bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term observation of a pollination network: fluctuation in species and interactions, relative invariance of network structure and implications for estimates of specialization
Authors: Petanidou Theodora , Kallimanis Athanasios S. , Tzanopoulos Joseph , Sgardelis Stefanos P. , Pantis John D.
Published: March 2008

We analysed the dynamics of a plant–pollinator interaction network of a scrub community surveyed over four consecutive years. Species composition within the annual networks showed high temporal variation. Temporal dynamics were also evident in the topology of the network, as interactions among plants and pollinators did not remain constant through time. This change involved both the number and the identity of interacting partners. Strikingly, few species and interactions were consistently present in all four annual plant–pollinator networks (53% of the plant species, 21% of the pollinator species and 4.9% of the interactions). The high turnover in species‐to‐species interactions was mainly the effect of species turnover (c. 70% in pairwise comparisons among years), and less the effect of species flexibility to interact with new partners (c. 30%). We conclude that specialization in plant–pollinator interactions might be highly overestimated when measured over short periods of time. This is because many plant or pollinator species appear as specialists in 1 year, but tend to be generalists or to interact with different partner species when observed in other years. The high temporal plasticity in species composition and interaction identity coupled with the low variation in network structure properties (e.g. degree centralization, connectance, nestedness, average distance and network diameter) imply (i) that tight and specialized coevolution might not be as important as previously suggested and (ii) that plant–pollinator interaction networks might be less prone to detrimental effects of disturbance than previously thought. We suggest that this may be due to the opportunistic nature of plant and animal species regarding the available partner resources they depend upon at any particular time.
Physiology, phylogeny and in situ evidence for bacterial and archaeal nitrifiers in the marine sponge Aplysina aerophoba
Authors: Bayer Kristina , Schmitt Susanne , Hentschel Ute
Published: March 2008

The potential for nitrification in the Mediterranean sponge Aplysina aerophoba was assessed using a combined physiological and molecular approach. Nitrate excretion rates in whole sponges reached values of up to 344 nmol g−1 dry weight (wt) h−1 (unstimulated) and 1325 nmol g−1 dry wt h−1 (stimulated). Addition of nitrapyrin, a nitrification‐specific inhibitor, effectively inhibited nitrate excretion. Ammonium was taken up by sponges in spring and excreted in fall, the sponges thus serving as either an ammonium sink or ammonium source. Nitrosospira cluster 1 and Crenarchaeota group I.1A 16S rRNA and amoA genes were recovered from A. aerophoba and other sponges from different world's oceans. The archaeal 16S rRNA genes formed a sponge‐specific subcluster, indicating that their representatives are members of the stable microbial community of sponges. On the other hand, clustering was not evident for Nitrosospira rRNA genes which is consistent with their presence in sediment and seawater samples. The presence of both Nitrosospira cluster 1 and crenarchaeal group 1 phylotypes in sponge tissue was confirmed using fluorescently labelled 16S rRNA gene probes. This study contributes to an ongoing effort to link microbial diversity with metabolic functions in the phylogenetically diverse, elusive and so far uncultivated microbial communities of marine sponges.
Effects of the Peer Group on the Development of Social Functioning and Academic Achievement: A Longitudinal Study in Chinese Children
Authors: Chen Xinyin , Chang Lei , Liu Hongyun , He Yunfeng
Published: March 2008

This longitudinal study examined, in a sample of Chinese children (initial mean ages = 9.5 and 12.7 years, N = 505), how the peer group contributed to social functioning and academic achievement and their associations. Data on informal peer groups, social functioning, and academic achievement were collected from multiple sources. Multilevel structural equation modeling revealed that group academic performance made direct contributions to children’s social development. Group academic performance also moderated the individual‐level relations between academic performance and later social functioning. Whereas high‐achieving groups strengthened the positive relations between academic achievement and social competence, low‐achieving groups facilitated the negative relations between academic achievement and social problems. The results indicate the significance of the peer group for social functioning from a developmental perspective.
Developmental Trajectories of Bullying and Associated Factors
Authors: Pepler Debra , Jiang Depeng , Craig Wendy , Connolly Jennifer
Published: March 2008

Trajectories in bullying through adolescence were studied along with individual, family, and peer relationship factors. At the outset, participants’ ages ranged from 10 to 14; 74% identified as European Canadian with the remainder from diverse backgrounds. With 8 waves of data over 7 years, 871 students (466 girls and 405 boys) were studied to reveal 4 trajectories: 9.9% reported consistently high levels of bullying, 13.4% reported early moderate levels desisting to almost no bullying at the end of high school, 35.1% reported consistently moderate levels, and 41.6% almost never reported bullying. Students who bullied had elevated risks in individual, parent, and peer relationship domains. Risk profiles and trajectories provide direction for interventions to curtail the development of power and aggression in relationships.
Alcohol use among HIV‐infected persons in care: results of a multi‐site survey*
Authors: Chander G , Josephs J , Fleishman JA , Korthuis PT , Gaist P , Hellinger J , Gebo K ,   for the HIV Research Network
Published: March 2008

Objective

We sought to determine the prevalence of any alcohol use and hazardous alcohol consumption among HIV‐infected individuals engaged in care and to identify factors associated with hazardous alcohol use.

Methods

During 2003, 951 patients were interviewed at 14 HIV primary care sites in the USA. Hazardous drinking was defined as >14 drinks/week or ≥5 drinks/occasion for men and >7 drinks/week or ≥4 drinks/occasion for women. Moderate alcohol use was consumption at less than hazardous levels. We used logistic regression to identify factors associated with any alcohol use and hazardous alcohol use.

Results

Forty per cent of the sample reported any alcohol use in the 4 weeks prior to the interview; 11% reported hazardous use. In multivariate regression, male sex [adjusted odds ratio (AOR) 1.52 (95% confidence interval, CI, 1.07–2.16)], a college education (compared to<high school) [AOR 1.87 (1.10–3.18)] and illicit drug use [AOR 2.69 (1.82–3.95)] were associated positively with any alcohol use, while CD4 nadir ≥500 cells/μL [AOR 2.65 (1.23–5.69)] and illicit drug use [AOR 2.67 (1.48–4.82)] were associated with increased odds of hazardous alcohol use (compared to moderate and none).

Conclusions

Alcohol use is prevalent among HIV‐infected individuals and is associated with a variety of socioeconomic and demographic characteristics. Screening for alcohol use should be routine practice in HIV primary care settings.
The changing pattern of tuberculosis and HIV co‐infection in immigrants and Spaniards in the last 20 years
Authors: Velasco M , Castilla V , Cervero M , Sanz J , Condes E , Gaspar G , Torres R , Arranz A , Barros C , Monereo A ,   for the COMESEM cohort
Published: March 2008

Objectives

To evaluate the impact of immigration on tuberculosis (TB)–HIV co‐infection in Spain in a prospective cohort of HIV patients.

Methods

Among 7761 HIV patients, we evaluated 1284 with at least one episode of TB between 1987 and 2006. Variables were compared between immigrants and Spaniards.

Results

Incidence of TB decreased from 20 to five cases per 100 patient‐years in 2006 (P<0.01) and was always higher in immigrants than in Spaniards. The proportion of immigrants increased, reaching almost 50% of both new cases of HIV and TB–HIV co‐infection in 2006. In 34.4% of patients, TB and HIV infection were diagnosed within the same year; simultaneous diagnosis was more frequent in immigrants (83.3%vs. 16.7%, P<0.001). Mortality was associated independently with age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01–1.05], TB diagnosis before 1996 (HR 2.6, 95% CI 1.8–3.6), use of highly active antiretroviral treatment (HR 0.494, 95% CI 0.37–0.66) and CD4 cell count at TB diagnosis (HR 0.996, 95% CI 0.995–0.997).

Conclusions

Immigrants have a major impact on the incidence of TB in HIV patients, slowing down the decreasing trend in Spain. Simultaneous diagnosis of the co‐infection in immigrants reveals a need to intensify HIV case finding in immigrants in Spain.
Steady‐state nevirapine plasma concentrations are influenced by pregnancy
Authors: Nellen JFJB , Damming M , Godfried MH , Boer K , Van Der Ende ME , Burger DM , De Wolf F , Wit FWNM , Prins JM
Published: March 2008

Objectives

Optimal plasma concentrations of antiretroviral drugs are required during pregnancy to treat maternal HIV infection and prevent mother‐to‐child transmission. We investigated the effect of pregnancy on nevirapine (NVP) plasma concentrations.

Methods

We included all HIV‐1‐infected women for whom NVP plasma concentrations were available as part of routine patient care at two university hospitals. Plasma NVP concentrations were compared for pregnant (n=45) and non‐pregnant (n=152) women. Univariate and multivariate linear regression analyses were used to identify and adjust for other confounding factors associated with NVP plasma concentrations. For pregnant women who had a plasma NVP concentration available both during and outside pregnancy, a paired analysis was performed.

Results

Steady‐state NVP plasma concentrations were lower in pregnant women: 5.2 mg/L (interquartile range 3.9–6.8)vs.5.8 mg/L (4.3–7.7) (P=0.08). After adjusting for confounders, both pregnancy (regression coefficient=–0.90 mg/L,P=0.046) and African descent (regression coefficient=+1.13 mg/L,P=0.005) influenced NVP concentrations significantly. The paired analysis showed mean concentrations of 4.8 mg/L during pregnancy and 5.8 mg/L outside pregnancy (pairedt‐test,P=0.073).

Conclusions

Pregnancy has a moderate but significant lowering effect on NVP plasma concentrations. Being of African descent compensates for the lowering effect of pregnancy on NVP concentrations.
Hepatotoxicity of nevirapine in virologically suppressed patients according to gender and CD4 cell counts*
Authors: De Lazzari E , León A , Arnaiz JA , Martinez E , Knobel H , Negredo E , Clotet B , Montaner J , Storfer S , Asenjo MA , Mallolas J , Miró JM , Gatell JM
Published: March 2008

Objectives

A warning advising a higher risk of hepatotoxicity in antiretroviral‐naive patients starting a nevirapine‐containing combination antiretroviral therapy (NcART) has been issued by health authorities. It is unclear whether this higher risk also applies to stable virologically suppressed patients starting NcART.

Methods

We performed a meta‐analysis of published randomized studies including virologically suppressed patients who switched to NcART with a follow‐up ≥3 months. CD4 cell cell counts were classified as high (HCD4) (400 cells/μL for males and 250 cells/μL for females) or low (LCD4). The main endpoint was hepatotoxicity within the first 3 months.

Results

Four studies with a pooled total of 410 patients were included. The risk of hepatotoxicity within the first 3 months was 2% and 4% in the LCD4 and HCD4 groups, respectively, with a combined odds ratio of 1.46 [95% confidence interval (CI) 0.43–4.98; P=0.54]. The risk of hepatotoxicity at any point during the study was similar in both groups, with a combined hazard ratio of 0.8 (95% CI 0.3–2.5; P=0.80).

Conclusions

In our study, virologically suppressed patients switching to nevirapine did not have a significantly higher risk of hepatotoxicity or rash when stratified by gender and CD4 cell count, although small differences may have gone undetected because of the sample size limitation.
Knowledge of their children's HIV status in HIV‐positive mothers attending a genitourinary medicine clinic in the UK
Authors: Eisenhut M , Sharma V , Kawsar M , Balachandran T
Published: March 2008

Objectives

To determine whether HIV‐infected mothers knew the HIV status of their children, enabling the offer of targeted testing of children at risk.

Methods

All HIV‐positive women attending the genitourinary medicine clinic at a district general hospital in the United Kingdom were asked whether they had children and the age, HIV status and residence of their children using a standardized proforma.

Results

A total of 297 HIV‐positive women were included in a prospective audit. Two hundred and fifty‐four women had 551 offspring; 143 had a total of 217 children aged <16 years. Of those children, 118 lived in the United Kingdom. Of the 99 children living abroad, 71% were living in Zimbabwe, 21% in other African countries (Zambia, Kenya, Burundi, Malawi and South Africa) and 5% in Jamaica and other Caribbean countries. Of the 118 children living in the UK, mothers knew the HIV status in 49 (42%), of whom nine (18%) were HIV positive. A further two older offspring were also HIV positive. Mothers were aware of the HIV status in significantly fewer children staying in the country of origin: nine (9%; P<0.05), of whom four were known to be HIV positive. All HIV‐positive children living in the United Kingdom were under the care of paediatricians with special expertise in paediatric HIV infection.

Conclusions

The HIV status of the majority of children of HIV‐positive immigrant mothers is unknown, particularly those children who remain in their country of origin.
Effect of aging on neurogenesis in the canine brain
Authors: Pekcec Anton , Baumgärtner Wolfgang , Bankstahl Jens P. , Stein Veronika M. , Potschka Heidrun
Published: March 2008

An age‐dependent decline in hippocampal neurogenesis has been reported in laboratory rodents. Environmental enrichment proved to be a strong trigger of neurogenesis in young and aged laboratory rodents, which are generally kept in facilities with a paucity of environmental stimuli. These data raise the question whether an age‐dependent decline in hippocampal cell proliferation and neurogenesis can also be observed in individuals exposed to diversified and varying surroundings. Therefore, we determined rates of canine hippocampal neurogenesis using post‐mortem tissue from 37 nonlaboratory dogs that were exposed to a variety of environmental conditions throughout their life. Expression of the neuronal progenitor cell marker doublecortin clearly correlated with age. The analysis of doublecortin‐labeled cells in dogs aged > 133 months indicated a 96% drop in the aged canine brain as compared to young adults. Expression of the proliferation marker Ki‐67 in the subgranular zone decreased until dogs were aged 85–132 months. In the aging canine brain amyloid‐beta peptide deposits have been described that might resemble an early pathophysiological change in the course of human Alzheimer's disease. Comparison of Ki‐67 and doublecortin expression in canine brain tissue with or without diffuse plaques revealed no differences. The data indicate that occurrence of diffuse plaques in the aging brain is not sufficient to trigger enhanced proliferation or enhanced neurogenesis such as described in human Alzheimer's disease. In addition, this study gives first proof that an age‐dependent decline also dominates hippocampal neurogenesis rates in individuals living in diversified environments.
George Tenet and the Last Great Days of the CIA
Authors: White Richard D.
Published: March 2008

George Tenet served as director of the Central Intelligence Agency from 1997 to 2004, an intense period spanning the administrations of Bill Clinton and George W. Bush and covering the terrorist attacks of September 11 and the U.S. invasion of Iraq. Few other central intelligence directors have served for so long, so energetically, or amid so much controversy. This profile examines the steep trajectory of Tenet’s career, his response to the al‐Qaeda threat, the role he played during the invasion of Iraq, and the eventual reorganization of the nation’s intelligence community. It describes a public servant caught between the warring factions of the White House decision‐making process, his own agency’s intelligence priorities, and, ultimately, his own conscience.
How Naked Is the Public Square? Religion, Public Service, and Implications for Public Administration
Authors: Houston David J. , Freeman Patricia K. , Feldman David L.
Published: March 2008

The study of public administration has a decidedly secular character, a result of an intentional effort to seek legitimacy through professionalization that can be traced back to the Progressive Era. But is this secular orientation wholly descriptive of the practice of public administration? To address this question, the authors examine the religiosity of public servants (governmental and nongovernmental) and non–public servants, as well as the secular attitudes held by members of each group. The study finds that individuals in governmental public service occupations generally are more religious and possess less secular attitudes than those in non–public service occupations.
Institutions, Policy Innovation, and E‐Government in the American States
Authors: Tolbert Caroline J. , Mossberger Karen , McNeal Ramona
Published: March 2008

Examining the rankings of American states in one fast‐growing policy area, e‐government, states with the most sophisticated and comprehensive policies varied over a five‐year period. What factors account for change in digital government policy innovation over time? Using time‐series analysis and 50‐state data, the authors find that state institutional capacity is important for continued innovation. They also find an association between reinvention in state governments and the institutionalization of information technology, suggesting a more general orientation toward government reform and modernization. Although state wealth and education were not significant in previous studies, they emerge as predictors of later innovation. The theoretical contribution of this study is to better understand the dynamic character of innovation over time and the role of institutions. The link between reinvention and e‐government raises the possibility that the modernization of state institutions generally facilitates innovation.
Real Time Three‐Dimensional Echocardiography Evaluation of Mitral Annular Characteristics in Patients with Myocardial Hypertrophy
Authors: Yalçin Fatih , Shiota Maiko , Greenberg Neil , Thomas James D. , Shiota Takahiro
Published: March 2008

It has been shown that systolic excursion of the mitral annulus (MA) correlates well with left ventricular (LV) systolic function. Evaluation of the complicated shape and dynamics of the mitral annulus, however, may require rigorous methodology. The aim of this study was to investigate differences in MA motion between hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) patients due to hypertension or aortic stenosis using real time three‐dimensional echocardiography (RT3DE). We studied 10 HCM, 10 LVH, and 10 controls. Mean MA area changes between early and late systole were 9.5 ± 4.3% in HCM, 26 ± 15% in LVH and 19 ± 10% in normal controls. MA apicobasal motion was 5.8 ± 4 mm in HCM, 11 ± 4 mm in LVH, and 13.6 ± 6 mm in normal controls. RT3DE with digital reconstruction of MA accurately display complicated MA geometry and dynamics during a cardiac cycle. Annular function in LVH was similar to that of the normal group while annular apicobasal motion and area changes were reduced in HCM.
Papillary Fibroelastoma of the Pulmonic Valve: Evaluation by Echocardiography and Magnetic Resonance Imaging
Authors: George Jon C , Tang Aaron , Markowitz Alan , Gilkeson Robert , Hoit Brian D
Published: March 2008

A 76‐year‐old male was admitted with increasing fatigue and shortness of breath. Transesophageal echocardiogram revealed moderate‐to‐severe mitral regurgitation and an oscillating mass on the pulmonic valve that was confirmed by magnetic resonance imaging. The patient underwent repair of the mitral valve and excision of the pulmonic valve mass, which was confirmed as a papillary fibroelastoma by histology.
Impact of Changes in Myocardial Velocity Assessed by Tissue Doppler Imaging during Exercise on Dynamic Mitral Regurgitation in Patients with Nonischemic Cardiomyopathy
Authors: Kang Soo‐Jin , Lim Hong‐Seok , Hwang Jungwon , Choi Jung‐Hyun , Seo Kyoung‐Woo , Choi Byung‐Joo , Choi So‐Yeon , Hwang Gyo‐Seung , Yoon Myeong‐Ho , Shin Joon‐Han , Tahk Seung‐Jea
Published: March 2008

Background: We evaluated the myocardial contractile reserve related to exercise‐induced changes in functional mitral regurgitation (MR) by tissue Doppler imaging (TDI). Methods: Supine bicycle exercise was performed in 35 patients with nonischemic cardiomyopathy (age 51 ± 12 years; EF < 40%) and resting, and peak exercise 2D echocardiographic parameters, and TDI data were obtained. Vavg was defined as the average of peak systolic velocities of six basal LV segments by TDI. Myocardial contractile reserve, which was calculated by [peak exercise Vavg– baseline Vavg], was represented as ΔVavg. Dyssynchrony index was derived from the standard deviation of the time to the peak systolic velocity of 12 LV segments. Results: During exercise (9.7 ± 2.4 minutes), the mean Vavg increased from 4.0 ± 0.8 cm/s to 5.5 ± 1.0 cm/s. The effective regurgitant orifice area (ERO) and the ratio of MR jet area to the left atrial area (JLA%) were 1.9 ± 2.9 mm2 and 12 ± 12%, respectively. During exercise, ERO and JLA% significantly increased to 6.2 ± 6.4 mm2 and 21 ± 13% (P < 0.05), respectively, with individually variable changes. Tenting area was found to be an independent factor that showed a relationship with the baseline severity of MR (r = 0.561, P < 0.001). Dyssynchrony index and ΔVavg were found to correlate with both maximal MR severity at peak exercise and changes in MR during exercise. By multivariate analysis, ΔVavg was found to be an independent determinant of exercise‐induced changes in ERO (ΔERO; r =−0.707, P< 0.001) and changes in JLA% (ΔJLA%; r =−0.663, P< 0.001). Conclusion: In patients with nonischemic cardiomyopathy, impaired contractile reserve assessed by TDI velocity data may be an independent determinant affecting exercise‐induced changes in dynamic MR.
Continuing Medical Education Program in Echocardiography
Authors: Fan Pohoey , Barton Michael , Kerut Edmund Kenneth , Hanawalt Curtis , D'Antonio Michael
Published: March 2008

Article Title: Appearance of the Duodenal Bulb in the Echocardiography Laboratory.
Evaluating Candidate Principal Surrogate Endpoints
Authors: Gilbert Peter B. , Hudgens Michael G.
Published: March 2008

Summary Frangakis and Rubin (2002, Biometrics 58, 21–29) proposed a new definition of a surrogate endpoint (a “principal” surrogate) based on causal effects. We introduce an estimand for evaluating a principal surrogate, the causal effect predictiveness (CEP) surface, which quantifies how well causal treatment effects on the biomarker predict causal treatment effects on the clinical endpoint. Although the CEP surface is not identifiable due to missing potential outcomes, it can be identified by incorporating a baseline covariate(s) that predicts the biomarker. Given case–cohort sampling of such a baseline predictor and the biomarker in a large blinded randomized clinical trial, we develop an estimated likelihood method for estimating the CEP surface. This estimation assesses the “surrogate value” of the biomarker for reliably predicting clinical treatment effects for the same or similar setting as the trial. A CEP surface plot provides a way to compare the surrogate value of multiple biomarkers. The approach is illustrated by the problem of assessing an immune response to a vaccine as a surrogate endpoint for infection.
The Black Soldier‐fly, Hermetia illucens (Diptera, Stratiomyidae), Used to Estimate the Postmortem Interval in a Case in Amapá State, Brazil*
Authors: Pujol‐Luz José R. , Francez Pablo Abdon da Costa , Ururahy‐Rodrigues Alexandre , Constantino Reginaldo
Published: March 2008

Abstract:  The black soldier‐fly (Hermetia illucens) is a generalist detritivore which is commonly present in corpses in later stages of decomposition and may be useful in forensic entomology. This paper describes the estimation of the postmortem interval (PMI) based on the life cycle of the black soldier‐fly in a case in northern Brazil. A male child was abducted from his home and 42 days later his corpse was found in an advanced stage of decay. Two black soldier‐fly larvae were found associated with the body. The larvae emerged as adults after 25–26 days. Considering the development cycle of H. illucens, the date of oviposition was estimated as 24–25 days after abduction. Since H. illucens usually (but not always) colonizes corpses in more advanced stages of decay, this estimate is consistent with the hypothesis that the child was killed immediately after abduction.
Suicidal Electrocution in Sydney—A 10‐Year Case Review*
Authors: Chan Peter , Duflou Johan
Published: March 2008

Abstract:  A retrospective study was undertaken of all cases of death due to suicidal electrocution in Sydney, Australia between 1996 and 2005. A total of 25 cases were identified with 20 cases (80%) as a result of direct attachment to an electrical outlet and five cases (20%) as a result of immersion in a body of water with an electrical appliance. Twenty of the 25 individuals were men (mean age = 57 years, range 22–90) and five were women (mean age 67, range 53–88). At least 35% of decedents were either currently working or had worked as electricians. Electrical timers had been used in eight (32%) cases, the fuse blown in one case, but the remaining 16 (64%) bodies were “live” on arrival of witnesses or electricity personnel. This study demonstrates the phenomenon of electrical suicide as a regular occurrence in Sydney. We highlight the need for investigators and emergency workers to remain vigilant upon discovery of electrical suicides, due to the fact that most bodies remain electrically active after death.
Dual Examinations for Identification of Urine as Being of Human Origin and for DNA‐Typing from Small Stains of Human Urine
Authors: Nakazono Takehiko , Kashimura Seiich , Hayashiba Yasuhiko , Hara Kenji , Matsusue Aya , Augustin Christa
Published: March 2008

Abstract:  Concurrent methods for identification of urine as being of human origin, and for DNA‐typing from small stains of human urine were examined. A urine stain was extracted with phosphate‐buffered saline (PBS), and the extract was filtered using a Centricon‐100 device. The filtrate was subjected to electrospray ionization liquid chromatography‐mass spectrometry (ESI‐LC‐MS) for identification of human urine and a DNA‐typing sample was obtained by dialfiltration of the residue using a DNA purification kit. After the purified residue was treated with an AmpflSTR® Profiler™ PCR amplification kit, the DNA‐types were analyzed by capillary electrophoresis using a Genetic Analyzer. It was possible to identify a urine stain as being of human origin, and complete DNA profiles could be successfully obtained from a urine stain which had been created by 50 μL of female urine. Serial analyses of urine stains found at a crime scene provide effective information for forensic investigation. This method is recommended for stain identification and for DNA‐typing from a urine stain.
Thiodicarb and Methomyl Tissue Distribution in a Fatal Multiple Compounds Poisoning
Authors: Hoizey Guillaume , Canas Frédéric , Binet Laurent , Kaltenbach Matthieu L. , Jeunehomme Gérard , Bernard Marie‐Hélène , Lamiable Denis
Published: March 2008

Abstract:  Thiodicarb is a nonsystemic carbamate insecticide whose acetylcholinesterase activity is related to its main methomyl degradation product. A 40‐year‐old woman was found dead in her car. Empty packages of medicines and an open bottle of Larvin® containing thiodicarb were found near her body. No signs of violence nor traumatic injuries were noticed upon autopsy, and police investigations strongly suggested a suicide. Systematic toxicological analysis performed on postmortem specimens revealed the presence of various sedatives, hypnotics, and antipsychotic drugs in blood, urine, and gastric content. Some of the compounds identified were determined at blood concentrations well above the known therapeutic concentrations: zolpidem (2.87 mg/L), bromazepam (2.39 mg/L), nordazepam (4.21 mg/L), and levopremazine (0.64 mg/L). Specific analysis of thiodicarb and of its methomyl metabolite was then performed on all fluids and tissues collected during autopsy by liquid chromatography ion trap tandem mass spectrometry (LC‐MS‐MS). The anticholinesterase capacity of blood, urine, and gastric content collected at autopsy was 83%, 82%, and 32%, respectively (normal value: 0%). The presence of thiodicarb in the bottle found near the body corroborates the hypothesis of an intake of that compound. Although thiodicarb was only detected in gastric content (24.3 mg/L), its methomyl metabolite was quantified in most postmortem tissues and fluids: gastric content (19.9 mg/L), peripheral blood (0.7 mg/L), urine (8.5 mg/L), bile (2.7 mg/L), liver (0.7 mg/kg), kidney (1.7 mg/kg), lung (1.5 mg/kg), brain (9.3 mg/kg), and heart (3.6 mg/kg).
On the Discriminability of the Handwriting of Twins
Authors: Srihari Sargur , Huang Chen , Srinivasan Harish
Published: March 2008

Abstract:  As handwriting is influenced by physiology, training, and other behavioral factors, a study of the handwriting of twins can shed light on the individuality of handwriting. This paper describes the methodology and results of such a study where handwriting samples of twins were compared by an automatic handwriting verification system. The results complement that of a previous study where a diverse population was used. The present study involves samples of 206 pairs of twins, where each sample consisted of a page of handwriting. The verification task was to determine whether two half‐page documents (where the original samples were divided into upper and lower halves) were written by the same individual. For twins there were 1236 verification cases—including 824 tests where the textual content of writing was different, and 412 tests where it was the same. An additional set of 1648 test cases were obtained from handwriting samples of nontwins (general population). To make the handwriting comparison, the system computed macro features (overall pictorial attributes), micro features (characteristics of individual letters), and style features (characteristics of whole‐word shapes and letter pairs). Four testing scenarios were evaluated: twins and nontwins writing the same text and writing different texts. Results of the verification tests show that the handwriting of twins is less discriminable than that of nontwins: an overall error rate of 12.91% for twins and 3.7% for nontwins. Error rates with identical twins were higher than with fraternal twins. Error rates in all cases can be arbitrarily reduced by rejecting (not making a decision on) borderline cases. A level of confidence in the results obtained is given by the fact that system error rates are comparable to that of humans (lower than that of lay persons and higher than that of questioned document examiners [QDEs]).
Genetic Data of Six STR Loci of Han Population in Henan Province (Central China)
Authors: Zeng Zhaoshu , Zheng Xudong , Zhang Guangzheng , Zhu Yunliang , Meng Xiansheng , Xiang Zhide , Yuan Baolong , Wu Chunling , Dong Ziming
Published: March 2008

Population:  Chinese.
Bone Notches
Authors: Foley John F.
Published: March 2008

Notch proteins are transmembrane receptors that are activated by their ligands, members of the Jagged and Delta-like families, which are present on the surfaces of adjacent cells. After ligand-binding, Notch proteins are processed by the γ-secretase complex, which releases the Notch intracellular domain (ICD), allowing it to translocate to the nucleus and activate gene transcription. Notch signaling is important in the control of cell fate during development, but Hilton
et
al
. investigated a role for Notch in the regulation of mesenchymal progenitor cells, the precursors of osteoblasts, in the bone marrow. Mice in which deletion of
Notch1
and
Notch2
was restricted to the limb mesenchyme (PNN mice) had, when 8 weeks of age, shorter long bones and increased bone radiodensity, as analyzed by x-ray radiography, than did wild-type mice. This skeletal phenotype was also observed in mice in which the γ-secretase complex catalytic subunits presenilin-1 and presenilin-2 were absent from the limb mesenchyme (PPS mice). The increased radiodensity in PNN and PPS mice was due to the presence of bone within the marrow cavity, which correlated with an increase in the number of active osteoblasts compared with that in wild-type mice. Similar defects were found in the embryos of PNN and PPS mice. Further experiments showed that, whereas mesenchymal progenitor cells were present in the bone marrow of wild-type mice, they were undetectable in PNN mice. This lack of progenitor cells correlated with a progressive loss of bone density in the PNN mice as they aged. These data suggest that Notch signaling helps to maintain a pool of progenitor cells in the bone marrow by inhibiting their differentiation into osteoblasts.

M. J. Hilton, X. Tu, X. Wu, S. Bai, H. Zhao, T. Kobayashi, H. M. Kronenberg, S. L. Teitelbaum, F. P. Ross, R. Kopan, F. Long, Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation.
Nat
.
Med
.
14
, 306-314 (2008).
[PubMed]
Directly Modulating Glucose Homeostasis
Authors: Ray L. Bryan
Published: March 2008

The concentration of glucose in the bloodstream is regulated by glucose itself, along with the hormones insulin and glucagon. Glucagon stimulates gluconeogenesis in part by regulating phosphorylation of a transcriptional coactivator known as cyclic adenosine monophosphate response element-binding protein 2 (CRTC2). Dentin
et al
. (see the Perspective by Birnbaum) found that high concentrations of circulating glucose also regulate CRTC2, but do so through stimulation of the hexosamine biosynthetic pathway and consequent
O
-linked glycosylation of the same serine residue in CRTC2 that is modified by phosphorylation. Thus, CRTC2 integrates signals from hormones and nutrients and might be a target for efforts to treat abnormalities of glucose homeostasis that are associated with diabetes.

R. Dentin, S. Hedrick, J. Xie, J. Yates, III, M. Montminy, Hepatic glucose sensing via the CREB coactivator CRTC2.
Science
319
, 1402-1405 (2008).
[Abstract]
[Full Text]

M. J. Birnbaum, Sweet conundrum.
Science
319
, 1348-1349 (2008).
[Summary]
[Full Text]
Plants Going TOPLESS
Authors: Purnell Beverly A.
Published: March 2008

The plant hormone auxin is a key regulator of proper plant development. Failure to properly respond to auxin leads to the inability to develop a root and vasculature during
Arabidopsis
embryogenesis. Szemenyei
et al
. now show that TOPLESS is an integral cofactor required for proper auxin response through the AUX/IAA pathway. These data provide insight into the mechanism by which auxin-mediated transcription directs plant development.

H. Szemenyei, M. Hannon, J. A. Long, TOPLESS mediates auxin-dependent transcriptional repression during
Arabidopsis
embryogenesis.
Science
319
, 1384-1386 (2008).
[Abstract]
[Full Text]
Keeping Things Moving
Authors: Foley John F.
Published: March 2008

The Rho guanosine triphosphatase (GTPase) family member Cdc42 is critical for cell migration. Cdc42 mediates the formation of membrane protrusions such as lamellipodia at the leading edge, and it participates in the polarization of centrosomes in migrating cells. Cdc42 is activated through the binding of GTP, which is facilitated by guanine nucleotide exchange factors. The GTPase-activating protein (GAP) Cdc42GAP catalyzes the hydrolysis of GTP, thus inhibiting Cdc42 activity. However, exactly how Cdc42GAP is regulated to ensure the appropriate abundance of active Cdc42 at the cell’s leading edge is unclear. Shen
et al
. investigated a role for Nudel, a protein that regulates the motor protein dynein, in the regulation of Cdc42GAP. Microscopic analysis showed that NIH 3T3 cells transfected with Nudel-specific RNA interference (RNAi) formed fewer protrusions, migrated less efficiently, and had less polarized localization of centrosomes compared with control cells. Nudel was recruited to the leading edge of migrating cells, where it colocalized with Cdc42GAP. Coimmunoprecipitation experiments confirmed this interaction and showed that Cdc42GAP interacted with either Nudel or Cdc42 but not with both at the same time. Pull-down assays demonstrated that Nudel competed with Cdc42 for binding to Cdc42GAP in a dose-dependent manner. A fluorescence-based assay showed that Cdc42 activation was lower in NIH 3T3 cells transfected with Nudel-specific RNAi than in control cells. Western blotting and microscopic analyses demonstrated that recruitment of Nudel to the leading edge was dependent on its phosphorylation by extracellular signal-regulated kinases. Together these data suggest a critical role for Nudel in cell migration through its binding to the Cdc42 inhibitor Cdc42GAP, thus allowing for increased Cdc42 activity.

Y. Shen, N. Li, S. Wu, Y. Zhou, Y. Shan, Q. Zhang, C. Ding, Q. Yuan, F. Zhao, R. Zeng, X. Zhu, Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells.
Dev
.
Cell
14
, 342-353 (2008).
[PubMed]
Novel Function for a Matrix Metalloprotease
Authors: VanHook Annalisa
Published: March 2008

As the family name clearly implies, matrix metalloproteases (MMPs) are localized to the extracellular matrix, where they function as proteases, modulating cell signaling by cleaving proteins such as growth factors or growth factor receptors. In the past few years, MMPs in some cell types have also been observed to function in the nucleus. Eguchi
et al.
implicate MMPs in a nuclear function that does not require its proteolytic activity, however. This alternative function was first suggested when the authors identified MMP3 in a screen for transcriptional regulators of the gene encoding connective tissue growth factor (CTGF), an insulin-like growth factor implicated in diverse physiological and morphogenetic processes, including arthritis, angiogenesis, and wound healing. MMP3 was detected in the nuclei of mouse chondrocytes both in vitro and in vivo, and in vitro knockdown of MMP3 by RNA interference suggested that MMP3 activated
CTGF
transcription. MMP3’s interaction with the
CTGF
promoter was direct and sequence-specific, as assayed by a luciferase reporter system and band-shift experiments. Furthermore, the catalytic domain of MMP3 was not required for its DNA-binding or transcriptional activator functions. Finally, binding to the
CTGF
enhancer was limited to MMP3; overexpression or inhibition of other MMPs did not affect
CTGF
expression. The results presented in this study suggest an unconventional role for MMPs in the regulation of gene expression.

T. Eguchi, S. Kubota, K. Kawata, Y. Mukudai, J. Uehara, T. Ohgawara, S. Ibaragi, A. Sasaki, T. Kuboki, M. Takigawa, Novel transcription factor-like function of human matrix metalloproteinase 3 regulating the
CTGF/CCN2
gene.
Mol. Cell. Biol.
28
, 2391-2413 (2008).
[Abstract]
[Full Text]
Codependents in the Stress Response
Authors: VanHook Annalisa
Published: March 2008

Exposure to stresses, such as heat shock or toxins, causes protein processing dysfunction in the endoplasmic reticulum (ER). If proper processing cannot be restored, the cell responds by initiating apoptosis. Qi and Mochly-Rosen used a combination of cell culture and in vivo experiments to investigate the role of protein kinase C δ (PKCδ) and the Abl tyrosine kinase in relaying the apoptotic signal from ER to mitochondria, where apoptosis is initiated. PKCδ and Abl, proapoptotic proteins with stress-dependent subcellular localization dynamics, are known to interact under conditions of stress. The authors coimmunoprecipitated Abl and PKCδ from ER cell fractions of cells treated with the toxin tunicamycin to induce ER stress and found that PKCδ was not activated in stressed cells when Abl transcripts were depleted by RNA interference. Expression and catalytic activity of both PKCδ and Abl were required to induce apoptosis, as measured by c-Jun N-terminal kinase (JNK) signaling activation and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. The subcellular dynamics and functional interaction of PKCδ and Abl were also supported by an in vivo rat stroke model. The authors propose a model in which ER stress induces the translocation of PKCδ to the ER, where it is activated by Abl. The PKCδ-Abl complex transduces the apoptotic signal to mitochondria by activating the JNK cascade. Whether JNK activation occurs in the ER, cytoplasm, or mitochondria is not known, nor is it known whether PKCδ and Abl interact directly or whether they are part of a larger complex.

X. Qi, D. Mochly-Rosen, The PKCδ-Abl complex communicates ER stress to the mitochondria – an essential step in subsequent apoptosis.
J. Cell Sci.
121
, 804-813 (2008).
[Abstract]
[Full Text]
An RGS for PI3K
Authors: Gough Nancy R.
Published: March 2008

Immunoglobulin E (IgE) triggers the activation of the FcεRI immune receptor, which signals through immunoreceptor-based tyrosine activation motifs, in response to allergens. FcεRI activation on mast cells produces an increase in intracellular calcium concentration, which causes degranulation and the release of inflammatory mediators such as histamine. The signaling pathway from the FcεRI to calcium involves the tyrosine kinases Lyn and Syk, the adaptor proteins Gab2 and Grb2, phosphoinositide 3-kinase (PI3K), and phospholipase C-mediated production of inositol 1,4,5-trisphosphate (IP
3
). G protein-coupled receptors, such as adenosine or prostaglandin receptors, may amplify IgE-mediated mast cell activation. Bansal
et al
. found that RGS13, a member of the R4 subfamily of regulator of G protein signaling (RGS) proteins, provided an inhibitory input into IgE-mediated mast cell degranulation through a mechanism involving the p85 subunit of PI3K instead of a G protein. RGS proteins are best known for attenuating G protein signaling through their actions as GTPase-activating proteins (GAPs) for specific Gα subunits and for interfering with the interactions between Gα subunits and downstream effectors. Bansal
et al
. studied bone marrow-derived mast cells (BMMCs) from
Rgs13
knockout (
Rgs13
-KO) mice and found that antigen-elicited degranulation was greater and inhibition of G proteins with pertussis toxin did not alter this enhanced response, suggesting that G proteins were not mediating the effect. Furthermore, reconstitution of the
Rgs13
-deficient BMMCs with mutant forms of RGS13 that could not interact with G proteins prevented the enhanced degranulation response. The
Rgs13
-KO mice also exhibited elevated cutaneous allergic response compared with wild-type mice, yet did not show altered mast cell numbers or morphology. Using glutathione
S
-transferase fused to RGS13, the p85 subunit of PI3K was identified from lysates of BMMCs as a tyrosine-phosphorylated protein that interacted with RGS13. The interaction between RGS13 and p85 was direct and occurred with recombinant proteins, although it did require p85 tyrosine phosphorylation (achieved by incubation with Lyn).
Rgs13
-deficient BMMCs showed increased production of IP
3
, phosphorylation of Akt, and increased intracellular calcium concentrations in response to antigen. Transduction of wild-type BMMCs with a cell-permeable RGS13 construct inhibited antigen-stimulated calcium flux and PI3K activity. Immunoprecipitation experiments with BMMCS transduced with the cell-permeable RGS13 indicated that RGS13 interfered with the recruitment of p85 to Gab2 of the FcεRI signaling complex.

G. Bansal, Z. Xie, S. Rao, K. H. Nocka, K. M. Druey, Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13.
Nat. Immunol.
9
, 73-80 (2008).
[PubMed]
Contraction-Mediated Release of TGF-β1
Authors: Gough Nancy R.
Published: March 2008

Wound healing requires the contraction of the tissue, which in turn involves the conversion of fibroblasts into myofibroblasts, which exhibit high contractility generated by α smooth muscle actin stress fibers. In fibrotic diseases, myofibroblasts contribute to tissue fibrosis. Transforming growth factor-β1 (TGF-β1) and mechanical stress are both required for myofibroblast formation. Wipff
et al
. show that myofibroblasts also contribute to the activation of latent TGF-β1, which is secreted and sequestered in the extracellular matrix (ECM) bound to latency associated protein (LAP) and latent TGF-β binding protein 1 (LTBP-1), through a contraction-mediated mechanism. The authors developed a culture system consisting of fibroblasts or myofibroblasts, transformed mink lung reporter cells (TMLCs) that produce luciferase in the presence of active TGF-β1, and extracted ECM containing latent TGF-β1. They used this system to show that myofibroblasts stimulated the release of active TGF-β1 to a greater extent than did other types of fibroblasts. Furthermore, agonists that triggered myofibroblast contraction promoted TGF-β1 release, whereas drugs that inhibited contraction prevented contraction-stimulating agonists from stimulating TGF-β1 release without affecting basal TGF-β1 release. Proteolysis is one known mechanism for releasing active TGF-β1 from the latent complex bound to the ECM; however, protease inhibitors failed to block TGF-β1 release triggered by myofibroblast contraction. TGF-β1 release triggered by myofibroblast contraction was blocked by interfering with the interaction between integrins and LAP or by function-blocking antibodies to αvβ5 integrin. By culturing the myofibroblasts on silicone membranes and then subjecting the cells to stretch, the authors showed that stretch stimulated TGF-β1 release and that this required an intact cytoskeleton. Substrate stiffness was also important for contraction-mediated release of TGF-β1. Monitoring the movement of LTBP-1 in response to myofibroblast contraction showed that LTBP-1 was displaced toward the center of the myofibroblast when present in soft substrates. In stiffer substrates, LTBP-1 was not displaced toward the center and, instead, sometimes the LTBP-1-labeled fibers were straighter after myofibroblast contraction. The authors propose a model whereby integrins on the myofibroblast grab LAP and then when the myofibroblast contracts, this pulls against the ECM and releases TGF-β1. Thus, the stiffness of the ECM and ECM remodeling at the wound site may contribute to TGF-β1 release.

P.-J. Wipff, D. B. Rifkin, J.-J. Meister, B. Hinz, Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix.
J. Cell Biol.
179
, 1311-1323 (2007).
[Abstract]
[Full Text]