bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothalamic ERK Mediates the Anorectic and Thermogenic Sympathetic Effects of Leptin
Authors: Rahmouni Kamal , Sigmund Curt D. , Haynes William G. , Mark Allyn L.
Published: December 2008

OBJECTIVE—Leptin is an adipocyte hormone that plays a major role in energy balance. Leptin receptors in the hypothalamus are known to signal via distinct mechanisms, including signal transducer and activator of transcription-3 (STAT3) and phosphoinositol-3 kinase (PI 3-kinase). Here, we tested the hypothesis that extracellular signal–regulated kinase (ERK) is mediating leptin action in the hypothalamus.

RESEARCH DESIGN AND METHODS—Biochemical, pharmacological, and physiological approaches were combined to characterize leptin activation of ERK in the hypothalamus in rats.

RESULTS—Leptin activates ERK1/2 in a receptor-mediated manner that involves JAK2. Leptin-induced ERK1/2 activation was restricted to the hypothalamic arcuate nucleus. Pharmacological blockade of hypothalamic ERK1/2 reverses the anorectic and weight-reducing effects of leptin. The pharmacological antagonists of ERK1/2 did not attenuate leptin-induced activation of STAT3 or PI 3-kinase. Blockade of ERK1/2 abolishes leptin-induced increases in sympathetic nerve traffic to thermogenic brown adipose tissue (BAT) but does not alter the stimulatory effects of leptin on sympathetic nerve activity to kidney, hindlimb, or adrenal gland. In contrast, blockade of PI 3-kinase prevents leptin-induced sympathetic activation to kidney but not to BAT, hindlimb, or adrenal gland.

CONCLUSIONS—Our findings indicate that hypothalamic ERK plays a key role in the control of food intake, body weight, and thermogenic sympathetic outflow by leptin but does not participate in the cardiovascular and renal sympathetic actions of leptin.
Endoplasmic Reticulum Stress Is Reduced in Tissues of Obese Subjects After Weight Loss
Authors: Gregor Margaret F. , Yang Ling , Fabbrini Elisa , Mohammed B. Selma , Eagon J. Christopher , Hotamisligil Gökhan S. , Klein Samuel
Published: December 2008

OBJECTIVE—Obesity is associated with insulin resistance and type 2 diabetes, although the mechanisms linking these pathologies remain undetermined. Recent studies in rodent models revealed endoplasmic reticulum (ER) stress in adipose and liver tissues and demonstrated that ER stress could cause insulin resistance. Therefore, we tested whether these stress pathways were also present in obese human subjects and/or regulated by weight loss.

RESEARCH DESIGN AND METHODS—Eleven obese men and women (BMI 51.3 ± 3.0 kg/m2) were studied before and 1 year after gastric bypass (GBP) surgery. We examined systemic insulin sensitivity using hyperinsulinemic-euglycemic clamp studies before and after surgery and collected subcutaneous adipose and liver tissues to examine ER stress markers.

RESULTS—Subjects lost 39 ± 9% body wt at 1 year after GBP surgery (P < 0.001), which was associated with a marked improvement in hepatic, skeletal muscle, and adipose tissue insulin sensitivity. Markers of ER stress in adipose tissue significantly decreased with weight loss. Specifically, glucose-regulated protein 78 (Grp78) and spliced X-box binding protein-1 (sXBP-1) mRNA levels were reduced, as were phosphorylated elongation initiation factor 2α (eIF2α) and stress kinase c-Jun NH2-terminal kinase 1 (JNK1) (all P values <0.05). Liver sections from a subset of subjects showed intense staining for Grp78 and phosphorylated eIF2α before surgery, which was reduced in post-GBP sections.

CONCLUSIONS—This study presents important evidence that ER stress pathways are present in selected tissues of obese humans and that these signals are regulated by marked weight loss and metabolic improvement. Hence, this suggests the possibility of a relationship between obesity-related ER stress and metabolic dysfunction in obese humans.
Contributions of Qualitative Research to Research on Teacher Qualifications
Authors: Kennedy Mary M.
Published: December 2008

The influence of teachers’ qualifications on their teaching practice has been subject to debate. Literature reviews do not settle these debates, partly because the literature is uneven and partly because reviews capture only narrow slices of literature. In particular, many reviews eliminate qualitative studies. Yet without examining qualitative evidence, variations in quantitative findings are difficult to interpret, disappointing findings are difficult to understand, and plausible explanations of patterns are in short supply. The present review focuses on qualitative studies and compares their findings with those from quantitative literature. The author finds that the qualitative literature agrees with quantitative literature in its inability to distinguish between teachers with different types of certificates or different teacher education backgrounds. On the other side, the author finds more evidence of benefit from content knowledge than quantitative studies have typically found. The qualitative studies also reveal competing influences and offer hypotheses about why the outcomes look the way they do.
Computational Insights on Sulfonamide Imprinted Polymers
Authors: Isarankura-Na-Ayudhya Chartchalerm , Nantasenamat Chanin , Buraparuangsang Prasit , Piacham Theeraphon , Ye Lei , Bülow Leif , Prachayasittikul Virapong
Published: December 2008

Molecular imprinting is one of the most efficient methods for preparing synthetic receptors that possess user defined recognition properties. Despite general success of non-covalent imprinting for a large variety of templates, some groups of compounds remain difficult to tackle due to their structural complexity. In this study we investigate preparation of molecularly imprinted polymers that can bind sulfonamide compounds, which represent important drug candidates. Compared to the biological system that utilizes metal coordinated interaction, the imprinted polymer provided pronounced selectivity when hydrogen bond interaction was employed in an organic solvent. Computer simulation of the interaction between the sulfonamide template and functional monomers pointed out that although methacrylic acid had strong interaction energy with the template, it also possessed high non-specific interaction with the solvent molecules of tetrahydrofuran as well as being prone to self-complexation. On the other hand, 1-vinyl-imidazole was suitable for imprinting sulfonamides as it did not cross-react with the solvent molecules or engage in self-complexation structures.
Synthesis of Novel Homo-N-Nucleoside Analogs Composed of a Homo-1,4-Dioxane Sugar Analog and Substituted 1,3,5-Triazine Base Equivalents
Authors: Yu Qiang , Schwidom Dirk , Exner Alexander , Carlsen Per
Published: December 2008

Enantioselective syntheses from dimethyl tartrate of 1,3,5-triazine homo-N-nucleoside analogs, containing a 1,4-dioxane moiety replacing the sugar unit in natural nucleosides, were accomplished. The triazine heterocycle in the nucleoside analogs was further substituted with combinations of NH2, OH and Cl in the 2,4-triazine positions.
ON POSSIBILITY OF SHORT‐TERM PROGNOSIS OF CYCLONIC ACTIVITY AFTER‐EFFECTS IN VILNIUS BY VARIATION OF HARD COSMIC RAY FLUX/CIKLONŲ AKTYVUMO PASEKMIŲ TRUMPALAIKĖS PROGNOZĖS GALIMYBĖS VILNIAUS MIESTE PAGAL KIETOSIOS KOSMINĖS SPINDULIUOTĖS SRAUTO VARIACIJAS/ О ВОЗМОЖНОСТИ КРАТКОВРЕМЕННОГО ПРОГНОЗА ПОСЛЕДСТВИЙ ЦИКЛОНИЧЕСКОЙ АКТИВНОСТИ В ВИЛЬНЮСЕ ПО КОЛЕБАНИЯМ ПОТОКА ЖЕСТКОГО ИЗЛУЧЕНИЯ
Authors: Styra Dmitrijus , Čiučelis Algirdas , Usovaitė Ana , Damauskaitė Jovita
Published: December 2008

Analysis of hard cosmic ray flux (HCRF) variation at an energy interval 1.2—1.6 MeV was carried out in Vilnius. Connection between HCRF decrease at the mentioned energy interval and the minimum atmospheric pressure in 3–6 days is defined. This phenomenon is registered from 8 up to 13 hours. According to the time interval of HCRF decrease, for instance 8–9 and 9–10 hours, the minimum pressure in Vilnius takes place in 3^1 days, and at time intervals 11–12, and 12–13 hours ‐ in 5–6 days. Realization of this prognosis at one of the presented time intervals was 56–67% in 2002–2003. The same investigation results, with the assumption of atmospheric pressure decrease from 1005 hPa and less, showed a high efficiency of prognosis of the minimum pressure in Vilnius at all the time intervals during 6 days ‐ 92%, and 82% in 2002 and 2003, correspondingly. Santrauka Atlikta kietosios kosminės spinduliuotės srauto variacijų analizė energijų intervale 1,2–1,6 MeV Vilniaus mieste. Nustatytas ryšis tarp kietosios kosminės spinduliuotės srauto (KKSS) sumažėjimo šiame intervale ir atmosferos slėgio kitimo, kuris įvyks per 3–4 paras. Toks ryšis registruojamas tik nuo 8 val. iki 13 val. KKSS mažėjimas Vilniaus mieste priklauso nuo laiko intervalo, pvz., nuo 8–9 ir 9–10 val. slėgis sumažėja po 3–4 dienų; 11–12 ir 12–13 val. slėgis sumažėja po 5–6 dienų. Prognozės efektyvumas viename iš laiko intervalų buvo nuo 56–67 % 2002–2003 m. atitinkamai. To paties tyrimo rezultatai, įskaitant ir atmosferos slėgio mažėjimą nuo 1005 hPa ir mažiau, parodė aukštą prognozės efektyvumą visuose laiko intervaluose per 6 dienas – 92 % ir 82 % 2002–2003 metais atitinkamai. Резюме Проведен анализ колебаний потока жесткого космического излучения (ПЖКИ) в энергетическом интервале 1,2– 1,6 МэВ в г. Вильнюсе. Установлена связь между падением ПЖКИ в этом энергетическом интервале и изменением атмосферного давления, которое произойдет через 3–6 суток. Такая связь регистрируется только с 8 час. до 13 часов. В зависимости от интервала времени регистрации падения ПЖКИ, в частности, 8–9 часов, 9–10 часов – наименьшее давление в г. Вильнюсе образуется через 3–4 суток, а 11–12 часов и 12–13 часов – через 5–6 суток. Выполнимость такого прогноза по падению ПЖКИ в одном временном интервале в среднем соответствовала 56– 67% в 2002–2003 гг. Результаты аналогичного исследования с учетом того, что атмосферное давление уменьшается, начиная с 1005 гПа и ниже, показали высокую эффективность прогноза формирования наименьшего давления в г. Вильнюсе по падению ПЖКИ во всех временных интервалах в течение 6 суток – 92% и 82% в 2002 и 2003 гг. соответственно.
Reproductive aging in captive and wild common chimpanzees: factors influencing the rate of follicular depletion
Authors: Atsalis Sylvia , Videan Elaine
Published: December 2008

We examine and discuss evidence of contrasting differences in fertility patterns between captive and wild female chimpanzees,Pan troglodytes, as they age; in the wild females reproduce in their 40s, but captive studies suggest that menopause occurs around that time. Thus, despite the increased longevity generally observed in captive populations reproductive life span is shortened. We outline a hypothesis to explain the apparent differential pace of reproductive decline observed between wild and captive populations. The breeding schedules of captive primates may contribute to accelerated reproductive senescence because continuous cycling in captive animals results in early depletion of the ovarian stock and premature senescence. Available evidence supports the hypothesis that women with patterns of high oocyte loss experience earlier menopause. Chimpanzees in captivity live longer, and thus, similar to humans, they may experience follicular depletion that precedes death by many years. In captivity, chimpanzees typically have an early age at menarche and first birth, shorter interbirth intervals associated with short lactational periods as young mature faster, and nursery rearing, which allows mothers to begin cycling earlier. Variables typical of wild chimpanzee populations, including late age at menarche and first birth, long interbirth intervals associated with prolonged lactational periods, and a long period of female infertility after immigration, spare ovulations and may be responsible for the later age at reproductive termination. Finally, we describe and discuss the timing of specific reproductive landmarks that occur as female chimpanzees age, distinguishing between functional menopause (age at last birth) and operational menopause (end of cycling). Am. J. Primatol. 71:271–282, 2009. © 2008 Wiley‐Liss, Inc.
Estimated 10‐year stroke risk by region and race in the United States
Authors: Cushman Mary , Cantrell Ronald A. , McClure Leslie A. , Howard George , Prineas Ronald J. , Moy Claudia S. , Temple Ella M. , Howard Virginia J.
Published: December 2008

Objective

Black individuals younger than 75 years have more than twice the risk for stroke death than whites in the United States. Regardless of race, stroke death is approximately 50% greater in the “stroke belt” and “stroke buckle” states of the Southeastern United States. We assessed geographic and racial differences in estimated 10‐year stroke risk.

Methods

The Reasons for Geographic and Racial Differences in Stroke study is a population‐based cohort of men and women 45 years or older, recruited February 2003 to September 2007 at this report, with oversampling of stroke belt/buckle residents and blacks. Racial and regional differences in the Framingham Stroke Risk Score were studied in 23,940 participants without previous stroke or transient ischemic attack.

Results

The mean age‐, race‐, and sex‐adjusted 10‐year predicted stroke probability differed slightly across regions: 10.7% in the belt, 10.4% in the buckle, and 10.1% elsewhere (p <0.001). Geographic differences were largest for the score components of diabetes and use of antihypertensive therapy. Blacks had a greater age‐ and sex‐adjusted mean 10‐year predicted stroke probability than whites: 11.3% versus 9.7%, respectively (p <0.001). Race differences were largest for the score components of hypertension, systolic blood pressure, diabetes, smoking, and left ventricular hypertrophy.

Interpretation

Although blacks had a greater predicted stroke probability than whites, regional differences were small. Results suggest that interventions to reduce racial disparities in stroke risk factors hold promise to reduce the racial disparity in stroke mortality. The same may not be true regarding geographic disparities in stroke mortality. Ann Neurol 2008;64:507–513
A critical evaluation of the Braak staging scheme for Parkinson's disease
Authors: Burke Robert E. , Dauer William T. , Vonsattel Jean Paul G.
Published: December 2008

Braak and colleagues have proposed that, within the central nervous system, Parkinson's disease (PD) begins as a synucleinopathy in nondopaminergic structures of the lower brainstem or in the olfactory bulb. The brainstem synucleinopathy is postulated to progress rostrally to affect the substantia nigra and cause parkinsonism at a later stage of the disease. In the context of a diagnosis of PD, made from current clinical criteria, the pattern of lower brainstem involvement accompanying mesencephalic synucleinopathy is often observed. However, outside of that context, the patterns of synucleinopathy that Braak described are often not observed, particularly in dementia with Lewy bodies and when synucleinopathy occurs in the absence of neurological manifestations. The concept that lower brainstem synucleinopathy represents “early PD” rests on the supposition that it has a substantial likelihood of progressing within the human lifetime to involve the mesencephalon, and thereby cause the substantia nigra pathology and clinical parkinsonism that have heretofore defined the disease. However, the predictive validity of this concept is doubtful, based on numerous observations made in populations of aged individuals who, despite the absence of neurological signs, have brain synucleinopathy ranging up to Braak stages 4 to 6 at postmortem. Furthermore, there is no relation between Braak stage and the clinical severity of PD. We conclude that the relation between patterns of abnormal synuclein immunostaining in the human brain and the disease entity now recognized as PD remains to be determined. Ann Neurol 2008;64:485–491
Mutation in BAG3 causes severe dominant childhood muscular dystrophy
Authors: Selcen Duygu , Muntoni Francesco , Burton Barbara K. , Pegoraro Elena , Sewry Caroline , Bite Anna V. , Engel Andrew G.
Published: December 2008

Objective

Myofibrillar myopathies (MFMs) are morphologically distinct but genetically heterogeneous muscular dystrophies in which disintegration of Z disks and then of myofibrils is followed by ectopic accumulation of multiple proteins. Cardiomyopathy, neuropathy, and dominant inheritance are frequent associated features. Mutations in αB‐crystallin, desmin, myotilin, Zasp, or filamin‐C can cause MFMs and were detected in 32 of 85 patients of the Mayo MFM cohort. Bag3, another Z‐disk–associated protein, has antiapoptotic properties, and its targeted deletion in mice causes fulminant myopathy with early lethality. We therefore searched for mutations in BAG3 in 53 unrelated MFM patients.

Methods

We searched for mutations in BAG3 by direct sequencing. We analyzed structural changes in muscle by histochemistry, immunocytochemistry, and electron microscopy, examined mobility of the mutant Bag3 by nondenaturing electrophoresis, and searched for abnormal aggregation of the mutant protein in COS‐7 (SV‐40 transformed monkey kidney fibroblast‐7) cells.

Results

We identified a heterozygous p.Pro209Leu mutation in three patients. All presented in childhood, had progressive limb and axial muscle weakness, and experienced development of cardiomyopathy and severe respiratory insufficiency in their teens; two had rigid spines, and one a peripheral neuropathy. Electron microscopy showed disintegration of Z disks, extensive accumulation of granular debris and larger inclusions, and apoptosis of 8% of the nuclei. On nondenaturing electrophoresis of muscle extracts, the Bag3 complex migrated faster in patient than control extracts, and expression of FLAG‐labeled mutant and wild‐type Bag3 in COS cells showed abnormal aggregation of the mutant protein.

Interpretation

We conclude mutation in Bag3 defines a novel severe autosomal dominant childhood muscular dystrophy. Ann Neurol 2008
Relative impacts of native and non‐native crayfish on shelter use by an indigenous benthic fish
Authors: Bubb Damian H. , O'Malley Oliver J. , Gooderham Angela C. , Lucas Martyn C.
Published: December 2008

The North American signal crayfish Pacifastacus leniusculus has been widely introduced throughout Europe where it is expanding its range and in many areas replacing the native white‐clawed crayfish Austropotamobius pallipes. There is concern with regards to the impact of this species replacement on benthic fish. Interspecific behavioural interactions and competition for shelter between the benthic fish, bullhead Cottus gobio and A. pallipes and P. leniusculus were measured to assess the comparative impact of native and non‐native crayfish.

Both white‐clawed crayfish and signal crayfish were dominant over bullhead. Bullheads moved away from approaches of crayfish, left shelters on entry of crayfish and rarely entered an occupied shelter. Signal crayfish made significantly more aggressive approaches towards bullheads than white‐clawed crayfish.

Alone, bullheads spent most of their time by day under shelter (median 96%), reflecting a highly entrained behavioural response, which was relaxed by night (median 60%). Both crayfish species reduced shelter use by bullheads although the extent of shelter sharing by bullheads was higher in trials with white‐clawed crayfish than with signal crayfish.

Sampling in the River Wharfe, northern England, where signal and white‐clawed crayfish and bullhead currently exist, demonstrated a negative relationship between the densities of signal crayfish and bullhead, with high bullhead abundance where crayfish were absent or where white‐clawed crayfish were present at low density.

Assuming that shelter is sometimes limited under natural conditions, crayfish are likely to displace bullheads from shelters, which may increase predation risk for bullheads. Although the effects of signal crayfish on bullhead shelter use were more intense, the pattern was highly evident for the native white‐clawed crayfish. The higher fecundity and densities attained by signal crayfish may be more significant than differences in the behaviour of the two crayfish species in determining the impact of crayfish on bullheads.

Copyright © 2008 John Wiley & Sons, Ltd.
Detritus accumulation and decomposition in a coastal lake (Acquatina–southern Italy)
Authors: Costantini M. Letizia , Rossi Loreto , Fazi Stefano , Rossi David
Published: December 2008

Knowledge about processes and dynamics underlying organic matter accumulation in transitional waters is crucial for the protection of these ecologically important coastal habitats. This study investigated the relationship between large particle accumulation and decomposition in a coastal lake included in a Site of Community Interest (SCI) using sediment trap and litterbag techniques.

Two sets of sediment traps were deployed at five sites along the longitudinal axis of the lake. One set was emptied once a month for 12 months, and the other twice a year. The contents of the monthly and the 6‐monthly traps and the superficial sediments were then compared to estimate the organic matter accumulation and loss. To determine the mass loss rate of the three major allochthonous sources of detritus (the reed Phragmites australis, the cordgrass Spartina juncea, and the seagrass Posidonia oceanica), litterbags were placed near the sediment traps at three out of the five sites at the beginning of each 6‐month period and retrieved monthly.

The amount of annual particulate organic matter (POM) deposition in the traps was 1320.2±58.5 g m−2 y−1 and consisted of 25% large particles (CPOM). Allochthonous litter comprised an important fraction of CPOM, and its breakdown rate changed with the plant species, site and season. Loss rate of CPOM accumulated at the lake bottom was significantly related with the mass loss rate of reed and cordgrass litter, but not with that of seagrass.

Due to slow litter breakdown and tidal landward advection, the lake acted as a sediment trap for allochthonous matter, especially from Posidonia. The important role of marine‐derived litter in organic matter sedimentation suggests addressing conservation strategies of the lake functioning towards the selective control of allochthonous CPOM inputs, in particular at the mouth where the incoming tide brings suspended material and salinity decelerates matter flow to the sea and decomposition. This study supports the hypothesis that sedimentation and decomposition dynamics are important factors for coastal lake evolution, and shows litterbag and sediment trap techniques as simple useful investigation tools in management strategies aiming at conserving transitional waters.

Copyright © 2008 John Wiley & Sons, Ltd.
Identification of endo‐ and exo‐polygalacturonase activity in Lygus hesperus (Knight) salivary glands
Authors: Celorio‐Mancera Maria de la Paz , Carl Greve L. , Teuber Larry R. , Labavitch John M.
Published: December 2008

Polygalacturonase (PG) activity found in the salivary gland apparatus of the western tarnished plant bug (WTPB, Lygus hesperus Knight) has been thought to be the main chemical cause of the damage inflicted by this mirid when feeding on its plant hosts. Early viscosity and thermal stability studies of the PG activity in L. hesperus protein extracts were difficult to interpret. Thus, it has been suggested that one or more PG protein(s) with different hydrolytic modes of action are produced by this mirid. In order to understand the quantitative complexity of the WTPB salivary PG activity, PG purification from a protein extract from salivary glands excised from L. hesperus insects was performed using affinity and ion exchange chromatography. To elucidate the qualitative complexity of the purified PGs, the digestion products generated by the PGs were separated using high performance anion exchange chromatography with pulsed amperometric detection. At least five PG proteins were detected; these differing in terms of their glycosylation, mass‐to‐charge ratios, and/or molecular mass. The characterization of the products generated by these PGs showed that endo‐ and exo‐acting PGs are produced by WTPB. Although none of the PGs was purified to homogeneity, the present work provides biochemical evidence of a multiplicity of PGs that degrade the pectin component of the plant tissue in different fashions. The implications of these findings affect the understanding of WTPB feeding damage and, potentially, help identify ways to control this important crop pest. Arch. Insect Biochem. Physiol. 2008. © 2008 Wiley‐Liss, Inc.
Teratology: From science to birth defects prevention
Authors: Rasmussen Sonja A. , Erickson J. David , Reef Susan E. , Ross Danielle S.
Published: December 2008

One of the goals of birth defects research is to better understand risk or preventive factors for birth defects so that strategies for prevention can be developed. In this article, we have selected four areas of birth defects research that have led to the development of prevention strategies. These areas include rubella virus as a cause of congenital rubella syndrome, folic acid as a preventive factor for neural tube defects, cytomegalovirus infection as a cause of birth defects and developmental disabilities, and alcohol as a cause of fetal alcohol spectrum disorders. For each of these areas, we review key clinical and research findings that led to the identification of the risk or preventive factor, milestones in the development of prevention strategies, and the progress made thus far toward prevention. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.
Maternal asthma, asthma medication use, and the risk of congenital heart defects
Authors: Lin Shao , Herdt‐Losavio Michele , Gensburg Lenore , Marshall Elizabeth , Druschel Charlotte
Published: December 2008

BACKGROUND:Asthma is a common problem that complicates pregnancy. Several drugs are considered acceptable for use during pregnancy, although none have been classified as safe. Few studies have assessed the health impact of maternal asthma/medication use on the fetus.METHODS:A population‐based case‐control study was conducted in New York State to determine if cardiac congenital malformations in offspring were associated with maternal use of asthma medication and/or maternal asthma. Cases were cardiac anomalies in the New York State Congenital Malformations Registry. Controls were live births without any major birth defects randomly selected from birth certificates and frequency matched by year of birth. Data were collected through a 30 min telephone interview. Exposure was maternal asthma/medication use, maternal asthma/no medication use, no asthma/medication use, and no asthma/no medication use (reference).RESULTS:A total of 502 (59.4%) cases and 1,066 (53.8%) controls participated. A positive association was seen between any heart defect and women with asthma who used medication (OR 2.38; 95% CI: 1.18, 4.82). No significant associations were observed between heart defects and either women with asthma who did not use medication or women without asthma who used asthma medications. When considering types of medication used, offspring of women with asthma who used bronchodilators had an increased risk of any heart defect (OR 2.20; 95%CI: 1.05, 4.61).CONCLUSIONS:These results suggest that both maternal asthma status (controlled vs. uncontrolled; severe vs. mild) and asthma medication use, particularly bronchodilators, may play a role in cardiac malformations in offspring. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.
Chromosomal abnormalities among children born with conotruncal cardiac defects
Authors: Lammer Edward J. , Chak Jacqueline S. , Iovannisci David M. , Schultz Kathleen , Osoegawa Kazutoyo , Yang Wei , Carmichael Suzan L. , Shaw Gary M.
Published: December 2008

BACKGROUND: Conotruncal heart defects compose 25% to 30% of nonsyndromic congenital heart defects. This study describes the frequency of chromosome abnormalities and microdeletion of 22q11 associated among infants and fetuses delivered with conotruncal heart malformations. METHODS: From a population base of 974,579 infants/fetuses delivered, 622 California infants/fetuses were ascertained with a defect of aortopulmonary septation. Infants whose primary cardiac defect was tetralogy of Fallot (n = 296) or d‐transposition of the great arteries (n = 189) were screened for microdeletion of 22q11. RESULTS: Of the infants who had routine karyotypes, 5% had chromosomal abnormalities, including four with extra sex chromosomes. Thirty infants had chromosome 22q11 microdeletions, providing a cause for 10% of infants whose primary defect was tetralogy of Fallot. Right aortic arch, abnormal branching patterns of the major arteries arising from the thoracic aorta, and pulmonary artery abnormalities were observed more frequently among infants with tetralogy of Fallot caused by 22q11 microdeletion. CONCLUSIONS: We found an unusual number of infants with an extra sex chromosome and a conotruncal defect. Infants with tetralogy of Fallot owing to 22q11 microdeletion showed more associated vascular anomalies than infants with tetralogy without a 22q11 microdeletion. Although these associated vascular anomalies provide clues as to which infants with tetralogy of Fallot are more likely to carry the microdeletion, the overall risk of 10% among infants with tetralogy of Fallot warrants chromosome analysis and fluorescent in situ hybridization (FISH) testing routinely, which may be supplanted by genome‐wide copy number testing as it becomes more widely utilized. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.
Mechanistic insights into folate supplementation fromCrooked tailand other NTD‐prone mutant mice
Authors: Gray Jason D. , Ross M. Elizabeth
Published: December 2008

Despite two decades of research since Smithells and colleagues began exploring its benefits, the mechanisms through which folic acid supplementation supports neural tube closure and early embryonic development are still unclear. The greatest progress toward a molecular‐genetic understanding of folate effects on neural tube defect (NTD) pathogenesis has come from animal models. The number of NTD‐associated mouse mutants accumulated and studied over the past decade has illuminated the complexity of both genetic factors contributing to NTDs and also NTD‐gene interactions with folate metabolism. This article discusses insights gained from mouse models into how folate supplementation impacts neurulation. A case is made for renewed efforts to systematically screen the folate responsiveness of the scores of NTD‐associated mouse mutations now identified. Designed afterCrooked tail, supplementation studies of additional mouse mutants could build the molecular network maps that will ultimately enable tailoring of therapeutic regimens to individual families. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.
A lifestage‐specific approach to hazard and dose‐response characterization for children's health risk assessment
Authors: Makris Susan L. , Thompson Chad M. , Euling Susan Y. , Selevan Sherry G. , Sonawane Babasaheb
Published: December 2008

In 2006, the U.S. EPA published a report entitled A Framework for Assessing Health Risks of Environmental Exposures to Children (hereafter referred to as the “Framework”) describing a lifestage approach to risk assessment that includes the evaluation of existing data from a temporal perspective (i.e., the timing of both the exposure and the outcome). This article summarizes the lifestage‐specific issues discussed in the Framework related to the qualitative and the quantitative hazard and dose‐response characterization. Lifestage‐specific hazard characterization includes an evaluation of relevant human and experimental animal studies, focusing on the identification of critical windows of development (i.e., exposure intervals of maximum susceptibility) for observed outcomes, evaluation of differential exposure at individual lifestages, the relevance and impact of lifestage‐specific toxicokinetic and toxicodynamic data, mode of action information, variability and latency of effects from early lifestage exposure, and describing uncertainties. The interpretation of the hazard data to determine the strength of association between early life exposures and the timing and type of outcomes depends upon the overall weight of evidence. Lifestage‐specific dose‐response characterization relies on the identification of susceptible lifestages in order to quantify health risk, information on the point of departure, key default assumptions, and descriptions of uncertainty, sensitivity, and variability. Discussion of the strength and limitations of the hazard and dose‐response data provides a basis for confidence in risk determinations. Applying a lifestage approach to hazard and dose‐response characterization is likely to improve children's health risk assessment by identifying data gaps and providing a better understanding of sources of uncertainty. Birth Defects Res (Part B), 2008. © 2008 Wiley‐Liss, Inc.
Skeletal muscle tissue engineering approaches to abdominal wall hernia repair
Authors: Falco Erin E. , Roth J. Scott , Fisher John P.
Published: December 2008

Abdominal wall hernias resulting from prior incisions are a common surgical complication affecting hundreds of thousands of Americans each year. The negative consequences associated with abdominal hernias may be considerable, including pain, bowel incarceration, vascular disruption, organ loss, and death. Current clinical approaches for the treatment of abdominal wall hernias focus on the implantation of permanent biomaterial meshes or acellular xenografts. However, these approaches are not infrequently associated with postoperative infections, chronic sinuses, or small bowel obstruction. Furthermore, the most critical complication, hernia recurrence, has been well described and may occur in a large percentage of patients. Despite many advances in repair techniques, wound healing and skeletal muscle regeneration is limited in many cases, resulting in a decrease in abdominal wall tissue function and contributing to the high hernia recurrence rate. This review will give an overview of skeletal muscle anatomy, skeletal muscle regeneration, and herniation mechanisms, as well as discuss the current and future clinical solutions for abdominal wall hernia repair. Birth Defects Research (Part C) 84:315–321, 2008. © 2008 Wiley‐Liss, Inc.
Engineered microenvironments for human stem cells
Authors: Godier Amandine F. G. , Marolt Darja , Gerecht Sharon , Tajnsek Urska , Martens Timothy P. , Vunjak‐Novakovic Gordana
Published: December 2008

Regulation of cell differentiation and assembly remains a fundamental question in developmental biology. During development, tissues emerge from coordinated sequences of the renewal, differentiation, and assembly of stem cells. Likewise, regeneration of an adult tissue is driven by the migration and differentiation of repair cells. The fields of stem cells and regenerative medicine are starting to realize how important is the entire context of the cell environment, with the presence of other cells, three‐dimensional matrices, and sequences of molecular and physical morphogens. The premise is that to unlock the full potential of stem cells, at least some aspects of the dynamic environments normally present in vivo need to be reconstructed in experimental systems used in vitro. We review here some recent work that utilized engineered environments for guiding the embryonic and adult human stem cells, and focus on vasculogenesis as a critical and universally important aspect of tissue development and regeneration. Birth Defects Research (Part C) 84:335–347, 2008. © 2008 Wiley‐Liss, Inc.
Regeneration in medicine: A plastic surgeons “tail” of disease, stem cells, and a possible future
Authors: Caterson Edward J. , Caterson Stephanie A.
Published: December 2008

Regeneration in medicine is a concept that has roots dating back to the earliest known records of medical interventions. Unfortunately, its elusive promise has still yet to become a reality. In the field of plastic surgery, we use the common tools of the surgeon grounded in basic operative principles to achieve the present day equivalent of regenerative medicine. These reconstructive efforts involve a broad range of clinical deformities, both congenital and acquired. Outlined in this review are comments on clinical conditions and the current limitations to reconstruct these clinical entities in the effort to practice regenerative medicine. Cleft lip, microtia, breast reconstruction, and burn reconstruction have been selected as examples to demonstrate the incredible spectrum and diverse challenges that plastic surgeons attempt to reconstruct. However, on a molecular level, these vastly different clinical scenarios can be unified with basic understanding of development, alloplastic integration, wound healing, cell–cell, and cell‐matrix interactions. The themes of current and future molecular efforts involve coalescing approaches to recapitulate normal development in clinical scenarios when reconstruction is needed. It will be a better understanding of stem cells, scaffolding, and signaling with extracellular matrix interactions that will make this future possible. Eventually, reconstructive challenge will utilize more than the current instruments of surgical steel but engage complex interventions at the molecular level to sculpt true regeneration. Immense amounts of research are still needed but there is promise in the exploding fields of tissue engineering and stem cell biology that hint at great opportunities to improve the lives of our patients. Birth Defects Research (Part C) 84:322–334, 2008. © 2008 Wiley‐Liss, Inc.
The phone connection: A qualitative exploration of how belongingness and social identification relate to mobile phone use amongst Australian youth
Authors: Walsh Shari P. , White Katherine M. , Young Ross McD.
Published: December 2008

Mobile phone use is a prevalent behaviour amongst youth; however, there is little research to determine psychological influences on mobile phone use. This paper reports the results of a qualitative exploration into social psychological factors relating to young people's mobile phone use. Focus groups were conducted with 32 participants, aged between 16 and 24 years. Three major themes, connectedness, belonging and social identity, were explored in relation to young people's mobile phone use. Easy contact with others when using a mobile phone facilitated connectedness between people. A need to remain connected emerged in participants' descriptions of their mobile phone use. Consequently, data were analysed for factors underpinning people's desire to be connected. It emerged that mobile phones were used to enhance feelings of belonging amongst youth. Additionally, group norms influenced mobile phone behaviour indicating that social identity processes are related to mobile phone use. Results in the study provide a foundation upon which to investigate further the relationship between mobile phone use and psychological factors impacting young people's social development. Copyright © 2008 John Wiley & Sons, Ltd.
Inactivation of the Ketoreductase gilU Gene of the Gilvocarcin Biosynthetic Gene Cluster Yields New Analogues with Partly Improved Biological Activity
Authors: Liu Tao , Kharel Madan K. , Zhu Lili , Bright Samuel A. , Mattingly Cynthia , Adams Val R. , Rohr Jürgen
Published: December 2008

Four new analogues of the gilvocarcin‐type aryl‐C‐glycoside antitumor compounds, namely 4′‐hydroxy gilvocarcin V (4′‐OH‐GV), 4′‐hydroxy gilvocarcin M, 4′‐hydroxy gilvocarcin E and 12‐demethyl‐defucogilvocarcin V, were produced through inactivation of the gilU gene. The 4′‐OH‐analogues showed improved activity against lung cancer cell lines as compared to their parent compounds without 4′‐OH group (gilvocarcins V and E). The structures of the sugar‐containing new mutant products indicate that the enzyme GilU acts as an unusual ketoreductase involved in the biosynthesis of the C‐glycosidically linked deoxysugar moiety of the gilvocarcins. The structures of the new gilvocarcins indicate substrate flexibility of the post‐polyketide synthase modifying enzymes, particularly the C‐glycosyltransferase and the enzyme responsible for the sugar ring contraction. The results also shed light into biosynthetic sequence of events in the late steps of biosynthetic pathway of gilvocarcin V.
The High Resolution NMR Structure of Parvulustat (Z‐2685) from Streptomyces parvulus FH‐1641: Comparison with Tendamistat from Streptomyces tendae 4158
Authors: Rehm Stephan , Han Sigeng , Hassani Ismail , Sokocevic Alma , Jonker Hendrik R. A. , Engels Joachim W. , Schwalbe Harald
Published: December 2008

The protein parvulustat (Z‐2685) from Streptomyces parvulus comprises 78 amino acids and functions as a highly efficient α‐amylase inhibitor. Parvulustat shares 29.6 % overall amino acid sequence identity to the well‐known α‐amylase inhibitor tendamistat. Among the conserved residues are the two disulfide bridges (C9–C25, C43–C70) and the active‐site motif (W16, R17, Y18). Here, we report the high‐resolution NMR structure of parvulustat based on NOEs, J couplings, chemical shifts and hydrogen‐exchange data. In addition, we studied the dynamical properties of parvulustat by heteronuclear relaxation measurements. We compare the structure of parvulustat with the structure of tendamistat in terms of secondary structure elements, charges and hydrophobicity. The overall structural composition is very similar, but there are distinct differences including the active‐site region. These structural and dynamical differences indicate that for parvulustat an induced‐fit mechanism for binding to α‐amylase might take place, since the structure of tendamistat does not change upon binding to α‐amylase.
Metal Binding Properties of Fluorescent Analogues of Trichogin GA IV: A Conformational Study by Time‐Resolved Spectroscopy and Molecular Mechanics Investigations
Authors: Venanzi Mariano , Bocchinfuso Gianfranco , Gatto Emanuela , Palleschi Antonio , Stella Lorenzo , Formaggio Fernando , Toniolo Claudio
Published: December 2008

The metal ion binding properties of two fluorescent analogues of trichogin GA IV, which is a natural undecapeptide showing significant antimicrobial activity, were studied by circular dichroism, time‐resolved optical spectroscopy, and molecular mechanics calculations. Binding of CaII and GdIII to the peptides investigated was shown to promote a structural transition from highly helical conformations to folded structures characterized by formation of a loop that embedded the metal ion. Time‐resolved spectroscopy revealed that peptide dynamics is also remarkably affected by ion binding: peptide‐backbone motions slowed down to the microsecond time scale. Finally, molecular mechanics calculations emphasized the role of the central Gly5‐Gly6 motif, which allowed for the twisting of the peptide segment that gave rise to the formation of the binding cavity.
Acute cerebral rescue during carotid artery stenting: A stroke of good fortune?
Authors: Jones Michael R. , Brooks William H.
Published: December 2008

Major stroke is a potentially devastating complication of carotid artery revascularization. Carotid artery stenting, unlike endarterectomy, offers the opportunity to attenuate this complication by allowing for the instantaneous detection and early endovascular treatment of neurologic defects complicating the procedure. We report a case that highlights the utility of aggressive endovascular cerebral rescue during a carotid artery stent procedure. © 2008 Wiley‐Liss, Inc.
Complication rate of diagnostic carotid angiography performed by interventional cardiologists
Authors: Al‐Ameri Hazim , Thomas Mottsin L. , Yoon Anthony , Mayeda Guy S. , Burstein Steven , Kloner Robert A. , Shavelle David M.
Published: December 2008

Objective: The aim of this study was to evaluate the complication rate of diagnostic carotid angiography performed by interventional cardiologists and compare it to previously published data. Background: Percutaneous treatment for carotid artery stenosis is increasingly being performed. Previously published data describes the complication rate of diagnostic carotid angiography performed by radiologists and vascular surgeons, yet the information regarding interventional cardiologists is sparse. Currently in the United States, interventional cardiologists perform a great deal of diagnostic carotid angiograms. Methods: A retrospective analysis was done on 333 patients who underwent diagnostic carotid angiography at a single medical center from January 2000 to February 2007. Medical records were reviewed for cardiovascular risk factors, indications for the procedure, angiography technique and in‐hospital complications. Complications were categorized as neurological and non‐neurological. Neurological complications were further grouped into transient (<7 days) or permanent. Non‐neurological complications were grouped into major (requiring additional treatment) or minor. Results: Three hundred and thirty‐three patients underwent 347 diagnostic carotid angiograms. Twelve (3.5%) complications occurred in 12 patients. No cerebral vascular accidents occurred and only one (0.3%) transient ischemic attack occurred. Two patients required blood transfusions following the index procedure yielding a major non‐neurological complication rate of 0.6%. Review of the literature revealed a transient neurological complication rate from 0 to 2.4% and a major non‐neurological complication rate of 0.26–4.3%. Conclusions: Neurological and non‐neurological complication rates for carotid angiograms performed by interventional cardiologists are low and compare well with the literature. Interventional cardiologists can safely perform diagnostic carotid angiography with low complication rates. © 2009 Wiley‐Liss, Inc.
The bifurcation study using 64 multislice computed tomography
Authors: Kawasaki Tomohiro , Koga Hisashi , Serikawa Takeshi , Orita Yoshiya , Ikeda Shinsuke , Mito Takahiro , Gotou Yoshitaka , Shintani Yoshiaki , Tanaka Atsushi , Tanaka Hidenori , Fukuyama Takaya , Koga Nobuhiko
Published: December 2008

Background: Various two‐stent techniques have been applied to aggressively treat bifurcation lesions as the introduction of drug‐eluting stents (DES) and the importance of the bifurcation angle and three‐dimensional (3D) structure has come to be recognized. Recent 64 multislice computed tomography (MSCT) technology provides accurate information about the 3D bifurcation geometry of the coronary arteries and with reproducibility. Objectives: The purpose of this study is to disclose the coronary bifurcation angle and 3D structure in humans and elucidate the importance of bifurcation angle for the crush technique using MSCT. Methods: Two hundred and nine patients who were suspected to have angina pectoris and underwent CT angiography using MSCT were examined. The 3D‐volume rendering (VR) image was reconstructed by two technicians and was used for the assessment of each coronary bifurcation angles. Results: The average LMT bifurcation angles (∠LMT‐LAD, ∠LMT‐LCx, ∠LAD‐LCx) were 143 ± 13°, 121 ± 21°, and 72 ± 22°, respectively, the average ∠LAD‐D was 138 ± 19°, the average ∠LCx‐OM was 134 ± 23°, the average distal RCA bifurcation angles (∠RCA‐4AV, ∠RCA‐4PD, ∠4AV‐4PD) were 152 ± 15°, 137 ± 20°, and 61 ± 21°, respectively. In addition, a percentage of steep angled bifurcation (<110°) was significantly higher in the LMT (26%) than in other bifurcations (P < 0.05). Conclusions: LMT bifurcation has been shown to have a higher rate of steep angled bifurcation in humans, it is therefore necessary to take the bifurcation angle into consideration in the case of LMT stenting. These data suggest that a bifurcation study using MSCT can clarify the 3D structure of coronary bifurcation and may provide useful information for bifurcation stenting. © 2009 Wiley‐Liss, Inc.