bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemerin Contributes to Inflammation by Promoting Macrophage Adhesion to VCAM-1 and Fibronectin through Clustering of VLA-4 and VLA-5
Authors: Hart Rosie , Greaves David R.
Published: August 2010

Chemerin is a potent macrophage chemoattractant protein. We used murine peritoneal exudate cells (PECs) in adhesion, flow cytometry, and confocal microscopy assays to test the hypothesis that chemerin can also contribute to inflammation by promoting macrophage adhesion. Chemerin stimulated the adhesion of PECs to the extracellular matrix protein fibronectin and to the adhesion molecule VCAM-1 within a minute, with an EC50 of 322 and 196 pM, respectively. Experiments using pertussis toxin and PECs from ChemR23−/− mice demonstrated that chemerin stimulated the adhesion of macrophages via the Gi protein-coupled receptor ChemR23. Blocking Abs against integrin subunits revealed that 89% of chemerin-stimulated adhesion to fibronectin was dependent on increased avidity of the integrin VLA-5 (α5β1) and that 88% of adhesion to VCAM-1 was dependent on increased avidity of VLA-4 (α4β1). Although chemerin was unable to induce an increase in integrin affinity as judged by the binding of soluble ligand, experiments using confocal microscopy revealed an increase in valency resulting from integrin clustering as the mechanism responsible for chemerin-stimulated macrophage adhesion. PI3K, Akt, and p38 were identified as key signaling mediators in chemerin-stimulated adhesion. The finding that chemerin can rapidly stimulate macrophage adhesion to extracellular matrix proteins and adhesion molecules, taken together with its ability to promote chemotaxis, suggests a novel role for chemerin in the recruitment and retention of macrophages at sites of inflammation.
MEKK3 Overexpression Contributes to the Hyperresponsiveness of IL-12–Overproducing Cells and CD4+ T Conventional Cells in Nonobese Diabetic Mice
Authors: Zhang Jiyan , Zhu Ning , Wang Qingyang , Wang Jing , Ma Yuanfang , Qiao Chunxia , Li Yan , Li Xinying , Su Bing , Shen Beifen
Published: August 2010

Elevated IL-12 production and higher rate of CD4+ T conventional (Tconv) cell proliferation in NOD mice have been implicated in the progression of type 1 diabetes. However, the underlying mechanisms remain largely unknown, even though enhanced activation of the IκB kinase (IKK)/NF-κB pathway has been revealed to mediate IL-12 overproduction. In this study, we report that deviated p38 MAPK activation also contributes to elevated IL-12 production with a mechanism involving MAPK-activated protein kinase-2–mediated stabilization of IL-12p40 mRNA. Aberrant p38 activation induced by various inflammatory stimuli in IL-12–overproducing cells is not due to defective MAPK phosphatase-1 induction in NOD mice. Deviated IKK and MAPKs activation also occurs in NOD CD4+ Tconv cells, which is associated with higher rates of proliferation. All of the above evidence suggests that the signaling defects occur at the level of MAPK kinase kinase (MAK3K or MEKK). Further exploration shows that MEKK3, but not other MAP3Ks, is overexpressed in NOD IL-12–overproducing cells and CD4+ Tconv cells independent of autoimmune inflammation. MEKK3 knockdown leads to reversal of the deviated IKK and MAPKs activation, resulting in reduced IL-12 production and decreased CD4+ Tconv cell proliferation. Thus, this study provides a molecular mechanism of the hyperresponsiveness of IL-12–overproducing cells and CD4+ Tconv cells in NOD mice.
Cutting Edge: Proteolytic Inactivation of Poly(ADP-Ribose) Polymerase 1 by the Nlrp3 and Nlrc4 Inflammasomes
Authors: Malireddi R. K. Subbarao , Ippagunta Sirish , Lamkanfi Mohamed , Kanneganti Thirumala-Devi
Published: August 2010

Caspase-mediated cleavage of the DNA damage sensor poly(ADP-ribose) polymerase 1 (PARP1) is a hallmark of apoptosis. However, it remains unclear whether PARP1 is processed during pyroptosis, a specialized cell-death program that occurs upon activation of caspase-1 in inflammasome complexes. In this article, we show that activation of the Nlrp3 and Nlrc4 inflammasomes induces processing of full-length PARP1 into a fragment of 89 kDa in a stimulus-dependent manner. Macrophages deficient for caspase-1 and those lacking the inflammasome adaptors Nlrp3, Nlrc4, and ASC were highly resistant to cleavage, whereas macrophages lacking the downstream inflammasome effector caspase-7 were partially protected. A modest, but statistically significant, reduction in Nlrp3 inflammasome-induced pyroptosis was observed in PARP1 knockout macrophages. Thus, protease-mediated inactivation of PARP1 is a shared feature of apoptotic, necrotic, and pyroptotic cells.
Evolution of Ectopic Lymphoid Neogenesis and In Situ Autoantibody Production in Autoimmune Nonobese Diabetic Mice: Cellular and Molecular Characterization of Tertiary Lymphoid Structures in Pancreatic Islets
Authors: Astorri Elisa , Bombardieri Michele , Gabba Silvia , Peakman Mark , Pozzilli Paolo , Pitzalis Costantino
Published: August 2010

A pivotal role for tertiary lymphoid structures (TLSs) in promoting Ag-specific humoral responses during chronic inflammation is emerging in several autoimmune conditions, including rheumatoid arthritis, Sjogren’s syndrome, and autoimmune thyroiditis. However, there is limited evidence on the cellular and molecular mechanisms underlying TLS formation and their contribution to autoimmunity in the pancreas during autoimmune insulitis. In this study, we performed a detailed and comprehensive assessment of the evolution of TLSs during autoimmune insulitis in 126 female NOD mice from 4 to 38 wk of age. We demonstrated that during progression from peri- to intrainsulitis in early diabetic mice, T and B cell infiltration follows a highly regulated process with the formation of lymphoid aggregates characterized by T/B cell segregation, follicular dendritic cell networks, and differentiation of germinal center B cells. This process is preceded by local upregulation of lymphotoxins α/β and lymphoid chemokines CXCL13 and CCL19, and is associated with infiltration of B220+/IgD+/CD23+/CD21− follicular B cells expressing CXCR5. Despite a similar incidence of insulitis, late diabetic mice displayed a significantly reduced incidence of fully organized TLSs and reduced levels of lymphotoxins/lymphoid chemokines. Upon development, TLSs were fully functional in supporting in situ autoreactive B cell differentiation, as demonstrated by the expression of activation-induced cytidine deaminase, the enzyme required for Ig affinity maturation and class switching, and the presence of CD138+ plasma cells displaying anti-insulin reactivity. Overall, our work provides direct evidence that TLSs are of critical relevance in promoting autoimmunity and chronic inflammation during autoimmune insulitis and diabetes in NOD mice.
Role of Topoisomerase IIβ in DNA Damage Response following IR and Etoposide
Authors: Sunter Nicola J. , Cowell Ian G. , Willmore Elaine , Watters Gary P. , Austin Caroline A.
Published: August 2010

The role of topoisomerase IIβ was investigated in cell lines exposed to two DNA damaging agents, ionising radiation (IR) or etoposide, a drug which acts on topoisomerase II. The appearance and resolution of γH2AX foci in murine embryonic fibroblast cell lines, wild type and null for DNA topoisomerase IIβ, was measured after exposure to ionising radiation (IR) or etoposide. Topoisomerase II‐DNA adduct levels were also measured. IR rapidly triggered phosphorylation of histone H2AX, less phosphorylation was seen in TOP2β−/− cells, but the difference was not statistically significant. IR did not produce topoisomerase II‐DNA adducts above control levels. Etoposide triggered the formation of topoisomerase II‐DNA adducts and the phosphorylation of histone H2AX,
the γH2AX foci appeared more slowly with etoposide than with IR. Topoisomerase II‐DNA complexes in WT cells but not TOP2β−/− cells increased significantly at 24 hours with the proteasome inhibitor MG132, suggesting topoisomerase IIβ adducts are removed by the proteasome.
The Survival Strategies of Malaria Parasite in the Red Blood Cell and Host Cell Polymorphisms
Authors: Dhangadamajhi Gunanidhi , Kar Shantanu Kumar , Ranjit Manoranjan
Published: August 2010

Parasite growth within the erythrocyte causes dramatic alterations of host cell which on one hand facilitates nutrients acquisition from extracellular environment and on other hand contributes to the symptoms of severe malaria. The current paper focuses on interactions between thePlasmodiumparasite and its metabolically highly reduced host cell, the natural selection of numerous polymorphisms in the genes encoding hemoglobin and other erythrocyte proteins.
Fusion categories and homotopy theory
Authors: Etingof Pavel , Nikshych Dmitri , Ostrik Victor
Published: August 2010

We apply the yoga of classical homotopy theory to classification problems of

G

-extensions of fusion and braided fusion categories, where G is a finite group. Namely, we reduce such problems to classification (up to homotopy) of maps from

BG

to classifying spaces of certain higher groupoids. In particular, to every fusion category

\mathcal C

we attach the 3-groupoid

\underline{\underline{\mathrm{BrPic}}}(\mathcal C)

of invertible

\mathcal C

-bimodule categories, called the Brauer–Picard groupoid of

\mathcal C

, such that equivalence classes of

G

-extensions of

\mathcal C

are in bijection with homotopy classes of maps from

BG

to the classifying space of

\underline{\underline{\mathrm{BrPic}}}(\mathcal C)

. This gives rise to an explicit description of both the obstructions to existence of extensions and the data parametrizing them; we work these out both topologically and algebraically.

One of the central results of the article is that the 2-truncation of

\underline{\underline{\mathrm{BrPic}}}(\mathcal C)

is canonically equivalent to the 2-groupoid of braided auto-equivalences of the Drinfeld center

\mathcal Z(\mathcal C)

of

\mathcal C

. In particular, this implies that the Brauer–Picard group

\mathrm{BrPic}(\mathcal C)

(i.e., the group of equivalence classes of invertible

\mathcal C

-bimodule categories) is naturally isomorphic to the group of braided auto-equivalences of

\mathcal Z(\mathcal C)

. Thus, if

\mathcal C = \mathrm{Vec}_A

, where

A

is a finite abelian group, then

\mathrm{BrPic}(\mathcal C)

is the orthogonal group

\mathrm{O}(A \oplus  A^*)

. This allows one to obtain a rather explicit classification of extensions in this case; in particular, in the case

G = \mathbb Z_2

, we re-derive (without computations) the classical result of Tambara and Yamagami. Moreover, we explicitly describe the category of all

(\mathrm{Vec}_{A_1},\mathrm{Vec}_{A_2})

-bimodule categories (not necessarily invertible ones) by showing that it is equivalent to the hyperbolic part of the category of Lagrangian correspondences.
Evaluation of simulated aerosol properties with the aerosol-climate model ECHAM5-HAM using observations from the IMPACT field campaign
Authors: Roelofs G.-J. , ten Brink H. , Kiendler-Scharr A. , de Leeuw G. , Mensah A. , Minikin A. , Otjes R.
Published: August 2010

Abstract. In May 2008, the measurement campaign IMPACT for observation of atmospheric aerosol and cloud properties was conducted in Cabauw, The Netherlands. With a nudged version of the coupled aerosol-climate model ECHAM5-HAM we simulate the size distribution and chemical composition of the aerosol and the associated aerosol optical thickness (AOT) for the campaign period. Synoptic scale meteorology is represented realistically through nudging of the vorticity, the divergence, the temperature and the surface pressure. Simulated concentrations of aerosol sulfate and organics at the surface are generally within a factor of two from observed values. The monthly averaged AOT from the model is 0.33, about 20% larger than observed. For selected periods of the month with relatively dry and moist conditions discrepancies are approximately −30% and +15%, respectively. Discrepancies during the dry period are partly caused by inaccurate representation of boundary layer (BL) dynamics by the model affecting the simulated AOT. The model simulates too strong exchange between the BL and the free troposphere, resulting in weaker concentration gradients at the BL top than observed for aerosol and humidity, while upward mixing from the surface layers into the BL appears to be underestimated. The results indicate that beside aerosol sulfate and organics also aerosol ammonium and nitrate significantly contribute to aerosol water uptake. The simulated day-to-day variability of AOT follows synoptic scale advection of humidity rather than particle concentration. Even for relatively dry conditions AOT appears to be strongly influenced by the diurnal cycle of RH in the lower boundary layer, further enhanced by uptake and release of nitric acid and ammonia by aerosol water.
Anthropogenic influence on biogenic secondary organic aerosol
Authors: Hoyle C. R. , Boy M. , Donahue N. M. , Fry J. L. , Glasius M. , Guenther A. , Hallar A. G. , Huff Hartz K. , Petters M. D. , Petäjä T. , Rosenoern T. , Sullivan A. P.
Published: August 2010

Abstract. Because of the climate and air quality effects of organic aerosol, it is important to quantify the influence of anthropogenic emissions on the aerosol burden, both globally and regionally, and both in terms of mass and number. Methods exist with which the fractions of organic aerosol resulting directly from anthropogenic and biogenic processes can be estimated. However, until now, the possible anthropogenic enhancement of secondary organic aerosol formation from naturally emitted precursors has not been explicitly accounted for. Here, we describe the mechanisms through which such an effect may occur and suggest methods suitable to detect it in measurements. An examination of published data reveals qualitative support for the existence of the enhancement effect.
A Chemical Ionization Mass Spectrometer for ambient measurements of Ammonia
Authors: Benson D. R. , Markovich A. , Al-Refai M. , Lee S.-H.
Published: August 2010

Abstract. This study presents a chemical ionization mass spectrometer (CIMS) for fast response, in-situ measurements of gas phase ammonia (NH3). The NH3 background level detected with the CIMS ranged between 0.3–1 ppbv, with an uncertainty of 30 pptv under optimized conditions. The instrument sensitivity varied from 4–25 Hz/pptv for >1 MHz of reagent ion signals (protonated ethanol ions), with a 30% uncertainty estimated based on variability in calibration signals. The CIMS detection limit for NH3 was ~60 pptv at a 1 min integration time (3 sigma). The CIMS time response was <30 s. This new NH3-CIMS has been used for ambient measurements in Kent, Ohio, for several weeks throughout three seasons. The measured NH3 mixing ratios were usually at the sub-ppbv level and higher in spring (200 ± 120 pptv) than in winter (60 ± 75 pptv) and fall (150 ± 80 pptv). High emissions of SO2 from power plants in this region, and thus possible high acidity of aerosol particles, may explain these low NH3 mixing ratios in general.
Estimating the effect of gang membership on nonviolent and violent delinquency: a counterfactual analysis
Authors: Barnes J.C. , Beaver Kevin M. , Miller J. Mitchell
Published: August 2010

This study reconsiders the well‐known link between gang membership and criminal involvement. Recently developed analytical techniques enabled the approximation of an experimental design to determine whether gang members, after being matched with similarly situated nongang members, exhibited greater involvement in nonviolent and violent delinquency. Findings indicated that while gang membership is a function of self‐selection, selection effects alone do not account for the greater involvement in delinquency exhibited by gang members. After propensity score matching was employed, gang members maintained a greater involvement in both nonviolent and violent delinquency when measured cross‐sectionally, but only violent delinquency when measured longitudinally. Additional analyses using inverse probability of treatment weights reaffirmed these conclusions. Aggr. Behav. 36:437–451, 2010. © 2010 Wiley‐Liss, Inc.
Association of spontaneous abortion and other reproductive effects with work in the semiconductor industry
Authors: Schenker Marc B. , Gold Ellen B. , Beaumont James J. , Eskenazi Brenda , Katharine S. Hammond , Lasley Bill L. , McCurdy Stephen A. , Samuels Steven J. , Saiki Cathy L. , Swan Shanna H.
Published: August 2010

This study tested the hypothesis that fabrication room (fab) work in the silicon‐based semiconductor industry is associated with an increased risk of spontaneous abortion (SAB). The study was conducted nationwide at 14 companies representing a spectrum of large to small manufacturers. A small increase in risk of SAB was observed among fab workers compared with nonfabrication room (nonfab) workers in two cohorts, historical (adjusted RR = 1.43, 95% confidence interval [CI] 0.95–2.09) and prospective (adjusted RR = 1.25, 95% CI = 0.63–1.76). Analysis of specific fab exposures in the historical cohort showed a consistent, dose‐response association of SAB with photoresist and developer solvents, whose major component was ethylene‐based glycol ethers. The consistency of our findings and the toxicological data for these agents suggest that this is a causal association. Independent associations of SAB with self‐reported stress and with etching fluorides were observed and require further research. No significant decrease in fertility was observed among men or women working in fabs, but reduced fecundability was suggested for some women fab workers.
Patterns of chemical use and exposure control in the semiconductor health study
Authors: Hallock Marilyn F. , Hammond S. Katharine , Hines Cynthia J. , Woskie Susan R. , Schenker Marc B.
Published: August 2010

Information on chemical use and exposure control between 1986 and 1990 was collected from 14 companies participating in the Semiconductor Health Study. Questionnaires and site visits provided data used to develop exposure categories for three epidemiological studies: prospective, historical, and cross‐sectional. Patterns of use of target chemicals were compiled for 82 silicon‐wafer fabrication rooms (fabs), including 47 from which subjects were selected for study. Chemical use was examined by operation, year, and epidemiological component. Target agents for epidemiological analyses were present in more than 50% of fabs. Use of these agents was fairly constant from 1986 to 1990, except for a moderate increase in use of propylene glycol monomethyl ether acetate, a solvent being substituted for ethylene‐based glycol ethers (EGE) in photoresists. The distribution of personal protective equipment, engineering controls, and other factors potentially affecting employee exposure was also examined. Controls designed to MAnage processes or high acute toxicity were present in most fabs; their prevalence remained unchanged from 1986 through 1990. Controls designed to reduce exposures to chemicals with low acute toxicity were less widely distributed; their prevalence increased moderately from 1986 to 1990.
Laboratory methods for evaluating early pregnancy loss in an industry‐based population
Authors: Lasley Bill L. , Lohstroh Peter , Kuo Andrew , Gold Ellen B. , Eskenazi Brenda , Samuels Steven J. , Stewart Dennis R. , Overstreet James W.
Published: August 2010

Laboratory methods were adapted or developed to analyze approximately 70,000 daily urine samples collected during more than 2,500 menstrual cycles from 448 women working in the semiconductor industry. An immunoenzymometric assay (IEMA) for Human chorionic gonadotropin (hCG) was employed for screening cycles in order to optimize laboratory resources and to reduce the number of samples requiring analysis by less efficient methods. The presence of hCG in urine was confirmed by the definitive immunoradiometric assay (IRMA). The screening assay eliminated 78% of cycles from further analysis because there was no evidence of conception. Thirty‐eight of 448 cycles identified as having significant levels of hCG with the IEMA were confirmed as hCG positive with the IRMA. HCG‐positive cycles were further evaluated by examination of daily diary data and by laboratory assays for ovarian and pituitary hormones. As a result of these evaluations, 17 of the 38 cycles identified by the IRMA as positive for hCG were found to be nonconceptive cycles. These results demonstrate the effectiveness of screening assays for hCG, as well as the importance of using multiple urinary biomarkers for the detection of early fetal loss with daily urine samples.
Prospectively assessed menstrual cycle characteristics in female wafer‐fabrication and nonfabrication semiconductor employees
Authors: Gold Ellen B. , Eskenazi Brenda , Hammond S. Katharine , Lasley Bill L. , Samuels Steven J. , O'Neill Rasor Marianne , Hines Cynthia J. , Overstreet James W. , Schenker Marc B.
Published: August 2010

Women aged 18–44 years in silicon‐wafer fabrication‐room (fab) jobs and frequency‐MAtched women in nonfab jobs were screened for a prospective study of reproductive health (n = 2,639). Among the 739 (28%) eligible women, 481 (65%) completed a baseline interview; 402 completed at least one menstrual cycle of follow‐up with daily diaries and urinary assays to exclude conceptive cycles. Adjusted mean cycle lengths (MCL) did not differ between fab and nonfab women (p = 0.97). Women working in thin film and ion implantation (TFII) had the highest adjusted MCL (34.8 ± 1.7 days) compared with nonfab workers (32.5 ± 1.4 days, p = 0.07). Among women working exclusively in one group, TFII women had significantly higher MCL (36.1 ± 2.04 days) than nonfab women (32.0 ± 1.38 days, p = 0.017). TFII women were also more likely to have all cycles >35 days (adjusted relative risk [RR] = 2.45; 95% CI = 0.85‐6.06). Variability was assessed by logarithmic transformation of the mean standard deviation (MLSD) in cycle length per woman and adjusted for age and ethnicity (4.5 days for fab vs. 4.0 days for nonfab, p = 0.16). Women working exclusively in TFII or photolithography (PHOTO) had significantly higher adjusted MLSD in cycle length (6.68 ± 1.28 and 5.72 ± 1.24 days, respectively) than women in nonfab (4.1 ± 1.16 days, p = 0.013 and 0.019, respectively). Fab and nonfab women did not differ significantly in mean days of bleeding or risk of having cycles >35 or <24 days. However, elevated risks of having cycles <24 days were seen in supervisor engineers (adjusted RR = 2.46, 95% CI = 1.19‐3.63) and PHOTO women (adjusted RR = 1.83, 95% CI = 0.94‐2.88).
Prospective monitoring of early fetal loss and clinical spontaneous abortion among female semiconductor workers
Authors: Eskenazi Brenda , Gold Ellen B. , Lasley Bill L. , Samuels Steven J. , Hammond S. Katharine , Wight Suzanne , O'Neill Rasor Marianne , Hines Cynthia J. , Schenker Marc B.
Published: August 2010

Women who work in silicon wafer fabrication rooms (fabs) have been reported to have an increased risk of spontaneous abortion (SAB). Although previous studies have included only clinically recognized SABs, more than two‐thirds of SABs MAy be clinically unrecognized. To determine whether fab work is associated with SAB, we recruited 152 fab and 251 nonfab workers, who collected urine samples for a 6‐month period. Samples were analyzed by immunoradiometric assay for the presence of human chorionic gonadotropin to detect early fetal losses. Approximately 63% of fab and 46% of nonfab pregnancies ended in SAB [adjusted relative risk (RR) = 1.25; 95% confidence interval (CI) = 0.63‐1.76]. Similar RR were seen for women who worked in dopant and thin‐film processes (adjusted RR = 1.30; 95% CI = 0.51‐1.96) or in MAsking (adjusted RR = 1.30; 95% CI = 0.59‐1.84). The four pregnancies among women who worked with ethylene‐based glycol ethers ended in SAB.
A cross‐sectional survey of respiratory and general health outcomes among semiconductor industry workers
Authors: McCurdy Stephen A. , Pocekay Dennis , Hammond S. Katharine , Woskie Susan R. , Samuels Steven J. , Schenker Marc B.
Published: August 2010

As part of the Semiconductor Health Study, we performed a cross‐sectional survey to assess prevalence of specific nonreproductive health outcomes and their association with occupational exposures. A total of 3,175 persons from eight manufacturing sites across the U.S. completed a health and work questionnaire (78% participation rate). After adjusting for confounders, responses from fabrication room (fab) workers indicated a greater risk than those of nonfab workers for upper respiratory symptoms (relative risk [RR] = 1.08; 95% confidence interval [CI] = 1.03‐1.13); a dose‐response effect with hours per day spent in fabs was observed. Fab workers also had greater prevalence for persistent wheezing (RR = 1.82; 95% CI = 1.15‐2.87), Dermatitis within the past year (RR = 1.19; 95% CI = 1.04‐1.35), and alopecia (RR = 1.73; 95% CI = 1.16‐2.54). Female sex, a somatization index score, and smoking were important nonoccupational covariates. Increased respiratory symptoms MAy result from occupational exposures in fabs; further research is needed to identify causal agents and develop prevention strategies.
Fertility history of currently employed male semiconductor workers
Authors: Samuels Steven J. , McCurdy Stephen A. , Pocekay Dennis , Katharine S. Hammond , Missell Lavon , Schenker Marc B.
Published: August 2010

Fertility among men working in semiconductor manufacturing during 1984‐89 was assessed in a 1990‐91 cross‐sectional study of eight companies. Men working in wafer fabrication rooms (fabs) (n = 241, 165 births) were compared to men in nonfabrication (nonfab) jobs (n = 447, 300 births). Results showed that 17% of fab men and 14% of nonfab men reported ever trying for 1 year to conceive [relative risk (RR) = 1.21, 95% confidence interval (CI) = 0.83‐1.74]. Crude birth rates (births/1,000 person months) were similar [15 fab, 17 nonfab; crude fertility ratio (FR) = 1.09, 95% CI = 0.86‐1.36], as were birth rates adjusted by Cox models for confounders (adjusted FR = 0.98, 95% CI = 0.80‐1.19, p = 0.79). Fab men who worked in furnace, thin‐film, or ion implantation areas were more likely than nonfab men to report previous difficulty conceiving (25%, RR = 1.79,95% CI = 1.09‐2.94), and their past fertility was lower (nine births/1,000 person months; crude FR = 0.66,95% CI = 0.40‐1.02; adjusted FR = 0.73, 95% CI = 0.50‐1.09, p = 0.12). Problems included lack of contraception data and misclassification of fab subgroups.
News from the west: Ancient DNA from a French megalithic burial chamber
Authors: Deguilloux Marie‐France , Soler Ludovic , Pemonge Marie‐Hélène , Scarre Chris , Joussaume Roger , Laporte Luc
Published: August 2010

Recent paleogenetic studies have confirmed that the spread of the Neolithic across Europe was neither genetically nor geographically uniform. To extend existing knowledge of the mitochondrial European Neolithic gene pool, we examined six samples of human skeletal material from a French megalithic long mound (c.4200 cal BC). We retrieved HVR‐I sequences from three individuals and demonstrated that in the Neolithic period the mtDNA haplogroup N1a, previously only known in central Europe, was as widely distributed as western France. Alternative scenarios are discussed in seeking to explain this result, including Mesolithic ancestry, Neolithic demic diffusion, and long‐distance matrimonial exchanges. In light of the limited Neolithic ancient DNA (aDNA) data currently available, we observe that all three scenarios appear equally consistent with paleogenetic and archaeological data. In consequence, we advocate caution in interpreting aDNA in the context of the Neolithic transition in Europe. Nevertheless, our results strengthen conclusions demonstrating genetic discontinuity between modern and ancient Europeans whether through migration, demographic or selection processes, or social practices. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.
Brief communication: Population data support the adaptive nature of HACNS1 sapiens/neandertal‐chimpanzee differences in a limb expression domain
Authors: Hünemeier Tábita , Ruiz‐Linares Andres , Silveira Álvaro , Paixão‐Côrtes Vanessa Rodrigues , Salzano Francisco M. , Bortolini Maria Cátira
Published: August 2010

The 546‐base pair enhancer of limb expression HACNS1, which is highly constrained in all terrestrial vertebrates, has accumulated 16 human‐specific changes after the human‐chimpanzee split. There has been discussion whether this process was driven by positive selection or biased gene conversion, without considering population data. We studied 83 South Amerindian, 11 Eskimo, 35 Europeans, 37 Bantu, and non‐Bantu Sub‐Saharan speakers, and 28 Brazilian mestizo samples and found no variation in this DNA region. Similar lack of variability in this region was found in four Africans, five Europeans or Euro‐derived, two Asians, one Paleo‐Eskimo, and one Neandertal sequence, whose whole genomes are publicly available. No difference was found. This result favors the interpretation of past positive and present conservative selection, as would expected in a region which influences Homo‐specific traits as important as opposable thumbs, manual dexterity, and bipedal walking. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.
Labor force participation among persons with musculoskeletal conditions, 1970‐1987: National estimates derived from a series of cross‐sections
Authors: Yelin Edward H. , Katz Patricia P.
Published: August 2010

In the present study, we estimated the labor force participation rate among persons with musculoskeletal conditions in 1987, compared this rate with that experienced by persons with other chronic conditions or with none, and estimated the change in labor force participation rates among persons with musculoskeletal conditions for the period 1970‐1987. Rates were estimated from 18 years of National Health Interview Survey data, and the sampling weights from this survey were used to obtain population estimates. To ensure statistically stable estimates, we averaged the rates over 6 years of data. In 1987, 42.9% of all working‐age persons with musculoskeletal conditions were out of the labor force, this study's definition of work disability. Overall labor force participation rates among persons with musculoskeletal conditions declined from 71% to 56% between 1976‐1981 and 1982‐1987, 22% in relative terms. Much of this decline was concentrated among men, especially men 55‐64 years of age. However, women 55‐64 years of age with musculoskeletal conditions also experienced declining labor force participation rates. Labor force participation patterns among persons with musculoskeletal conditions fit more general labor market trends, with gains among younger women more than offset by declines among older men and women. However, these trends appear to be more accentuated among persons with musculoskeletal conditions, suggesting that enforcement of the employment provisions of the Americans with Disabilities Act of 1990 place special emphasis on labor force participation among such persons.
A Semiquantitative measure of cardiac involvement that improves prediction of prognosis in systemic sclerosis
Authors: Clements Philip J. , Lachenbruch Peter A. , Furst Daniel E. , Paulus Harold E. , Sterz Mildred G.
Published: August 2010

Cardiac involvement, assessed yearly by a semiquantitative cardiac scoring technique (the sum of 2 variables, scored 0 or 1 for left axis deviation, and 0 or 2 for moderate‐large pericardial effusion) and outcome at 10 years were evaluated in 90 systemic sclerosis (SSc) patients enrolled in a 3‐year prospective drug trial. Higher cardiac scores were associated with decreased survival. The inverse relationship of survival with cardiac score was more significant than the relationship between survival and any of the cardiopulmonary variables individually (P < 0.0000003). Predicted 6‐year survival was 79% in patients with a cardiac score of 0, 51% in those with a score of 1, 15% in those with a score of 2, and 0% in those with a score of 3. We conclude that a simple 2‐variable weighted cardiac score, derived from routine electrocardiography and echocardiography, is a useful predictor of survival in patients with SSc, and we propose that the application of this cardiac score be tested in other populations of SSc patients.
Radiographic grading of the severity of knee osteoarthritis: Relation of the kellgren and lawrence grade to a grade based on joint space narrowing, and correlation with arthroscopic evidence of articular cartilage degeneration
Authors: Brandt Kenneth D. , Fife Rose S. , Braunstein Ethan M. , Katz Barry
Published: August 2010

We examined standing knee radiographs of 92 patients who had chronic knee pain and radiographic evidence of mild or moderate osteoarthritis (OA) according to the Kellgren and Lawrence (K/L) criteria. Because the K/L criteria overemphasize osteophytosis relative to joint space narrowing (JSN), we graded OA severity also with a scoring system that placed greater emphasis on JSN than on osteophytes. In each case, the articular cartilage was visualized directly at arthroscopy. Of 17 patients whose radiographic findings were normal by both the K/L criteria and our JSN‐weighted criteria, 7 had advanced tibiofemoral and/or patellofemoral compartment changes of OA seen at arthroscopy, emphasizing the insensitivity of the radiograph for detecting early articular cartilage loss. In addition, tibiofemoral JSN was common in the presence of normal articular cartilage. The JSN‐weighted scale provided no advantage over the K/L criteria for assessing the severity of articular cartilage changes of OA.
Cathepsin B in synovial cells at the site of joint destruction in rheumatoid arthritis
Authors: Trabandt Andreas , Gay Renate E. , Fassbender Hans‐Georg , Gay Steffen
Published: August 2010

Based on the concept that proteolytic enzymes, like cathepsins, are associated with tissue destruction, we investigated the expression of the matrix‐degrading cysteine proteinase cathepsin B in synovial tissues from the joints of patients with rheumatoid arthritis. The data indicate an enhanced transcription of cathepsin B in synovial cells when compared with normal fibroblasts, cathepsin B‐producing epithelial tumor cells (SW1116), or fibroblasts derived from inflamed tonsils. Immunolocalization of cathepsin B appeared to be restricted mainly to the synovial cells attached to cartilage and bone at sites of rheumatoid joint erosion.
Granulocyte–macrophage colony‐stimulating factor augments neutrophil‐mediated cartilage degradation and neutrophil adherence
Authors: Kowanko Ingeborg C. , Ferrante Antonio
Published: August 2010

Granulocyte–macrophage colony‐stimulating factor (GM‐CSF) is produced in large quantities by synoviocytes in the inflamed arthritic joint and is known to be a neutrophil activator. Neutrophils predominate during acute flares of arthritis and are important mediators of cartilage destruction. In this investigation, we show that treatment of neutrophils with 10–1,000 units/ml of GM‐CSF augments their ability to degrade cartilage proteoglycan in vitro. This was associated with increased neutrophil adherence to cartilage and increased release of oxygen‐derived reactive species and granule enzymes in response to cartilage. Coating the cartilage with heat‐aggregated human immunoglobulin G (AHG) enhanced both neutrophil adherence to the tissue and tissue degradation. GM‐CSF, however, augmented these neutrophil effects independently of the presence of AHG. In contrast, neutrophil‐mediated inhibition of proteoglycan synthesis was unaffected by GM‐CSF.
Selecting negative examples for hierarchical text classification: An experimental comparison
Authors: Fagni Tiziano , Sebastiani Fabrizio
Published: August 2010

Hierarchical text classification (HTC) approaches have recently attracted a lot of interest on the part of researchers in human language technology and machine learning, since they have been shown to bring about equal, if not better, classification accuracy with respect to their “flat” counterparts while allowing exponential time savings at both learning and classification time. A typical component of HTC methods is a “local” policy for selecting negative examples: Given a category c, its negative training examples are by default identified with the training examples that are negative for c and positive for the categories which are siblings of c in the hierarchy. However, this policy has always been taken for granted and never been subjected to careful scrutiny since first proposed 15 years ago. This article proposes a thorough experimental comparison between this policy and three other policies for the selection of negative examples in HTC contexts, one of which (BEST LOCAL (k)) is being proposed for the first time in this article. We compare these policies on the hierarchical versions of three supervised learning algorithms (boosting, support vector machines, and naïve Bayes) by performing experiments on two standard TC datasets, REUTERS‐21578 and RCV1‐V2.
The odontode explosion: The origin of tooth‐like structures in vertebrates
Authors: Fraser Gareth J. , Cerny Robert , Soukup Vladimir , Bronner‐Fraser Marianne , Streelman J. Todd
Published: August 2010

Essentially we show recent data to shed new light on the thorny controversy of how teeth arose in evolution. Essentially we show (a) how teeth can form equally from any epithelium, be it endoderm, ectoderm or a combination of the two and (b) that the gene expression programs of oral versus pharyngeal teeth are remarkably similar. Classic theories suggest that (i) skin denticles evolved first and odontode‐inductive surface ectoderm merged inside the oral cavity to form teeth (the ‘outside‐in’ hypothesis) or that (ii) patterned odontodes evolved first from endoderm deep inside the pharyngeal cavity (the ‘inside‐out’ hypothesis). We propose a new perspective that views odontodes as structures sharing a deep molecular homology, united by sets of co‐expressed genes defining a competent thickened epithelium and a collaborative neural crest‐derived ectomesenchyme. Simply put, odontodes develop ‘inside and out’, wherever and whenever these co‐expressed gene sets signal to one another. Our perspective complements the classic theories and highlights an agenda for specific experimental manipulations in model and non‐model organisms.
Control of DNA replication: A new facet of Hox proteins?
Authors: Miotto Benoit , Graba Yacine
Published: August 2010

Hox proteins are well‐known as developmental transcription factors controlling cell and tissue identity, but recent findings suggest that they are also part of the cell replication machinery. Hox‐mediated control of transcription and replication may ensure coordinated control of cell growth and differentiation, two processes that need to be tightly and precisely coordinated to allow proper organ formation and patterning. In this review we summarize the available data linking Hox proteins to the replication machinery and discuss the developmental and pathological implications of this new facet of Hox protein function.
Investigation of the mesoscale structure and volumetric features of biofilms using optical coherence tomography
Authors: Wagner Michael , Taherzadeh Danial , Haisch Christoph , Horn Harald
Published: August 2010

Optical coherence tomography (OCT) was successfully applied to visualize the mesoscale structure of three different heterotrophic biofilms. For this purpose, biofilm volumes of 4 × 4 × 1.6 mm3 were scanned with spatial resolutions lower than 20 µm within an acquisition time of 2 min. A heterogeneous structure was detected for biofilms cultivated in laminar as well as transient flow conditions. The structure was found to be more homogeneous for the biofilm grown in turbulent flow. This biofilm structure was characterized by a volumetric porosity of 0.36, whereas the porosity calculated for biofilms grown in laminar and transient conditions was 0.65. These results were directly generated from the distribution of porosity calculated from the OCT images acquired and can be linked to structural properties. Up to now, the mesoscale biofilm structure was only observable with time‐consuming and expensive studies, for example, magnetic resonance microscopy. OCT will most certainly be helpful for improved understanding and prediction of biofilm physics with respect to macroscale processes, for example, mass transfer and detachment as the information about mesoscale is easily accessible using this method. In the context of this study, we show that CLSM images do not necessarily provide an accurate representation of the biofilm structure at the mesoscale. Additionally, the typical characteristic parameters obtained from CLSM image stacks differ largely from those calculated from OCT images. Nevertheless, to determine the local distribution of biofilm constituents, microscopic methods such as confocal laser scanning microscopy are required. Biotechnol. Bioeng. 2010;107: 844–853. © 2010 Wiley Periodicals, Inc.
Enhanced gene expression in insect cells and silkworm larva by modified polyhedrin promoter using repeated burst sequence and very late transcriptional factor‐1
Authors: Manohar Suganthi Lavender , Kanamasa Shin , Nishina Takuya , Kato Tatsuya , Park Enoch Y.
Published: August 2010

The Burst of expression from polyhedrin (polh) promoter during very late phase of baculovirus infection requires a sequence located between TAAG and the translation initiation site, typically referred to as burst sequence (BS). The expression of polh promoter is stimulated by specifically binding of very late transcriptional factor 1 (VLF‐1) to BS. In order to enhance the production of recombinant proteins the polh promoter was modified via a multiple BS bacmid system in which the number of BSs was increased. Compared to an expression from a normal polh promoter, β‐glucuronidase (GUS) activity in High Five insect cells was three times higher with a modified polh promoter containing two BSs. Using a modified polh promoter that contains nine BSs in silkworm expression system, β1‐3‐N‐acetylglucosaminyltransferase 2 (β3GnT2) activity per larva was 6.8‐fold higher than control. Furthermore, the co‐expression of modified promoters along with VLF‐1‐enhanced β3GnT activity. Thus, an increased optimal number of BS and its co‐expression with VLF‐1 leads to the production of higher level of gene expression in insect cells and silkworm larvae. This new modified promoter engineered in the current study is the strongest promoter for overexpressing foreign proteins in an eukaryotic cell and system, thus leading a progress in baculovirus–insect cell and silkworm biotechnology. Biotechnol. Bioeng. 2010;107: 909–916. © 2010 Wiley Periodicals, Inc.
A GFP complementation system for monitoring and directing nanomaterial mediated protein delivery to human cellular organelles
Authors: Bale Shyam Sundhar , Kwon Seok Joon , Shah Dhiral A. , Kane Ravi S. , Dordick Jonathan S.
Published: August 2010

Protein‐based therapeutics are gaining importance for their biocompatibility and activity toward specific targets. When these targets are intracellular, it is critical to deliver biomolecules to sites in the cell cytoplasm while retaining biomolecule activity in the complex cellular milieu. However, intracellular protein delivery is not viable unless accompanied by an active uptake mechanism or carrier mediated delivery. Moreover, once entry into the cell is achieved, detection of the biomolecule requires laborious techniques that lack real‐time measurement. We have developed a fluorescence‐based complementary protein delivery sensing system using split green fluorescence protein (GFP1–10 and GFP11) fragments, which can be used as an indicator for protein delivery and retention of activity, and as a means to pinpoint subcellular localization. We demonstrate in vitro localized delivery by expressing the GFP11 fragment onto the mitochondrial outer membrane of human cells, and using a model carrier (15 nm silica nanoparticles) to deliver GFP1–10 and image trafficking and mitochondrial localization of protein delivery. Our results indicate that nanoscale materials can be used as protein carriers for targeting cell constituents including functional molecules, signaling pathways, and organelles. We envision that this GFP complementation system is ideally suited for directing nanoparticle‐based delivery of drugs and other bioactive molecules into subcellular locations within cells, which can impact protein–protein interactions, signal transduction pathways, and organelle function in vitro within the context of high‐throughput screening protocols. Biotechnol. Bioeng. 2010;107: 1040–1047. © 2010 Wiley Periodicals, Inc.
Functional characterization of propane‐enhanced N‐nitrosodimethylamine degradation by two actinomycetales
Authors: Sharp Jonathan O. , Sales Christopher M. , Alvarez‐Cohen Lisa
Published: August 2010

Propane‐induced cometabolic degradation of n‐nitrosodimethylamine (NDMA) by two propanotrophs is characterized through kinetic, gene presence, and expression studies. After growth on propane, resting cells of Rhodococcus sp. RR1 possessed a maximum transformation rate (vmax,n) of 44 ± 5 µg NDMA (mg protein)−1 h−1; the rate for Mycobacterium vaccae (austroafricanum) JOB‐5 was modestly lower with vmax,n of 28 ± 3 µg NDMA (mg protein)−1 h−1. Both strains were capable of degrading environmentally relevant, trace quantities of NDMA to below the experimental limit of detection, calculated as 20 ng NDMA L−1. However, a comparison of half saturation constants (Ks,n) and NDMA degradation in the presence of propane revealed pronounced differences between the strains. The Ks,n for strain RR1 was 36 ± 10 µg NDMA L−1 while the propane concentration needed to inhibit NDMA rates by 50% (Kinh) occurred at 7,700 µg propane L−1 (R2 = 0.9669). In contrast, strain JOB‐5 had a markedly lower affinity for NDMA verses propane with a calculated Ks,n of 2,200 ± 1,000 µg NDMA L−1 and Kinh of 120 µg propane L−1 (R2 = 0.9895). Genomic and transcriptional investigations indicated that the functional enzymes involved in NDMA degradation and propane metabolism are different for each strain. For Rhodococcus sp. RR1, a putative propane monooxygenase (PrMO) was identified and implicated in NDMA oxidation. In contrast, JOB‐5 was not found to possess a PrMO homologue and two functionally analogous alkane monoxygenases (AlkMOs) were not induced by growth on propane. Differences between the PrMO in this Rhodococcus and the unidentified enzyme(s) in the Mycobacterium may explain differences in NDMA degradation and inhibition kinetics between these strains. Biotechnol. Bioeng. 2010;107: 924–932. © 2010 Wiley Periodicals, Inc.
Getting more from cell size distributions: Establishing more accurate biovolumes by estimating viable cell populations
Authors: Sokolenko Stanislav , Cheng Yu‐Lei , Aucoin Marc Gordon
Published: August 2010

Current approaches for cell size distribution modeling are attempting to describe the behavior of the entire distribution with respect to time. Although some advances have been made in this area, the modeling process requires a large number of culture‐specific parameters and an a priori assumption of the distribution nature (Poisson, Gaussian, etc.). In this work, we propose a deconvolution of the distribution into size ranges and an iterative regression process with respect to a single culture variable, such as viability. Following this approach, two example applications are outlined using data collected with a Coulter Counter Multisizer. In the first, traditional biovolume measurements are corrected to account for the noneven distribution of nonviable cells. These corrections amount to an average increase of 7–65% in the calculated biovolume from 24 to 72 h postinfection and are expected to aid in the development of a new basis for nutrient consumption postinfection. In the second example, viability is predicted from the cell size distribution using both linear and exponential regressions. Differences between predicted and measured viabilities were found to be normally distributed with means of 0.4% and 0% as well as standard deviations of 7.6% and 8.1% for linear and exponential regression, respectively. Although only viability relationships were tested, our approach yielded significant results for both applications, allowing the possibility for further development. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010