use change on pollinator communities and crop productivity, and can inform landscape conservation efforts that balance the needs of native species and people.
Prevalence and risk factors for diabetic neuropathy in an urban south Indian population: the Chennai Urban Rural Epidemiology Study (CURES‐55)
Authors: Pradeepa R. , Rema M. , Vignesh J. , Deepa M. , Deepa R. , Mohan V.
Published: February 2008

Aims  This study was conducted to determine the prevalence of, and risk factors for, diabetic neuropathy (DN) in south Indian Type 2 diabetic subjects.

Methods  Subjects were recruited from the Chennai Urban Rural Epidemiology Study, conducted on a representative cohort from Chennai city. A total of 1629 diabetic subjects were included, of whom 1291 were known to have diabetes (KD) subjects and 338 were randomly selected newly detected diabetic (NDD) subjects. Neuropathy was diagnosed if vibratory perception threshold at the great toe, measured by biothesiometry, exceeded mean + 2 sd of a healthy non‐diabetic study population aged 20–45 years (cut point ≥ 20 V).

Results  The overall prevalence of DN was 26.1% (age‐adjusted 13.1%) with no significant difference in gender. The prevalence of neuropathy was significantly higher in KD subjects compared with NDD subjects (27.8 vs. 19.5%, P = 0.002). The prevalence of diabetic retinopathy (24.1 vs. 15.3%, P < 0.0001) and hypertension (51.1 vs. 40.0%, P < 0.0001) were higher in those with neuropathy compared with those without. The odds ratio for neuropathy in subjects with duration of diabetes > 15 years compared with ≤ 5 years was 5.7 (95% confidence interval: 3.52–9.08, P < 0.0001). Regression analysis showed age (P < 0.0001), glycated haemoglobin (P = 0.001) and duration of diabetes (P = 0.045) to be significantly associated with neuropathy.

Conclusions  This cross‐sectional population‐based study shows that, among urban south Indian Type 2 diabetic subjects, the prevalence of DN is 26.1% and that DN is significantly associated with age, glycated haemoglobin and duration of diabetes.
Patients’ perceptions and experiences of taking oral glucose‐lowering agents: a longitudinal qualitative study
Authors: Lawton J. , Peel E. , Parry O. , Douglas M.
Published: February 2008

Aims  The aims of this study were to examine Type 2 diabetic patients’ expectations, perceptions and experiences of oral glucose‐lowering agents (OGLAs), including their reasons for taking/not taking these drugs as prescribed and to provide recommendations for developing interventions to improve OGLA adherence.

Methods  Longitudinal, qualitative study using repeat in‐depth interviews with patients (n = 20) over 4 years following clinical diagnosis. Respondents were recruited from primary and secondary care settings across Lothian, Scotland, UK.

Results  Despite experiences of side‐effects, dislikes and concerns about taking multiple drugs and a belief that OGLAs could themselves cause one's diabetes to progress, most respondents appeared motivated to take these drugs as prescribed. This motivation seemed to arise from respondents’ experiences of taking OGLAs and observing them to ‘work’. Some respondents described feeling better after taking OGLAs, others, typically those who were asymptomatic, used blood glucose self‐monitoring and/or glycated haemoglobin results to observe and evidence the effects of their OGLAs. Most respondents demonstrated a ‘passive’ expectation that health professionals should be responsible for decisions about medications. Hence, non‐adherence typically resulted from forgetfulness rather than ambivalence about either medication or consultation style. Respondent concern about OGLA's largely centred upon lack of knowledge about the medication and what to do when doses were missed.

Conclusion  The findings call for multifaceted strategies to promote adherence. These could include education to address misconceptions and advise patients how to respond to missed doses; reminders to help patients remember to take their drugs; and structured feedback on the impact of OGLAs on glycaemic control.
An empirical validation of a dynamic systems model of interaction: do children of different sociometric statuses differ in their dyadic play?
Authors: Steenbeek Henderien , Van Geert Paul
Published: February 2008

Studying short‐term dynamic processes and change mechanisms in interaction yields important knowledge that contributes to understanding long‐term social development of children. In order to get a grip on this short‐term dynamics of interaction processes, the authors made a dynamic systems model of dyadic interaction of children during one play session. The control parameters of the model relate to children's goal‐directedness, concerns, emotional appraisals, social power, and social competence. Three groups of dyads of different sociometric statuses are represented by specific control parameter values. The model's order parameters consist of children's emotional expressions and other‐ versus self‐directed actions. This article describes the empirical validation of the model and the methods needed for such validation. It focuses on the model's predictions of averages and distributions of the major variables, of the occurrence of attractors and power law distributions, and on the model's sensitivity. Overall, the model fits the empirical data well. In the discussion, we reflect on the developmental and methodological implications for explaining social interaction on the short‐term as well as on the long‐term time scale. In addition, implications for intervention and assessment are presented, in particular relating to the problem of rejection.
Disappearing Defendants versus Judgment‐Proof Injurers
Authors: DARI‐MATTIACCI GIUSEPPE , MANGAN BARBARA M.
Published: February 2008

In this paper we analyse two ways in which liability can be reduced: caps (the judgment proof problem), and proportional reductions (the disappearing defendant problem). We show that these two problems have different incentive effects and hence yield dissimilar levels of social welfare. Moreover, when they occur simultaneously they may have offsetting effects. We also show that the negligence rule with cause‐in‐fact may yield lower (rather than higher) levels of social welfare than strict liability. Finally, we analyse the optimal setting of the negligence standard. Our model encompasses different precaution technologies as well as monetary v. non‐monetary precautions.
Early vs. Non-Early Intervention in Acute Migraine — ‘Act When Mild (AwM)’. A Double-Blind, Placebo-Controlled Trial of Almotriptan
Authors: Goadsby PJ , Zanchin G , Geraud G , de Klippel N , Diaz-Insa S , Gobel H , Cunha L , Ivanoff N , Falques M , Fortea J
Published: February 2008

The study was designed to compare the response to almotriptan in migraine patients who take medication early in the course of the attack with that when medication is taken after pain has become moderate or severe. A randomized, four-arm, multicentre, multinational, double-blind, placebo-controlled trial of almotriptan (12.5 mg) comparing treatment administration when pain intensity was mild and within 1 h of headache onset vs. pain that had become moderate or severe was conducted. Of 491 migraineurs enrolled, 403 were evaluable [intention-to-treat population (ITT)]. Their mean age was 38 years, 84% were female and they had a mean of 3.7 attacks/month. Of these patients, 10% did not take medication according to their randomly allocated basal pain intensity (mild or moderate/severe) and were subsequently reassigned to that group for this analysis —'Act when Mild (AwM)' group. In the almotriptan arms, 53% of mild basal pain and 38% of moderate/severe basal pain patients were pain free at 2 h ( P = 0.03; primary end-point). Corresponding proportions in the placebo groups were 25% and 17% (statistically significant vs. respective almotriptan arms). Secondary end-points (ITT) were also significantly in favour of early intervention with almotriptan, both between and across treatment groups, such as sustained pain free: 45.6% vs. 30.5% ( P = 0.02). Adverse events were reported in < 5% of treated patients in all groups (NS), with no serious events. Treatment with almotriptan while migraine pain is still mild provides statistically significant and clinically relevant enhancements in efficacy compared with treatment when pain has reached higher severity levels.
Guidelines for Controlled Trials of Prophylactic Treatment of Chronic Migraine in Adults
Authors: Silberstein S , Tfelt-Hansen P , Dodick DW , Limmroth V , Lipton RB , Pascual J , Wang SJ ,   for the Task Force of the International Headache Society Clinical Trials Subcommittee
Published: February 2008

In 1991 the Clinical Trials Subcommittee of the International Headache Society (IHS) developed and published its first edition of the Guidelines on controlled trials of drugs in episodic migraine because only quality trials can form the basis for international collaboration on drug therapy, and these Guidelines would ‘improve the quality of controlled clinical trials in migraine’. With the current trend for large multinational trials, there is a need for increased awareness of methodological issues in clinical trials of drugs and other treatments for chronic migraine. These Guidelines are intended to assist in the design of well-controlled clinical trials of chronic migraine in adults, and do not apply to studies in children or adolescents.
Significant Association Between TIM1 Promoter Polymorphisms and Protection Against Cerebral Malaria in Thailand
Authors: Nuchnoi P. , Ohashi J. , Kimura R. , Hananantachai H. , Naka I. , Krudsood S. , Looareesuwan S. , Tokunaga K. , Patarapotikul J.
Published: February 2008

Although cerebral malaria is a major life‐threatening complication of Plasmodium falciparum infection, its pathophysiology is not well understood. Prolonged activation of the T helper type 1 (Th1) response characterized by the production of pro‐inflammatory cytokines such as IFN‐γ and TNF‐α has been suggested to be responsible for immunopathological process leading to cerebral malaria unless they are downregulated by the anti‐inflamatory cytokines produced by the Th2 response. The T cell immunoglobulin and mucin domain (TIM) family of proteins are cell surface proteins involved in regulating Th1 and Th2 immune responses. In this study, the possible association between the polymorphisms of TIM1, TIM3, and TIMD4 genes and the severity of malaria was examined in 478 adult Thai patients infected with P. falciparum malaria. The TIM1 promoter haplotype comprising three derived alleles, ‐1637A (rs7702919), ‐1549C (rs41297577) and ‐1454A (rs41297579), which were in complete linkage disequilibrium, was significantly associated with protection against cerebral malaria (OR = 0.41; 95% CI = 0.24–0.71; P= 0.0009). Allele‐specific transcription quantification analysis revealed that the level of mRNA transcribed from TIM1 was higher for the protective promoter haplotype than for the other promoter haplotype (P= 0.004). Engagement with TIM1 in combination with T cell receptor stimulation induces anti‐inflammatory Th2 cytokine production, which can protect the development of cerebral malaria caused by overproduction of pro‐inflammatory Th1 cytokines. The present results suggest that the higher TIM1 expression associated with the protective TIM1 promoter haplotype confers protection against cerebral malaria.
A Mutation Analysis of the Phenylalanine Hydroxylase (PAH) Gene in the Israeli Population
Authors: Bercovich D. , Elimelech A. , Yardeni T. , Korem S. , Zlotogora J. , Gal N. , Goldstein N. , Vilensky B. , Segev R. , Avraham S. , Loewenthal R. , Schwartz G. , Anikster Y.
Published: February 2008

Hyperphenylalaninemia (HPA) is a group of diseases characterized by a persistent elevation of phenylalanine levels in tissues and biological fluids. The most frequent form is phenylalanine hydroxylase deficiency, causing phenylketonuria (PKU). Among 159 Israeli patients (Jews, Muslim and Christian Arabs and Druze) with HPA, in whom at least one of the mutations was characterized, a total of 43 different mutations were detected, including seven novel ones. PKU was very rare among Ashkenazi Jews and relatively frequent among Jews from Yemen, the Caucasian Mountains, Bukhara and Tunisia. The mutations responsible for the high frequency were: exon3del (Yemenite Jews), L48S (Tunisian Jews) and E178G, P281L and L48S (Jews from the Caucasian Mountains and Bukhara). Among the non‐Jewish Israeli citizens, the disease was relatively frequent in the Negev and in the Nazareth vicinity, and in many localities a unique mutation was detected, often in a single family. While marked genetic heterogeneity was observed in the Arab and Jewish populations, only one mutation A300S, was frequent in all of the communities. Several of the other frequent mutations were shared by the non‐Ashkenazi Jews and Arabs; none were mutual to Ashkenazi Jews and Arabs.
Down‐regulation of astrocytic GLAST by microglia‐related inflammation is abrogated in dibutyryl cAMP‐differentiated cultures
Authors: Tilleux Sébastien , Hermans Emmanuel
Published: February 2008

The influence of neuroinflammation on glutamate uptake by glial cells was examined after exposing primary cultures of rat astrocytes to conditioned culture medium from lipopolysaccharide‐activated microglia. While such treatment triggered an inflammatory response in astrocytes, as revealed by the induction of cytokine expression, a significant decrease in GLAST expression and activity was observed after 72 h. This regulation of glutamate transporter was not observed with medium from naive microglia, but was mimicked by direct addition of tumor necrosis factor‐alpha (TNF‐α), a major cytokine released from activated microglia. Hence, on its own, TNF‐α also triggered inflammation in astrocyte cultures, highlighting complex cross‐talk between astrocytes and microglia in inflammatory conditions. This putatively detrimental regulation of GLAST in response to inflammation was also studied in cells exposed to dibutyryl cAMP, recognized as a model of astrocytes exhibiting a typical differentiated or activated phenotype. In this model, the conditioned culture medium from activated microglia, as well as TNF‐α, were found to increase glutamate uptake capacity. Consistently, both of these treatments caused only modest induction of an inflammatory response in dibutyryl cAMP‐matured astrocytes as compared to undifferentiated astrocytes. Together, these results suggest that differentiated/activated astrocytes are endowed with the capacity to confront inflammatory insults and that drugs influencing the astrocytes phenotype would deserve further consideration in the treatment of neurological disorders.
Release‐enhancing pre‐synaptic muscarinic and nicotinic receptors co‐exist and interact on dopaminergic nerve endings of rat nucleus accumbens
Authors: Grilli Massimo , Patti Laura , Robino Federica , Zappettini Stefania , Raiteri Maurizio , Marchi Mario
Published: February 2008

Dopaminergic nerve endings in the corpus striatum possess nicotinic (nAChRs) and muscarinic cholinergic receptors (mAChRs) mediating release of dopamine (DA). Whether nAChRs and mAChRs co‐exist and interact on the same nerve endings is unknown. We here investigate on these possibilities using rat nucleus accumbens synaptosomes pre‐labeled with [3H]DA and exposed in superfusion to cholinergic receptor ligands. The mixed nAChR–mAChR agonists acetylcholine (ACh) and carbachol provoked [3H]DA release partially sensitive to the mAChR antagonist atropine but totally blocked by the nAChR antagonist mecamylamine. Addition of the mAChR agonist oxotremorine at the minimally effective concentration of 30 μmol/L, together with 3, 10, or 100 μmol/L (−)nicotine provoked synergistic effect on [3H]DA overflow. The [3H]DA overflow elicited by 100 μmol/L (−)nicotine plus 30 μmol/L oxotremorine was reduced by atropine down to the release produced by (−)nicotine alone and it was abolished by mecamylamine. The ryanodine receptor blockers dantrolene or 8‐bromo‐cADP‐ribose, but not the inositol 1,4,5‐trisphosphate receptor blocker xestospongin C inhibited the (−)nicotine/oxotremorine evoked [3H]DA overflow similarly to atropine. This overflow was partly sensitive to 100 nmol/L methyllycaconitine which did not prevent the synergistic effect of (−)nicotine/oxotremorine. Similarly to (−)nicotine, the selective α4β2 nAChR agonist RJR2403 exhibited synergism when added together with oxotremorine. To conclude, in rat nucleus accumbens, α4β2 nAChRs exert a permissive role on the releasing function of reportedly M5mAChRs co‐existing on the same dopaminergic nerve endings.
Dystrophin deficiency in Drosophila reduces lifespan and causes a dilated cardiomyopathy phenotype
Authors: Taghli‐Lamallem Ouarda , Akasaka Takeshi , Hogg Grant , Nudel Uri , Yaffe David , Chamberlain Jeffrey S. , Ocorr Karen , Bodmer Rolf
Published: February 2008

A number of studies have been conducted recently on the model organism Drosophila to determine the function of genes involved in human disease, including those implicated in neurological disorders, cancer and metabolic and cardiovascular diseases. The simple structure and physiology of the Drosophila heart tube together with the available genetics provide a suitable in vivo assay system for studying cardiac gene functions. In our study, we focus on analysis of the role of dystrophin (Dys) in heart physiology. As in humans, the Drosophila dys gene encodes multiple isoforms, of which the large isoforms (DLPs) and a truncated form (Dp117) are expressed in the adult heart. Here, we show that the loss of dys function in the heart leads to an age‐dependent disruption of the myofibrillar organization within the myocardium as well as to alterations in cardiac performance. dys RNAi‐mediated knockdown in the mesoderm also shortens lifespan. Knockdown of all or deletion of the large isoforms increases the heart rate by shortening the diastolic intervals (relaxation phase) of the cardiac cycle. Morphologically, loss of the large DLPs isoforms causes a widening of the cardiac tube and a lower fractional shortening, a phenotype reminiscent of dilated cardiomyopathy. The dilated dys mutant phenotype was reversed by expressing a truncated mammalian form of dys (Dp116). Our results illustrate the utility of Drosophila as a model system to study dilated cardiomyopathy and other muscular‐dystrophy‐associated phenotypes.
Automatic accommodation: The role of personality
Authors: PERUNOVIC MIHAILO , HOLMES JOHN G.
Published: February 2008

The current study tested whether agreeableness, conscientiousness, and attachment styles would be associated with automatic accommodation in dating relationships. Accommodation refers to the tendency to respond to a romantic partner’s potentially destructive relationship act by inhibiting one’s own negative impulses and replacing them with a relatively deliberate, relationship enhancing act. Sixty‐five young adult participants from a Canadian university participated online. Participants selected either constructive or destructive responses to hypothetical negative behaviors their partner enacted either under time pressure or normally. Results showed that the difference in level of accommodation between participants high and low in agreeableness and avoidance became even greater under time pressure, suggesting that for some people, accommodation may in fact be more automatic.
Adult attachment, sexual satisfaction, and relationship satisfaction: A study of married couples
Authors: BUTZER BETHANY , CAMPBELL LORNE
Published: February 2008

The goal of this research was to extend prior work on adult attachment and sexuality, which has tended to focus on samples of adolescents and undergraduate students. A Canadian sample of 116 married couples aged 21–75 years completed self‐report measures of adult attachment, marital, and sexual satisfaction. Results revealed that participants with higher levels of anxiety and avoidance reported lower levels of sexual satisfaction at the individual level. Individuals with more avoidant spouses also reported lower levels of sexual satisfaction. Furthermore, the relationship between sexual and marital satisfaction was stronger for more anxiously attached individuals and those with more anxiously attached spouses. These results suggest that attachment is linked in theoretically predictable ways to marital and sexual satisfaction.
Human Impacts on Regional Avian Diversity and Abundance
Authors: LEPCZYK CHRISTOPHER A. , FLATHER CURTIS H. , RADELOFF VOLKER C. , PIDGEON ANNA M. , HAMMER ROGER B. , LIU JIANGUO
Published: February 2008

Abstract: Patterns of association between humans and biodiversity typically show positive, negative, or negative quadratic relationships and can be described by 3 hypotheses: biologically rich areas that support high human population densities co‐occur with areas of high biodiversity (productivity); biodiversity decreases monotonically with increasing human activities (ecosystem stress); and biodiversity peaks at intermediate levels of human influence (intermediate disturbance). To test these hypotheses, we compared anthropogenic land cover and housing units, as indices of human influence, with bird species richness and abundance across the Midwestern United States. We modeled richness of native birds with 12 candidate models of land cover and housing to evaluate the empirical evidence. To assess which species were responsible for observed variation in richness, we repeated our model‐selection analysis with relative abundance of each native species as the response and then asked whether natural‐history traits were associated with positive, negative, or mixed responses. Native avian richness was highest where anthropogenic land cover was lowest and housing units were intermediate based on model‐averaged predictions among a confidence set of candidate models. Eighty‐three of 132 species showed some pattern of association with our measures of human influence. Of these species approximately 40% were negatively associated, approximately 6% were positively associated, and approximately 7% showed evidence of an intermediate relationship with human influence measures. Natural‐history traits were not closely related to the direction of the relationship between abundance and human influence. Nevertheless, pooling species that exhibited any relationship with human influence and comparing them with unrelated species indicated they were significantly smaller, nested closer to the ground, had shorter incubation and fledging times, and tended to be altricial. Our results support the ecosystem‐stress hypothesis for the majority of individual species and for overall species diversity when focusing on anthropogenic land cover. Nevertheless, the great variability in housing units across the land‐cover gradient indicates that an intermediate‐disturbance relationship is also supported. Our findings suggest preemptive conservation action should be taken, whereby areas with little anthropogenic land cover are given conservation priority. Nevertheless, conservation action should not be limited to pristine landscapes because our results showed that native avian richness and the relative abundance of many species peaked at intermediate housing densities and levels of anthropogenic land cover.
Effects of Conversion of Dry Tropical Forest to Agricultural Mosaic on Herpetofaunal Assemblages
Authors: SUAZO‐ORTUÑO IRERI , ALVARADO‐DÍAZ JAVIER , MARTÍNEZ‐RAMOS MIGUEL
Published: February 2008

Abstract:  We explored the impact of forest conversion to agricultural mosaic on anuran, lizard, snake, and turtle assemblages of Neotropical dry forests. Over 2 years, we sampled 6 small watersheds on the west coast of Mexico, 3 conserved and 3 disturbed. The disturbed watersheds were characterized by a mosaic of pastures and cultivated fields (corn, beans, squash) intermingled with patches of different successional stages of dry forest. In each watershed, we conducted 11 diurnal and nocturnal time‐constrained searches in 10 randomly established plots. We considered vulnerability traits of species in relation to habitat modification. Eighteen anuran, 18 lizard, 23 snake, and 3 turtle species were recorded. Thirty‐six species (58%) occurred in both forest conditions, and 14 (22%) and 12 species (19%) occurred only in the conserved and disturbed sites, respectively. Assemblages responded differently to disturbance. Species richness, diversity, and abundance of lizards were higher in disturbed forests. Anuran diversity and species richness were lower in disturbed forest but abundance was similar in both forest conditions. Diversity, richness, and abundance of turtles were lower in disturbed forest. The structure and composition of snake assemblages did not differ between forest conditions. We considered species disturbance sensitive if their abundance was significantly less in disturbed areas. Four anuran (22%), 2 lizard (11%), and 3 turtle (100%) species were sensitive to disturbance. No snake species was sensitive. The decline in abundance of disturbance‐sensitive species was associated with the reduction of forest canopy cover, woody stem cover, roots, and litter‐layer ground cover. Anuran species with small body size and direct embryonic development were especially sensitive to forest disturbance. An important goal for the conservation of herpetofauna should be the determination of species traits associated with extinction or persistence in agricultural mosaics.
Headache as the Only Presentation of Intravascular Lymphoma
Authors: Im So‐Hyang , Lee Seo‐Young , Kim Nam‐Hee
Published: February 2008

Intravascular lymphoma (IVL) is a rare extranodal lymphoma, presenting with confusing clinical presentations and most cases have been diagnosed during the postmortem review. We report a case of IVL diagnosed by cerebrospinal fluid (CSF) examination and bone marrow biopsy in a patient with a daily headache from onset. In case of a daily headache from onset with normal neuroimagings, CSF examination may give any significant diagnostic clue and should be a consideration to exclude such causes as hematolymphoid malignancies, including the very rare IVL.
Early treatment suppresses the development of spike‐wave epilepsy in a rat model
Authors: Blumenfeld Hal , Klein Joshua P. , Schridde Ulrich , Vestal Matthew , Rice Timothy , Khera Davender S. , Bashyal Chhitij , Giblin Kathryn , Paul‐Laughinghouse Crystal , Wang Frederick , Phadke Anuradha , Mission John , Agarwal Ravi K. , Englot Dario J. , Motelow Joshua , Nersesyan Hrachya , Waxman Stephen G. , Levin April R.
Published: February 2008

Summary

Purpose: Current treatments for epilepsy may control seizures, but have no known effects on the underlying disease. We sought to determine whether early treatment in a model of genetic epilepsy would reduce the severity of the epilepsy phenotype in adulthood.

Methods: We used Wistar albino Glaxo rats of Rijswijk (WAG/Rij) rats, an established model of human absence epilepsy. Oral ethosuximide was given from age p21 to 5 months, covering the usual period in which seizures develop in this model (age ∼3 months). Two experiments were performed: (1) cortical expression of ion channels Nav1.1, Nav1.6, and HCN1 (previously shown to be dysregulated in WAG/Rij) measured by immunocytochemistry in adult treated rats; and (2) electroencephalogram (EEG) recordings to measure seizure severity at serial time points after stopping the treatment.

Results: Early treatment with ethosuximide blocked changes in the expression of ion channels Nav1.1, Nav1.6, and HCN1 normally associated with epilepsy in this model. In addition, the treatment led to a persistent suppression of seizures, even after therapy was discontinued. Thus, animals treated with ethosuximide from age p21 to 5 months still had a marked suppression of seizures at age 8 months.

Discussion: These findings suggest that early treatment during development may provide a new strategy for preventing epilepsy in susceptible individuals. If confirmed with other drugs and epilepsy paradigms, the availability of a model in which epileptogenesis can be controlled has important implications both for future basic studies, and human therapeutic trials.
Increased thalamic inhibition in the absence seizure prone DBA/2J mouse
Authors: Tan Heneu O. , Reid Christopher A. , Chiu Cindy , Jones Mathew V. , Petrou Steven
Published: February 2008

Summary

Genetic background plays a significant role in producing variable seizure outcomes in patients and animal models. The neurobiological mechanism underlying this heterogeneity is not clear. Here we compare GABAergic synaptic properties within the thalamocortical circuit of two commonly used inbred mice strains, the C57B/6 and spike‐and‐wave discharge (SWD) prone DBA/2J. Differences between the strains occur in amplitude, kinetics, and frequency of miniature inhibitory postsynaptic currents (mIPSCs) in a region‐specific manner. The biggest difference in synaptic inhibition was seen in the thalamus where DBA/2J mice showed a doubling of mIPSC frequency when compared to C57B/6. EEG analysis revealed higher power in the 6–12 Hz band during non–rapid eye movement sleep in DBA/2J mice. Increased susceptibility of the DBA2/J strain to develop SWDs and increase in the 6–12 Hz EEG power may be due to a hypersynchronous ventrobasal thalamus as a consequence of increased GABAergic input.
Homozygous W748S mutation in the POLG1 gene in patients with juvenile‐onset Alpers syndrome and status epilepticus
Authors: Uusimaa Johanna , Hinttala Reetta , Rantala Heikki , Päivärinta Markku , Herva Riitta , Röyttä Matias , Soini Heidi , Moilanen Jukka S. , Remes Anne M. , Hassinen Ilmo E. , Majamaa Kari
Published: February 2008

Summary

Purpose: Polymerase gamma (POLG) is the sole enzyme in the replication of mitochondrial DNA (mtDNA). Numerous mutations in the POLG1 gene have been detected recently in patients with various phenotypes including a classic infantile‐onset Alpers‐Huttenlocher syndrome (AHS). Here we studied the molecular etiology of juvenile‐onset AHS manifesting with status epilepticus and liver disease in three teenagers.

Patients and Methods: We examined 14‐ and 17‐year‐old female siblings (patients 1 and 2) and an unrelated 15‐year‐old girl (patient 3) with juvenile‐onset AHS, sequenced POLG1, and the entire mtDNA, examined mtDNA deletions by amplification of the full‐length mtDNA with the long PCR method and used real‐time PCR to quantify mtDNA in the tissue samples.

Results: The initial manifestations were migraine‐like headache and epilepsy, and the terminal manifestations status epilepticus and hepatic failure. A homozygous W748S mutation in POLG1 was detected in the three patients. No deletions or pathogenic point mutations were found in mtDNA, but all three patients had mtDNA depletion.

Conclusions: POLG mutations should be considered in cases of teenagers and young adults with a sudden onset of intractable seizures or status epilepticus, and acute liver failure. The W748S POLG1 mutation seems to lead to tissue‐specific, partial mtDNA depletion in patients with juvenile‐onset Alpers syndrome. Valproic acid should be avoided in the treatment of epileptic seizures in these patients.