bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis
Authors: Cuker Adam , Gimotty Phyllis A. , Crowther Mark A. , Warkentin Theodore E.
Published: September 2012

The 4Ts is a pretest clinical scoring system for heparin-induced thrombocytopenia (HIT). Although widely used in clinical practice, its predictive value for HIT in diverse settings and patient populations is unknown. We performed a systematic review and meta-analysis to estimate the predictive value of the 4Ts in patients with suspected HIT. We searched PubMed, Cochrane Database, and ISI Web of Science for studies that included patients with suspected HIT, who were evaluated by both the 4Ts and a reference standard against which the 4Ts could be compared. Quality of eligible studies was assessed by QUADAS-2 criteria. Thirteen studies, collectively involving 3068 patients, fulfilled eligibility criteria. A total of 1712 (55.8%) patients were classified by 4Ts score as having a low probability of HIT. The negative predictive value of a low probability 4Ts score was 0.998 (95% CI, 0.970-1.000) and remained high irrespective of the party responsible for scoring, the prevalence of HIT, or the composition of the study population. The positive predictive value of an intermediate and high probability 4Ts score was 0.14 (0.09-0.22) and 0.64 (0.40-0.82), respectively. A low probability 4Ts score appears to be a robust means of excluding HIT. Patients with intermediate and high probability scores require further evaluation.
The T1048I mutation in ATP7A gene causes an unusual Menkes disease presentation
Authors: León-García Gregorio , Santana Alfredo , Villegas-Sepúlveda Nicolás , Pérez-González Concepción , Henrríquez-Esquíroz José M , de León-García Carlota , Wong Carlos , Baeza Isabel
Published: September 2012

Background

The ATP7A gene encodes the ATP7A protein, which is a trans-Golgi network copper transporter expressed in the brain and other organs. Mutations in this gene cause disorders of copper metabolism, such as Menkes disease. Here we describe the novel and unusual mutation (p.T1048I) in the ATP7A gene of a child with Menkes disease. The mutation affects a conserved DKTGT1048 phosphorylation motif that is involved in the catalytic activity of ATP7A. We also describe the clinical course and the response to copper treatment in this patient.

Case presentation

An 11-month-old male Caucasian infant was studied because of hypotonia, ataxia and global developmental delay. The patient presented low levels of serum copper and ceruloplasmin, and was shown to be hemizygous for the p.T1048I mutation in ATP7A. The diagnosis was confirmed when the patient was 18 months old, and treatment with copper-histidinate (Cu-His) was started immediately. The patient showed some neurological improvement and he is currently 8 years old. Because the p.T1048I mutation affects its catalytic site, we expected a complete loss of functional ATP7A and a classical Menkes disease presentation. However, the clinical course of the patient was mild, and he responded to Cu-His treatment, which suggests that this mutation leads to partial conservation of the activity of ATP7A.

Conclusion

This case emphasizes the important correlation between genotype and phenotype in patients with Menkes disease. The prognosis in Menkes disease is associated with early detection, early initiation of treatment and with the preservation of some ATP7A activity, which is necessary for Cu-His treatment response. The description of this new mutation and the response of the patient to Cu-His treatment will contribute to the growing body of knowledge about treatment response in Menkes disease.
Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue
Authors: Kolak Maria , Gertow Joanna , Westerbacka Jukka , Summers Scott A , Liska Jan , Franco-Cereceda Anders , Orešič Matej , Yki-Järvinen Hannele , Eriksson Per , Fisher Rachel M
Published: September 2012

Background

Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue.

Methods

Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject.

Results

Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot.

Conclusions

Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue.
An induction of microRNA, miR-7 through estrogen treatment in breast carcinoma
Authors: Masuda Mariko , Miki Yasuhiro , Hata Shuko , Takagi Kiyoshi , Sakurai Minako , Ono Katsuhiko , Suzuki Koyu , Yang Yang , Abe Eriko , Hirakawa Hisashi , Ishida Takanori , Suzuki Takashi , Ohuchi Noriaki , Sasano Hironobu
Published: September 2012

Background

Estrogen plays an important role in the development of estrogen-dependent breast carcinoma. Recently, several studies demonstrated a possible involvement of several micro RNAs (miRNAs) in the development of resistance to endocrine therapy in breast cancer patients, but the correlation between estrogen actions and miRNA expression in breast carcinoma still remains largely unknown. Therefore, in this study, we examined the in vitro effects of estrogen upon miRNA expression profiles in breast carcinoma.

Methods

We first screened the miRNA expression profiles induced by 17β-Estradiol (E2) using RT2 miRNA PCR Array in the ER-positive breast carcinoma cell line MCF-7. We identified miR-7 as the important miRNA associated with estrogen actions in these cells and further examined the changes of estrogen-dependent EGFR expression by miR-7 in ER-positive or -negative breast carcinoma cell lines including MCF-7. We also evaluated the correlation between miR-7 and EGFR expression in breast carcinoma cells derived from 21 patients using laser capture microdissection combined with quantitative reverse transcriptase-PCR.

Results

Seventeen miRNAs were significantly induced by E2 treatment in the MCF-7 cell line. Among 17 miRNAs induced by estradiol treatment, only miR-7 expression was significantly decreased by subsequent ICI treatment. The expression of miR-7 was up-regulated 2.94-fold by E2 treatment. miR-7 was reported to suppress epidermal growth factor receptor (EGFR) expression in several human malignancies. Transfection of miR-7 significantly suppressed EGFR mRNA levels in MCF-7 cells. Depletion of E2 from cell culture media also increased the expression level of EGFR mRNA in MCF-7 and T-47D cells but not in ER-negative, MDA-MB-231 and SK-BR-3 cells. We also evaluated the status of miR-7 in breast carcinoma tissues, but the correlation between the status of miR-7 and EGFR in carcinoma cells isolated by laser capture microscopy was not detected.

Conclusions

These results suggest that miR-7 may play a role in the development of resistance to endocrine therapy in breast cancer patients through regulating EGFR expression of carcinoma cells.
Comparing serum levels of cardiac biomarkers in cancer patients receiving chemotherapy and subjects with chronic periodontitis
Authors: Loo Wings TY , Yue Yuan , Fan Chang-bin , Bai Lan-jun , Dou Yi-ding , Wang Min , Liang Hao , Cheung Mary NB , Chow Louis WC , Li Jin-le , Tian Ye , Qing Liu
Published: September 2012

Background

Chronic periodontitis (CP) is a chronic inflammation associated with elevations of several inflammatory and cardiac markers. Studies implicated CP as one of the etiologies in coronary heart disease (CHD). Cardiotoxicity is a major complication of anticancer drugs, including anthracyclines and 5-fluorouracil (5FU). The most severe cardiac complications are heart failure, arrhythmia and coronary heart disease (CHD). In this study, we compared the level of inflammatory factors and cardiac markers between chronic periodontitis patients and cancer patients receiving chemotherapy.

Methods

108 blood samples of periodontally healthy subjects were obtained on random from Hong Kong Red Cross, and these represented the controlled population. Forty-four patients diagnosed with chronic periodontitis were recruited from the West China Hospital of Stomatology, Sichuan University. They have received scaling and root planning with mean pocket depths of 6.05 mm. Thirty breast cancer patients diagnosed with invasive ductal carcinoma from UNIMED Medical Institute, Hong Kong gave consent to participate in this study. They received 4 cycles of 500mg/m2 5-fluorouracil, 75 mg/m2 epirubicin and 500mg/m2 cyclophosphamide at a 3-week interval between each cycle. Peripheral venous blood from each group was taken for measurement of blood cells, inflammatory marker (P-selectin, high sensitvity C-reactive protein) and cardiac markers (troponin T; troponin I; N-terminal pro brain natriuretic peptide (Nt-proBNP) and Lactate dehydrogenase (LDH).

Results

The lymphocyte count was higher (p < 0.05) in periodontitis patients than the other two groups, and more neutrophils (p < 0.05) were seen in cancer patients receiving chemotherapy. The two test groups demonstrated higher levels (p < 0.01) of inflammatory and cardiac markers than the control group.

Conclusions

The elevated cardiac markers found in periodontitis patients suggested that they may carry potential risks in developing cardiac lesions. Troponin T, troponin I, pro-BNP, LDH and high sensitvity C-reactive protein may be used as markers to monitor cardiac lesions in chronic inflammatory patients.
Anti-periodic solutions for nonlinear evolution equations
Authors: Cheng Yi , Cong Fuzhong , Hua Hongtu
Published: September 2012

In this paper, we use the homotopy method to establish the existence and uniqueness of anti-periodic solutions for the nonlinear anti-periodic problem

{

x
˙

+
A
(
t
,
x
)
+
B
x
=
f
(
t
)

a.e. 
t
∈
R
,

x
(
t
+
T
)
=
−
x
(
t
)
,

where

A
(
t
,
x
)

is a nonlinear map and B is a bounded linear operator from

R
N

to

R
N

. Sufficient conditions for the existence of the solution set are presented. Also, we consider the nonlinear evolution problems with a perturbation term which is multivalued. We show that, for this problem, the solution set is nonempty and weakly compact in

W

1
,
2

(
I
,

R
N

)

for the case of convex valued perturbation and prove the existence theorems of anti-periodic solutions for the nonconvex case. All illustrative examples are provided.
Primary pulmonary malignant melanoma: a clinicopathologic study of two cases
Authors: Gong Li , Liu Xiao-Yan , Zhang Wen-Dong , Zhu Shao-Jun , Yao Li , Han Xiu-Juan , Lan Miao , Li Yan-Hong , Zhang Wei
Published: September 2012

Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions.

Virtual slide

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.
Anterolateral minithoracotomy versus median sternotomy for the treatment of congenital heart defects: a meta-analysis and systematic review
Authors: Ding Chao , Wang Chunmao , Dong Aiqiang , Kong Minjian , Jiang Daming , Tao Kaiyu , Shen Zhonghua
Published: September 2012

Background

Anterolateral Minithoracotomy (ALMT) for the radical correction of Congenital Heart Defects is an alternative to Median Sternotomy (MS) due to reduce operative trauma accelerating recovery and yield a better cosmetic outcome after surgery. Our purpose is to conduct whether ALMT would bring more short-term benefits to patients than conventional Median Sternotomy by using a meta-analysis of case–control study in the published English Journal.

Methods

6 case control studies published in English from 1997 to 2011 were identified and synthesized to compare the short-term postoperative outcomes between ALMT and MS. These outcomes were cardiopulmonary bypass time, aortic cross-clamp time, intubation time, intensive care unit stay time, and postoperative hospital stay time.

Results

ALMT had significantly longer cardiopulmonary bypass times (8.00 min more, 95% CI 0.36 to 15.64 min, p = 0.04). Some evidence proved that aortic cross-clamp time of ALMT was longer, yet not significantly (2.38 min more, 95% CI −0.15 to 4.91 min, p = 0.06). In addition, ALMT had significantly shorter intubation time (1.66 hrs less, 95% CI −3.05 to −0.27 hrs, p = 0.02). Postoperative hospital stay time was significantly shorter with ALMT (1.52 days less, 95% CI −2.71 to −0.33 days, p = 0.01). Some evidence suggested a reduction in ICU stay time in the ALMT group. However, this did not prove to be statistically significant (0.88 days less, 95% CI −0.81 to 0.04 days, p = 0.08).

Conclusion

ALMT can bring more benefits to patients with Congenital Heart Defects by reducing intubation time and postoperative hospital stay time, though ALMT has longer CPB time and aortic cross-clamp time.
Cleavage pattern and fate map of the mesentoblast, 4d, in the gastropod Crepidula: a hallmark of spiralian development
Authors: Lyons Deirdre C , Perry Kimberly J , Lesoway Maryna P , Henry Jonathan Q
Published: September 2012

Background

Animals with a spiral cleavage program, such as mollusks and annelids, make up the majority of the superphylum Lophotrochozoa. The great diversity of larval and adult body plans in this group emerges from this highly conserved developmental program. The 4d micromere is one of the most conserved aspects of spiralian development. Unlike the preceding pattern of spiral divisions, cleavages within the 4d teloblastic sublineages are bilateral, representing a critical transition towards constructing the bilaterian body plan. These cells give rise to the visceral mesoderm in virtually all spiralians examined and in many species they also contribute to the endodermal intestine. Hence, the 4d lineage is an ideal one for studying the evolution and diversification of the bipotential endomesodermal germ layer in protostomes at the level of individual cells. Little is known of how division patterns are controlled or how mesodermal and endodermal sublineages diverge in spiralians. Detailed modern fate maps for 4d exist in only a few species of clitellate annelids, specifically in glossiphoniid leeches and the sludge worm Tubifex. We investigated the 4d lineage in the gastropod Crepidula fornicata, an established model system for spiralian biology, and in a closely related direct-developing species, C. convexa.

Results

High-resolution cell lineage tracing techniques were used to study the 4d lineage of C. fornicata and C. convexa. We present a new nomenclature to name the progeny of 4d, and report the fate map for the sublineages up through the birth of the first five pairs of teloblast daughter cells (when 28 cells are present in the 4d sublineage), and describe each clone’s behavior during gastrulation and later stages as these undergo differentiation. We identify the precise origin of the intestine, two cells of the larval kidney complex, the larval retractor muscles and the presumptive germ cells, among others. Other tissues that arise later in the 4d lineage include the adult heart, internal foot tissues, and additional muscle and mesenchymal cells derived from later-born progeny of the left and right teloblasts. To test whether other cells can compensate for the loss of these tissues (that is, undergo regulation), specific cells were ablated in C. fornicata.

Conclusions

Our results present the first fate map of the 4d micromere sublineages in a mollusk. The fate map reveals that endodermal and mesodermal fates segregate much later than previously thought. We observed little evidence of regulation between sublineages, consistent with a lineage-driven cell specification process. Our results provide a framework for comparisons with other spiralians and lay the groundwork for investigation of the molecular mechanisms of endomesoderm formation, germ line segregation and bilateral differentiation in Crepidula.
KNDy (Kisspeptin/Neurokinin B/Dynorphin) Neurons Are Activated during Both Pulsatile and Surge Secretion of LH in the Ewe
Authors: Merkley Christina M. , Porter Katrina L. , Coolen Lique M. , Hileman Stanley M. , Billings Heather J. , Drews Sara , Goodman Robert L. , Lehman Michael N.
Published: September 2012

KNDy (kisspeptin/neurokinin B/dynorphin) neurons of the arcuate nucleus (ARC) appear to mediate the negative feedback actions of estradiol and are thought to be key regulators of pulsatile LH secretion. In the ewe, KNDy neurons may also be involved with the positive feedback actions of estradiol (E2) to induce the LH surge, but the role of kisspeptin neurons in the preoptic area (POA) remains unclear. The goal of this study was to identify which population(s) of kisspeptin neurons is (are) activated during the LH surge and in response to the removal of E2-negative feedback, using Fos as an index of neuronal activation. Dual-label immunocytochemistry for kisspeptin and Fos was performed on sections containing the ARC and POA from ewes during the luteal phase of the estrous cycle, or before or after the onset of the LH surge (experiment 1), and from ovary-intact, short-term (24 h) and long-term (>30 d) ovariectomized (OVX) ewes in anestrus (experiment 2). The percentage of kisspeptin neurons expressing Fos in both the ARC and POA was significantly higher during the LH surge. In contrast, the percentage of kisspeptin/Fos colocalization was significantly increased in the ARC, but not POA, after both short- and long-term E2 withdrawal. Thus, POA kisspeptin neurons in the sheep are activated during, and appear to contribute to, E2-positive feedback, whereas ARC kisspeptin (KNDy) neurons are activated during both surge and pulsatile modes of secretion and likely play a role in mediating both positive and negative feedback actions of E2 on GnRH secretion in the ewe.
Building a Movement, Dismantling the Republic: Women, Gender, and Political Extremism in the Croix de Feu/Parti Social Français, 1927–1940
Authors: Campbell Caroline
Published: September 2012

Women were at the center of extremist politics in the late Third Republic. This article focuses on one of the largest political movements in French history, the Croix de Feu, and enters into a debate over the degree of women’s influence on the movement and its conception of women’s role in French society. Informed by rich archival records, it concludes that a multivalent gender ideology enabled Croix de Feu women to subvert a powerful “women in the home” movement by placing themselves at the center of national rejuvenation. They did so by appropriating republican conceptions of civic space to build an ultranationalistic social program. Organizing a women’s section from scratch, Croix de Feu women implemented the movement’s social program in over 90 percent of French departments, ultimately contributing to a rightward shift in 1930s French political culture and laying the groundwork for the Vichy regime.

Cet article examine les femmes et la politiques d’extrême droite dans l’entredeuxguerres. En se concentrant sur l’un des plus grands mouvements politiques dans l’histoire française, les Croix de feu, l’article entre dans un débat sur l’influence féminine sur le mouvement et sur sa conception du rôle des femmes dans la société française. Un clair examen des femmes Croix de feu démontre qu’elles étaient au centre des activités les plus importantes du mouvement. Elles ont utilisé une idéologie du genre qui défi une campagne du retour « la femme au foyer » et qui plaçait les femmes au centre d’une renaissance nationale. Ces femmes militantes se sont servies des conceptions républicaines de l’espace civique afin de construire un programme social et ultranationaliste. Elles ont organisé une section féminine et mis en œuvre leur programme social dans plus de 90 pour cent de départements français. Ainsi, les femmes Croix de feu ont influencé la culture politique française et ont contribué à l’avènement du régime de Vichy.
Political Surveillance and Colonial Urban Rule: “Suspicious” Politics and Urban Space in Dakar, Senegal, 1918–1939
Authors: Keller Kathleen A.
Published: September 2012

Police surveillance in interwar Dakar, Senegal, was initiated because of anxieties about the influence of international politics in the empire, but surveillance quickly became a phenomenon of urban control. This article analyzes the emergence, implementation, and broader implications of police surveillance to shed light on the way French colonial authorities imagined and attempted to impose order on cities. Surveillance of “suspicious” persons developed primarily in urban areas because the profile of a suspect was shaped by fears of an increasingly cosmopolitan and diverse population in the interwar era. Police tactics were influenced by republicanstyle methods from the metropole and relied on the legibility of urban space, creating a unique urban surveillance that contrasted with rural methods. Despite this desire for ubiquitous surveillance, some urban spaces escaped the purview of colonial authorities and some individuals evaded state control.

Cet article consacré à la surveillance policière à Dakar met en lumière la manière dont la surveillance politique de l’entredeuxguerres s’est constituée comme un phénomène urbain. Ce programme de contrôle urbain révèle une façon d’imaginer et d’essayer d’imposer l’ordre dans la ville de la part des autorités. La surveillance des « suspects » en Afrique Occidentale Française s’est développée dans l’espace urbain à cause de la crainte des autorités d’une population urbaine de plus en plus cosmopolite et contrastée. Les stratégies utilisées par les autorités ont été élaborées au prisme des méthodes républicaines de la métropole. Dépendantes pour leur conception de la lisibilité de l’espace urbain, elles ont généré une forme unique de surveillance en opposition à la surveillance rurale. Malgré le désir des autorités de créer un mode de contrôle omniprésent, certains espaces urbains échappaient néanmoins au regard de l’état et certains individus arrivaient à se soustraire à ces méthodes policières.
From Communism to Capitalism, from Production to Consumption
Authors: Ryabchuk Anastasiya , Onyshchenko Natalia
Published: September 2012

This article reflects upon the intersection of the urban landscape, class, and consumption in Kyiv, Ukraine, taking the Bilshovyk plant and shopping center as a case study. Despite the plant's central location in a large industrial building next to the metro station, for many city dwellers it does not constitute part of the urban landscape or their everyday experiences in the city. The invisibility of the plant stands in sharp contrast to the excessive visibility of the Bilshovyk shopping center, constructed in one of the former plant buildings and currently the biggest shopping mall in Kyiv. Listening to workers' experiences and looking into the past and the present of the Bilshovyk plant, the authors were able to see three aspects of the transformation of post-Soviet cities: transformations in dominant ideology, class structure, and urban space.
Adaptive Bayesian Analysis of Serum Creatinine as a Marker for Drug-Induced Renal Impairment in an Early-Phase Clinical Trial
Authors: Sottas Pierre-Edouard , Kapke Gordon F , Leroux Jean-Marc
Published: September 2012

BACKGROUND

A concern with using creatinine for the identification of drug-induced renal impairment is that small changes in serum creatinine (SCr) that frequently are perceived as measurement bias or imprecision translate into important changes in the glomerular filtration rate. Important drug-generated changes in creatinine are difficult to detect because they are frequently observed within the reference interval. The design of a crossover drug protocol is an opportunity to use study participants as their own control to identify these small but important changes.

METHODS

Twenty individuals participating in a phase I clinical trial were evaluated for SCr changes beyond those expected for biological variation according to individual Z scores derived from an adaptive Bayesian model. After 2 screening tests, participants were administered either drug (n = 11) or placebo (n = 9) during the first dosing interval. A washout period followed, and drug was then administered to the group that initially received placebo, and vice versa (10 visits total per participant).

RESULTS

Although all creatinine values fell within the reference interval, 8 participants individually showed increased concentrations (Z scores >2.33). These 8 participants were confirmed at unblinding to have received the drug in the identified dosing period, with 1 exception.

CONCLUSIONS

The ability to identify a drug effect on an individual-participant basis in early-phase studies permits drug developers to recognize issues early in development and rapidly engage in risk–benefit analysis. These results suggest that SCr monitoring is able to detect early kidney dysfunction when individual-based reference intervals are used.
Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow’s milk allergy in toddlers
Authors: Kalach Nicolas , Kapel Nathalie , Waligora-Dupriet Anne-Judith , Castelain Marie-Christine , Cousin Marie Odile , Sauvage Christine , Ba Fatimata , Nicolis Ioannis , Campeotto Florence , Butel Marie José , Dupont Christophe
Published: September 2012

Background: Food allergy is a common problem in France involving 4%–6% of toddlers. As opposed to IgE-mediated cow’s milk allergy (CMA), delayed-onset CMA, mostly, non-IgE-mediated, remains difficult to diagnose in toddlers. Our study assessed the diagnostic performances of intestinal permeability and of fecal markers, in comparison with the standard allergic work-up in children referred for CMA diagnosis.

Methods: Twenty-five consecutive children, mean age (standard deviation) 6.3 months (4.8) with digestive and/or extra-digestive manifestations suggesting CMA, were prospectively studied based on a standardized allergic work-up (specific cow’s protein IgE and IgG, skin prick test, atopy patch test and oral open cow’s milk challenge) and digestive work-up including fecal microbiota analysis, intestinal permeability determination (urinary lactitol/mannitol ratio) and fecal markers measurement, i.e., α1-antitrypsin, tumor necrosis factor-α, calprotectin, β-defensin2, secretory IgA and eosinophil-derived neurotoxin (EDN). Receiver operating characteristic (ROC) curves were calculated for all markers in order to define cut-off levels.

Results: The cow’s milk challenge was positive in 11 children and negative in 14. The global test performances, i.e., the number of true positive+negative cases/the total number of cases, were 76% for intestinal permeability; 72% for fecal EDN; contrasting with atopy patch test, 68%; IgE, 60%; skin prick test, 55% and IgG, 52%.

Conclusions: In this routine diagnosis allergy work-up for CMA in toddlers, the best efficacy was seen for intestinal permeability compared to IgE, IgG, skin prick test and atopy patch test. Moreover, fecal EDN in a single spot sample displayed a similar performance.
Studying thermal conductivity of wood at cell wall level by scanning thermal microscopy (SThM)
Authors: Vay Oliver , Obersriebnig Michael , Müller Ulrich , Konnerth Johannes , Gindl-Altmutter Wolfgang
Published: September 2012

Local variability in the thermal conductivity of the cell wall of beech wood fibers was studied by means of scanning thermal microscopy (SThM). In the cross section, the thermal conductivity of the secondary cell wall was essentially higher than that of the compound middle lamella (CML). In sections parallel to the cell axis, the overall conductivity of the S1 layer was lower than that of the secondary cell wall, but the S2 layer and the CML showed similar conductivities. This is attributed to the orientation of the cellulose microfibrils playing a key role in the observed anisotropies concerning the thermal conductivity. The deviating thermal conductivities on different sections are attributed to the depth effect of the thermal scanning. SThM proves to be a technique with considerable potential for wood research.
Decoding the Contents of Visual Short-Term Memory from Human Visual and Parietal Cortex
Authors: Christophel Thomas B. , Hebart Martin N. , Haynes John-Dylan
Published: September 2012

How content is stored in the human brain during visual short-term memory (VSTM) is still an open question. Different theories postulate storage of remembered stimuli in prefrontal, parietal, or visual areas. Aiming at a distinction between these theories, we investigated the content-specificity of BOLD signals from various brain regions during a VSTM task using multivariate pattern classification. To participate in memory maintenance, candidate regions would need to have information about the different contents held in memory. We identified two brain regions where local patterns of fMRI signals represented the remembered content. Apart from the previously established storage in visual areas, we also discovered an area in the posterior parietal cortex where activity patterns allowed us to decode the specific stimuli held in memory. Our results demonstrate that storage in VSTM extends beyond visual areas, but no frontal regions were found. Thus, while frontal and parietal areas typically coactivate during VSTM, maintenance of content in the frontoparietal network might be limited to parietal cortex.
Dissection of Gain Control Mechanisms inDrosophilaMechanotransduction
Authors: Chadha Abhishek , Cook Boaz
Published: September 2012

Mechanoreceptor cells respond to a vast span of stimulus intensities, which they transduce into a limited response-range using a dynamic regulation of transduction gain. Weak stimuli are detected by enhancing the gain of responses through the process of active mechanical amplification. To preserve responsiveness, the gain of responses to prolonged activation is rapidly reduced through the process of adaptation. We investigated long-term processes of mechanotransduction gain control by studying responses from single mechanoreceptor neurons inDrosophila. We found that mechanical stimuli elicited a sustained reduction of gain that we termed long-term adaptation. Long-term adaptation and the adaptive decay of responses during stimuli had distinct kinetics and they were independently affected by manipulations of mechanotransduction. Therefore, long-term adaptation is not associated with the reduction of response gain during stimulation. Instead, the long-term adaptation suppressed canonical features of active amplification which were the high gain of weak stimuli and the spontaneous emission of noise. In addition, depressing amplification using energy deprivation recapitulated the effects of long-term adaptation. These data suggest that long-term adaptation is mediated by suppression of active amplification. Finally, the extent of long-term adaptation matched with cytoplasmic Ca2+levels and dTrpA1-induced Ca2+elevation elicited the effects of long-term adaptation. Our data suggest that mechanotransduction employs parallel adaptive mechanisms: while a rapid process exerts immediate gain reduction, long-term adjustments are achieved by attenuating active amplification. The slow adjustment of gain, manifest as diminished sensitivity, is associated with the accumulation of Ca2+.
Astrocyte-Derived Thrombospondins Mediate the Development of Hippocampal Presynaptic PlasticityIn Vitro
Authors: Crawford Devon C. , Jiang Xiaoping , Taylor Amanda , Mennerick Steven
Published: September 2012

Astrocytes contribute to many neuronal functions, including synaptogenesis, but their role in the development of synaptic plasticity remains unclear. Presynaptic muting of hippocampal glutamatergic terminals defends against excitotoxicity. Here we studied the role of astrocytes in the development of presynaptic muting at glutamatergic synapses in rat hippocampal neurons. We found that astrocytes were critical for the development of depolarization-dependent and Gi/o-dependent presynaptic muting. The ability of cAMP analogues to modulate presynaptic function was also impaired by astrocyte deficiency. Although astrocyte deprivation resulted in postsynaptic glutamate receptor deficits, this effect appeared independent of astrocytes' role in presynaptic muting. Muting was restored with chronic, but not acute, treatment with astrocyte-conditioned medium, indicating that a soluble factor is permissive for muting. Astrocyte-derived thrombospondins (TSPs) are likely responsible because TSP1 mimicked the effect of conditioned medium, and gabapentin, a high-affinity antagonist of TSP binding to the α2δ-1 calcium channel subunit, mimicked astrocyte deprivation. We found evidence that protein kinase A activity is abnormal in astrocyte-deprived neurons but restored by TSP1, so protein kinase A dysfunction may provide a mechanism by which muting is disrupted during astrocyte deficiency. In summary our results suggest an important role for astrocyte-derived TSPs, acting through α2δ-1, in maturation of a potentially important form of presynaptic plasticity.
Spinal Cord Injury Induces Serotonin Supersensitivity without Increasing Intrinsic Excitability of Mouse V2a Interneurons
Authors: Husch Andreas , Van Patten Gabrielle N. , Hong Diana N. , Scaperotti Moira M. , Cramer Nathan , Harris-Warrick Ronald M.
Published: September 2012

Denervation-induced plastic changes impair locomotor recovery after spinal cord injury (SCI). Spinal motoneurons become hyperexcitable after SCI, but the plastic responses of locomotor network interneurons (INs) after SCI have not been studied. Using an adult mouse SCI model, we analyzed the effects of complete spinal cord lesions on the intrinsic electrophysiological properties, excitability, and neuromodulatory responses to serotonin (5-HT) in mouse lumbar V2a spinal INs, which help regulate left–right alternation during locomotion. Four weeks after SCI, V2a INs showed almost no changes in baseline excitability or action potential properties; the only parameter that changed was a reduced input resistance. However, V2a INs became 100- to 1000-fold more sensitive to 5-HT. Immunocytochemical analysis showed that SCI caused a coordinated loss of serotonergic fibers and the 5-HT transporter (SERT). Blocking the SERT with citalopram in intact mice did not increase 5-HT sensitivity to the level seen after SCI. SCI also evoked an increase in 5-HT2Creceptor cluster number and intensity, suggesting that several plastic changes cooperate in increasing 5-HT sensitivity. Our results suggest that different components of the spinal neuronal network responsible for coordinating locomotion are differentially affected by SCI, and highlight the importance of understanding these changes when considering therapies targeted at functional recovery.
Jedi-1 and MEGF10 Signal Engulfment of Apoptotic Neurons through the Tyrosine Kinase Syk
Authors: Scheib Jami L. , Sullivan Chelsea S. , Carter Bruce D.
Published: September 2012

During the development of the peripheral nervous system there is extensive apoptosis, and these neuronal corpses need to be cleared to prevent an inflammatory response. Recently, Jedi-1 and MEGF10, both expressed in glial precursor cells, were identified in mouse as having an essential role in this phagocytosis (Wu et al., 2009); however, the mechanisms by which they promote engulfment remained unknown. Both Jedi-1 and MEGF10 are homologous to theDrosophila melanogasterreceptor Draper, which mediates engulfment through activation of the tyrosine kinase Shark. Here, we identify Syk, the mammalian homolog of Shark, as a signal transducer for both Jedi-1 and MEGF10. Syk interacted with each receptor independently through the immunoreceptor tyrosine-based activation motifs (ITAMs) in their intracellular domains. The interaction was enhanced by phosphorylation of the tyrosines in the ITAMs by Src family kinases (SFKs). Jedi association with Syk and activation of the kinase was also induced by exposure to dead cells. Expression of either Jedi-1 or MEGF10 in HeLa cells facilitated engulfment of carboxylated microspheres to a similar extent, and there was no additive effect when they were coexpressed. Mutation of the ITAM tyrosines of Jedi-1 and MEGF10 prevented engulfment. The SFK inhibitor PP2 or a selective Syk inhibitor (BAY 61-3606) also blocked engulfment. Similarly, in cocultures of glial precursors and dying sensory neurons from embryonic mice, addition of PP2 or knock down of endogenous Syk decreased the phagocytosis of apoptotic neurons. These results indicate that both Jedi-1 and MEGF10 can mediate phagocytosis independently through the recruitment of Syk.
Crystal structure of (2S, 4R)-2-benzyl 1-tert-butyl 4-(tosyloxy)pyrrolidine- 1,2-dicarboxylate, C24H29NO7S
Authors: Ghosh Munmun , Mallick Arijit , Díaz David Díaz
Published: September 2012

C24H29NO7S, triclinic, P1 (no. 1) , a = 6.5903(3) Å, b = 9.7193(5) Å, c = 9.9874(4) Å, α = 82.462(4)°, β = 77.197(3)°, γ = 85.6180(4)°,V = 617.7 Å3, Z = 1, Rgt(F) = 0.0351, wRref(F2) = 0.0967, T = 123 K.
Crystal structure of aqua-[(2,2'-bipyridine)]-[(2,4-dihydroxypyrimidine- 5-carboxylato)] perchloratocopper(II), Cu(H2O)(C10H8N2)(C5H3N2O4)(ClO4), C15H13ClCuN4O9
Authors: Liu Qi , Xiao Bo , Chen Min-Dong
Published: September 2012

C15H13ClCuN4O9, monoclinic, P21/n (no. 14), a = 8.1493(3) Å, b = 11.4761(4) Å, c = 19,3483(6) Å, β = 97.7438(3)°, V=1793.05(11)Å3, Z=4,Rgt(F)=0.0459,wRref(F2)=0.1149, T = 296 K
Histone deacetylase 5 regulates glucose uptake and insulin action in muscle cells
Authors: Raichur Suryaprakash , Hooi Teh Song , Ohwaki Kenji , Gaur Vidhi , Chau Long Yun , Hargreaves Mark , McGee Sean L , Kusunoki Jun
Published: September 2012

The class IIa histone deacetylases (HDACs) act as transcriptional repressors by altering chromatin structure through histone deacetylation. This family of enzymes regulates muscle development and phenotype, through regulation of muscle-specific genes including myogenin and MyoD (MYOD1). More recently, class IIa HDACs have been implicated in regulation of genes involved in glucose metabolism. However, the effects of HDAC5 on glucose metabolism and insulin action have not been directly assessed. Knockdown of HDAC5 in human primary muscle cells increased glucose uptake and was associated with increased GLUT4 (SLC2A4) expression and promoter activity but was associated with reduced GLUT1 (SLC2A1) expression. There was no change in PGC-1α (PPARGC1A) expression. The effects of HDAC5 knockdown on glucose metabolism were not due to alterations in the initiation of differentiation, as knockdown of HDAC5 after the onset of differentiation also resulted in increased glucose uptake and insulin-stimulated glycogen synthesis. These data show that inhibition of HDAC5 enhances metabolism and insulin action in muscle cells. As these processes in muscle are dysregulated in metabolic disease, HDAC inhibition could be an effective therapeutic strategy to improve muscle metabolism in these diseases. Therefore, we also examined the effects of the pan HDAC inhibitor, Scriptaid, on muscle cell metabolism. In myotubes, Scriptaid increased histone 3 acetylation, GLUT4 expression, glucose uptake and both oxidative and non-oxidative metabolic flux. Together, these data suggest that HDAC5 regulates muscle glucose metabolism and insulin action and that HDAC inhibitors can be used to modulate these parameters in muscle cells.
Design of Π-conjugated Graft and Block Copolymers: A Tool Box for Nanostructured Materials in Optoelectronic Devices
Authors: Brochon Cyril , Mougnier Sebastien-Jun , Cloutet Eric , Hadziioannou Georges
Published: September 2012

Semi-conducting conjugated (co)polymers are well soluble and can be processed easily in a large scale. Among these materials, rod-coil block and graft copolymers, show very particular properties of self-assembly, and are very promising in organic electronic, as organic photovoltaic materials for example.

The post-functionalization of poly(3-hexylthiophene) (P3HT) from ω-allyl terminated P3HT via various synthetic routes is reported in order to obtain well-defined block and graft copolymers for optoelectronic or photovoltaic applications. First, a well-defined and monofunctional P3HT-based macro-initiator has been obtained through a clean and versatile process. Well-defined rod-coil block copolymers were obtained by nitroxide mediated radical polymerization (NMRP) with various monomers. Finally, three different novel P3HT-based graft copolymers were synthesized following two routes.
Surface modification of bacterial magnetic nanoparticles using artificial polypeptides consisting of a repeated asparagine-serine dipeptide and a transmembrane peptide
Authors: Honda Toru , Yoshino Tomoko , Tanaka Tsuyoshi , Matsunaga Tadashi
Published: September 2012

Surface modification is an important part of fabricating nanoparticles with specific properties and functions. We have designed a dipeptide, which we call NS polypeptide, that consists of four asparagine (N) residues and one serine (S) residue, as a molecule for nanoparticle surface modification. Surface modification of magnetic nanoparticles with the NS polypeptide results in reduction of particle-particle and particle-cell interactions. Here, we describe the surface modification and functionalization of bacterial magnetic particles (BacMPs) by spontaneous integration of temporin L conjugated to NS polypeptide. BacMP membranes were modified temporin L. Furthermore, peptide-modified BacMPs showed high dispersibility in aqueous solution compared to unmodified BacMPs. This surface modification technique may represent a new strategy for reducing non-specific binding of nanoparticles to proteins or cells for use in a variety of protein- or cell-associated applications.
Evaluation of Infection Resistance of Biological Implants through CMP based Micro-Patterning
Authors: Basim G. Bahar , Ozdemir Zeynep , Karagoz Ayse
Published: September 2012

Biomaterials are widely used for dental implants, orthopedic devices, cardiac pacemakers and catheters. One of the main concerns on using bio-implants is the risk of infection on the materials used. In this study, our aim is to quantify the effect of controlled surface roughness on the infection resistance of the titanium based bio-materials which are commonly used for orthopedic devices and dental implants. To modify the surface roughness of the surfaces in a controlled manner, Chemical Mechanical Polishing (CMP) technique, which is extensively used in semiconductor industry for the planarization of the interlayer dielectrics and metals, is utilized. To determine the infection resistance of the created films with varying surface roughness, bacteria growth response was studied on titanium plates after CMP.
Comparative study of corrosion and tribocorrosion resistance of some biomaterials
Authors: Takadoum J. , El Mansouri J. , Ivanescu S. , Stanciu D.
Published: September 2012

Corrosion and tribocorrosion tests have been conducted on titanium, Ti-6Al-4V and Ti-10Zr-10Nb-5Ta alloys. The experiments have been conducted in four different electrolytes: NaCl solution, Ringer’s solution, phosphate buffered saline solution (PBS) with and without an addition of bovine serum albumin (BSA).

The electrochemical study showed that, whatever the electrolyte, the passivating film formed on Ti-10Zr-10Nb-5Ta surface is more stable than those obtained on the surface of titanium or Ti-6Al-4V alloy. In addition, Ti-10Zr-10Nb-5Ta presents a better resistance to corrosion. In PBS solution, open circuit potential (OCP) moved to more positive value in comparison with results obtained in NaCl and Ringer’s solutions, whereas addition of BSA moved OCP value towards more negative potential indicating a detrimental effect.

Tribocorrosion tests have been conducted at OCP when sliding against an alumina ball. Friction coefficient, current and volume of material removal at the end of tests have been measured and the results discussed. The influence of the presence of proteins molecules has been particularly analyzed.
Características clínicas e anatomo-histopatologicas da infecção experimental mista por Orthoreovirus aviario e Mycoplasma synoviae em frangos de corte
Authors: Reck Carolina , Menin Álvaro , Pilati Celso , Miletti Luiz Cláudio
Published: September 2012

A artrite infecciosa em frangos de corte representa um problema sanitário e econômico de grande impacto, provocando perdas de produtividade e nos processos de produção e industrialização. Os principais agentes etiológicos associados aos casos de artrites e tenossinovites infecciosas em aves são Mycoplasma synoviae (MS) e Orthoreovirus aviario (ARV). Esse trabalho propôs investigar as alterações anatomohistopatológicas causadas pela infecção experimental concomitante por Mycoplasma synoviae e Orthoreovirus aviario em frangos de corte e confirmar a presença dos agentes através das técnicas de PCR e imuno-luorescência indireta (RIFI). Para tal foram utilizados 16 frangos de corte, alojados em cama, com fornecimento de ração e água ad libitum. A infecção experimental foi realizada utilizando amostras atenuadas de MS e de ARV. Clinicamente as aves inoculadas apresentaram apatia e edemaciação da região da articulação tíbiotársica. Após 30 dias procedeu-se a eutanásia e a necropsia das aves. Na análise histopatológica constatou-se o efeito da infecção mista com MS e ARV sobre os diferentes órgãos/tecidos. Todos os animais apresentaram quadro de artrite e tenossinovite caracterizado pela presença de infiltrado inflamatório linfohistiocitário difuso, com acúmulo de heterófilos na cápsula articular/membrana sinovial e tendão flexor digital. Além disso, foi possível observar infiltrado inflamatório na traquéia, nos pulmões e sacos aéreos, no fígado, baço, pericárdio e proventrículo. A utilização da RIFI foi necessária para visualizar a presença de ambos os agentes nas articulações, identificando a presença de antígenos do ARV e do MS. A técnica de PCR constatou positividade do MS na traquéia, pulmões/sacos aéreos, cápsula articular/membrana sinovial e liquido sinovial. Já para o ARV a PCR foi positiva em amostras de fígado, baço, cápsula articular/membrana sinovial e tendão flexor digital. Com base nas lesões observadas e nos dados da literatura, sugere-se a ação concomitante por MS e ARV nos diferentes tecidos.