bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunodeficiency in Vici syndrome: A heterogeneous phenotype
Authors: Finocchi Andrea , Angelino Giulia , Cantarutti Nicoletta , Corbari Maurizio , Bevivino Elsa , Cascioli Simona , Randisi Francesco , Bertini Enrico , Dionisi‐Vici Carlo
Published: September 2011

Vici syndrome is a rare congenital multisystem disorder characterized by agenesis of the corpus callosum, hypotonia, developmental delay, hypopigmentation, cataract, cardiomyopathy, and immunological abnormalities. Recurrent infections, mainly affecting the respiratory tract, have been reported in the majority of cases, representing an important risk factor for morbidity and mortality. The immunological phenotype of patients is extremely variable, ranging from a combined immunodeficiency to nearly normal immunity. We report on a new patient with Vici syndrome, in whom we have extensively investigated immunological features. Despite a mild impairment of the cellular compartment, a defect of humoral immunity was found, requiring treatment with intravenous immunoglobulin. A wider knowledge of immune system abnormalities of Vici syndrome will help to plan strategies for treatment and prevention of infections, such as immunoglobulin replacement and antimicrobial prophylaxis, resulting in improved survival rates. © 2011 Wiley Periodicals, Inc.
Revisit of multiple epiphyseal dysplasia: Ethnic difference in genotypes and comparison of radiographic features linked to the COMP and MATN3 genes
Authors: Kim Ok‐Hwa , Park Hyunwoong , Seong Moon‐Woo , Cho Tae‐Joon , Nishimura Gen , Superti‐Furga Andrea , Unger Sheila , Ikegawa Shiro , Choi In Ho , Song Hae‐Ryong , Kim Hyun Woo , Yoo Won Joon , Shim Jong Sup , Chung Chin Youb , Oh Chang‐Wug , Jeong Changhoon , Song Kwang Soon , Seo Sang Gyo , Cho Sung Im , Yeo Im Kyung , Kim So Yeon , Park Seungman , Park Sung Sup
Published: September 2011

Multiple epiphyseal dysplasia (MED) is a genetically heterogeneous group of diseases characterized by variable degrees of epiphyseal abnormality primarily involving the hip and knee joints. The purpose of this study was to investigate the frequency of mutations in individuals with a clinical and radiographic diagnosis of MED and to test the hypothesis that characteristic radiological findings may be helpful in predicting the gene responsible. The radiographs of 74 Korean patients were evaluated by a panel of skeletal dysplasia experts. Six genes known to be associated with MED (COMP,MATN3,COL9A1,COL9A2,COL9A3, andDTDST) were screened by sequencing. Mutations were found in 55 of the 63 patients (87%).MATN3mutations were found in 30 patients (55%), followed byCOMPmutations in 23 (41%), andCOL9A2andDTDSTmutations in one patient (2%) each. Comparisons of radiographic findings in patients withCOMPandMATN3mutations showed that albeit marked abnormalities in hip and knee joints were observed in both groups, the degree of involvement and the morphology of dysplastic epiphyses differed markedly. The contour of the pelvic acetabulum, the presence of metaphyseal vertical striations, and/or the brachydactyly of the hand were also found to be highly correlated with the genotypes. The study confirms thatMATN3andCOMPare the genes most frequently responsible for MED and that subtle radiographic signs may give precious indications on which gene(s) should be prioritized for mutational screening in a given individual. © 2011 Wiley Periodicals, Inc.
Clinical characterization of a newly described neonatal diabetes syndrome caused by RFX6 mutations
Authors: Spiegel Ronen , Dobbie Angus , Hartman Corina , de Vries Liat , Ellard Sian , Shalev Stavit A.
Published: September 2011

Mutations in the RFX6 gene were recently described to underlie a distinct autosomal recessive syndrome of neonatal diabetes comprising intestinal atresia and hepatobiliary abnormalities. Until now, only six patients harboring RFX6 mutations have been reported. We report on a new case due to a novel homozygous splice site mutation and update on the clinical outcome of a previously reported patient. In addition we review the clinical and molecular features of all RFX6 mutated cases to better characterize the syndrome. Our results suggest that despite the early postnatal fulminant course, patients who survive may expect a relatively favorable prognosis. © 2011 Wiley Periodicals, Inc.
Correlation of intercentromeric distance, mosaicism, and sexual phenotype: Molecular localization of breakpoints in isodicentric Y chromosomes
Authors: Bergeron Mélanie Beaulieu , Brochu Pierre , Lemyre Emmanuelle , Lemieux Nicole
Published: September 2011

Isodicentric chromosomes are among the structural abnormalities of the Y chromosome that are commonly identified in patients. The simultaneous 45,X cell line that is generated in cell division due to instability of the isodicentric Y chromosome [idic(Y)] has long been hypothesized to explain the variable sexual development of these patients, although gonads have been studied in only a subset of cases. We report here on the molecular localization of breakpoints in ten patients with an idic(Y). Breakpoints were mapped by FISH using BACs; gonads and fibroblasts were also analyzed when possible to evaluate the level of mosaicism. First, we demonstrate great tissue variability in the distribution of idic(Y). Second, palindromes and direct repeats were near the breakpoint of several idic(Y), suggesting that these sequences play a role in the formation of idic(Y). Finally, our data suggest that intercentromeric distance has a negative influence on the stability of idic(Y), as a greater proportion of cells with breakage or loss of the idic(Y) were found in idic(Y) with a greater intercentromeric distance. Females had a significantly greater intercentromeric distance on their idic(Y) than did males. In conclusion, our study indicates that the Y chromosome contains sequences that are more prone to formation of isodicentric chromosomes. We also demonstrate that patients with an intercentromeric distance greater than 20 Mb on their idic(Y) are at increased risk of having a female sexual phenotype. © 2011 Wiley Periodicals, Inc.
Fetal akinesia in metatropic dysplasia: The combined phenotype of chondrodysplasia and neuropathy?
Authors: Unger Sheila , Lausch Ekkehart , Stanzial Franco , Gillessen‐Kaesbach Gabriele , Stefanova Irina , Di Stefano Cristina Maria , Bertini Enrico , Dionisi‐Vici Carlo , Nilius Bernd , Zabel Bernhard , Superti‐Furga Andrea
Published: September 2011

Dominant mutations in the receptor calcium channel gene TRPV4 have been associated with a family of skeletal dysplasias (metatropic dysplasia, pseudo‐Morquio type 2, spondylometaphyseal dysplasia, Kozlowski type, brachyolmia, and familial digital arthropathy) as well as with dominantly inherited neuropathies (hereditary motor and sensory neuropathy 2C, scapuloperoneal spinal muscular atrophy, and congenital distal spinal muscular atrophy). While there is phenotypic overlap between the various members of each group, the two groups were considered to be totally separate with the former being strictly a structural skeletal condition and the latter group being confined to the peripheral nervous system. We report here on fetal akinesia as the presenting feature of severe metatropic dysplasia, suggesting that certain TRPV4 mutations can cause both a skeletal and a neuropathic phenotype. Three cases were detected on prenatal ultrasound because of absent movements in the second trimester. Case 4 presented with multiple joint contractures and absent limb movements at birth and was diagnosed with “fetal akinesia syndrome”. Post‐interruption and post‐natal X‐rays showed typical features of metatropic dysplasia in all four. Sequencing of the TRPV4 gene confirmed the presence of de novo heterozygous mutations predicting G78W (Case 1), T740I (Cases 2 and 3), and K276E (Case 4). Although some degree of restriction of movements is not uncommon in fetuses with skeletal dysplasia, akinesia as leading sign is unusual and suggests that certain TRPV4 mutations produce both chondrodysplasia and a peripheral neuropathy resulting in a severe “overlap” phenotype. © 2011 Wiley Periodicals, Inc.
Inbreeding in Finland
Authors: Jorde L.B. , Pitkänen K.J.
Published: September 2011

We have compiled data on the frequency of first‐cousin marriages in Finland using royal dispensation records for the time period 1810–1872 and national population statistics for the time period 1878–1920. For the earlier period, 0.315% of Finland's marriages were contracted between first cousins (2,331 of 739,387). During the second time period, 0.174% of Finland's marriages took place between first cousins (1,325 of 761,976). These figures, which yield average kinship coefficients of 0.00020 and 0.00011, respectively, show that the level of inbreeding in Finland due to first‐cousin marriage has been quite low. An analysis of individual parishes shows that first‐cousin marriages are, on average, substantially less frequent than predicted by a random‐mating model. In order to evaluate determinants of first‐cousin marriage, several predictive variables have been examined: parish ethnic composition (proportion of Swedish and Finnish speakers), husband's occupation (graded into 6 socioeconomic levels), geographic distance between spouses' premarital residences, population density, parish endogamy, and urban vs. rural residence. Various logistic and linear regression models were analyzed in which consanguinity was the dependent variable. The best predictors of consanguinity were ethnic composition and occupation. The other variables were not in general significant predictors. These results show that many of the “mate availability” factors that would be predicted theoretically to account for consanguinity variation (population density, geographic isolation, urban vs. rural residence) do not. Instead, the best predictors of consanguinity at the first‐cousin level are cultural factors such as ethnicity and occupation. Evaluation of cultural variables can provide a greatly enriched interpretation of complex biosocial phenomena such as inbreeding.
Genetic variation in Arizona Mexican Americans: Estimation and interpretation of admixture proportions
Authors: Long Jeffrey C. , Williams Robert C. , McAuley Joan E. , Medis Robin , Partel Rosalinda , Tregellas W. Michael , South Susan F. , Rea Ann E. , McCormick Steven B. , Iwaniec Urszula
Published: September 2011

Mexican Americans are a numerous and fast growing ethnic population in the United States. Yet little is known about their genetic structure. Since they are a hybrid, it is of interest to identify their parental populations and to estimate the relative contributions of these groups. This information is relevant to historical, biomedical, and evolutionary concerns.

New genetic typings on 730 Arizona Mexican Americans for the HLA‐A, HLA‐B, ABO, Rh, MNSs, Duffy, Kidd, and Kell loci are presented here and they are used to estimate ancestral contributions. We considered both a dihybrid model with Amerindians and Spaniards as proposed ancestors, and a trihybrid model with Amerindians, Spaniards, and Africans as proposed ancestors. A modified weighted least squares method that allows for linkage disequilibrium was used to estimate ancestral contributions for each model. The following admixture estimates were obtained: Amerindian, 0.29 ± 0.04; Spaniard, 0.68 ± 0.05; and African, 0.03 ± 0.02.

The interpretation of these results with respect to Amerindian and Spanish ancestry is straightforward. African ancestry is strongly supported by the presence of a marker of African descent, Fy, despite the fact that the standard error of the estimate is as large as the estimated admixture proportion.

An evaluation of the sensitivity of these results to a number of variables is presented: 1) our choices of ancestral allele frequencies, 2) the possibility of selection at HLA and the blood groups, and 3) genetic drift in Mexican Americans.
Variance in intrinsic rates of growth among free‐ranging rhesus monkey groups
Authors: Stucki Barbara R. , Dow Malcolm M. , Sade Donald Stone
Published: September 2011

Differential rates of intrinsic growth for the population of Macaca mulatta on Cayo Santiago partitioned by social group and dominance rank of genealogies indicate that the potential for increase is not uniformly distributed throughout the population. In the period from 1973 to 1974, high‐ranking genealogies were growing at a faster rate than low‐ranking genealogies. Large differences in r among the social groups indicate the possible existence of demographic, genetic, or social differences between groups. A random resampling procedure was employed to assess the statistical significance of differences in the intrinsic rate of growth among the 5 natural social groups and the 3 partitions formed by, respectively, lumping members of high‐, middle‐, and low‐ranking genealogies across several social groups. Comparisons among social groups shows that there are significant differences in the rate of growth between Group J and Group M, and between Group J and Group F for the period from 1973 to 1974. Among dominance ranks of genealogies, significant differences in r were found between the partitions of the high‐ and middle‐ranking genealogies. These findings suggest that differential reproductive success is influenced and maintained by underlying variations in the distribution of behavioral traits in the population.
Activity patterns in the Sahara Desert: An interpretation based on cross‐sectional geometric properties
Authors: Nikita Efthymia , Ysi Siew Yun , Stock Jay , Mattingly David , Mirazón Lahr Marta
Published: September 2011

The Garamantian civilization flourished in modern Fezzan, Libya, between 900 BC and 500 AD, during which the aridification of the Sahara was well established. Study of the archaeological remains suggests a population successful at coping with a harsh environment of high and fluctuating temperatures and reduced water and food resources. This study explores the activity patterns of the Garamantes by means of cross‐sectional geometric properties. Long bone diaphyseal shape and rigidity are compared between the Garamantes and populations from Egypt and Sudan, namely from the sites of Kerma, el‐Badari, and Jebel Moya, to determine whether the Garamantian daily activities were more strenuous than those of other North African populations. Moreover, sexual dimorphism and bilateral asymmetry are assessed at an intra‐ and inter‐population level. The inter‐population comparisons showed the Garamantes not to be more robust than the comparative populations, suggesting that the daily Garamantian activities necessary for survival in the Sahara Desert did not generally impose greater loads than those of other North African populations. Sexual dimorphism and bilateral asymmetry in almost all geometric properties of the long limbs were comparatively low among the Garamantes. Only the lower limbs were significantly stronger among males than females, possibly due to higher levels of mobility associated with herding. The lack of systematic bilateral asymmetry in cross‐sectional geometric properties may relate to the involvement of the population in bilaterally intensive activities or the lack of regular repetition of unilateral activities. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
Structure−property relationships of halogen‐free flame‐retarded poly(butylene terephthalate) and glass fiber reinforced PBT
Authors: Köppl T. , Brehme S. , Wolff‐Fabris F. , Altstädt V. , Schartel B. , Döring M.
Published: September 2011

Flame retardancy for thermoplastics is a challenging task where chemists and engineers work together to find solutions to improve the burning behavior without strongly influencing other key properties of the material. In this work, the halogen‐free additives aluminum diethylphosphinate (AlPi‐Et) and a mixture of aluminum phosphinate (AlPi) and resorcinol‐bis(di‐2,6‐xylyl phosphate) (AlPi‐H + RXP) are employed in neat and reinforced poly(butylene terephthalate) (PBT), and the morphology, mechanical performance, rheological behavior, and flammability of these materials are compared. Both additives show submicron dimensions but differ in terms of particle and agglomerate sizes und shapes. The overall mechanical performance of the PBT flame‐retarded with AlPi‐Et is lower than that with AlPi‐H‐RXP, due to the presence of larger agglomerates. Moreover, the flow behavior of the AlPi‐Et/PBT materials is dramatically changed as the larger rod‐like primary particles build a percolation threshold. In terms of flammability, both additives perform similar in the UL 94 test and under forced‐flaming combustion. Nevertheless, AlPi‐Et performs better than AlPi‐H + RXP in the LOI test. The concentration required to achieve acceptable flame retardancy ranges above 15 wt %. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Properties of styrene butadiene rubber (SBR)/recycled acrylonitrile butadiene rubber (NBRr) blends: The effects of carbon black/silica (CB/Sil) hybrid filler and silane coupling agent, Si69
Authors: Noriman Nik Z. , Ismail Hanafi
Published: September 2011

The recycling or reuse of waste rubber by means of blending together with polymeric materials in addition of filler such as hybrid carbon black and silica (CB/Sil) to a polymer system can provides an opportunity to explore alternative product specifications. Therefore, in this work the investigation of recycled rubber blends based on styrene butadiene rubber/recycled acrylonitrile butadiene rubber (SBR/NBRr) blends reinforced with 50/0, 40/10, 30/20, 20/30, 40/10, 0/50 phr of carbon black/silica (CB/Sil) hybrid filler treated with and without silane coupling agent (Si69) were determined. Cure characteristics, tensile properties, and morphological behavior of selected SBR/NBRr blends at a fix 85/15 blend ratio were evaluated. Results showed that, cure time t90, minimum torque (ML), and maximum torque (MH) of CB/Sil hybrid fillers filled SBR/NBRr blends with and without Si69 increased as silica content increased. However, t90 and ML of SBR/NBRr blends with Si69 were lower than without Si69 except for (MH). The optimum scorch time (ts2) of SBR/NBRr blends with and without Si69 was obtained at 30/20 phr of CB/Sil hybrid filler. However, ts2 of SBR/NBRr blends with Si69 were longer than SBR/NBRr blends without Si69. The incorporation of Si69 has improved the tensile properties [(tensile strength, elongation at break (Eb), stress at 100% elongation (M100), and stress at 300% elongation (M300)] of CB/Sil hybrid fillers filled SBR/NBRr blends. These properties were influenced by the degree of crosslinked density as the silica content is increased. Scanning electron microscopy (SEM) of the tensile fracture surfaces indicated that, with the addition of Si69 improved the dispersion of hybrid fillers and NBRr in SBR/NBRr matrix. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Fire performance and post‐fire mechanical properties of polymer composites coated with hybrid carbon nanofiber paper
Authors: Zhuge Jinfeng , Gou Jihua , Chen Ruey‐Hung , Zhou Aixi , Yu Ziqing
Published: September 2011

In this study, glass fiber reinforced polyester composites were coated with carbon nanofiber/clay/ammonium polyphosphate (CCA) paper and carbon nanofiber/exfoliated graphite nanoplatelets/ammonium polyphosphate (CXA) paper. The composites were exposed to a heat flux of 35 kW/m2 during the cone calorimeter testing. The testing results showed a significant reduction in both heat release rates and mass loss rates. The peak heat release rate (PHRR) of CCA and CXA composite samples in the major decomposition period are 23 and 34% lower than the control sample, respectively. The time to reach the PHRR for the CCA and CXA composite samples are ∼ 125% longer than the control sample. After the composite samples were exposed to heat for different time periods, their post‐fire mechanical properties were determined by three‐point bending testing. The three‐point bending testing results show that the composite samples coated with such hybrid papers exhibit more than 20% improvement in mechanical resistance at early stages of combustion. The mechanism of hybrid carbon nanofiber paper protecting the underlying laminated composites is discussed. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Synthesis and Biological Evaluation of 4α/4β‐Imidazolyl Podophyllotoxin Analogues as Antitumor Agents
Authors: Shang Hai , Chen Hong , Zhao Dongmei , Tang Xiaowei , Liu Yongfeng , Pan Li , Cheng Maosheng
Published: September 2011

A series of 4α/4β‐imidazolyl podophyllotoxin analogues have been designed and synthesized. All of the compounds were evaluated for their anticancer activity against a panel of three human cancer cell lines. Within the cell lines tested, some of the synthesized compounds showed promising anticancer activity. Compound 12, in particular, exhibited remarkable cytotoxicity, demonstrating effects against all tumor cell lines, including the K562/ADM cell line.
Molecular imaging of cartilage damage of finger joints in early rheumatoid arthritis with delayed gadolinium‐enhanced magnetic resonance imaging
Authors: Miese Falk , Buchbender Christian , Scherer Axel , Wittsack Hans‐Jörg , Specker Christof , Schneider Matthias , Antoch Gerald , Ostendorf Benedikt
Published: September 2011

Objective

To assess cartilage glycosaminoglycan content and cartilage thickness in the metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis (RA) and healthy volunteers.

Methods

After review board approval and informed consent were obtained, 22 subjects were prospectively enrolled (9 patients with early RA [7 women and 2 men with a mean ± SD age of 49 ± 13 years; range 25–68 years] and 13 healthy volunteers [10 women and 3 men with a mean ± SD age of 51 ± 12 years; range 25–66 years). In a total of 44 MCP joints of the index and middle fingers, measurements of cartilage thickness and delayed gadolinium‐enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index (T1 [msec]) were obtained using the variable flip‐angle method and a 3T MR scanner. MRIs were evaluated for bone edema, erosions, and synovitis (using the RA MRI Scoring criteria). Student's t‐test was used to test the significance of differences between groups.

Results

The mean ± SD dGEMRIC index was 497 ± 86 msec in healthy volunteers and was significantly lower in the early RA group (421 ± 76 msec) (P = 0.042). There was no joint space narrowing seen on standard radiographs. No significant difference was found between cartilage thickness in patients with early RA and that in controls (index finger mean ± SD 1.27 ± 0.23 mm in RA patients versus 1.46 ± 0.34 mm in controls [P = 0.16] and middle finger 1.26 ± 0.23 mm in RA patients versus 0.97 ± 0.47 mm in controls [P = 0.10]). No significant correlation was noted between cartilage thickness and dGEMRIC index (R = 0.36, P = 0.88 in RA patients; R = 0.156, P = 0.445 in controls).

Conclusion

Our findings indicate that cartilage damage is present in the MCP joints of patients with early RA despite the absence of joint space narrowing on standard radiographs and MRI. Cartilage damage in RA can be imaged with dGEMRIC.
Prescribing practices in a US cohort of rheumatoid arthritis patients before and after publication of the American College of Rheumatology treatment recommendations
Authors: Harrold Leslie R. , Harrington J. Timothy , Curtis Jeffrey R. , Furst Daniel E. , Bentley Mary Jane , Shan Ying , Reed George , Kremer Joel , Greenberg Jeffrey D.
Published: September 2011

Objective

To examine prescribing practices in the use of biologic and nonbiologic disease‐modifying antirheumatic drugs (DMARDs) to treat patients with rheumatoid arthritis (RA), before and after publication of the American College of Rheumatology (ACR) treatment recommendations.

Methods

Biologics‐naive RA patients under the care of a rheumatologist in the US were identified from the Consortium of Rheumatology Researchers of North America registry. Patients were included if their visits occurred prior to and/or at least 6 months after publication of the ACR treatment recommendations (time periods of February 2002–June 2008 versus December 2008–December 2009). The population was divided into 2 mutually exclusive cohorts: 1) methotrexate (MTX) monotherapy users, and 2) multiple nonbiologic DMARD users. Initiation or dose escalation of biologic and nonbiologic DMARDs in response to active disease was assessed cross‐sectionally and longitudinally in comparison to the ACR recommendations. The impact of the publication of the ACR recommendations on treatment practices was assessed using logistic regression, stratified by disease activity and adjusted for clustering of physicians and geographic region.

Results

After 1 visit, 24–37% of patients receiving MTX monotherapy who had moderate disease activity and a poor prognosis or high disease activity received care consistent with the ACR recommendations; after 2 visits, 34–56% of the MTX monotherapy group received care consistent with the recommendations. In the patients receiving multiple nonbiologic DMARDs, 31–47% of those with moderate or high disease activity received care consistent with the recommendations after 1 visit, and 43–51% received such care after 2 visits. Publication of the recommendations did not significantly change treatment patterns for those with active disease.

Conclusion

Substantial numbers of RA patients with active disease did not receive care consistent with the current ACR treatment recommendations. Innovative approaches to improve care are necessary.
Time trends and geographic variations in the prevalence of hypospadias in China
Authors: Li Yuehua , Mao Meng , Dai Li , Li Kesheng , Li Xiaohong , Zhou Guangxuan , Wang Yanping , Li Qi , He Chunhua , Liang Juan , Zhu Jun
Published: September 2011

BACKGROUND: Little is known about the main epidemiologic characteristics of hypospadias prevalence in China. We investigated the time trends and geographic variations in the prevalence of hypospadias in China from 1996 to 2008. METHODS: Data were retrieved from the hospital‐based birth defects monitoring system in China from 1996 to 2008. We used prevalence ratios (PRs) to describe the difference in prevalence of hypospadias between urban and rural areas, as well as among different regions. Poisson regression was used to explore the long time trend for the prevalence of hypospadias and its regional disparity. RESULTS: The prevalences of hypospadias for isolated anomalies, multiple anomalies, and overall cases were 7.64, 1.39, and 9.03 per 10,000 births, respectively. The national PRs (urban vs. rural) of hypospadias for overall and isolated cases were 1.25 (95% confidence interval [CI], 1.16–1.35) and 1.27 (95% CI, 1.17–1.38), respectively. The highest prevalence (12.10 per 10,000 births) was observed in the eastern region. A positive correlation was found between the prevalence of hypospadias and maternal age (p < 0.01). The average annual increase of 7.43% (95% CI, 5.52–9.38%) was observed in the overall prevalence of hypospadias in China; it was 5.28% (95% CI, 4.16–6.43%) in urban areas, 9.79% (95% CI, 7.72–11.90%) in rural areas, 9.08% (95% CI, 6.36–11.86%) in the eastern region, 4.76% (95% CI, 2.93–6.62%) in the central region, and 6.57% (95% CI, 4.44–8.74%) in the western region.CONCLUSION: The increasing trends and differences of hypospadias prevalence by urban‐rural classification and geographical location suggest that environmental exposure and maternal age might have a critical role in the development of hypospadias. Birth Defects Research (Part A), 2012. © 2011 Wiley Periodicals, Inc.
Challenges in studying genomic structural variant formation mechanisms: The short‐read dilemma and beyond
Authors: Onishi‐Seebacher Megumi , Korbel Jan O.
Published: September 2011

Next‐generation sequencing (NGS) technologies have revolutionised the analysis of genomic structural variants (SVs), providing significant insights into SV de novo formation based on analyses of rearrangement breakpoint junctions. The short DNA reads generated by NGS, however, have also created novel obstacles by biasing the ascertainment of SVs, an aspect that we refer to as the ‘short‐read dilemma’. For example, recent studies have found that SVs are often complex, with SV formation generating large numbers of breakpoints in a single event (multi‐breakpoint SVs) or structurally polymorphic loci having multiple allelic states (multi‐allelic SVs). This complexity may be obscured in short reads, unless the data is analysed and interpreted within its wider genomic context. We discuss how novel approaches will help to overcome the short‐read dilemma, and how integration of other sources of information, including the structure of chromatin, may help in the future to deepen the understanding of SV formation processes.
Perfusion regulation of hMSC microenvironment and osteogenic differentiation in 3D scaffold
Authors: Kim Junho , Ma Teng
Published: September 2011

The combination of hMSCs with 3D scaffolds has become an important approach to creating functional bone constructs. Bioreactors are important tools to mitigate mass transfer limitations and to provide controlled physiochemical and biomechanical environments for the 3D bone construct development. Media flow in the bioreactor systems is generally controlled either parallel or transverse with respect to the 3D construct, creating different cellular and biomechanical microenvironments in the 3D constructs. In this study, a custom designed modular perfusion bioreactor system was operated under either the parallel or transverse flow. The influence of the flow patterns on the characteristics of the hMSCs' cellular microenvironment and subsequent construct development was investigated. The parallel flow configuration retained ECM proteins and mitogenic growth factors within the scaffold, effectively preserving hMSC progenicity and proliferation potential (e.g., CFU‐F, proliferation, and OCT‐4), whereas the transverse flow induced hMSC osteogenic differentiation with higher ALP activity and calcium deposition and up‐regulation of osteogenic bone markers (e.g., BMP‐2, ALP, RUNX2, OSX, and OC). These results demonstrate the regulatory role of the macroscopic flow on the cellular microenvironment of the 3D hMSC construct, and suggest configuring media flow as a strategy for directing hMSC fate and 3D bone construct development in the perfusion bioreactor. Biotechnol. Bioeng. 2012;109: 252–261. © 2011 Wiley Periodicals, Inc.
Borderland stories about teaching college in prison
Authors: Spaulding Susanna
Published: September 2011

Part‐time professors often feel marginal to the educational process of their schools, and this outsider status is exacerbated for those who teach college in prison.
Evaluating f‐Element Bonding from Structure and Thermodynamics
Authors: Minasian Stefan G. , Krinsky Jamin L. , Arnold John
Published: September 2011

The practical goal to measure and understand the thermodynamic properties of molecules and materials containing f‐elements is often achieved through indirect methods. Of the characterization tools available to inorganic chemists, few are more powerful than X‐ray crystallography. Yet for lanthanides and actinides, interpretation of a bond length is a challenging undertaking that involves a complex interplay of steric and electronic forces. In this Concept article, we perform an analysis of selected examples in which structural criteria alone have been used to draw qualitative conclusions about chemical bonding. In other instances for which such an analysis is not valid, thermodynamic information is evaluated side by side with structural data to provide reasonable interpretations of a covalent/ionic mode of bonding. A geometric variation larger than 3σ is not necessarily correlated to a change in bonding, nor is an increase in bond energy related to a bond with more covalent character. However, careful consideration of thermodynamic information can lead to reasonable interpretations of electronic structure, and may provide a more reliable benchmark for the theoretical methods which can describe f‐elements.
Palladium Nanoparticles Encapsulated in a Metal–Organic Framework as Efficient Heterogeneous Catalysts for Direct C2 Arylation of Indoles
Authors: Huang Yuanbiao , Lin Zujin , Cao Rong
Published: September 2011

Highly dispersed palladium nanoparticles (Pd NPs) encapsulated in the mesoporous cages of the metal–organic framework (MOF) MIL‐101(Cr) have been prepared by using the wetness impregnation method. The Pd NPs were characterized by powder X‐ray diffraction (PXRD), N2 adsorption, transmission electron microscopy, inductively coupled plasma atomic emission spectroscopy (ICP‐AES), and X‐ray photoelectron spectroscopy (XPS). The particles size ((2.6±0.5) nm) of the obtained Pd NPs was in good agreement with the cage diameters (2.9 and 3.4 nm) of the MOF. The resulting Pd/MIL‐101(Cr) catalyst exhibited extremely high catalytic activities in the direct C2 arylation of substituted indoles by using only 0.1 mol % of the Pd catalyst. Moreover, the catalyst is easily recoverable and can be reused several times without leaching into solution and loss of activity. The combination of the highly dispersible Pd NPs within the accessible mesoporous cages and the favorable adsorption of the aryl halides on MIL‐101 are suspected to be the main reasons for the observed high activities of the Pd/MIL‐101(Cr) catalyst in the direct C2 arylation of indoles.
Self‐Assembly of Short Peptide Amphiphiles: The Cooperative Effect of Hydrophobic Interaction and Hydrogen Bonding
Authors: Han Shuyi , Cao Sasa , Wang Yuming , Wang Jiqian , Xia Daohong , Xu Hai , Zhao Xiubo , Lu Jian R.
Published: September 2011

The interplay between hydrogen bonding, hydrophobic interaction and the molecular geometry of amino acid side‐chains is crucial to the development of nanostructures of short peptide amphiphiles. An important step towards developing their practical use is to understand how different amino acid side‐chains tune hydrophobic interaction and hydrogen bonding and how this process leads to the control of the size and shape of the nanostructures. In this study, we have designed and synthesized three sets of short amphiphilic peptides (I3K, LI2K and L3K; L3K, L4K and L5K; I3K, I4K and I5K) and investigated how I and L affected their self‐assembly in aqueous solution. The results have demonstrated a strong tendency of I groups to promote the growth of β‐sheet hydrogen bonding and the subsequent formation of nanofibrillar shapes. All ImK (m=3–5) peptides assembled into nanofibers with consistent β‐sheet conformation, whereas the nanofiber diameters decreased as m increased due to geometrical constraint in peptide chain packing. In contrast, L groups had a weak tendency to promote β‐sheet structuring and their hydrophobicity became dominant and resulted in globular micelles in L3K assembly. However, increase in the number of hydrophobic sequences to L5K induced β‐sheet conformation due to the cooperative hydrophobic effect and the consequent formation of long nanofibers. The assembly of L4K was, therefore, intermediate between L3K and L5K, similar to the case of LI2K within the set of L3K, LI2K and I3K, with a steady transition from the dominance of hydrophobic interaction to hydrogen bonding. Thus, changes in hydrophobic length and swapping of L and I can alter the size and shape of the self‐assembled nanostructures from these simple peptide amphiphiles.
How the 1D‐NOESY suppresses solvent signal in metabonomics NMR spectroscopy: An examination of the pulse sequence components and evolution
Authors: Mckay Ryan T.
Published: September 2011

Metabonomics has become an increasingly shared pursuit in international research. Presently the two most common techniques are mass spectrometry and nuclear magnetic resonance (NMR) spectrometry either in isolation or in conjunction. The 1D‐1H‐NOESY is the most utilized (Beckonert et al., Nat Protoc 2007;2:2692–2703) NMR pulse sequence for the collection of metabonomics NMR data from biological samples such as blood plasma, serum, urine, cerebrospinal fluid, sputum, or homogenized tissue extracts. While the 1D version of the 2D‐1H,1H‐NOESY pulse sequence has become widely used in metabonomics studies, the understanding of the mechanism of solvent suppression has not kept pace. This article will examine the mechanisms by which the 1D‐NOESY suppresses solvent signals and detail the pulse sequence's components in terms of function, phase cycle, and performance. © 2011 Wiley Periodicals, Inc. Concepts Magn Reson Part A 38: 197–220, 2011.
Expression of ki‐67 as proliferation biomarker in imprint smears of endometrial carcinoma
Authors: Kosmas K. , Stamoulas M. , Marouga A. , Kavantzas N. , Patsouris E. , Athanassiadou P.
Published: September 2011

The aims of this study were to determine the expression of Ki‐67 in type I and type II endometrial adenocarcinomas as well as normal endometrium in imprint smears and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients. During a 29‐month period, 255 patients were evaluated with entometrial imprint cytology. Endometrial samples freshly resected from women who underwent total abdominal hysterectomy were studied. One hundred twenty‐six patients had endometrial carcinoma and 129 cases were diagnosed as normal endometrium. The expression of Ki‐67 was assessed by immunocytochemistry. Positive staining was correlated with increased stage, grade and lymph node metastases. High expression was more frequent in type II than type I endometrial adenocarcinoma and high‐grade endometrial carcinoma had higher proportions of Ki‐67 positive immunostaining compared with low‐grade carcinoma. Proliferative endometrium showed high Ki‐67 expression level, even higher than those of grade 1 and type I. On the other hand, secretory endometrium Ki‐67 positive cells were markedly diminished and even disappeared. Completely negative staining was found to be related to atrophic endometrium. Immunocytochemical findings from Ki‐67 stain, in addition to cytomorphologic features, appeared to be useful for the diagnosis of endometrial carcinoma in endometrial cytology with imprint smears. High Ki‐67 expression correlates with morphologic features of aggressiveness and the expression pattern of Ki‐67 correspond to the expected cyclic/atrophic pattern in normal endometrium. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.
Hepatocellular carcinoma presenting with multiple bone and soft tissue metastases and atypical cytomorphological features—A rare case report
Authors: Rastogi Archana , Bihari Chhagan , Jain Deepak , Gupta Navin Lajpatrai , Sarin Shiv Kumar
Published: September 2011

Hepatocellular carcinoma (HCC) with atypical cytomorphological features and presenting with bone and soft tissue metastasis is very rare. We report a 65‐year‐old male patient of HCC who presented with bone and soft tissue metastases and was clinically and radiologically suspected to have a soft tissue sarcoma. The patient presented with severe cervical pain with palpable masses in right scapular, nape of neck, and occiput area of scalp. Radiologically, these were large, bulky soft tissue masses expansile, destructive, and lytic in nature. Cytomorphologic studies revealed HCC with uncommon features of multinucleated osteoclast‐like giant cell and very prominent intracytoplasmic hyaline bodies (IHBs). Cytology, immunohistochemistry on cell block preparation, rising serum α‐fetoprotein (AFP) levels (1121.93–5000 ng/ml), and PIVKA II levels confirmed the diagnosis. The patient has been on follow‐up on sorafinib for 2 months and is doing well. This case emphasizes the need for systematic approach in cases of HCC with atypical clinical presentation and unusual cytomorphology. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.
Visual experience affects both behavioral and neuronal aspects in the individual life history of the desert ant Cataglyphis fortis
Authors: Stieb Sara Mae , Hellwig Anna , Wehner Rüdiger , Rössler Wolfgang
Published: September 2011

The individual life history of the desert ant Cataglyphis fortis is characterized by a fast transition from interior tasks to mainly visually guided foraging. Previous studies revealed a remarkable structural synaptic plasticity in visual and olfactory input regions within the mushroom bodies of the ants' brain centers involved in learning and memory. Reorganization of synaptic complexes (microglomeruli) was shown to be triggered by sensory exposure rather than an internal program. Using video analyses at the natural nest site and activity recordings after artificial light treatments we investigated whether the ants get exposed to light before onset of foraging and whether this changes the ants' activity levels. We asked whether synaptic reorganization occurs in a similar time window by immunolabeling and quantification of pre‐ and postsynaptic compartments of visual and olfactory microglomeruli after periods of light‐exposure. Ants reverted back to dark nest conditions were used to investigate whether synaptic reorganization is reversible. The behavior analyses revealed that late‐interior ants (diggers) are exposed to light and perform exploration runs up to 2 days before they start foraging. This corresponds well with the result that artificial light treatment over more than 2–3 days significantly increased the ants' locomotor activities. At the neuronal level, visual exposure of more than 1 day was necessary to trigger reorganization of microglomeruli, and light‐induced changes were only partly reversible in the dark. We conclude that visual preexposure is an important and flexible means to prepare the ants' visual pathway for orientation capabilities essential during foraging. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 729–742, 2012
Analysis of Pax7 expressing myogenic cells in zebrafish muscle development, injury, and models of disease
Authors: Seger Claudia , Hargrave Murray , Wang Xingang , Chai Ruth Jinfen , Elworthy Stone , Ingham Philip W.
Published: September 2011

The transcription factor Pax7 is a marker and regulator of muscle progenitors and satellite cells that contribute to the embryonic development and postembryonic growth of skeletal muscle in vertebrates, as well as to its repair and regeneration. Here, we identify Pax7+ve myogenic cells in the zebrafish and characterize their behavior in postembryonic stages. Mononucleate Pax7+ve cells can first be found associated with myofibers at 72 hours post fertilization (hpf). To follow the behavior of muscle progenitor cells in vivo, we generated transgenic lines expressing fluorescent proteins under the control of the pax7a or pax3a promoters. We established an injury model using cardiotoxin injection and monitored cell proliferation and myogenic regulatory factor expression in myogenic precursors cells and muscle fibers after injury using proliferation markers and the transgenic lines. We also analyzed Pax7+ve cells in animals with dystrophic phenotypes and found an increased number compared with wild‐type. Developmental Dynamics 240:2440–2451, 2011. © 2011 Wiley‐Liss, Inc.
Platelet‐activating factor detection, metabolism, and inhibitors in the ethanologenic bacterium Zymomonas mobilis
Authors: Tsoupras Alexandros B. , Demopoulos Constantinos A. , Pappas Katherine M.
Published: September 2011

Platelet‐activating factor (PAF) is a signaling phospholipid with a significant physiological role in multicellular and unicellular organisms, including fermentative organisms such as yeast. Zymomonas mobilis is an ethanologenic α‐proteobacterium currently studied for bioethanol production. In order to examine the presence of PAF and/or PAF inhibitors in Z. mobilis, a new one‐step high performance liquid chromatography (HPLC) separation procedure of total lipids was performed, using a C8 reversed‐phase semi‐preparative column. According to this method and to bioassays based on washed rabbit platelet aggregation, two lipid molecules with PAF‐like activity and same retention times as those of standard PAF were detected; electron‐spray ionization MS and MS/MS analysis revealed that they share similar structure with 16:0 and 18:0 PAF. Furthermore, other lipids extracted from Z. mobilis were found to exhibit a potent anti‐PAF activity. Enzyme activities indicative of key PAF biosynthetic enzymes, such as dithiothreitol‐insensitive cholinephosphotransferase (PAF‐CPT) and lyso‐PAF acetyltransferase were detected in Z. mobilis homogenates. As for PAF degradation, activity similar to that of PAF acetylhydrolase was also discovered. Overall, the presence of PAF, PAF‐specific inhibitors, and enzyme activities relating to PAF metabolism, suggests that PAF may play an intrinsic role in this biotechnological organism.

Practical applications: Z. mobilis is a platform microorganism for bioethanol production and a potential source of high‐value chemicals of interest to the food and healthcare industries. Further investigation of PAF's role is bound to affect applications involving this and other biotechnological organisms. The finding that Z. mobilis lipids exhibit potent anti‐PAF activity opens up prospects for their identification, overproduction and pharmaceutical use. The presented HPLC method for lipid fractionation accomplishes a one‐step separation of lipids from dense samples, which may be successfully employed to other lipid‐rich sources such as blood.
Changes in fatty acids and volatile components in mackerel by broiling
Authors: Chung Hyun , Choi Arum , Cho In Hee , Kim Young‐Suk
Published: September 2011

Mackerel is known to be a rich source of omega‐3 family PUFAs. The acid value and conjugated dienoic acid value of mackerel, known as indices of oxidation, were determined. Fatty acids in both raw and broiled mackerels were analyzed by GC. PUFAs and saturated fatty acids were observed at a low level in broiled mackerel, possibly as a result of thermal degradation of the lipids. In addition, volatile components in mackerel extracted by solvent‐assisted flavor evaporation were analyzed by GC‐MS. In total, 38 volatile components were detected in raw mackerel, whereas 53 volatiles were found in broiled mackerel. Hydrocarbons and methyl‐ and/or ethyl‐substituted benzenes were quantitatively dominant. Levels of aldehydes and alcohols were significantly enhanced in broiled mackerel, as was the level of benzothiazole, which possibly forms as a result of the condensation of thermal degradation products from amino acids and/or proteins, and lipids.