bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking conceptual mechanisms and transcriptomic evidence of plasticity‐driven diversification
Authors: Young Rebecca L.
Published: August 2013

The East African cichlid fishes provide text book examples of adaptive radiation. Diversification and speciation of cichlids associate with variation in diet and trophic morphologies among other ecological, behavioural and morphological phenotypes (Kocher 2004). Numerous case studies in cichlids reveal a role of developmental plasticity in generating jaw ecomorphs in response to variation in feeding ecology that can facilitate niche exploitation and subsequent diversification (e.g. Meyer 1987). Specifically, genetic divergence among such environmentally induced morphs can occur via reproductive isolation due to divergence in habitat and resource use in combination with genetic assimilation of environmentally induced phenotypes (West‐Eberhard 2003; Pfennig et al. 2010). Expansion of this conceptual model has been hampered in part by the limited knowledge of the molecular mechanisms of plasticity in nonstandard model systems and the associated lack of evidence linking the molecular mechanisms of plasticity to those that generate phenotypic divergence among populations and taxa. In this issue of Molecular Ecology, Gunter et al. (2013) identify the transcriptional mechanisms of diet‐induced lower pharyngeal jaw (LPJ) plasticity in the cichlid fish Astatoreochromis alluaudi. Natural populations of A. alluaudi exhibit variation in jaw morphology in relation to diet hardness. Among the plastic responses to diet are adjustments to the LPJ ranging from a robust molariform morph in response to a hard diet to a more gracile papilliform morph in response to a soft diet (Fig. 1). Gunter and colleagues induced developmental plasticity of the A. alluaudi jaw using diet manipulations and compared LPJ transcriptomic profiles of the resulting morphs. In this foundational work, the authors identify 187 differentially expressed genes that underlie the development and maintenance of diet‐induced LPJ morphologies. This list includes a wide range of genes spanning from broad‐acting transcription factors to signalling molecules and structural genes. Here, I examine the ontogeny of the molecular response to mechanical strain imposed by diet hardness and discuss the role of the stages of this response in the evolution of plasticity and plasticity‐driven diversification.

Phenotypic plasticity in the lower pharyngeal jaws of the cichlid fish Astatoreochromis alluaudi. A mechanically stimulating diet such as hard‐shelled snails induces a molariform phenotype with larger molar‐like teeth set in a larger, denser jaw, in comparison with the papilliform phenotype, which develops in response to a soft, nutritionally equivalent diet of pulverized snails. Photographs were kindly provided by Helen Gunter.

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Contributions of the σW, σM and σX regulons to the lantibiotic resistome of Bacillus subtilis
Authors: Kingston Anthony W. , Liao Xiaojie , Helmann John D.
Published: August 2013

In Bacillus subtilis, the extracytoplasmic function (ECF) σ factors σM, σW and σX all contribute to resistance against lantibiotics. Nisin, a model lantibiotic, has a dual mode of action: it inhibits cell wall synthesis by binding lipid II, and this complex also forms pores in the cytoplasmic membrane. These activities can be separated in a nisin hinge‐region variant (N20P M21P) that binds lipid II, but no longer permeabilizes membranes. The major contribution of σM to nisin resistance is expression of ltaSa, encoding a stress‐activated lipoteichoic acid synthase, and σX functions primarily by activation of the dlt operon controlling d‐alanylation of teichoic acids. Together, σM and σX regulate cell envelope structure to decrease access of nisin to its lipid II target. In contrast, σW is principally involved in protection against membrane permeabilization as it provides little protection against the nisin hinge region variant. σW contributes to nisin resistance by regulation of a signal peptide peptidase (SppA), phage shock proteins (PspA and YvlC, a PspC homologue) and tellurite resistance related proteins (YceGHI). These defensive mechanisms are also effective against other lantibiotics such as mersacidin, gallidermin and subtilin and comprise an important subset of the intrinsic antibiotic resistome of B. subtilis.
Model systems for a no‐analog future: species associations and climates during the last deglaciation
Authors: Williams John W. , Blois Jessica L. , Gill Jacquelyn L. , Gonzales Leila M. , Grimm Eric C. , Ordonez Alejandro , Shuman Bryan , Veloz Samuel D.
Published: August 2013

As the earth system moves to a novel state, model systems (experimental, observational, paleoecological) are needed to assess and improve the predictive accuracy of ecological models under environments with no contemporary analog. In recent years, we have intensively studied the no‐analog plant associations and climates in eastern North America during the last deglaciation to better constrain their spatiotemporal distribution, test hypotheses about climatic and megaherbivory controls, and assess the accuracy of species‐ and community‐level models. The formation of no‐analog plant associations was asynchronous, beginning first in the south‐central United States; at sites in the north‐central United States, it is linked to declining megafaunal abundances. Insolation and temperature were more seasonal than present, creating climates currently nonexistent in North America, and shifting species–climate relationships for some taxa. These shifts pose a common challenge to empirical paleoclimatic reconstructions, species distribution models (SDMs), and conservation–optimization models based on SDMs. Steps forward include combining recent and paleoecological data to more fully describe species’ fundamental niches, employing community‐level models to model shifts in species interactions under no‐analog climates, and assimilating paleoecological data with mechanistic ecosystem models. Accurately modeling species interactions under novel environments remains a fundamental challenge for all forms of ecological models.
Chemical properties of upland forest soils in the Catskills region
Authors: Johnson Chris E.
Published: August 2013

The Catskills forest provides a valuable array of ecosystem services for local and regional populations, including the provision of forest products, wildlife habitats, and high‐quality water. These services depend on chemical and biological processes that occur in forest soils. In 2011, we sampled soils in 25 headwater catchments in the Catskills region to quantify the pools of soil nutrients and examine the variation in soil properties in the region. The average soil depth in the 50 excavated pits was 56.6 cm. Average soil mass was 205 kg/m2. The pools of soil carbon and nitrogen averaged 58.5 and 3.95 Mg/ha, respectively. The thin organic horizons accounted for less than 1% of soil mass, but included 14% of the soil carbon and 11% of soil nitrogen. Catskills forest soils are highly acidic, with mean pH ranging between 3.9 and 4.75. Base saturation was high (>60%) in organic horizons and low (12–31%) in mineral soils. The pool of exchangeable calcium is approximately equivalent to 20 years of calcium export from headwater streams, raising concerns regarding the ability of these catchments to maintain current stream calcium concentrations. The data and samples collected in this study provide a baseline for future soil monitoring in the region.
Differential expression of transglutaminase genes in patients with chronic periodontitis
Authors: Currò M , Matarese G , Isola G , Caccamo D , Ventura VP , Cornelius C , Lentini M , Cordasco G , Ientile R
Published: August 2013

Objective

Gingival epithelium plays a key role in the protection of oral tissues from microbial challenge, especially during the periodontal disease. This study was aimed to evaluate levels of mRNA transcripts of different forms of transglutaminase in the human gingival tissues from patients with chronic periodontitis and relative controls.

Subjects and Methods

This study included 22 patients with chronic periodontitis (CP) and 22 healthy controls. For each patient, the values of probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were recorded. Gene expression of transglutaminase 1, transglutaminase 2, transglutaminase 3, and metalloprotease 2 was evaluated by real‐time PCR, while that of Factor XIIIA and metalloprotease 9 by RT‐PCR.

Results

The values of all the clinical parameters were significantly higher in the CP group than in the healthy control group (P < 0.05). In the CP group, the mRNA expression of transglutaminase 1 and transglutaminase 3 was significantly decreased in comparison with healthy control group. A slight nonsignificant changes of transglutaminase 2 gene expression were observed in samples from CP patients in comparison with controls.

Conclusions

These observations suggest that transglutaminase gene expression may be modified in response to chronic injury in the damaged gingival and emphasizes the key role of these enzymes in gingival remodelling/healing and adaptive processes.
Metabolic engineering of β‐carotene in orange fruit increases its in vivo antioxidant properties
Authors: Pons Elsa , Alquézar Berta , Rodríguez Ana , Martorell Patricia , Genovés Salvador , Ramón Daniel , Rodrigo María Jesús , Zacarías Lorenzo , Peña Leandro
Published: August 2013

Orange is a major crop and an important source of health‐promoting bioactive compounds. Increasing the levels of specific antioxidants in orange fruit through metabolic engineering could strengthen the fruit's health benefits. In this work, we have afforded enhancing the β‐carotene content of orange fruit through blocking by RNA interference the expression of an endogenous β‐carotene hydroxylase gene (Csβ‐CHX) that is involved in the conversion of β‐carotene into xanthophylls. Additionally, we have simultaneously overexpressed a key regulator gene of flowering transition, the FLOWERING LOCUS T from sweet orange (CsFT), in the transgenic juvenile plants, which allowed us to obtain fruit in an extremely short period of time. Silencing the Csβ‐CHX gene resulted in oranges with a deep yellow (‘golden’) phenotype and significant increases (up to 36‐fold) in β‐carotene content in the pulp. The capacity of β‐carotene‐enriched oranges for protection against oxidative stress in vivo was assessed using Caenorhabditis elegans as experimental animal model. Golden oranges induced a 20% higher antioxidant effect than the isogenic control. This is the first example of the successful metabolic engineering of the β‐carotene content (or the content of any other phytonutrient) in oranges and demonstrates the potential of genetic engineering for the nutritional enhancement of fruit tree crops.
Immunohistochemical analysis of thoracic endometriosis
Authors: Haga Takahiro , Kumasaka Toshio , Kurihara Masatoshi , Kataoka Hideyuki , Miura Myouta
Published: August 2013

Thoracic endometriosis is a rare disease responsible for catamenial pneumothorax. The immunohistochemical features of thoracic endometriosis are not well understood. An immunohistochemical examination of 84 diaphragmatic specimens of catamenial pneumothorax using antibodies against estrogen receptor (ER), progesterone receptor (PgR), CD10 and smooth muscle actin (SMA) was conducted. The endometrial tissue was small, and focally located around the chasm of the tendon on the side of the thoracic cavity. Endometrial stroma were detected in 84/84 (100%) of the specimens, endometrial glands were detected in 21/84 (25%) and smooth muscle was detected in 1/84 (1.2%). The endometrial stroma exhibited positive staining for ER in 74/84 (88.1%) of the specimens, PgR in 84/84 (100%), CD10 in 74/84 (88.1%) and SMA in 46/84 (54.8%). Because thoracic endometriosis is small in size, and only 25% of the resected tissue specimens were accompanied with the endometrial gland, an immunohistochemical analysis can be useful for their detection. The fact that over half of the thoracic endometrial stroma showed positive staining for SMA, and the existence of thoracic endometriosis accompanied by smooth muscle, indicated that some part of the thoracic endometriosis may have the ability to differentiate into smooth muscle, although further studies are needed to confirm this hypothesis.
Collective De Se Thoughts and Centered Worlds
Authors: Liao Shen‐yi
Published: August 2013

Two lines of investigation into the nature of mental content have proceeded in parallel until now. The first looks at thoughts that are attributable to collectives, such as bands' beliefs and teams' desires. So far, philosophers who have written on collective belief, collective intentionality, etc. have primarily focused on third‐personal attributions of thoughts to collectives. The second looks at de se, or self‐locating, thoughts, such as beliefs and desires that are essentially about oneself. So far, philosophers who have written on the de se have primarily focused on de se thoughts of individuals.

This paper looks at where these two lines of investigations intersect: collective de se thoughts, such as bands' and teams' beliefs and desires that are essentially about themselves. There is a surprising problem at this intersection: the most prominent framework for modeling de se thoughts, the framework of centered worlds, cannot model a special class of collective de se thoughts. A brief survey of this problem's solution space shows that collective de se thoughts pose a new challenge for modeling mental content.
Detection of chronic obstructive pulmonary disease in community‐based annual lung cancer screening: Chiba Chronic Obstructive Pulmonary Disease Lung Cancer Screening Study Group
Authors: Sekine Yasuo , Fujisawa Takehiko , Suzuki Kiminori , Tsutatani Shuko , Kubota Kazuko , Ikegami Hiroshi , Isobe Yuji , Nakamura Mitsugu , Takiguchi Yuichi , Tatsumi Koichiro
Published: August 2013

Background and objective

Detection of chronic obstructive pulmonary disease (COPD) is crucial in the management of COPD. The aim of this study was to establish the utility of a community‐based lung cancer screening for detecting COPD.

Methods

In Japan, community‐based lung cancer screening for residents who are 40 years or older using chest radiography is well established. A screening system in Chiba City, Japan, was used to detect COPD. The criteria to consider COPD at screening included age of 60 years or older, a smoking history and chronic respiratory symptoms. Participants fulfilling these criteria were referred for diagnostic evaluation consisting of pulmonary function testing (PFT) and chest computed tomography (CT).

Results

Of 89 100 Chiba City residents who underwent lung cancer screening, 72 653 residents were 60 years or older. Among them, 878 (1.0%) were identified with suspected COPD and referred for further evaluation. Of those identified, a total of 567 residents (64.6%, 567/878) underwent further evaluations, and 161 (28.4%) were reported to have COPD, with 38.5% of them requiring COPD treatment. To verify the diagnoses from the secondary evaluation centres, PFT and CT data were collected from 228 study participants, and 24.9% were diagnosed with COPD. CT findings classified according to the Goddard classification revealed that 20.1% of these participants had moderate to severe emphysema.

Conclusions

COPD screening added to a community‐based lung cancer screening programme may be effective in the detection of patients with COPD.
Quadriceps strength and endurance in fibrotic idiopathic interstitial pneumonia
Authors: Mendoza Laura , Gogali Athena , Shrikrishna Dinesh , Cavada Gabriel , Kemp Samuel V. , Natanek Samantha A. , Jackson Abigail S. , Polkey Michael I. , Wells Athol U. , Hopkinson Nicholas S.
Published: August 2013

Background and objective

Quadriceps muscle dysfunction is an important contributor to exercise limitation in chronic obstructive pulmonary disease, but little is known about skeletal muscle function and its impact on exercise capacity in patients with fibrotic idiopathic interstitial pneumonia (IIP). The aim of the study was to compare quadriceps strength and endurance in patients with fibrotic IIP and healthy controls, and relate it to exercise capacity.

Methods

Quadriceps strength and endurance, as well as respiratory muscle strength, and 6‐min walk distance were compared among 25 patients with fibrotic IIP, forced vital capacity mean (standard deviation) 78.7 (14.0) %predicted, carbon monoxide transfer factor 40.3 (10.9) %predicted and 33 age‐matched healthy controls using non‐volitional measures. Quadriceps strength was assessed using magnetic femoral nerve stimulation (quadriceps twitch force), and endurance using the decay in force in response to repetitive magnetic stimulation of the quadriceps over 5 min.

Results

Both groups had comparable anthropometrics, gender proportion and respiratory muscle strength. Patients were significantly weaker than controls; quadriceps twitch force 10.1 (3.0) kg versus 8.0 (2.4) kg (P = 0.013). Quadriceps force in response to repetitive magnetic stimulation declined significantly more rapidly in patients during the endurance protocol (P < 0.001). In controls, there was a significant relationship between 6‐min walk distance and quadriceps twitch force (r 0.40, P = 0.038), and quadriceps endurance (r 0.59, P = 0.016). In patients, only PaO2 and inspiratory muscle strength were retained as independent correlates of 6‐min walk distance (r2 = 0.3 P = 0.022).

Conclusions

Quadriceps strength and endurance are reduced in patients with fibrotic IIP compared with healthy controls, but are less tightly correlated with exercise performance.
Measuring (In)Security in the Event of Unemployment: Are We Forgetting Someone?
Authors: Berloffa Gabriella , Modena Francesca
Published: August 2013

In this paper we argue that the consequences of the unemployment risk may be quite different according to the number of household members who depend on the income of the earners. We propose new measures for the aggregate economic (in)security related to employment risk, that take into account the household composition: a per‐earner amount corresponding to the aggregate equivalent expected loss, and the inactive‐unemployed dependency rate (IUDR), i.e. the average number of persons not in the labor force that each unemployed has to provide for (beyond herself). Both have a simple interpretation but the latter has an advantage in terms of data‐requirement. Our results suggest that the overall level of insecurity associated with similar unemployment and replacement rates increases if we consider all the individuals in the households that are potentially affected by this risk. Moreover, the use of net rather than gross incomes and of micro‐level data changes quite significantly the relative position of countries in terms of insecurity levels.
Evaluating adult patients’ sleep: an integrative literature review in critical care
Authors: Ritmala‐Castren Marita , Lakanmaa Riitta‐Liisa , Virtanen Irina , Leino‐Kilpi Helena
Published: August 2013

Background

Patients in a critical care unit sleep quite poorly even when they appear to be sleeping. Sleep is light and fragmented. Acute lack of sleep causes patients suffering in the form of fatigue, irritability, disorientation and hallucinations. It may also affect their recovery and immune defence. To promote sleep, nurses must be able to evaluate patients’ sleep reliably.

Aim and objectives

Our aim was to form a comprehensive overview of the sleep evaluation methods in critical care. Our objectives were to determine the content and the quality of the methods as reported by the researchers. This overview hopefully improves the use of the sleep evaluation methods as part of sleep promoting nursing interventions and practices.

Method

The literature search was performed from the Ovid MEDLINE, CINAHL, an ‘All EBM Reviews’, and PsycINFO databases. The search terms sleep, evaluating sleep and critical care were used. An integrative review method was used to analyse the data.

Results

According to the 52 articles of this review, there is a wide variety of methods to evaluate patients’ sleep in critical care by observation, by asking for patient's own perception and by objective measures. Most instruments evaluate only total sleep time or the quality of sleep in general. The validity and reliability of the instruments has been insufficiently reported. Some questionnaires for patients’ perception have been tested and used in several studies.

Conclusion

Sleep evaluation instruments do not cover all dimensions of sleep since they mostly measure total sleep time or estimate the overall quality of sleep. The quality of the sleep evaluation instruments varies from scientifically tested tools to untested instruments. This review will allow nurses to recognise the strengths and limitations of sleep evaluation instruments when selecting one to be used in critical care. Valid information about patients’ sleep enables nurses to facilitate it.
TLR2 and TLR4 in Cutaneous Leishmaniasis Caused by Leishmania major
Authors: Tolouei S. , Hejazi S. H. , Ghaedi K. , Khamesipour A. , Hasheminia S. J.
Published: August 2013

Cutaneous leishmaniasis (CL) is a self‐healing skin disease which rarely for unknown reason(s) the lesion develops to a non‐healing form. It seems that the initial contact of Leishmania parasites with the host innate immune system is an important step in the outcome of the disease. Recent studies suggested that toll‐like receptors (TLRs) play a role in Leishmania recognition. In this study, the level of TLR2 and TLR4 was checked in patients with healing form of lesion and compared with that of patients with non‐healing form of lesion caused by Leishmania major. Gene expression of TLR2 and TLR4 in peripheral blood‐derived macrophages, before and after stimulation with live L. major promastigotes, was evaluated using quantitative real‐time reverse transcription PCR and flow cytometry. The results showed that the mean relative gene expression and difference membrane expression of TLR2 in macrophages of patients with healing form of lesion were significantly higher than patients with non‐healing form of lesion (P < 0.0001 and P = 0.0034), respectively, and the mean relative gene expression and difference in protein expression of TLR4 in macrophages of patients with healing form of lesion were significantly higher than that of patients with non‐healing form of lesion (P = 0.021 and P = 0.002), respectively. The data suggested a possible role for TLR2 and TLR4 in the outcome of CL lesion. Further studies are needed to understand more about the detail role of the immune factors in leishmaniasis.
Social Policy, “Deservingness,” and Sociotemporal Marginalization: Katrina Survivors and FEMA
Authors: Reid Megan
Published: August 2013

Limiting assistance in the context of the neoliberal U.S. welfare state relies on a distinction between the deserving and undeserving poor. Hurricane Katrina survivors were caught between two opposing cultural characterizations—”deserving” disaster victims and “undeserving” welfare cheats. In this article, I examine Hurricane Katrina survivors' experiences with the Federal Emergency Management Agency (FEMA)'s rental assistance policies and practices, as their experiences reveal important aspects of how aid is allocated in the context of the contemporary U.S. welfare state, and what consequences this has for marginalized populations. I analyze in‐depth interviews and field observations with displaced Katrina survivors and find that FEMA policies and practices assumed a “middle class” model of family structure and economic standing. Those who did not fit into this model were made to wait while their cases were investigated, which had negative psychological and material consequences. I argue that being made to wait, or temporal domination, is a central component of the larger sociotemporal marginalization of the poor, or the way in which time structures social stratification. Temporal domination is a feature of neoliberal social policy, neither maliciously intended nor entirely unintended, that has the consequence of punishing the “undeserving.”
Novel facial cosmetic area ‘O zone’ shows unique characteristics in sebum excretion and acne lesion distribution
Authors: Youn Sung Hwan , Choi Chong Won , Choi Jae Woo , Kim Bo Ri , Byun Sang Young , Youn Sang Woong
Published: August 2013

Background

We usually divided cosmetic facial zone into the T zone and U zone by the level of sebum secretion. Our recent studies suggested that the perioral area showed different characteristics in the aspect of acne development.

Objective

To investigate the unique characteristics of the O zone (perioral area) among the three facial areas.

Methods

A total of 102 patients clinically diagnosed as acne vulgaris were included. The acne lesions were counted from the clinical digital photographs by facial areas. The sebum level was measured using Sebumeter®. Area‐weighted (AW) sebum and AW density of three areas of face were calculated. Statistical analysis was performed according to age and gender.

Results

There were no differences in the mean AW sebum level between the gender and age groups. Male has higher AW density of acne lesions than female at the O zone. The mean AW density of acne lesions on the NT zone, U zone, and whole face showed decrease by age, but at the O zone, 21–30 years group showed the highest mean AW density of acne.

Limitations

Age‐ and gender‐matched patients do not represent the whole acne patients.

Conclusion

We suggested that the O zone is an independent facial zone, which showed a moderate‐to‐high sebum secreting area, maintained the acne lesions development by age, and predominated acne lesions in the male acne patients than female acne patients. Therefore, the O zone should be separated from the usual cosmetic T zone, and NT zone should replace the old T zone.
Advancing allele group‐specific amplification of the complete HLA‐C gene—isolation of novel alleles from three allele groups (C*04, C*07 and C*08)
Authors: Cisneros E. , Martínez‐Pomar N. , Vilches M. , Martín P. , de Pablo R. , Nuñez del Prado N. , Nieto A. , Matamoros N. , Moraru M. , Vilches C.
Published: August 2013

A variety of strategies have been designed for sequence‐based HLA typing (SBT) and for the isolation of new human leucocyte antigen (HLA) alleles, but unambiguous characterization of complete genomic sequences remains a challenge. We recently reported a simple method for the group‐specific amplification (GSA) and sequencing of a full‐length C*04 genomic sequence in isolation from the accompanying allele. Here we build on this strategy and present homologous methods that enable the isolation of HLA‐C alleles belonging to another two allele groups. Using this approach, which can be applied to sequence‐based typing in some clinical settings, we have successfully characterized three novel HLA‐C alleles (C*04:128, C*07:01:01:02, and C*08:62).
Two novel HLA class II alleles, DRB1*11:131 and DQB1*05:01:05, identified by sequence‐based typing
Authors: Jakubauskas A. , Valatkaite B. , Griskevicius L.
Published: August 2013

Two novel class II human leukocyte antigen alleles HLA‐DRB1*11:131 and HLA‐DQB1*05:01:05 are described.
Epstein–Barr virus‐associated smooth muscle tumors in a composite tissue allograft and a pediatric liver transplant recipient
Authors: Conrad A. , Brunet A.‐S. , Hervieu V. , Chauvet C. , Buron F. , Collardeau‐Frachon S. , Rivet C. , Cassier P. , Testelin S. , Lachaux A. , Morelon E. , Thaunat O.
Published: August 2013

Epstein–Barr virus (EBV) is known to establish latent infections in B‐lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV‐associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV‐associated post‐transplant smooth muscle tumors (EBV‐PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post‐transplant lymphoproliferative disorder before the diagnosis of EBV‐PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV‐PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV‐PTSMT are discussed based on a comprehensive review of the literature.
Decontamination of prions in a plasma product manufacturing environment
Authors: Bellon Anne , Comoy Emmanuel , Simoneau Steve , Mornac Sandrine , Dehen Capucine , Perrin Audrey , Arzel Aude , Arrabal Samuel , Baron Henry , Laude Hubert , You Bruno , Deslys Jean‐Philippe , Flan Benoit
Published: August 2013

Background

The high resistance of prions to inactivating treatments requires the proper management of decontaminating procedures of equipment in contact with materials of human or animal origin destined for medical purposes. Sodium hydroxide (NaOH) is widely used today for this purpose as it inactivates a wide variety of pathogens including prions.

Study Design and Methods

Several NaOH treatments were tested on prions bound to either stainless steel or chromatographic resins in industrial conditions with multiple prion strains.

Results

Data show a strong correlation between inactivation results obtained by immunochemical detection of the prion protein and those obtained with infectivity assays and establish effective inactivation treatments for prions bound to stainless steel or chromatographic resins (ion exchange and affinity), including treatments with lower NaOH concentrations. Furthermore, no obvious strain‐specific behavior difference was observed between experimental models.

Conclusion

The results generated by these investigations show that industrial NaOH decontamination regimens (in combination with the NaCl elution in the case of the chromatography process) attain substantial prion inactivation and/or removal between batches, thus providing added assurance to the biologic safety of the final plasma‐derived medicinal products.
Methylprednisolone fails to attenuate lung injury in a mouse model of transfusion related acute lung injury
Authors: Müller Marcella C.A. , Tuinman Pieter R. , van der Sluijs Koenraad F. , Boon Louis , Roelofs Joris J. , Vroom Margreeth B. , Juffermans Nicole P.
Published: August 2013

Background

Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related morbidity and mortality. Anecdotally, TRALI patients have been treated with corticosteroids. However, evidence for its therapeutic rationale in TRALI is lacking. We determined the effects of corticosteroids on lung injury in a “two‐hit” mouse model of antibody‐mediated TRALI.

Study Design and Methods

BALB/c mice were primed with lipopolysaccharide, after which TRALI was induced by injecting major histocompatibility complex (MHC)‐I antibody against H2Kd. Mice infused with phosphate‐buffered saline served as controls. Simultaneously, one group of TRALI mice was infused with methylprednisolone (MPS; 2 mg/kg). Mice were supported by mechanical ventilation for 2 hours, after which bronchoalveolar lavage fluid (BALF) and lung homogenate were obtained. Statistics were obtained by one‐way analysis of variance or Kruskal‐Wallis.

Results

Injection of MHC‐I antibodies resulted in TRALI, indicated by pulmonary edema and increased BALF levels of protein and the proinflammatory mediators macrophage inflammatory protein‐2, keratinocyte‐derived chemokine, and interleukin (IL)‐6. Administration of MPS did not affect the amount of edema nor pulmonary protein and chemokine levels. MPS reduced systemic inflammatory reaction as well as IL‐6 levels in the BALF.

Conclusion

In a two‐hit model of antibody‐mediated TRALI, MPS attenuated the IL‐6 host response, but failed to prevent the development of lung injury.
Utility of cross‐matched platelet transfusions in patients with hypoproliferative thrombocytopenia: a systematic review
Authors: Vassallo Ralph R. , Fung Mark , Rebulla Paolo , Duquesnoy Rene , Saw Chee Loong , Slichter Sherrill J. , Tanael Susano , Shehata Nadine ,   International Collaboration for Guideline Development, Implementation and Evaluation for Transfusion Therapies. Collaborators (22)
Published: August 2013

Background

Multiply transfused hypoproliferative thrombocytopenic (HT) patients with alloimmune transfusion refractoriness require specially selected platelets (PLTs). Cross‐matching apheresis PLTs is a popular support option, avoiding requirements for large panels of typed donors for HLA‐based selection. We undertook a systematic review of the utility of various cross‐matching techniques on mortality reduction, prevention of hemorrhage, alloimmunization and refractoriness, and improvement in PLT utilization or count increments.

Study Design and Methods

A systematic review to December 2012 was conducted of MEDLINE, EMBASE, and Cochrane databases along with a bibliographic search of pertinent references.

Results

Of 146 retrieved citations, 20 met inclusion criteria. Eleven more were chosen from bibliographies, describing 29 unique cohorts. All but five enrolled transfusion‐refractory, predominantly alloimmunized patients. Cross‐match impact on mortality and hemorrhage could not be assessed from these studies. Two studies demonstrated durable corrected count increments and/or breadth of alloimmunization throughout cross‐match support; none addressed development or persistence of refractoriness. In alloimmunized refractory patients and nonrefractory cohorts with greater than 25% alloimmunization, higher increments were seen with cross‐match–compatible PLTs than incompatible or un–cross‐matched units. In two nonrefractory, nonalloimmunized cohorts, the lack of utility of cross‐match was reflected by test sensitivity of less than 20%. Comparison of cross‐matched PLT success with that of HLA‐identical units revealed inferior success rates for the former in one study and equivalent rates in another. No trend was observed regarding relative utility of the various commonly employed techniques.

Conclusion

Cross‐matched PLTs are useful in increasing PLT counts in alloimmunized, transfusion‐refractory HT patients, but data about their impact on hemorrhage and mortality are lacking.
Determination of platinum surface contamination in veterinary and human oncology centres using inductively coupled plasma mass spectrometry
Authors: Janssens T. , Brouwers E. E. M. , de Vos J. P. , de Vries N. , Schellens J. H. M. , Beijnen J. H.
Published: August 2013

The objective of this study was to determine the surface contamination with platinum‐containing antineoplastic drugs in veterinary and human oncology centres. Inductively coupled plasma mass spectrometry was used to measure platinum levels in surface samples. In veterinary and human oncology centres, 46.3 and 68.9% of the sampled surfaces demonstrated platinum contamination, respectively. Highest platinum levels were found in the preparation rooms (44.6 pg cm−2) in veterinary centres, while maximal levels in human centres were found in oncology patient‐only toilets (725 pg cm−2). Transference of platinum by workers outside areas where antineoplastic drugs were handled was observed in veterinary and human oncology centres. In conclusion, only low levels of platinum contamination attributable to carboplatin were found in the sampled veterinary oncology centres. However, dispersion of platinum outside areas where antineoplastic drugs were handled was detected in veterinary and human oncology centres. Consequently, not only personnel, but also others may be exposed to platinum.
Intravital Förster resonance energy transfer imaging reveals elevated [Ca2+]i and enhanced sympathetic tone in femoral arteries of angiotensin II‐infused hypertensive biosensor mice
Authors: Wang Youhua , Chen Ling , Wier W. Gil , Zhang Jin
Published: August 2013

Key points

It is desirable to study altered artery function in hypertension in living animals, where factors influencing artery function are intact.

We infused ‘biosensor’ mice chronically with angiotensin II to produce hypertension, and used intravital Förster resonance energy transfer microscopy to measure, simultaneously, [Ca2+]i and artery diameter in vivo.

Femoral arteries in hypertensive mice had increased basal (resting) [Ca2+]i and were more constricted than femoral arteries in saline‐infused mice. These differences were abolished by blocking (1) all peripheral sympathetic nerve activity (SNA), or (2) vascular α1‐adrenoceptors, but not by blocking vascular angiotensin II or arginine vasopressin receptors.

Neither contractility nor structural changes were found in femoral arteries of angiotensin II‐infused mice.

The results support previous suggestions that angiotensin II infusion raises blood pressure by acting on the CNS to increase SNA, which increases smooth muscle [Ca2+]i. Infused angiotensin II does not act directly on arterial angiotensin II receptors.

Abstract  Artery narrowing in hypertension can only result from structural remodelling of the artery, or increased smooth muscle contraction. The latter may occur with, or without, increases in [Ca2+]i. Here, we sought to measure, in living hypertensive mice, possible changes in artery dimensions and/or [Ca2+]i, and to determine some of the mechanisms involved. Ca2+/calmodulin biosensor (Förster resonance energy transfer‐based) mice were made hypertensive by s.c. infusion of angiotensin II (Ang II, 400 ng kg−1 min−1, 2–3 weeks). Intravital fluorescence microscopy was used to determine [Ca2+]i and outer diameter of surgically exposed, intact femoral artery (FA) of anaesthetized mice. Active contractile FA ‘tone’ was calculated from the basal‐state diameter and the passive (i.e. Ca2+‐free) diameter (PD). Compared to saline control, FAs of Ang II‐infused mice had (1) ∼21% higher active tone and (2) ∼78 nm higher smooth muscle [Ca2+]i, but (3) the same PDs. The local Ang II receptor (AT1R) blocker losartan had negligible effect on tone or [Ca2+]i in control FAs, but reduced the basal tone by ∼9% in Ang II FAs. Both i.v. hexamethonium and locally applied prazosin abolished the difference in FA tone and [Ca2+]i, suggesting a dominant role of sympathetic nerve activity (SNA). Changes in diameter and [Ca2+]i in response to locally applied phenylephrine, Ang II, arginine vasopressin, elevated [K+]o and acetylcholine were not altered. In summary, FAs of living Ang II hypertensive mice have higher [Ca2+]i, and are more constricted, due, primarily, to elevated SNA and some increased arterial AT1R activation. Evidence of altered artery reactivity or remodeling was not found.
Closed-Form Analytical Solutions for Laminar Natural Convection on Horizontal Plates
Authors: Guha Abhijit , Samanta Subho
Published: August 2013

A boundary layer based integral analysis has been performed to investigate laminar natural convection heat transfer characteristics for fluids with arbitrary Prandtl number over a semi-infinite horizontal plate subjected either to a variable wall temperature or variable heat flux. The wall temperature is assumed to vary in the form T¯w(x¯)-T¯∞=ax¯n whereas the heat flux is assumed to vary according to qw(x¯)=bx¯m. Analytical closed-form solutions for local and average Nusselt number valid for arbitrary values of Prandtl number and nonuniform heating conditions are mathematically derived here. The effects of various values of Prandtl number and the index n or m on the heat transfer coefficients are presented. The results of the integral analysis compare well with that of previously published similarity theory, numerical computations and experiments. A study is presented on how the choice for velocity and temperature profiles affects the results of the integral theory. The theory has been generalized for arbitrary orders of the polynomials representing the velocity and temperature profiles. The subtle role of Prandtl number in determining the relative thicknesses of the velocity and temperature boundary layers for natural convection is elucidated and contrasted with that in forced convection. It is found that, in natural convection, the two boundary layers are of comparable thickness if Pr ≤ 1 or Pr ≈ 1. It is only when the Prandtl number is large (Pr > 1) that the velocity boundary layer is thicker than the thermal boundary layer.
Quantitative Stability Analysis Using Real-Valued Frequency Response Data
Authors: Schmid Martin , Blumenthal Ralf S. , Schulze Moritz , Polifke Wolfgang , Sattelmayer Thomas
Published: August 2013

Models for the analysis of thermoacoustic instabilities are conveniently formulated in the frequency domain. In this case one often faces the difficulty that the response behavior of some elements of the system is only known at real-valued frequencies, although the transfer behavior at complex-valued frequencies is required for the quantification of the growth rates of instabilities. The present paper discusses various methods for extrapolation of frequency response data at real-valued frequencies into the complex plane. Some methods have been used previously in thermoacoustic stability analysis; others are newly proposed. First the pertinent mathematical background is reviewed, then the sensitivity of predicted growth rates on the extrapolation scheme is explored. This is done by applying different methods to a simple thermoacoustic system, i.e., a ducted premixed flame, for which an analytical solution is known. A short analysis determining the region of confidence of the extrapolated transfer function is carried out to link the present study to practical applications. The present study can be seen as a practical guideline for using frequency response data collected for a set of real-valued frequencies in quantitative linear stability analysis.
Adhesion Map for Thin Membranes
Authors: Li Guangxu , Wan Kai-tak
Published: August 2013

A new Tabor's parameter ψ is defined for adhesion-delamination of thin membranes. A small ψ corresponds to a thick, small, and stiff membrane under the influence of a long-range weak surface force, as in the Derjaguin–Muller–Toporov (DMT) limit. A large ψ corresponds to a thin, large, and flexible membrane under the influence of a short-range strong surface force, as in the Johnson–Kendall–Roberts (JKR) limit. A new adhesion map based on ψ is drawn to summarize the “pull-off” events and the delamination trajectory for membranes under mixed stretching-bending deformation. Maps are generated for one- and two-dimensional membranes clamped at the edge.
Recent search for new superhard materials: Go nano!
Authors: Veprek Stan
Published: August 2013

High elastic moduli do not guarantee high hardness because upon finite shear electronic instabilities often occur that result in transformation to softer phases. Therefore, the author concentrates on the extrinsically superhard nanostructured materials, which are the most promising. Decreasing crystallite size results in strengthening and hardening because the grain boundaries impede the plasticity (e.g., Hall–Petch strengthening in case of dislocation activity). However, this hardening is limited to a crystallite size down to 10–15 nm below which softening due to grain boundary shear dominates. This softening can be reduced by forming low energy grain boundaries or a strong interfacial layer. In such a way, much higher hardness enhancement can be achieved. The emphasis will be on the understanding of the mechanisms of the hardness enhancement. A special section deals with examples of the present industrial applications of such coatings on tools for machining in order to illustrate that these materials are already in large-scale use. In the last section, the author summarizes the open questions and limitations for the preparation of the super- and ultrahard nanocomposite coatings and possible ways on how to overcome them.
Automated treatment planning for a dedicated multi‐source intra‐cranial radiosurgery treatment unit accounting for overlapping structures and dose homogeneity
Authors: Ghobadi Kimia , Ghaffari Hamid R. , Aleman Dionne M. , Jaffray David A. , Ruschin Mark
Published: August 2013

Purpose:

The purpose of this work is to advance the two‐step approach for Gamma Knife® Perfexion™ (PFX) optimization to account for dose homogeneity and overlap between the planning target volume (PTV) and organs‐at‐risk (OARs).

Methods:

In the first step, a geometry‐based algorithm is used to quickly select isocentre locations while explicitly accounting for PTV‐OARs overlaps. In this approach, the PTV is divided into subvolumes based on the PTV‐OARs overlaps and the distance of voxels to the overlaps. Only a few isocentres are selected in the overlap volume, and a higher number of isocentres are carefully selected among voxels that are immediately close to the overlap volume. In the second step, a convex optimization is solved to find the optimal combination of collimator sizes and their radiation duration for each isocentre location.

Results:

This two‐step approach is tested on seven clinical cases (comprising 11 targets) for which the authors assess coverage, OARs dose, and homogeneity index and relate these parameters to the overlap fraction for each case. In terms of coverage, the meanV99 for the gross target volume (GTV) was 99.8% while the V95 for the PTV averaged at 94.6%, thus satisfying the clinical objectives of 99% for GTV and 95% for PTV, respectively. The mean relative dose to the brainstem was 87.7% of the prescription dose (with maximum 108%), while on average, 11.3% of the PTV overlapped with the brainstem. The mean beam‐on time per fraction per dose was 8.6 min with calibration dose rate of 3.5 Gy/min, and the computational time averaged at 205 min. Compared with previous work involving single‐fraction radiosurgery, the resulting plans were more homogeneous with average homogeneity index of 1.18 compared to 1.47.

Conclusions:

PFX treatment plans with homogeneous dose distribution can be achieved by inverse planning using geometric isocentre selection and mathematical modeling and optimization techniques. The quality of the obtained treatment plans are clinically satisfactory while the homogeneity index is improved compared to conventional PFX plans.
Closing the Loop
Authors: Vinson Valda
Published: August 2013

Differences in the rate of an internal protein loop closure are coupled to differences in enzyme reaction rates.
Tipping the Vasculogenic Balance
Authors: Berndt Jason D.
Published: August 2013

The cytokine TNFSF15 limits angiogenesis by modulating the abundance of VEGFR isoforms.
Taking Fatty Liver Disease Down a Notch
Authors: Ferrarelli Leslie K.
Published: August 2013

Notch activates a transcriptional program that promotes fat metabolism in the liver.
Up-Regulation of PD-L1, IDO, and T
regs
in the Melanoma Tumor Microenvironment Is Driven by CD8
+
T Cells
Authors: Spranger Stefani , Spaapen Robbert M. , Zha Yuanyuan , Williams Jason , Meng Yuru , Ha Thanh T. , Gajewski Thomas F.
Published: August 2013

CD8
+
T cells induce immunosuppressive mechanisms in the tumor microenvironment.
Curing Consortium Fatigue
Authors: Papadaki Magdalini , Hirsch Gigi
Published: August 2013

The complex pathology of consortium fatigue provides diagnostic data on how to improve collaboration in biomedical innovation.
Estimation of Blood Flow Resistance in the Lung with MRI
Authors: Tonelli Adriano R.
Published: August 2013

Cardiac magnetic resonance can be used to monitor pulmonary vascular resistance changes in animal models of pulmonary hypertension.