bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial dysfunction is a potential contributor to multiple organ failure and mortality in aged mice subjected to septic shock: preclinical studies in a murine model of cecal ligation and puncture
Authors: Coletta Ciro , Módis Katalin , Oláh Gábor , Brunyánszki Attila , Herzig Daniela S , Sherwood Edward R , Ungvári Zoltán , Szabo Csaba
Published: September 2014

Introduction

The goal of the current study was to investigate the effect of aging on the development of endothelial dysfunction in a murine model of sepsis, and to compare it with the effect of genetic deficiency of the endothelial isoform of nitric oxide synthase (eNOS).

Methods

Cecal ligation and puncture (CLP) was used to induce sepsis in mice. Survival rates were monitored and plasma indices of organ function were measured. Ex vivo studies included the measurement of vascular function in thoracic aortic rings, assessment of oxidative stress/cellular injury in various organs and the measurement of mitochondrial function in isolated liver mitochondria.

Results

eNOS deficiency and aging both exacerbated the mortality of sepsis. Both eNOS-deficient and aged mice exhibited a higher degree of sepsis-associated multiple organ dysfunction syndrome (MODS), infiltration of tissues with mononuclear cells and oxidative stress. A high degree of sepsis-induced vascular oxidative damage and endothelial dysfunction (evidenced by functional assays and multiple plasma markers of endothelial dysfunction) was detected in aortae isolated from both eNOS-/- and aged mice. There was a significant worsening of sepsis-induced mitochondrial dysfunction, both in eNOS-deficient mice and in aged mice. Comparison of the surviving and non-surviving groups of animals indicated that the severity of endothelial dysfunction may be a predictor of mortality of mice subjected to CLP-induced sepsis.

Conclusions

Based on the studies in eNOS mice, we conclude that the lack of endothelial nitric oxide production, on its own, may be sufficient to markedly exacerbate the severity of septic shock. Aging markedly worsens the degree of endothelial dysfunction in sepsis, yielding a significant worsening of the overall outcome. Thus, endothelial dysfunction may constitute an early predictor and independent contributor to sepsis-associated MODS and mortality in aged mice.
Traditional landmark versus ultrasound guided tracheal puncture during percutaneous dilatational tracheostomy in adult intensive care patients: a randomised controlled trial
Authors: Rudas Máté , Seppelt Ian , Herkes Robert , Hislop Robert , Rajbhandari Dorrilyn , Weisbrodt Leonie
Published: September 2014

Introduction

Long-term ventilated intensive care patients frequently require tracheostomy. Although overall risks are low, serious immediate and late complications still arise. Real-time ultrasound guidance has been proposed to decrease complications and improve the accuracy of the tracheal puncture. We aimed to compare the procedural safety and efficacy of real-time ultrasound guidance with the traditional landmark approach during percutaneous dilatational tracheostomy (PDT).

Methods

A total of 50 patients undergoing PDT for clinical indications were randomly assigned, after obtaining informed consent, to have the tracheal puncture procedure carried out using either traditional anatomical landmarks or real-time ultrasound guidance. Puncture position was recorded via bronchoscopy. Blinded assessors determined in a standardised fashion the deviation of the puncture off midline and whether appropriate longitudinal position between the first and fourth tracheal rings was achieved. Procedural safety and efficacy data, including complications and number of puncture attempts required, were collected.

Results

In total, 47 data sets were evaluable. Real-time ultrasound guidance resulted in significantly more accurate tracheal puncture. Mean deviation from midline was 15 ± 3° versus 35 ± 5° (P = 0.001). The proportion of appropriate punctures, defined a priori as 0 ± 30° from midline, was significantly higher: 20 (87%) of 23 versus 12 (50%) of 24 (RR = 1.74; 95% CI = 1.13 to 2.67; P = 0.006). First-pass success rate was 20 (87%) of 23 in the ultrasound group and 14 (58%) of 24 in the landmark group (RR = 1.49; 95% CI = 1.03 to 2.17; P = 0.028). The observed decrease in procedural complications was not statistically significant: 5 (22%) of 23 in the ultrasound group versus 9 (37%) of 24 in the landmark group (RR = 0.58; 95% CI = 0.23 to 1.47; P = 0.24).

Conclusions

Ultrasound guidance significantly improved the rate of first-pass puncture and puncture accuracy. Fewer procedural complications were observed; however, this did not reach statistical significance. These results support wider general use of real-time ultrasound guidance as an additional tool to improve PDT.

Trial registration

Australian New Zealand Clinical Trials Registry ID: ACTRN12611000237987 (registered 4 March 2011)
Sodium bicarbonate in the prevention of cardiac surgery-associated acute kidney injury: a systematic review and meta-analysis
Authors: Tie Hong-Tao , Luo Ming-Zhu , Luo Ming-Jing , Zhang Min , Wu Qing-Chen , Wan Jing-Yuan
Published: September 2014

Introduction

Sodium bicarbonate (SBIC) was reported to be a promising approach to prevent cardiac surgery-associated acute kidney injury (CSA-AKI). However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of SBIC on the prevention of CSA-AKI in adult patients undergoing cardiac surgery.

Methods

PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of SBIC versus placebo on the prevention of CSA-AKI in adult patients undergoing cardiac surgery were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcome was the incidence of CSA-AKI. Meta-analysis was performed using random-effects models.

Results

Five RCTs involving 1079 patients were included in the meta-analysis. Overall, compared with placebo, SBIC was not associated with a reduced risk of CSA-AKI (relative risk [RR] 0.99; 95% confidence interval [CI] 0.78 to 1.24; P = 0.911). SBIC failed to alter the clinical outcomes of hospital length of stay (weighted mean difference [WMD] 0.23 days; 95%CI -0.88 to 1.33 days; P = 0.688), renal replacement therapy (RR 0.94; 95%CI 0.49 to 1.82; P = 0.861), hospital mortality (RR 1.37; 95%CI 0.46 to 4.13; P = 0.572), postoperative atrial fibrillation (RR 1.02; 95%CI 0.65 to 1.61; P = 0.915). However, SBIC was associated with significant increased risks in longer duration of ventilation (WMD 0.64 hours; 95%CI 0.16 to 1.11 hours; P = 0.008), longer ICU length of stay (WMD 2.06 days; 95%CI 0.54 to 3.58 days; P = 0.008), and increased incidence of alkalemia (RR 2.21; 95%CI 1.42 to 3.42; P <0.001).

Conclusions

SBIC could not reduce the incidence of CSA-AKI. Contrarily, SBIC prolongs the duration of ventilation and ICU length of stay, and increases the risk of alkalemia. Thus, SBIC should not be recommended for the prevention of CSA-AKI and perioperative SBIC infusion should be administrated with caution.
Therapeutic drug monitoring: linezolid too?
Authors: Richards Guy A , Brink Adrian J
Published: September 2014

Numerous factors interfere with the ability to achieve optimal pharmacokinetic and pharmacodynamic targets and this has been associated with greater mortality and lower cure rates. The recent study by Zoller and colleagues examining linezolid levels in critically ill patients emphasises this point. Their study is unique in the description of the intra-patient and inter-patient variability that occurs and in the degree to which therapy is inadequate; 63% of patients had insufficient levels and only 17% maintained optimal trough values (between 2 and 10 mg/l) throughout the 4 study days. Precisely why this result occurred is uncertain because albumin levels, free linezolid pharmacokinetics and the presence of augmented renal clearance were not recorded in the current study. The extent of this variability makes the case for therapeutic drug monitoring since an area under the inhibitory curve greater than 80 to 120 and the time above the minimum inhibitory concentration over the entire dosing interval strongly correlate with linezolid treatment efficacy. Accordingly, therapeutic drug monitoring where available or, if not available, alternative approaches to drug delivery such as continuous infusion or a dose increase - but particularly the former - may be the answer.
Quantitative estimation of pesticide-likeness for agrochemical discovery
Authors: Avram Sorin , Funar-Timofei Simona , Borota Ana , Chennamaneni Sridhar Rao , Manchala Anil Kumar , Muresan Sorel
Published: September 2014

Background

The design of chemical libraries, an early step in agrochemical discovery programs, is frequently addressed by means of qualitative physicochemical and/or topological rule-based methods. The aim of this study is to develop quantitative estimates of herbicide- (QEH), insecticide- (QEI), fungicide- (QEF), and, finally, pesticide-likeness (QEP).

In the assessment of these definitions, we relied on the concept of desirability functions.

Results

We found a simple function, shared by the three classes of pesticides, parameterized particularly, for six, easy to compute, independent and interpretable, molecular properties: molecular weight, logP, number of hydrogen bond acceptors, number of hydrogen bond donors, number of rotatable bounds and number of aromatic rings. Subsequently, we describe the scoring of each pesticide class by the corresponding quantitative estimate. In a comparative study, we assessed the performance of the scoring functions using extensive datasets of patented pesticides.

Conclusions

The hereby-established quantitative assessment has the ability to rank compounds whether they fail well-established pesticide-likeness rules or not, and offer an efficient way to prioritize (class-specific) pesticides. These findings are valuable for the efficient estimation of pesticide-likeness of vast chemical libraries in the field of agrochemical discovery.
Self-adaptive moving mesh schemes for short pulse type equations and their Lax pairs
Authors: Feng Bao-Feng , Maruno Kenichi , Ohta Yasuhiro
Published: September 2014

Integrable self-adaptive moving mesh schemes for short pulse type equations (the short pulse equation, the coupled short pulse equation, and the complex short pulse equation) are investigated. Two systematic methods, one is based on bilinear equations and another is based on Lax pairs, are shown. Self-adaptive moving mesh schemes consist of two semi-discrete equations in which the time is continuous and the space is discrete. In self-adaptive moving mesh schemes, one of two equations is an evolution equation of mesh intervals which is deeply related to a discrete analogue of a reciprocal (hodograph) transformation. An evolution equations of mesh intervals is a discrete analogue of a conservation law of an original equation, and a set of mesh intervals corresponds to a conserved density which play an important role in generation of adaptive moving mesh. Lax pairs of self-adaptive moving mesh schemes for short pulse type equations are obtained by discretization of Lax pairs of short pulse type equations, thus the existence of Lax pairs guarantees the integrability of self-adaptive moving mesh schemes for short pulse type equations. It is also shown that self-adaptive moving mesh schemes for short pulse type equations provide good numerical results by using standard time-marching methods such as the improved Euler’s method.
WIP: more than a WASp-interacting protein
Authors: Fried Sophia , Matalon Omri , Noy Elad , Barda-Saad Mira
Published: September 2014

WIP plays an important role in the remodeling of the actin cytoskeleton, which controls cellular activation, proliferation, and function. WIP regulates actin polymerization by linking the actin machinery to signaling cascades. WIP binding to WASp and to its homolog, N-WASp, which are central activators of the actin-nucleating complex Arp2/3, regulates their cellular distribution, function, and stability. By binding to WASp, WIP protects it from degradation and thus, is crucial for WASp retention. Indeed, most mutations that result in WAS, an X-linked immunodeficiency caused by defective/absent WASp activity, are located in the WIP-binding region of WASp. In addition, by binding directly to actin, WIP promotes the formation and stabilization of actin filaments. WASp-independent activities of WIP constitute a new research frontier and are discussed extensively in this article. Here, we review the current information on WIP in human and mouse systems, focusing on its associated proteins, its molecular-regulatory mechanisms, and its role as a key regulator of actin-based processes in the immune system.
Isoliquiritigenin is a potent inhibitor of NLRP3 inflammasome activation and diet-induced adipose tissue inflammation
Authors: Honda Hiroe , Nagai Yoshinori , Matsunaga Takayuki , Okamoto Naoki , Watanabe Yasuharu , Tsuneyama Koichi , Hayashi Hiroaki , Fujii Isao , Ikutani Masashi , Hirai Yoshikatsu , Muraguchi Atsushi , Takatsu Kiyoshi
Published: September 2014

Inflammasome activation initiates the development of many inflammatory diseases, including obesity and type 2 diabetes. Therefore, agents that target discrete activation steps could represent very important drugs. We reported previously that ILG, a chalcone from Glycyrrhiza uralensis, inhibits LPS-induced NF-κB activation. Here, we show that ILG potently inhibits the activation of NLRP3 inflammasome, and the effect is independent of its inhibitory potency on TLR4. The inhibitory effect of ILG was stronger than that of parthenolide, a known inhibitor of the NLRP3 inflammasome. GL, a triterpenoid from G. uralensis, had similar inhibitory effects on NLRP3 activity, but high concentrations of GL were required. In contrast, activation of the AIM2 inflammasome was inhibited by GL but not by ILG. Moreover, GL inhibited NLRP3- and AIM2-activated ASC oligomerization, whereas ILG inhibited NLRP3-activated ASC oligomerization. Low concentrations of ILG were highly effective in IAPP-induced IL-1β production compared with the sulfonylurea drug glyburide. In vivo analyses revealed that ILG potently attenuated HFD-induced obesity, hypercholesterolemia, and insulin resistance. Furthermore, ILG treatment improved HFD-induced macrovesicular steatosis in the liver. Finally, ILG markedly inhibited diet-induced adipose tissue inflammation and IL-1β and caspase-1 production in white adipose tissue in ex vivo culture. These results suggest that ILG is a potential drug target for treatment of NLRP3 inflammasome-associated inflammatory diseases.
Complement modulation of T cell immune responses during homeostasis and disease
Authors: Clarke Elizabeth V , Tenner Andrea J
Published: September 2014

The complement system is an ancient and critical effector mechanism of the innate immune system as it senses, kills, and clears infectious and/or dangerous particles and alerts the immune system to the presence of the infection and/or danger. Interestingly, an increasing number of reports have demonstrated a clear role for complement in the adaptive immune system as well. Of note, a number of recent studies have identified previously unknown roles for complement proteins, receptors, and regulators in T cell function. Here, we will review recent data demonstrating the influence of complement proteins C1q, C3b/iC3b, C3a (and C3aR), and C5a (and C5aR) and complement regulators DAF (CD55) and CD46 (MCP) on T cell function during homeostasis and disease. Although new concepts are beginning to emerge in the field of complement regulation of T cell function, future experiments should focus on whether complement is interacting directly with the T cell or is having an indirect effect on T cell function via APCs, the cytokine milieu, or downstream complement activation products. Importantly, the identification of the pivotal molecular pathways in the human systems will be beneficial in the translation of concepts derived from model systems to therapeutic targeting for treatment of human disorders.
Unraveling the complexity of lipid body organelles in human eosinophils
Authors: Melo Rossana C N , Weller Peter F
Published: September 2014

Lipid-rich organelles are common in many cell types. In cells, such as adipocytes, these organelles are termed LDs, whereas in other cells, such as leukocytes, they are called LBs. The study of leukocyte LBs has attracted attention as a result of their association with human diseases. In leukocytes, such as eosinophils, LB accumulation has been documented extensively during inflammatory conditions. In these cells, LBs are linked to the regulation of immune responses by compartmentalization of several proteins and lipids involved in the control and biosynthesis of inflammatory mediators (eicosanoids). However, it has been unclear how diverse proteins, including membrane-associated enzymes involved in eicosanoid formation, incorporate into LBs, especially if the internal content of LBs is assumed to consist solely of stores of neutral lipids, as present within adipocyte LDs. Studies of the formation, function, and ultrastructure of LBs in eosinophils have been providing insights pertinent to LBs in other leukocytes. Here, we review current knowledge of the composition and function of leukocyte LBs as provided by studies of human eosinophil LBs, including recognitions of the internal architecture of eosinophil LBs based on 3D electron tomographic analyses.
Functional impairment in adolescents and young adults with
emerging mood disorders
Authors: Scott Jan , Scott Elizabeth M. , Hermens Daniel F. , Naismith Sharon L. , Guastella Adam J. , White Django , Whitwell Bradley , Lagopoulos Jim , Hickie Ian B.
Published: September 2014

Background

Between 30 and 60% of adults with unipolar or bipolar disorders exhibit
impairments across multiple domains. However, little is known about
impaired functioning in youth with mood disorders.

Aims

To examine the prevalence of objective, subjective and observer-rated
disability in a large, representative sample of young people with a
primary mood disorder.

Method

Individuals aged 16–25 years presenting to youth mental health services
for the first time with a primary mood disorder participated in a
systematic diagnostic and clinical assessment. Impairment was assessed
using objective (unemployment or disability payments), observer- (Social
and Occupational Functioning Assessment Scale; SOFAS) and self-rated
measures (role functioning according to the Brief Disability
Questionnaire).

Results

Of 1241 participants (83% unipolar; 56% female), at least 30% were
functionally impaired on the objective, self-rated and/or observer-rated
measures, with 16% impaired according to all three criteria. Even when
current distress levels were taken into account, daily use of cannabis
and/or nicotine were significantly associated with impairment, with odds
ratios (OR) ranging from about 1.5 to 3.0. Comorbid anxiety disorders
were related to lower SOFAS scores (OR = 2–5).

Conclusions

Levels of disability were significant, even in those presenting for
mental healthcare for the first time. Functional impairment did not
differ between unipolar and bipolar cases, but some evidence suggested
that females with bipolar disorder were particularly disabled. The
prevalence of comorbid disorders (50%) and polysubstance use (28%) and
their association with disability indicate that more meaningful
indicators of mood episode outcomes should focus on functional rather
than symptom-specific measures. The association between functioning and
nicotine use requires further exploration.
Hippocampal abnormalities and age in chronic schizophrenia:
morphometric study across the adult lifespan
Authors: Pujol N. , Penadés R. , Junqué C. , Dinov I. , Fu C. H. Y. , Catalán R. , Ibarretxe-Bilbao N. , Bargalló N. , Bernardo M. , Toga A. , Howard R. J. , Costafreda S. G.
Published: September 2014

Background

Hippocampal abnormalities have been demonstrated in schizophrenia. It is
unclear whether these abnormalities worsen with age, and whether they
affect cognition and function.

Aims

To determine whether hippocampal abnormalities in chronic schizophrenia
are associated with age, cognition and socio-occupational function.

Method

Using 3 T magnetic resonance imaging we scanned 100 persons aged 19–82
years: 51 were out-patients with stable schizophrenia at least 2 years
after diagnosis and 49 were healthy volunteers matched for age and
gender. Automated analysis was used to determine hippocampal volume and
shape.

Results

There were differential effects of age in the schizophrenia and control
samples on total hippocampal volume (group×age interaction:
F(1,95) = 6.57, P = 0.012), with steeper
age-related reduction in the schizophrenia group. Three-dimensional shape
analysis located the age-related deformations predominantly in the
mid-body of the hippocampus. In the schizophrenia group similar patterns
of morphometric abnormalities were correlated with impaired cognition and
poorer socio-occupational function.

Conclusions

Hippocampal abnormalities are associated with age in people with chronic
schizophrenia, with a steeper decline than in healthy individuals. These
abnormalities are associated with cognitive and functional deficits,
suggesting that hippocampal morphometry may be a biomarker for cognitive
decline in older patients with schizophrenia.
The splicing factor PQBP1 regulates mesodermal and neural development through FGF signaling
Authors: Iwasaki Yasuno , Thomsen Gerald H.
Published: September 2014

Alternative splicing of pre-mRNAs is an important means of regulating developmental processes, yet the molecular mechanisms governing alternative splicing in embryonic contexts are just beginning to emerge. Polyglutamine-binding protein 1 (PQBP1) is an RNA-splicing factor that, when mutated, in humans causes Renpenning syndrome, an X-linked intellectual disability disease characterized by severe cognitive impairment, but also by physical defects that suggest PQBP1 has broader functions in embryonic development. Here, we reveal essential roles for PQBP1 and a binding partner, WBP11, in early development of Xenopus embryos. Both genes are expressed in the nascent mesoderm and neurectoderm, and morpholino knockdown of either causes defects in differentiation and morphogenesis of the mesoderm and neural plate. At the molecular level, knockdown of PQBP1 in Xenopus animal cap explants inhibits target gene induction by FGF but not by BMP, Nodal or Wnt ligands, and knockdown of either PQBP1 or WBP11 in embryos inhibits expression of fgf4 and FGF4-responsive cdx4 genes. Furthermore, PQBP1 knockdown changes the alternative splicing of FGF receptor-2 (FGFR2) transcripts, altering the incorporation of cassette exons that generate receptor variants (FGFR2 IIIb or IIIc) with different ligand specificities. Our findings may inform studies into the mechanisms underlying Renpenning syndrome.
A regulatory network controls nephrocan expression and midgut patterning
Authors: Hou Juan , Wei Wei , Saund Ranajeet S. , Xiang Ping , Cunningham Thomas J. , Yi Yuyin , Alder Olivia , Lu Daphne Y. D. , Savory Joanne G. A. , Krentz Nicole A. J. , Montpetit Rachel , Cullum Rebecca , Hofs Nicole , Lohnes David , Humphries R. Keith , Yamanaka Yojiro , Duester Gregg , Saijoh Yukio , Hoodless Pamela A.
Published: September 2014

Although many regulatory networks involved in defining definitive endoderm have been identified, the mechanisms through which these networks interact to pattern the endoderm are less well understood. To explore the mechanisms involved in midgut patterning, we dissected the transcriptional regulatory elements of nephrocan (Nepn), the earliest known midgut specific gene in mice. We observed that Nepn expression is dramatically reduced in Sox17−/− and Raldh2−/− embryos compared with wild-type embryos. We further show that Nepn is directly regulated by Sox17 and the retinoic acid (RA) receptor via two enhancer elements located upstream of the gene. Moreover, Nepn expression is modulated by Activin signaling, with high levels inhibiting and low levels enhancing RA-dependent expression. In Foxh1−/− embryos in which Nodal signaling is reduced, the Nepn expression domain is expanded into the anterior gut region, confirming that Nodal signaling can modulate its expression in vivo. Together, Sox17 is required for Nepn expression in the definitive endoderm, while RA signaling restricts expression to the midgut region. A balance of Nodal/Activin signaling regulates the anterior boundary of the midgut expression domain.
Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice
Authors: Nielsen Corinne M. , Cuervo Henar , Ding Vivianne W. , Kong Yupeng , Huang Eric J. , Wang Rong A.
Published: September 2014

Arteriovenous malformations (AVMs) are tortuous vessels characterized by arteriovenous (AV) shunts, which displace capillaries and shunt blood directly from artery to vein. Notch signaling regulates embryonic AV specification by promoting arterial, as opposed to venous, endothelial cell (EC) fate. To understand the essential role of endothelial Notch signaling in postnatal AV organization, we used inducible Cre-loxP recombination to delete Rbpj, a mediator of canonical Notch signaling, from postnatal ECs in mice. Deletion of endothelial Rbpj from birth resulted in features of AVMs by P14, including abnormal AV shunting and tortuous vessels in the brain, intestine and heart. We further analyzed brain AVMs, as they pose particular health risks. Consistent with AVM pathology, we found cerebral hemorrhage, hypoxia and necrosis, and neurological deficits. AV shunts originated from capillaries (and possibly venules), with the earliest detectable morphological abnormalities in AV connections by P8. Prior to AV shunt formation, alterations in EC gene expression were detected, including decreased Efnb2 and increased Pai1, which encodes a downstream effector of TGFβ signaling. After AV shunts had formed, whole-mount immunostaining showed decreased Efnb2 and increased Ephb4 expression within AV shunts, suggesting that ECs were reprogrammed from arterial to venous identity. Deletion of Rbpj from adult ECs led to tortuosities in gastrointestinal, uterine and skin vascular beds, but had mild effects in the brain. Our results demonstrate a temporal requirement for Rbpj in postnatal ECs to maintain proper artery, capillary and vein organization and to prevent abnormal AV shunting and AVM pathogenesis.
Gata6, Nanog and Erk signaling control cell fate in the inner cell mass through a tristable regulatory network
Authors: Bessonnard Sylvain , De Mot Laurane , Gonze Didier , Barriol Manon , Dennis Cynthia , Goldbeter Albert , Dupont Geneviève , Chazaud Claire
Published: September 2014

During blastocyst formation, inner cell mass (ICM) cells differentiate into either epiblast (Epi) or primitive endoderm (PrE) cells, labeled by Nanog and Gata6, respectively, and organized in a salt-and-pepper pattern. Previous work in the mouse has shown that, in absence of Nanog, all ICM cells adopt a PrE identity. Moreover, the activation or the blockade of the Fgf/RTK pathway biases cell fate specification towards either PrE or Epi, respectively. We show that, in absence of Gata6, all ICM cells adopt an Epi identity. Furthermore, the analysis of Gata6+/− embryos reveals a dose-sensitive phenotype, with fewer PrE-specified cells. These results and previous findings have enabled the development of a mathematical model for the dynamics of the regulatory network that controls ICM differentiation into Epi or PrE cells. The model describes the temporal dynamics of Erk signaling and of the concentrations of Nanog, Gata6, secreted Fgf4 and Fgf receptor 2. The model is able to recapitulate most of the cell behaviors observed in different experimental conditions and provides a unifying mechanism for the dynamics of these developmental transitions. The mechanism relies on the co-existence between three stable steady states (tristability), which correspond to ICM, Epi and PrE cells, respectively. Altogether, modeling and experimental results uncover novel features of ICM cell fate specification such as the role of the initial induction of a subset of cells into Epi in the initiation of the salt-and-pepper pattern, or the precocious Epi specification in Gata6+/− embryos.
EphA4-dependent Brachyury expression is required for dorsal mesoderm involution in the Xenopus gastrula
Authors: Evren Sevan , Wen Jason W. H. , Luu Olivia , Damm Erich W. , Nagel Martina , Winklbauer Rudolf
Published: September 2014

Xenopus provides a well-studied model of vertebrate gastrulation, but a central feature, the movement of the mesoderm to the interior of the embryo, has received little attention. Here, we analyze mesoderm involution at the Xenopus dorsal blastopore lip. We show that a phase of rapid involution – peak involution – is intimately linked to an early stage of convergent extension, which involves differential cell migration in the prechordal mesoderm and a new movement of the chordamesoderm, radial convergence. The latter process depends on Xenopus Brachyury, the expression of which at the time of peak involution is controlled by signaling through the ephrin receptor, EphA4, its ligand ephrinB2 and its downstream effector p21-activated kinase. Our findings support a conserved role for Brachyury in blastopore morphogenesis.
Semaphorin 6B acts as a receptor in post-crossing commissural axon guidance
Authors: Andermatt Irwin , Wilson Nicole H. , Bergmann Timothy , Mauti Olivier , Gesemann Matthias , Sockanathan Shanthini , Stoeckli Esther T.
Published: September 2014

Semaphorins are a large family of axon guidance molecules that are known primarily as ligands for plexins and neuropilins. Although class-6 semaphorins are transmembrane proteins, they have been implicated as ligands in different aspects of neural development, including neural crest cell migration, axon guidance and cerebellar development. However, the specific spatial and temporal expression of semaphorin 6B (Sema6B) in chick commissural neurons suggested a receptor role in axon guidance at the spinal cord midline. Indeed, in the absence of Sema6B, post-crossing commissural axons lacked an instructive signal directing them rostrally along the contralateral floorplate border, resulting in stalling at the exit site or even caudal turns. Truncated Sema6B lacking the intracellular domain was unable to rescue the loss-of-function phenotype, confirming a receptor function of Sema6B. In support of this, we demonstrate that Sema6B binds to floorplate-derived plexin A2 (PlxnA2) for navigation at the midline, whereas a cis-interaction between PlxnA2 and Sema6B on pre-crossing commissural axons may regulate the responsiveness of axons to floorplate-derived cues.
Structures of Naphthol–AOT Self-assembly Organogels and Their Applications to Dispersing Media of Rare-earth Complexes
Authors: Katsube Shotaro , Harada Takashi , Umecky Tatsuya , Takamuku Toshiyuki , Kaji Toshihiko , Hiramoto Masahiro , Katsumoto Yukiteru , Nishiyama Katsura
Published: September 2014

The compound 2-naphthol and surfactant AOT have been found to form gels in nonpolar solvents via self-assembly. The gel can be applied to an emitting organogel upon UV excitation. NMR spectroscopy revealed that 2-naphthol has a stacked structure in which naphthyl π–π overlap is maximized, and the exterior of this structure is surrounded by AOT. This organogel emits blue light under UV excitation because of dense stacking of the 2-naphthol framework. When a Eu3+ complex exhibiting orange emission was dispersed in the gel, pinkish-white emission was observed because of an additive color-tuning of the gel body and the Eu3+ complex dispersed in it.
Profesor Aleksander Todorow Mańkowski (1868-1946) – Polak z Podola, rosyjski biały emigrant w Bułgarii, twórca Instytutu Histologii i Embriologii Uniwersytetu w Sofii
Authors: Mańkowski Andrzej Emeryk
Published: September 2014

The biographical sketch devoted to Aleksander Mańkowski (1868-1946) presents and recalls the relatively less-known figure of a distinguished scientist of Polish origin, a Russian scholar, a many-year lecturer at the University of Sophia and a translator of specialist literature in the field of medicine into Bulgarian. He derived from a Podolia noble family with the Jastrzębiec coat of arms. He grew up in the Ukrainian-Moldovan borderland in relatively humble financial conditions. In order to start his university studies he took advantage of a scholarship awarded by the Bender powiat in the Bessarabian Governorate. As a person of a Roman Catholic faith, he experienced difficulties in advancing in his academic career. His numerous brothers, who like himself did not succumb to the temptation of converting into the Orthodox faith, achieved their education in schools for cadets, probably due to the material situation of their family. They served in the tsarist army as non-commissioned officers. Mańkowski lectured at the St. Volodymyr University in Kiev in 1894-1902; he was a professor at the New Russian University in Odessa in 1902-1919. In 1919 he made his way by sea away from Odessa in the Ukraine which was in revolutionary turmoil and settled in Bulgaria. In 1920-1929 he was a professor at the University of Sophia. He established the department of Histology and Embriology at the latter university; in 1930-1933 he worked at Prof. Witold Orłowski’s clinic in Warsaw. He maintained close contacts with the apostolic nuncio in Bulgaria – the archbishop Angelo Giuseppe Roncalli – the later Holy Pope John XXIII. He died in Bulgaria in 1946. His tomb was renovated in 2010 as a part of a programme conducted by the Polish Cultural and Educational Association in Bulgaria.
W stolicy Rusi Halickiej
Authors: Biedrzycka Agnieszka
Published: September 2014

The text is a translation of the article by Grigory Aleksandrovich Vorobyev Въ столице Галицкой Руси published in 1901 in the 86th volume of “Istorichesky Vestnik”, a historical and literary periodical published in Sankt Petersburg. Vorobyev (1860-1907), collegial councillor in the Płock Governorate, the president of the Military and Police Division of the Łomża Governorate, court councillor and justice of the peace in Ostrołęka, and also a passionate historian and amateur ethnologue, manifested kindness towards the Poles, rarely expressed by Russian officials, and showed interest in Polish history and culture, evident in his numerous publications in Polish and Russian periodicals. In early June 1900 he presumably visited Lviv on the occasion of his participation in the Third Convention of Polish Historians in Kraków. The monuments of Jan III Sobieski and Jan Kiliński, the Roman Catholic, Greek Catholic and Armenian Catholic cathedrals, the chapel of the Boim family, the Jesuit Church and the Dominican Church, the Wallachian Church, the Church of St. Nicholas, the Church of St. Onuphrius, The Orthodox Church of St. Paraskeva, the Monastery of the Order of Saint Basil the Great, the Golden Rose Synagogue, The Market Square, the Stauropegial Institute, the National Ossoliński Institute, The Dzieduszycki Museum, Lychakiv Cemetery, archives and libraries are the monuments which he described in the present article, enhanced by a brief historical note and his impressions of the life of the city.
Karol Jaroszyński (1878-1929) – europejski finansista i wizjoner z Kresów
Authors: Wasyl Franciszek
Published: September 2014

Karol Jaroszyński (1878-1929) – an European financier and visionary from the Borderlands

The article is devoted to the life and activities of Karol Jaroszyński, one of the richest and most influential people in czarist Russia at the time of its twilight. K. Jaroszyński was descended from a Polish family settled in the Borderlands (in the Kiev region). Educated within the sphere of Western and Catholic culture, he owed his financial prosperity to successful investments in the banking system of the Romanov family, and also to wide contacts and connections. K. Jaroszyński personally knew czar Nicholas II’s family, and also influential financiers and entrepreneurs who were active in Russia before the outbreak of the I World War (inter alios Emanuel Nobel, Boris Abramovich Kamienka, Vladislav Zhukowsky). He was an adherent of a theory that as a result of the domination of German capital and its “tacit” collaboration with the Bolsheviks in 1917-1918, the consolidation and eventual victory of the “red” dictatorship occurred. K. Jaroszyński took part in a plot to save the czar’s family from the hands of Bolshevist murderers (the plot was unsuccessful). He also explored, together with the British intelligence, the chances of deposition of communist dictatorship on the basis of available economic and organisational resources. In 1919 he left Russia and travelled across Western Europe, where his great determination was met with even greater lack of understanding as he attempted to form a front against the communist dictatorship in Russia which he considered, similarly to W. Churchill, as a great danger to mankind. Eventually he settled in Poland where he became famous as the founder of the Catholic University of Lublin, a Polish institution of education modelled after the Catholic University of Leuven. K. Jaroszyński was unsuccessful in his business matters conducted in his fatherland; he did not start a family. He died in poverty and solitude in Warsaw on 8 September 1929. The article features two never-before-published memoirs of people who were friends with K. Jaroszyński. These are the accounts of Kazimierz and Karol Górski, father and son. Karol Górski went on to become a professor of the Nicolaus Copernicus University in Toruń.

The writing of the article was possible thanks to the kindness and assistance of K. Jaroszyński’s family and relatives: Józef Jaroszyński, Paweł Dembinski, Teresa Bisping née Starowieyska and Wojciech Starowieyski.
calidad de la enseñanza de E/LE y de la traducción: un camino hacia la profesionalización
Authors: Albin Joanna
Published: September 2014

THE QUALITY OF TEACHING SPANISH AND TRANSLATION SKILLS: TOWARDS PROFESSIONALIZATION

The aim of this paper is to analyse affective and motivational factors during the didactic process within the bachelor studies of “Applied Spanish language”. According to the data collected, a motivational crisis can be observed when students reach the communicative level of Spanish. On the contrary, motivation does not drop in translation classes, while the main problem is low self-efficacy along with high anxiety then facing a translation task. My conclusions point at the renewal of quality conception by reformulating teaching curricula as vocational training. As for the recommended methodology, I propose simultaneous teaching of linguistic and translation skills, according to the principle of co-emergence of competencies, based on students’ autonomy, respect and taking advantage of students’ experience and personal goals.
Situación de los docentes de español /LE en centros de enseñanza secundaria en Cracovia: aproximación a un análisis de expectativas y satisfacción profesional
Authors: Balches Arenas R. Sergio
Published: September 2014

THE SITUATION OF SECONDARY SCHOOL SPANISH TEACHERS IN CRACOW: AN ANALISIS OF THEIR EXPECTATIONS AND THEIR JOB SATISFACTION

The goal of this paper is to offer –from a synchronic perspective– an empirical analysis of the way Secondary School teachers within the Cracow metropolitan area perceive their teaching and the students they work with. Thanks to the conducted survey we will be able to observe the evaluation of aspects such as work environment and atmosphere, the teaching institution, salary, the strengths and weaknesses of educational centres, etc. This will be preceded by a brief study into the Polish education system which will provide an introductory reference to the context the research was carried out in.
Construções perifrásticas portuguesas dever + infinitivo e ter de/que + infinitivo – um problema didático
Authors: Drzazgowska Joanna
Published: September 2014

PORTUGUESE VERBAL PERIPHRASIS WITH DEVER AS A TEACHING PROBLEM

This article attempts to highlight the problems in teaching and learning of two Portuguese periphrastic modal constructions. The aforementioned problem is related to polysemy of periphrases with dever and supposed synonymy in specific contexts of those periphrases.
Globalización y español intercultural
Authors: Fuentes González Antonio Daniel
Published: September 2014

GLOBALISATION AND THE INTERCULTURAL SPANISH

The actual process of the electronic-financial globalisation requires a certain symbolic uniformity, which, in turn, needs languages, even in the most marginal way, although generally this globalised system tends to consider them as a ballast. From the perspective of this symbolic platform, we can talk about the Global Glasshouse, with thin and transparent sides, from/to which one can be expulsed and/or admitted. Languages, thanks to their constitutive malleability, accommodate themselves to this big glasshouse. For that reason, we can say that the intercultural Spanish language as a communicative breath can cushion an unreal-speculative globalisation, which, however, is meant to have ability to (re)convert languages – despite all its initial restrictions – into a permanently exchangeable merchandise within the flow of the symbolic market.
Rasgos competenciales en los (sub)procesos de escritura académica entre estudiantes de español como segunda lengua (E/LE)
Authors: Romero Oliva Manuel Francisco
Published: September 2014

COMPETENCE FEATURES IN THE (SUB)PROCESS OF ACADEMIC WRITING AMONG THE STUDENTS OF SPANISH AS A SECOND LANGUAGE

This article tries to elaborate a competence profile of Polish students in relation to the academic literacy in the second language (E/LE). The study of the different cognitive (sub) processes that appear in the development of writing has been realized across paragraphs of evaluation that will allow the elaboration of a qualitative analysis of the competence levels; whereas the findings obtained from the linguistic examined corpus will have to affect, both the teacher and the apprentices in the improvement of the teaching and learning processes of the target language.
política educativa en Polonia en el ámbito de enseñanza de lenguas extranjeras y su influencia en la situación y perspectivas del español en escuelas polacas
Authors: Tatoj Cecylia
Published: September 2014

THE FOREIGN LANGUAGE EDUCATIONAL POLICY OF POLAND AND ITS INFLUENCE ON THE SITUATION OF SPANISH AT POLISH SCHOOLS

In the present article, I comment on the educational policy of Poland in the area of teaching foreign languages. One of the main focal points is to analyze that educational policy and its influence on the actual situation of teaching foreign languages, particularly concentrating on the position of Spanish language. The primary objective of this work is to present the perspectives of Spanish language in Poland. In order for the research to be complete, I presents data concerning Spanish being taught at all the levels of teaching in Poland.
centros educativos como comunidades de práctica: la práctica reflexiva colectiva como modelo de formación
Authors: Ruescas Olga Esteve
Published: September 2014

MUTUAL REFLECTIVE PRACTICE AS A MODEL OF PROFESSIONAL DEVELOPMENT IN EDUCATIONAL CENTRES

It has been shown that among the different modalities of teacher training, those that take place within a group, with interaction among the teachers themselves and aimed at achieving a common objective are the most suitable for improving teaching practices. Nevertheless, this type of formative process is only effective if it is carried out systematically and if it is really participative. Therefore, efforts would be made to help organizations like schools to become communities of practice.
Colectivos con necesidades específicas, una nueva realidad universitaria
Authors: Palka Ewa
Published: September 2014

STUDENTS WITH SPECIAL EDUCATIONAL NEEDS – A NEW CHALLENGE FOR UNIVERSITIES: A SUPPORT MODEL FOR SPANISH LANGUAGE LEARNERS WITH VISUAL IMPAIRMENTS

Special educational needs is an umbrella term for different groups of people including students with learning difficulties or disabilities. Over the last few decades the education solutions for the disabled have evolved towards the inclusive model, recommended in the UN Convention on the Rights of People with Disabilities, which was ratified by Poland in 2012. The Convention establishes a new reality which needs attention almost immediately by the Institute of Roman Philologies of the Jagiellonian University of Cracow, due to the matriculation of a student with visual disability. Having analysed different options, it has been decided to offer the necessary support under the form of a new academic subject entitled Assistance to the disabled in educational environments, organised and developed in co-operation with the Disability Support Service of the Jagiellonian University. The final evaluation has proved that the subject is a success and benefits all the people involved. The added value of the project is the training of the first group of Spanish teachers in Poland who know how to teach visually disabled learners. In this way the situation which, at first, was a problem has turned into an opportunity. Taking into consideration the results achieved the programme will continue during the following academic years.
Las redes sociales como canal comunicativo: el caso de las asociaciones de consumidores de España y Portugal
Authors: Canavilhas Joao , González-Molina Sonia
Published: September 2014

Este trabajo estudia el uso que hacen de los social media (Facebook y Twitter), las dos principales organizaciones de consumidores de Portugal y España, DECO y OCU, respectivamente. La investigación, que se fundamenta metodológi-camente en el estudio de caso, se basa en los postulados de la comunicación dialógica digital para analizar cómo se legitiman las organizaciones en estas plataformas y cuál es su compromiso con esta forma de relación a partir de variables como el número de mensajes respondidos, la rapidez en la respuesta y el número de seguidores. Los resultados confirman su eficacia como canal comunicativo para satisfacer las dudas de los usuarios de manera responsable, recíproca y con sentido de comunidad.
Editorial 1. Cumplimos un lustro
Authors: Tur-Viñes Victoria
Published: September 2014

Revista Mediterránea de Comunicación/Mediterranean Journal of Communication alcanza un lustro publicando de forma ininterrumpida resultados de investigación y reflexiones relacionadas con la Comunicación. El número de textos recibidos, la calidad de los mismos, la responsabilidad de los revisores y la indexación de la revista en un número mayor de bases de datos permiten pensar que la revista comienza su consolidación.
Editorial 2. Contextos y audiencias digitales (II)
Authors: Marta Lazo Carmen , Gabelas Barroso José Antonio
Published: September 2014

Vivimos en una constante mutación hacia nuevas formas de interaccionar con las pantallas y los mensajes que ellas nos proporcionan. El contexto digital alberga nuevos entornos que posibilitan nuevos usos, consumos e intercambios de comunicación. En este monográfico de la Revista Mediterránea de Comunicación, publicado en dos fases (diciembre de 2013 y junio de 2014), se incluye un compendio de artículos que reflexionan y analizan la nueva realidad en un contexto cada vez más convergente. En este nuevo panorama en el que las multipantallas generan nuevos discursos, el “EMIREC” (emisor-receptor) (Cloutier, 1975), “prosumidor” (productor-consumidor) (Toffler, 1979) o “perceptor-participante” (perceptor-partícipe-actante) (Marta-Lazo, 2005) alcanzan sus máximas cuotas de interacción. De este modo, pasamos de las audiencias tradicionales, que se caracterizaban por una exposición unidireccional y bancaria a los mensajes, a un nuevo modelo en el que prima la interrelación y la autoría en conglomerados de nuevas plataformas y redes sociales.