bluuebunny/crossref_metadata_2025 huggingface dataset:
Thirst beats hunger – declining hydration during drought prevents carbon starvation in Norway spruce saplings
Authors: Hartmann Henrik , Ziegler Waldemar , Kolle Olaf , Trumbore Susan
Published: May 2013

Drought‐induced tree mortality results from an interaction of several mechanisms. Plant water and carbon relations are interdependent and assessments of their individual contributions are difficult. Because drought always affects both plant hydration and carbon assimilation, it is challenging to disentangle their concomitant effects on carbon balance and carbon translocation. Here, we report results of a manipulation experiment specifically designed to separate drought effects on carbon and water relations from those on carbon translocation.

In a glasshouse experiment, we manipulated the carbon balance of Norway spruce saplings exposed to either drought or carbon starvation (CO2 withdrawal), or both treatments, and compared the dynamics of carbon exchange, allocation and storage in different tissues.

Drought killed trees much faster than did carbon starvation. Storage C pools were not depleted at death for droughted trees as they were for starved, well‐watered trees. Hence drought has a significant detrimental effect on a plant's ability to utilize stored carbon.

Unless they can be transported to where they are needed, sufficient carbon reserves alone will not assure survival of a drought except under specific conditions, such as moderate drought, or in species that maintain plant water relations required for carbon re‐mobilization.
What can stimulated emission do for bioimaging?
Authors: Wei Lu , Min Wei
Published: May 2013

Advances in bioimaging have revolutionized our ability to study life phenomena at a microscopic scale. In particular, the stimulated emission process, a universal mechanism that competes with spontaneous emission, has emerged as a powerful driving force for advancing light microscopy. The present review summarizes and compares three related techniques that each measure a different physical quantity involved in the stimulated emission process in order to tackle various challenges in light microscopy. Stimulated emission depletion microscopy, which detects the residual fluorescence after quenching, can break the diffraction‐limited resolution barrier in fluorescence microscopy. Stimulated emission microscopy is capable of imaging nonfluorescent but absorbing chromophores by detecting the intensity gain of the stimulated emission beam. Very recently, stimulated emission reduced fluorescence microscopy has been proposed, in which the reduced fluorescence due to focal stimulation is measured to extend the fundamental imaging‐depth limit of two‐photon microscopy. Thus, through ingenious spectroscopy design in distinct microscopy contexts, stimulated emission has opened up several new territories for bioimaging, allowing examination of biological structures that are ever smaller, darker, and deeper.
Anti‐β2‐glycoprotein I antibodies
Authors: Willis Rohan , Pierangeli Silvia S.
Published: May 2013

Anti‐β2‐glycoprotein I (anti‐β2GPI) antibodies are the main antiphospholipid antibodies, along with anticardiolipin and lupus anticoagulant, that characterize the autoimmune disease antiphospholipid syndrome (APS). While the exact physiological functions of β2GPI are unknown, there is overwhelming evidence that anti‐β2GPI antibodies are pathogenic, contributing to thrombosis, pregnancy morbidity, and accelerated atherosclerosis in APS and systemic lupus erythematosus patients. The revelation that these antibodies play a central role in the pathogenesis and pathophysiology of APS has driven research to characterize the physiology and structure of β2GPI as well as the pathogenic effects of anti‐β2GPI antibodies. It has also resulted in the development of improved testing methodologies for detecting these antibodies. In this review we discuss the characteristics of β2GPI; the generation, pathogenic effects, and standardized testing of anti‐β2GPI antibodies; and the potential use of therapies that target the β2GPI/ anti‐β2GPI interaction in the treatment of APS.
Control of inflammatory heart disease by CD4+ T cells
Authors: Barin Jobert G. , Čiháková Daniela
Published: May 2013

This review focuses on autoimmune myocarditis and its sequela, inflammatory dilated cardiomyopathy (DCMI), and the inflammatory and immune mechanisms underlying the pathogenesis of these diseases. Several mouse models of myocarditis and DCMI have improved our knowledge of the pathogenesis of these diseases, informing more general problems of cardiac remodeling and heart failure. CD4+ T cells are critical in driving the pathogenesis of myocarditis. We discuss in detail the role of T helper cell subtypes in the pathogenesis of myocarditis, the biology of T cell–derived effector cytokines, and the participation of other leukocytic effectors in mediating disease pathophysiology. We discuss interactions between these subsets in both suppressive and collaborative fashions. These findings indicate that cardiac inflammatory disease, and autoimmunity in general, may be more diverse in divergent effector mechanisms than has previously been appreciated.
Relationships between molds and asthma suggesting non‐allergic mechanisms. A rural‐urban comparison
Authors: Flamant‐Hulin Marion , Annesi‐Maesano Isabella , Caillaud Denis
Published: May 2013

Background

A fungal index, based on specific microbial volatile organic compounds (MVOCs) emission, was employed and related to asthma in children from rural and urban dwellings after stratification on the children atopic status.

Methods

A nested case‐control design was used to draw, from 2 cross‐sectional surveys, 20 asthmatics and 26 controls living in urban areas, and 24 asthmatics and 25 controls in rural areas. MVOCs levels were assessed in the living‐room during one week; during that week, children performed clinical tests and their parents were invited to fill in a questionnaire on respiratory health.

Results

According to the objective fungal index, 70.5% of cases and 49.0% of controls were exposed to molds. More children with current asthma had experienced mold exposure in their homes (OR=3.38, 95% CI (1.16; 9.90)), especially amongst children living in rural areas. Atopic status modified this association: exposure to molds was found to be related to current asthma only in non‐atopic children (OR=10.42, 95% CI (2.42; 44.81)). Among urban ‐dwelling children that could be screened at hospital, asthmatic children living in contaminated dwellings had a higher proportion of blood neutrophils and a lower FEV1 (forced expiratory volume in 1 second) than non‐exposed ones.

Conclusion

Our findings based on an objective assessment of MVOCs suggest adverse respiratory effects of molds. Our results suggest that when looking at the aetiology of non‐atopic asthma, mold exposure should be systematically assessed.
Markers of operational immune tolerance after pediatric liver transplantation in patients under immunosuppression
Authors: Schulz‐Juergensen S. , Marischen L. , Wesch D. , Oberg H. H. , Fändrich F. , Kabelitz D. , Burdelski M.
Published: May 2013

A prospective identification of the estimated 20–50% of pediatric LTX recipients developing operational tolerance would be of great clinical advantage. So far markers of immune tolerance – T‐cell subpopulations or gene expression profiles – have been investigated only retrospectively in successfully weaned patients. Fifty children aged 8–265 months (median 89) were investigated 1–180 months (median 44) after LTX under ongoing immunosuppression. T‐cell subpopulations were measured during regular post‐transplant visits using FACS (Vδ1‐ vs. Vδ2‐γδ‐T cells and Tregs). A Vδ1/Vδ2‐γδ‐T‐cell ratio ≥1.42 previously reported in operational tolerance was found in 12 of 50 (24%) patients. In analogy, a Treg count ≥44 per μL was found in 35 of 50 (70%) patients and a Treg proportion ≥2.23% of CD3+‐T cells in 39 of 50 (78%) patients. Only 9 of 50 patients (18%) fulfilled both criteria. The parameters Vδ1/Vδ2‐γδ‐T‐cell ratio and Tregs were not significantly correlated to each other or with donor type or immunosuppression. Vδ1/Vδ2‐γδ‐T‐cell ratio was more stable in serial examinations compared with Treg analyses. The observed proportion of 18% pediatric LTX patients with potential operational tolerance is in accordance with previous reports. However, clinical experience shows that rejections may happen even after long‐time weaning of immunosuppression. This suggests that operational tolerance is a dynamic process, with uncertain prediction by Vδ1/Vδ2‐γδ‐T‐cell ratio and/or Tregs under immunosuppression.
Hematopoietic stem cell transplantation for children with primary immunodeficiency diseases: Single center experience in Jordan
Authors: Amayiri Nisreen , Al‐Zaben Abdulhadi , Ghatasheh Lubna , Frangoul Haydar , Hussein Ayad Ahmed
Published: May 2013

HSCT can be curative for many PID. Little is known about the outcome of HSCT for patients with PID in the developing countries. We retrospectively reviewed all children with PID who received HSCT at KHCC in Jordan between August 2003 and October 2011. Twenty‐eight patients were identified. The median age was 16 months (3 months–17 yr). Patients' diagnoses were SCID (n = 16), CHS (n = 3), HLH (n = 3), WAS (n = 2), Griscelli syndrome (n = 1), ALPS (n = 1), Omenn's syndrome (n = 1), and DiGeorge syndrome (n = 1). Seventeen patients received HLA‐matched related HSCT, eight received maternal un‐manipulated haploidentical HSCT, and three received unrelated cord blood transplantation. Nine patients (32%) developed BCGosis secondary to reactivation of pretransplant vaccination. Three died while still receiving anti‐tuberculosis drugs, one still on treatment, and all others have recovered. Six patients had graft failure; four of them received no conditioning regimens. At a median follow up of 32 months (range 1‐67), 21 patients are alive, with overall survival of 72%. We conclude that HSCT for PID patients can be performed with a good outcome in developing countries; however, delayed diagnosis or referral and BCG reactivation are unique challenges.
Opsins are involved in nymphal photoperiodic responses in the cricket Modicogryllus siamensis
Authors: TAMAKI SAORI , TAKEMOTO SAKI , URYU OUTA , KAMAE YUICHI , TOMIOKA KENJI
Published: May 2013

The cricket Modicogryllus siamensis Chopard shows photoperiod‐dependent changes in the duration of nymphal development: nymphs become adult within 60 days after hatching, undergoing seven moults under long‐day conditions, whereas, under short‐day conditions, nymphal development takes much longer (approximately 180 days) with an increased number of moults. Because removal of the compound eyes alters this photoperiodic response, the eyes may be involved in light detection during the photoperiodic response. The role of opsins, expressed in the compound eye, is examined in the present study with reference to the photoperiodic response. Molecular cloning identifies cDNAs of three opsins, opsin‐Ultra Violet (Ms'op‐UV), opsin‐Blue (Ms'op‐B) and opsin‐Long Wave (Ms'op‐LW), and in situ hybridization reveals that the opsin genes are expressed in specific regions of the compound eye in a gene‐specific manner. RNA interference (RNAi) technology using the opsin genes results in a partial disruption in the long‐day responses; most of the treated crickets showed eight or more moults and up to 23.5% show a prolonged nymphal period that is typical of short‐day responses. Under short‐day conditions, op‐UV RNAi crickets show earlier adult development, whereas no distinct alterations are observed in op‐B and op‐LW RNAi insects. The results suggest that the opsin genes may play differential roles in the photoperiodic response in the cricket and that the results can be at least partially explained in terms of the external coincidence model of photoperiodic time measurement.
Superresolution Imaging with Switchable Fluorophores Based on Oxazine Auxochromes
Authors: Petriella Marco , Deniz Erhan , Swaminathan Subramani , Roberti Maria J. , Raymo Françisco M. , Bossi Mariano L.
Published: May 2013

The spatial resolution of fluorescence microscopes is limited by diffraction to about half of the light wavelength, hampering the observation of many important intracellular processes. Recent emerging techniques have overcome that diffraction barrier using the temporal discrimination of close objects that are otherwise unresolved or blurred within the spatial resolution of the microscope. The key of these techniques is to switch the signal of fluorescence markers on and off exploiting their distinct molecular states, and detect and localize these markers at the single‐molecule level. This underlying principle highlights the critical role of the photophysical properties of the probes, and the importance of finding adequate switching mechanisms. Here, we present strategies to achieve fluorescence modulation based on novel molecular assemblies containing a [1,3]oxazine as the two states, building block responsible for the transformation. Two different triggering events, based on the photochromic and halochromic properties of the oxazine, induce a large absorption and emission bathochromic shift of a pendant fluorophore, as the ultimate fluorescence switching event. The implementation of these approaches to achieve spatial resolution beyond the diffraction limit is also discussed.
Against Doxastic Compatibilism
Authors: Peels Rik
Published: May 2013

William Alston has argued that the so‐called deontological conception of epistemic justification, on which epistemic justification is to be spelled out in terms of blame, responsibility, and obligations, is untenable. The basic idea of the argument is that this conception is untenable because we lack voluntary control over our beliefs and, therefore, cannot have any obligations to hold certain beliefs. If this is convincing, however, the argument threatens the very idea of doxastic responsibility. For, how can we ever be responsible for our beliefs if we lack control over them? Several philosophers have argued that the idea that we bear responsibility for our beliefs can be saved, because absence of voluntary control over our beliefs is perfectly compatible with having obligations to hold particular beliefs. With others, I call this view ‘doxastic compatibilism’. It comes in two varieties. On the first variety, doxastic obligations do not require any kind of doxastic control whatsoever. I argue that this variety of doxastic compatibilism fails because it confuses doxasticresponsibilitywith other closely related phenomena. On the second variety, doxastic obligations do not require voluntary doxastic control, but only compatibilist doxastic control (roughly, reason‐responsiveness) and we do in fact have such control. I grant that we have such control, but also argue that having such control is insufficient for bearing doxastic responsibility. The plausibility of the examples put forward by doxastic compatibilists in support of the claim that itissufficient for doxastic responsibility derives from the fact that in these examples, the subjects have control over factors that influence what they believe rather than control over those beliefs themselves.
D2‐40‐positive lymphatic vessel invasion is not a poor prognostic factor in stage I lung adenocarcinoma
Authors: Shimizu Kei , Funai Kazuhito , Sugimura Haruhiko , Sekihara Keigo , Kawase Akikazu , Shiiya Norihiko
Published: May 2013

The present study investigates whether lymphatic vessel invasion (LVI) detected by D2‐40 staining is a prognostic factor for stage I adenocarcinoma of the lung. We retrospectively reviewed 124 patients who underwent complete resection for stage I adenocarcinoma of the lung from January 1983 to June 2003. LVI was microscopically evaluated using D2‐40 immunostaining. The median follow‐up was 71 months. The LVI positive rate was 37%. The 5‐year cancer‐specific survival rates of the D2‐40 positive LVI and negative groups were 88.8% and 84.3%, respectively (P = 0.630). The stage I lung adenocarcinoma patients who were determined to be LVI positive based on D2‐40 immunostaining did not have a significantly poorer prognosis than the LVI negative cases. Thus, lymphatic microinvasion may not be a prognostic indicator in early lung cancer, although advanced LVI does appear to correlate with survival. It is therefore unnecessary to use D2‐40 immunostaining to diagnose LVI in practical settings, and Hematoxylin‐Eosin and Elastica van Gieson staining should continue to be used to predict the prognosis of patients with stage I lung adenocarcinoma.
Cytoskeleton organisation during the infection of three brown algal species, Ectocarpus siliculosus,Ectocarpus crouaniorum and Pylaiella littoralis, by the intracellular marine oomycete Eurychasma dicksonii
Authors: Tsirigoti A. , Küpper F. C. , Gachon C. M. M. , Katsaros C.
Published: May 2013

Oomycete diseases in seaweeds are probably widespread and of significant ecological and economic impact, but overall still poorly understood. This study investigates the organisation of the cytoskeleton during infection of three brown algal species, Pylaiella littoralis, Ectocarpus siliculosus, and Ectocarpus crouaniorum, by the basal marine oomycete Eurychasma dicksonii. Immunofluorescence staining of tubulin revealed how the development of this intracellular biotrophic pathogen impacts on microtubule (MT) organisation of its algal host. The host MT cytoskeleton remains normal and organised by the centrosome until very late stages of the infection. Additionally, the organisation of the parasite's cytoskeleton was examined. During mitosis of the E. dicksonii nucleus the MT focal point (microtubule organisation centre, MTOC, putative centrosome) duplicates and each daughter MTOC migrates to opposite poles of the nucleus. This similarity in MT organisation between the host and pathogen reflects the relatively close phylogenetic relationship between oomycetes and brown algae. Moreover, actin labelling with rhodamine‐phalloidin in E. dicksonii revealed typical images of actin dots connected by fine actin filament bundles in the cortical cytoplasm. The functional and phylogenetic implications of our observations are discussed.
Mono‐ and digalactosyldiacylglycerol composition of the marennine‐producing diatom, Haslea ostrearia: Comparison to a selection of pennate and centric diatoms
Authors: Dodson V. Joshua , Dahmen Jeremy L. , Mouget Jean‐Luc , Leblond Jeffrey D.
Published: May 2013

Diatoms are one of the largest groups of primary producers in the oceans, yet despite their environmental importance little is known about their plastidial lipid biochemistry. It has been previously reported that Skeletonema species contain primarily C16/C16 and C20/C16 forms of mono‐ and digalactosyldiacylglycerol (MGDG and DGDG, respectively). Likewise, it was also reported that Phaeodactylum tricornutum contains primarily C16/C16 and C20/C20 forms of MGDG and DGDG. We seek to relate their studies to other diatoms, both in the centrics and pennates, with particular focus on the marennine‐producing pennate diatom, Haslea ostrearia. To this end, the composition and positional distribution of fatty acids of MGDG and DGDG were examined using positive‐ion electrospray ionization/mass spectrometry (ESI/MS). Two centric diatoms, Skeletonema marinoi and Thalassiosira weissflogii, and the pennate diatom, P. tricornutum, contained primarily C20/C16 (sn‐1/sn‐2) and C18/C16 forms of MGDG and DGDG. The other pennate diatoms, H. ostrearia and Navicula perminuta, contained primarily C18/C16 or C18/C18 forms of MGDG and DGDG, indicating a previously unrecognized fatty acid diversity in diatom MGDG and DGDG.
Application of Reproductive Biotechnology for the Recovery of Endangered Breeds: Birth of the First Calf of Murciana–Levantina Bovine Breed Derived by OPU, In vitro Production and Embryo Vitrification
Authors: Ruiz S , Romero‐Aguirregomezcorta J , Astiz S , Peinado B , Almela L , Poto A
Published: May 2013

Contents

In a conservation project, reproductive biotechnology was implemented for the recovery and conservation of an endangered bovine breed in Spain. The breed Murciana–Levantina, declared to be worthy of special protection status (http://www.fao.org/newsroom/en/news/2006/1000464/index.html), is of great interest because of its hardness, longevity, docility and disease resistance. This contribution describes the birth of the first calf of this breed obtained by reproductive biotechnology, using ultrasound‐guided punction and aspiration of ovarian follicles, in vitro embryo production, vitrification of embryos by a cryotop device and, finally, the transfer of cryopreserved embryos to recipient heifers of a commercial dairy herd.
The Effect of Lactation on Post‐Partum Uterine Involution in Holstein Dairy Cows
Authors: Scully S , Maillo V , Duffy P , Kelly AK , Crowe MA , Rizos D , Lonergan P
Published: May 2013

Contents

The objective was to examine the effect of lactation on uterine involution in post‐partum dairy cows. Holstein primiparous cows were used (n = 19, mean age: 3.9 ± 0.1 years). At calving, cows were randomly assigned to one of two treatment groups, lactating (n = 11) or non‐lactating (i.e. dried off at calving, n = 8). Examination of the reproductive tract was carried out by ultrasonography twice weekly until week 7 post‐partum. Blood samples were collected twice weekly for the analysis of progesterone to indicate the resumption of cyclicity and metabolites indicative of energy status. Uterine involution was assessed in terms of size of the uterine horns, uterine body diameter and uterine fluid volume as assessed by the amount of non‐echogenic material measured by ultrasound and position of the uterus. Vaginal mucous score was taken on day 28 post‐partum for the assessment of uterine inflammation. Resumption of cyclicity (serum progesterone > 1 ng/ml) had occurred in both groups on average by day 21 post‐partum. Concentrations of non‐esterified fatty acids and beta‐hydroxybutyrate were higher, whereas concentrations of glucose, insulin and IGF‐1 were lower (p < 0.05) in lactating compared to non‐lactating cows. Lactating cows had a smaller mean uterine body diameter (p < 0.05) than non‐lactating cows from days 28 to 42 post‐partum (day 28: 20.2 ± 1.3 vs 24.9 ± 1.5 mm, respectively) and had a lower mean uterine fluid volume up to day 49 (p < 0.05). By day 49, there was no difference in uterine diameter (15.2 ± 1.8 vs 15.2 ± 1.6 mm) or uterine fluid volume (0.11 ± 0.38 vs 0.18 ± 0.46) between lactating and non‐lactating cows, respectively. Vaginal mucous score revealed no evidence of uterine inflammation in either group. In conclusion, while lactation induced significant alterations in metabolic status, it did not have a major effect on the rate of uterine involution as defined in this study.
Polymorphism in the Interleukin‐7 Receptor‐alpha and Outcome after Allogeneic Hematopoietic Cell Transplantation with Matched Unrelated Donor
Authors: Shamim Z. , Spellman S. , Haagenson M. , Wang T. , Lee S. J. , Ryder L. P. , Müller K.
Published: May 2013

Interleukin‐7 (IL‐7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The α‐chain of the IL‐7R is polymorphic with the existence of SNPs that give rise to non‐synonymous amino acid substitutions. We previously found an association between donor genotypes and increased treatment‐related mortality (TRM) (rs1494555G) and acute graft versus host disease (aGvHD) (rs1494555G and rs1494558T) after hematopoietic cell transplantation (HCT). Some studies have confirmed an association between rs6897932C and multiple sclerosis. In this study, we evaluated the prognostic significance of IL‐7Rα SNP genotypes in 590‐recipient/donor pairs that received HLA‐matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis. The Tallele of rs6897932 was suggestive of an association with increased frequency of relapse by univariate analysis (P = 0.017) and multivariate analysis (P = 0.015). In conclusion, this study provides further evidence of a role of the IL‐7 pathway and IL‐7Rα SNPs in HCT.
Epstein–Barr virus (EBV) load in cerebrospinal fluid and peripheral blood of patients with EBV‐associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation
Authors: Liu Q.‐F. , Ling Y.‐W. , Fan Z.‐P. , Jiang Q.‐L. , Sun J. , Wu X.‐L. , Zhao J. , Wei Q. , Zhang Y. , Yu G.‐P. , Wu M.‐Q. , Feng R.
Published: May 2013

Background

To evaluate the diagnostic and prognostic utility of monitoring the Epstein–Barr virus (EBV) load in the cerebrospinal fluid (CSF) and peripheral blood for the patients with EBV‐associated central nervous system (CNS) diseases after allogeneic hematopoietic stem cell transplantation (allo‐HSCT), 172 patients undergoing allo‐HSCT were enrolled in the study.

Methods

The EBV DNA levels of blood were monitored regularly in recipients of transplants for 3 years post transplantation. The EBV DNA levels of CSF were monitored in patients with EBV‐associated CNS diseases before the treatment and at different points following the treatment.

Results

Post‐transplant EBV‐associated diseases developed in 27 patients, including 12 patients with EBV‐associated CNS diseases. The 3‐year cumulative incidences of EBV‐associated diseases and EBV‐associated CNS diseases were 19.5 ± 3.5% and 8.6 ± 2.4%, respectively. Patients with EBV‐associated diseases showed higher loads of EBV DNA in their blood compared with patients with EBV DNA‐emia. No difference was seen between the EBV DNA levels of blood in patients with CNS involvement and patients without CNS involvement. The EBV DNA loads of blood increased 3–14 days before the clinical manifestations of EBV‐associated diseases emerged. The EBV DNA loads of CSF were higher than that of blood in patients with EBV‐associated CNS diseases. In 12 patients with EBV‐associated CNS diseases, EBV DNA levels were declining in both blood and CSF with the control of diseases, and the EBV DNA loads of CSF decreased faster than that of blood in 5 patients who responded to treatment, and the EBV DNA levels of CSF increased in 5 patients who were unresponsive to treatment. On multivariate analysis, the use of anti‐thymocyte globulin and intensified conditioning regimens were independent risk factors for EBV‐associated diseases and EBV‐associated CNS diseases.

Conclusions

EBV‐associated CNS diseases are not rare after allo‐HSCT. The EBV DNA loads of CSF could act as an important indicator, but the EBV DNA loads of blood could not, for the diagnosis, prognosis, and therapeutic evaluation of EBV‐associated CNS diseases.
Antenatal and intrapartum care of pregnancy complicated by lethal fetal anomaly
Authors: McNamara Karen , O'Donoghue Keelin , O'Connell Orla , Greene Richard A
Published: May 2013

Key content

Congenital anomalies are the number one cause of infant mortality in the developed world. Antenatal diagnosis of lethal fetal abnormality is likely to have a profound psychological impact.

The multidisciplinary team should aim to meet the medical, emotional and spiritual needs of the family, through appropriate referral in the latter aspect.

Learning objectives

To consider the psychological impact of an antenatal diagnosis of lethal fetal abnormality.

To review the principles of informing parents about the diagnosis.

To provide a framework for the management of a pregnancy involving a lethal fetal anomaly.

To increase the awareness of the emotional and spiritual needs of the family.

Ethical issues

The dilemma of psychological impact of carrying a pregnancy with a lethal fetal anomaly for a mother and a family.

The issues around care including feeding the liveborn baby with an anomaly.
Independent control of reciprocal and lateral inhibition at the axon terminal of retinal bipolar cells
Authors: Tanaka Masashi , Tachibana Masao
Published: May 2013

Key points

Two different forms of feedback inhibition, reciprocal and lateral inhibition, are ubiquitously observed throughout the nervous system.

In the retina, the axon terminal of bipolar cells receives reciprocal and lateral GABAergic inhibitory inputs from amacrine cells, but how a variety of visual inputs activate each inhibition remains largely unexplored.

Here we show that each inhibition is independently controlled by different types of bipolar cell outputs; reciprocal inhibition is driven by strong output from each bipolar cell, whereas lateral inhibition is driven by outputs from multiple bipolar cells even when each output is weak.

Composition of transmitter receptors and localization of Na+ channels were different between two inhibitory pathways, suggesting that different amacrine cells may mediate each inhibition.

The dual feedback inhibition can cooperatively reduce bipolar cell outputs in response to various visual inputs without deteriorating the quality of visual signals, thereby contributing to efficient signal transmission in the visual pathway.

Abstract  Bipolar cells (BCs), the second order neurons in the vertebrate retina, receive two types of GABAergic feedback inhibition at their axon terminal: reciprocal and lateral inhibition. It has been suggested that two types of inhibition may be mediated by different pathways. However, how each inhibition is controlled by excitatory BC output remains to be clarified. Here, we applied single/dual whole cell recording techniques to the axon terminal of electrically coupled BCs in slice preparation of the goldfish retina, and found that each inhibition was regulated independently. Activation voltage of each inhibition was different: strong output from a single BC activated reciprocal inhibition, but could not activate lateral inhibition. Outputs from multiple BCs were essential for activation of lateral inhibition. Pharmacological examinations revealed that composition of transmitter receptors and localization of Na+ channels were different between two inhibitory pathways, suggesting that different amacrine cells may mediate each inhibition. Depending on visual inputs, each inhibition could be driven independently. Model simulation showed that reciprocal and lateral inhibition cooperatively reduced BC outputs as well as background noise, thereby preserving high signal‐to‐noise ratio. Therefore, we conclude that excitatory BC output is efficiently regulated by the dual operating mechanisms of feedback inhibition without deteriorating the quality of visual signals.
Recent Advances in High-Flux, Two-Phase Thermal Management
Authors: Mudawar Issam
Published: May 2013

Recent developments in applications such as computer data centers, electric vehicle power electronics, avionics, radars, and lasers have led to alarming increases in heat dissipation rate, which now far exceeds the capability of air cooling schemes and even the most aggressive single-phase liquid cooling schemes. This trend is responsible for a recent transition to two-phase cooling, which capitalizes upon the coolant's latent heat rather than sensible heat alone to achieve several order-of-magnitude increases in heat transfer coefficient. Three two-phase cooling configurations have surfaced as best contenders for the most demanding applications: mini/microchannel, jet, and spray. This study will explore the implementation of these configurations into practical cooling packages, assess available predictive tools, and identify future research needs for each. It is shown that the design and performance assessment of high-flux, two-phase cooling systems are highly dependent on empirical or semiempirical predictive tools and, to a far lesser extent, theoretical mechanistic models. A major challenge in using such tools is the lack of databases for coolants with drastically different thermophysical properties, and which cover broad ranges of such important parameters as flow passage size, mass velocity, quality, and pressure. Recommendations are therefore made for future research to correct any critical knowledge gaps, including the need for robust computer algorithms. Also discussed is a new class of “hybrid” cooling schemes that capitalize upon the merits of multiple cooling configurations. It is shown that these hybrid schemes not only surpass the basic cooling configurations in heat dissipation rate, but they also provide better surface temperature uniformity.
Noise Generation and Propagation Within Corrugated Pipes
Authors: Goyder Hugh
Published: May 2013

Corrugated pipes have the advantage of being flexible but the disadvantage of generating unacceptable levels of noise. The noise generated within these pipes is due to oscillation of vortices formed within the corrugations. The noise can induce vibration and unacceptable fatigue damage. Consequently, it is desirable to have a method for predicting the flow conditions that facilitate noise and the noise levels that are generated. This paper develops a theoretical model for the noise generation by considering the interaction of an acoustic wave with the vortices. The key issue that emerges is the delay or phase angle between vortex production in the corrugations and an acoustic standing wave. For the usual conditions, where there are many corrugations in a wavelength, it is possible to form a differential equation for the build-up and saturation of an acoustic resonance. The relative few parameters within this differential equation provide a good basis for modeling the occurrence and level of noise produced. It is anticipated that some experimental input will always be needed for particular corrugation geometries.
Eukaryotic G Protein Signaling Evolved to Require G Protein–Coupled Receptors for Activation
Authors: Bradford William , Buckholz Adam , Morton John , Price Collin , Jones Alan M. , Urano Daisuke
Published: May 2013

As eukaryotic organisms evolved, their Gα proteins switched from being self-activating to requiring an activating receptor.
mTORC1 Stimulates Glutamine Metabolism
Authors: Foley John F.
Published: May 2013

The mammalian target of rapamycin complex 1 promotes glutamine metabolism by repressing expression of the gene encoding the sirtuin SIRT4.
Autoantibodies: Double Agents in Human Disease
Authors: Acharya Nimish K. , Nagele Eric P. , Han Min , Nagele Robert G.
Published: May 2013

Autoantibodies bind to PAD4, increasing its enzymatic activity and leading to worse outcomes for patients with rheumatoid arthritis (Darrah
et al
., this issue).
Epidemiology of Isoniazid Resistance Mutations and Their Effect on Tuberculosis Treatment Outcomes
Authors: Huyen Mai N. T. , Cobelens Frank G. J. , Buu Tran N. , Lan Nguyen T. N. , Dung Nguyen H. , Kremer Kristin , Tiemersma Edine W. , van Soolingen Dick
Published: May 2013

Isoniazid resistance is highly prevalent in Vietnam. We investigated the molecular and epidemiological characteristics and the association with first-line treatment outcomes of the main isoniazid resistance mutations in
Mycobacterium tuberculosis
in codon 315 of the
katG
and in the promoter region of the
inhA
gene.
Mycobacterium tuberculosis
strains with phenotypic resistance to isoniazid from consecutively diagnosed smear-positive tuberculosis patients in rural Vietnam were subjected to Genotype MTBDR
plus
testing to identify
katG
and
inhA
mutations. Treatment failure and relapse were determined by sputum culture. In total, 227 of 251 isoniazid-resistant strains (90.4%) had detectable mutations: 75.3% in
katG
codon 315 (
katG
315
) and 28.2% in the
inhA
promoter region.
katG
315
mutations were significantly associated with pretreatment resistance to streptomycin, rifampin, and ethambutol but not with the Beijing genotype and predicted both unfavorable treatment outcome (treatment failure or death) and relapse;
inhA
promoter region mutations were only associated with resistance to streptomycin and relapse. In tuberculosis patients,
M. tuberculosis
katG
315
mutations but not
inhA
mutations are associated with unfavorable treatment outcome.
inhA
mutations do, however, increase the risk of relapse, at least with treatment regimens that contain only isoniazid and ethambutol in the continuation phase.
Potentiation of Azole Antifungals by 2-Adamantanamine
Authors: LaFleur Michael D. , Sun Lingmei , Lister Ida , Keating John , Nantel Andre , Long Lisa , Ghannoum Mahmoud , North Jeffrey , Lee Richard E. , Coleman Ken , Dahl Thomas , Lewis Kim
Published: May 2013

Azoles are among the most successful classes of antifungals. They act by inhibiting α-14 lanosterol demethylase in the ergosterol biosynthesis pathway. Oropharyngeal candidiasis (OPC) occurs in about 90% of HIV-infected individuals, and 4 to 5% are refractory to current therapies, including azoles, due to the formation of resistant biofilms produced in the course of OPC. We reasoned that compounds affecting a different target may potentiate azoles to produce increased killing and an antibiofilm therapeutic. 2-Adamantanamine (AC17) was identified in a screen for compounds potentiating the action of miconazole against biofilms of
Candida albicans
. AC17, a close structural analog to the antiviral amantadine, did not affect the viability of
C. albicans
but caused the normally fungistatic azoles to become fungicidal. Transcriptome analysis of cells treated with AC17 revealed that the ergosterol and filamentation pathways were affected. Indeed, cells exposed to AC17 had decreased ergosterol contents and were unable to invade agar.
In vivo
, the combination of AC17 and fluconazole produced a significant reduction in fungal tissue burden in a guinea pig model of cutaneous candidiasis, while each treatment alone did not have a significant effect. The combination of fluconazole and AC17 also showed improved efficacy (
P
value of 0.018) compared to fluconazole alone when fungal lesions were evaluated. AC17 is a promising lead in the search for more effective antifungal therapeutics.
MBX-500 Is Effective for Treatment of Clostridium difficile Infection in Gnotobiotic Piglets
Authors: Steele Jennifer , Zhang Quanshun , Beamer Gillian , Butler Michelle , Bowlin Terry , Tzipori Saul
Published: May 2013

The novel antibiotic MBX-500, dosed at 100, 200, or 400 mg/kg twice daily for 7 days, was evaluated for the treatment of
Clostridium difficile
infection (CDI) in the gnotobiotic pig model. MBX-500 increased survival at all doses and at high doses improved clinical signs and reduced lesion severity, similar to vancomycin. Our results show that MBX-500 is an effective antibiotic for the treatment of diarrhea associated with CDI and prevents severe systemic disease.
Identification and Mechanism of Action of the Plant Defensin NaD1 as a New Member of the Antifungal Drug Arsenal against Candida albicans
Authors: Hayes Brigitte M. E. , Bleackley Mark R. , Wiltshire Jennifer L. , Anderson Marilyn A. , Traven Ana , van der Weerden Nicole L.
Published: May 2013

In recent decades, pathogenic fungi have become a serious threat to human health, leading to major efforts aimed at characterizing new agents for improved treatments. Promising in this context are antimicrobial peptides produced by animals and plants as part of innate immune systems. Here, we describe an antifungal defensin, NaD1, with activity against the major human pathogen
Candida albicans
, characterize the mechanism of killing, and identify protection strategies used by the fungus to survive defensin treatment. The mechanism involves interaction between NaD1 and the fungal cell surface followed by membrane permeabilization, entry into the cytoplasm, hyperproduction of reactive oxygen species, and killing induced by oxidative damage. By screening
C. albicans
mutant libraries, we identified that the high-osmolarity glycerol (HOG) pathway has a unique role in protection against NaD1, while several other stress-responsive pathways are dispensable. The involvement of the HOG pathway is consistent with induction of oxidative stress by NaD1. The HOG pathway has been reported to have a major role in protection of fungi against osmotic stress, but our data indicate that osmotic stress does not contribute significantly to the adverse effects of NaD1 on
C. albicans
. Our data, together with previous studies with human beta-defensins and salivary histatin 5, indicate that inhibition of the HOG pathway holds promise as a broad strategy for increasing the activity of antimicrobial peptides against
C. albicans
.
High-Throughput Screening of a Collection of Known Pharmacologically Active Small Compounds for Identification of Candida albicans Biofilm Inhibitors
Authors: Siles Samuel A. , Srinivasan Anand , Pierce Christopher G. , Lopez-Ribot José L. , Ramasubramanian Anand K.
Published: May 2013

Candida albicans
is the most common etiologic agent of systemic fungal infections with unacceptably high mortality rates. The existing arsenal of antifungal drugs is very limited and is particularly ineffective against
C. albicans
biofilms. To address the unmet need for novel antifungals, particularly those active against biofilms, we have screened a small molecule library consisting of 1,200 off-patent drugs already approved by the Food and Drug Administration (FDA), the Prestwick Chemical Library, to identify inhibitors of
C. albicans
biofilm formation. According to their pharmacological applications that are currently known, we classified these bioactive compounds as antifungal drugs, as antimicrobials/antiseptics, or as miscellaneous drugs, which we considered to be drugs with no previously characterized antifungal activity. Using a 96-well microtiter plate-based high-content screening assay, we identified 38 pharmacologically active agents that inhibit
C. albicans
biofilm formation. These drugs were subsequently tested for their potency and efficacy against preformed biofilms, and we identified three drugs with novel antifungal activity. Thus, repurposing FDA-approved drugs opens up a valuable new avenue for identification and potentially rapid development of antifungal agents, which are urgently needed.
The Bordetella pertussis Type III Secretion System Tip Complex Protein Bsp22 Is Not a Protective Antigen and Fails To Elicit Serum Antibody Responses during Infection of Humans and Mice
Authors: Villarino Romero Rodrigo , Bibova Ilona , Cerny Ondrej , Vecerek Branislav , Wald Tomas , Benada Oldrich , Zavadilova Jana , Osicka Radim , Sebo Peter
Published: May 2013

The type III secretion system (T3SS) of pathogenic bordetellae employs a self-associating tip complex protein Bsp22. This protein is immunogenic during infections by
Bordetella bronchiseptica
and could be used as a protective antigen to immunize mice against
B. bronchiseptica
challenge. Since low-passage clinical isolates of the human pathogen
Bordetella pertussis
produce a highly homologous Bsp22 protein (97% homology), we examined its vaccine and diagnostic potential. No Bsp22-specific antibodies were, however, detected in serum samples from 36 patients with clinically and serologically confirmed whooping cough disease (pertussis syndrome). Moreover, although the induction of Bsp22 secretion by the laboratory-adapted 18323 strain in the course of mice lung infection was observed, the
B. pertussis
18323-infected mice did not mount any detectable serum antibody response against Bsp22. Furthermore, immunization with recombinant Bsp22 protein yielded induction of high Bsp22-specific serum antibody titers but did not protect mice against an intranasal challenge with
B. pertussis
18323. Unlike for
B. bronchiseptica
, hence, the Bsp22 protein is nonimmunogenic, and/or the serum antibody response to it is suppressed, during
B. pertussis
infections of humans and mice.
Malaria-Associatedl-Arginine Deficiency Induces Mast Cell-Associated Disruption to Intestinal Barrier Defenses against Nontyphoidal Salmonella Bacteremia
Authors: Chau Jennifer Y. , Tiffany Caitlin M. , Nimishakavi Shilpa , Lawrence Jessica A. , Pakpour Nazzy , Mooney Jason P. , Lokken Kristen L. , Caughey George H. , Tsolis Renee M. , Luckhart Shirley
Published: May 2013

Coinfection with malaria and nontyphoidalSalmonellaserotypes (NTS) can cause life-threatening bacteremia in humans. Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model. Our findings reveal that malarial-parasite-infected mice, like humans, developl-arginine deficiency, which is associated with intestinal mastocytosis, elevated levels of histamine, and enhanced intestinal permeability. Prevention or reversal ofl-arginine deficiency blunts mastocytosis in ileal villi as well as bacterial translocation, measured as numbers of mesenteric lymph node CFU of noninvasiveEscherichia coliNissle andSalmonella entericaserotype Typhimurium, the latter of which is naturally invasive in mice. Dietary supplementation of malarial-parasite-infected mice withl-arginine orl-citrulline reduced levels of ileal transcripts encoding interleukin-4 (IL-4), a key mediator of intestinal mastocytosis and macromolecular permeability. Supplementation withl-citrulline also enhanced epithelial adherens and tight junctions in the ilea of coinfected mice. These data suggest that increasingl-arginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans.
Fitness, Stress Resistance, and Extraintestinal Virulence in Escherichia coli
Authors: Bleibtreu Alexandre , Gros Pierre-Alexis , Laouénan Cédric , Clermont Olivier , Le Nagard Hervé , Picard Bertrand , Tenaillon Olivier , Denamur Erick
Published: May 2013

The extraintestinal virulence of
Escherichia coli
is dependent on numerous virulence genes. However, there is growing evidence for a role of the metabolic properties and stress responses of strains in pathogenesis. We assessed the respective roles of these factors in strain virulence by developing phenotypic assays for measuring
in vitro
individual and competitive fitness and the general stress response, which we applied to 82 commensal and extraintestinal pathogenic
E. coli
strains previously tested in a mouse model of sepsis. Individual fitness properties, in terms of maximum growth rates in various media (Luria-Bertani broth with and without iron chelator, minimal medium supplemented with gluconate, and human urine) and competitive fitness properties, estimated as the mean relative growth rate per generation in mixed cultures with a reference fluorescent
E. coli
strain, were highly diverse between strains. The activity of the main general stress response regulator, RpoS, as determined by iodine staining of the colonies, H
2
O
2
resistance, and
rpoS
sequencing, was also highly variable. No correlation between strain fitness and stress resistance and virulence in the mouse model was found, except that the maximum growth rate in urine was higher for virulent strains. Multivariate analysis showed that the number of virulence factors was the only independent factor explaining the virulence in mice. At the species level, growth capacity and stress resistance are heterogeneous properties that do not contribute significantly to the intrinsic virulence of the strains.
Life-threatening rhabdomyolysis after prolonged hypoperfusion of the lower legs
Authors: Abrahamsen Sebastian Ørskov , Stilling Maiken
Published: May 2013

Rhabdomyolysis is a potentially life-threatening condition to be considered when muscular damage is suspected. We present a case of a 39-year-old woman who developed rhabdomyolysis after prolonged circulatory insufficiency to the legs, leading to life-threatening complications including bilateral tibial compartment syndrome, acute kidney failure, hyperkalaemia with cardiac arrhythmia and finally lifesaving bilateral transfemoral amputation. This case emphasises that early diagnosis, removal of triggering factor, early and aggressive fluid therapy and treatment and prevention of complications are essential for the patient’s morbidity and mortality.