bluuebunny/crossref_metadata_2025 huggingface dataset:
Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I
Authors: Pievani Alice , Azario Isabella , Antolini Laura , Shimada Tsutomu , Patel Pravin , Remoli Cristina , Rambaldi Benedetta , Valsecchi Maria Grazia , Riminucci Mara , Biondi Andrea , Tomatsu Shunji , Serafini Marta
Published: October 2014

Key Points

Allogeneic BMT into newborn MPS I mice allows high donor-derived hematopoietic engraftment and prevents bone deformities. Bones of transplanted MPS I mice show significant improvements at radiographic, microcomputed tomography, and histological analyses.
Nonlinearities distribution Laplace transform-homotopy perturbation method
Authors: Filobello-Nino Uriel , Vazquez-Leal Hector , Benhammouda Brahim , Hernandez-Martinez Luis , Hoyos-Reyes Claudio , Perez-Sesma Jose Antonio Agustin , Jimenez-Fernandez Victor Manuel , Pereyra-Diaz Domitilo , Marin-Hernandez Antonio , Diaz-Sanchez Alejandro , Huerta-Chua Jesus , Cervantes-Perez Juan
Published: October 2014

This article proposes non-linearities distribution Laplace transform-homotopy perturbation method (NDLT-HPM) to find approximate solutions for linear and nonlinear differential equations with finite boundary conditions. We will see that the method is particularly relevant in case of equations with nonhomogeneous non-polynomial terms. Comparing figures between approximate and exact solutions we show the effectiveness of the proposed method.
Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome
Authors: Tian Yuan , Voineagu Irina , Paşca Sergiu P , Won Hyejung , Chandran Vijayendran , Horvath Steve , Dolmetsch Ricardo E , Geschwind Daniel H
Published: October 2014

Background

Common genetic variation and rare mutations in genes encoding calcium channel subunits have pleiotropic effects on risk for multiple neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. To gain further mechanistic insights by extending previous gene expression data, we constructed co-expression networks in Timothy syndrome (TS), a monogenic condition with high penetrance for ASD, caused by mutations in the L-type calcium channel, Cav1.2.

Methods

To identify patient-specific alterations in transcriptome organization, we conducted a genome-wide weighted co-expression network analysis (WGCNA) on neural progenitors and neurons from multiple lines of induced pluripotent stem cells (iPSC) derived from normal and TS (G406R in CACNA1C) individuals. We employed transcription factor binding site enrichment analysis to assess whether TS associated co-expression changes reflect calcium-dependent co-regulation.

Results

We identified reproducible developmental and activity-dependent gene co-expression modules conserved in patient and control cell lines. By comparing cell lines from case and control subjects, we also identified co-expression modules reflecting distinct aspects of TS, including intellectual disability and ASD-related phenotypes. Moreover, by integrating co-expression with transcription factor binding analysis, we showed the TS-associated transcriptional changes were predicted to be co-regulated by calcium-dependent transcriptional regulators, including NFAT, MEF2, CREB, and FOXO, thus providing a mechanism by which altered Ca2+ signaling in TS patients leads to the observed molecular dysregulation.

Conclusions

We applied WGCNA to construct co-expression networks related to neural development and depolarization in iPSC-derived neural cells from TS and control individuals for the first time. These analyses illustrate how a systems biology approach based on gene networks can yield insights into the molecular mechanisms of neural development and function, and provide clues as to the functional impact of the downstream effects of Ca2+ signaling dysregulation on transcription.
Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies
Authors: Kryštůfková Olga , Helmers Sevim Barbasso , Venalis Paulius , Malmström Vivianne , Lindroos Eva , Vencovský Jiří , Lundberg Ingrid E
Published: October 2014

Introduction

Anti-Jo-1 and anti-Ro52 autoantibodies are common in patients with myositis, but the mechanisms behind their production are not known. Survival of autoantibody-producing cells is dependent on B-cell-activating factor of the tumour necrosis factor family (BAFF). BAFF levels are elevated in serum of anti-Jo-1-positive myositis patients and are influenced by type-I interferon (IFN). IFN-producing cells and BAFF mRNA expression are present in myositis muscle. We investigated expression of the receptors for BAFF in muscle tissue in relation to anti-Jo-1 and anti-Ro52/anti-Ro60 autoantibodies and type-I IFN markers.

Methods

Muscle biopsies from 23 patients with myositis selected based on autoantibody profile and 7 healthy controls were investigated for expression of BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Nineteen samples were assessed for plasma (CD138) and B-cell (CD19) markers. The numbers of positive cells per area were compared with the expression of plasmacytoid dendritic cell (pDC) marker blood dendritic cell antigen-2 (BDCA-2) and IFNα/β-inducible myxovirus resistance-1 protein (MX-1).

Results

BAFF-R, BCMA and TACI were expressed in five, seven and seven patients, respectively, and more frequently in anti-Jo-1-positive and/or anti-Ro52/anti-Ro60-positive patients compared to controls and to patients without these autoantibodies (P = BAFF-R: 0.007, BCMA: 0.03 and TACI: 0.07). A local association of receptors with B and plasma cells was confirmed by confocal microscopy. The numbers of CD138-positive and BCMA-positive cells were correlated (r = 0.79; P = 0.001). Expression of BDCA-2 correlated with numbers of CD138-positive cells and marginally with BCMA-positive cells (r = 0.54 and 0.42, respectively; P = 0.04 and 0.06, respectively). There was a borderline correlation between the numbers of positively stained TACI cells and MX-1 areas (r = 0.38, P = 0.08).

Conclusions

The expression pattern of receptors for BAFF on B and plasma cells in muscle suggests a local role for BAFF in autoantibody production in muscle tissues of patients with myositis who have anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies. BAFF production could be influenced by type-I IFN produced by pDCs. Thus, B-cell-related molecular pathways may participate in the pathogenesis of myositis in this subset of patients.
Successful nucleofection of rat adipose-derived stroma cells with Ambystoma mexicanum epidermal lipoxygenase (AmbLOXe)
Authors: Fülbier Angela , Schnabel Reinhild , Michael Stefanie , Vogt Peter M , Strauß Sarah , Reimers Kerstin , Radtke Christine
Published: October 2014

Introduction

Adipose-derived stroma cells (ASCs) are attractive cells for cell-based gene therapy but are generally difficult to transfect. Nucleofection has proven to be an efficient method for transfection of primary cells. Therefore, we used this technique to transfect ASCs with a vector encoding for Ambystoma mexicanum epidermal lipoxygenase (AmbLOXe) which is a promising bioactive enzyme in regenerative processes. Thereby, we thought to even further increase the large regenerative potential of the ASCs.

Methods

ASCs were isolated from the inguinal fat pad of Lewis rats and were subsequently transfected in passage 1 using Nucleofector® 2b and the hMSC Nucleofector kit. Transfection efficiency was determined measuring co-transfected green fluorescent protein (GFP) in a flow cytometer and gene expression in transfected cells was detected by reverse transcription polymerase chain reaction (RT-PCR). Moreover, cell migration was assessed using a scratch assay and results were tested for statistical significance with ANOVA followed by Bonferroni’s post hoc test.

Results

High initial transfection rates were achieved with an average of 79.8 ± 2.82% of GFP positive cells although longer cultivation periods reduced the number of positive cells to below 5% after four passages. Although successful production of AmbLOXe transcript could be proven the gene product had no measureable effect on cell migration.

Conclusions

Our study demonstrates the feasibility of ASCs to serve as a vehicle of AmbLOXe transport for gene therapeutic purposes in regenerative medicine. One potential field of applications could be peripheral nerve injuries.
Visceral Archives of the Body
Authors: Tortorici Zeb
Published: October 2014

This essay focuses on how viscerality refracts as an issue for archival studies of early modern sexuality (and beyond). Through a microhistorical examination of textual representations of necrophilia, fellatio, masturbation, and erotic religious visions from colonial Mexican historical archives, this essay traces what I term the visceral archives of the body to show how particular acts and desires come into archival being (and thus into historicity) by eliciting visceral responses — “gut feelings” — on the part of suspects, witnesses, colonial authorities, scribes, archivists, and historians. I further argue that a metaphorics of consumption undergirds historical archives and archival documents, as they are produced, ordered, read, and interpreted. By working through such complex affective archival engagements, we gain a more nuanced understanding of the erotic chains that structure and confuse the taxonomizing impulses of the archive itself.
Understanding the structure of flowers—The wonderful tool of floral formulae: A response to Prenner & al.
Authors: Ronse de Craene Louis , Iwamoto Akitoshi , Bull-Hereñu Kester , Dos Santos Patricia , Luna Javier A. , Farrar Jennifer
Published: October 2014

This paper is a discussion and elaboration of a paper by Prenner & al. (2010), entitled “Floral formulae updated for routine inclusion in formal taxonomic descriptions”. The aim of the Prenner paper was to promote the use of floral formulae in botany and to reach a consensus among botanists for best practice. An important purpose of floral formulae is to induce users to observe and describe flowers accurately. It is proposed that additional information on anther, ovule, style and stigma should be included. Also, only visible organs should be included in a formula and theoretical speculations should be illustrated with floral diagrams, which are complementary to formulae, unless there is good reason to include absent organs. We propose a universal, standardized method to accurately shorthand a description of a flower. The level of detail given in the formula can be highly flexible and depends on the intentions of the user.
Bibliography of Ewdoksia Papuci-Władyka
Authors: Machowski Wojciech S. , Zając Barbara
Published: October 2014

Compiled by Wojciech S. Machowski and Barbara Zając
More on the Labyrinth on the Coins of Knossos
Authors: Mielczarek Mariusz
Published: October 2014

In his ‘Natural History’ (36.84-93), Pliny the Elder lists four buildings termed ‘labyrinths’. His second labyrinth, which came directly after the Egyptian one, was built by Daedalus in Crete, not far from Knossos, and appears on Knossian coins as the symbol of Knossos. The main aim of this article is to discuss the differing forms of this labyrinth and their origins. The first coins of Knossos appeared around 470 BC and bore a pattern of four meanders to indicate a labyrinth. A square labyrinth pattern followed and this was finally replaced by one of circular form.
Attalos III, King and Sculptor
Authors: Polański Tomasz
Published: October 2014

In his epitome Justin related Pompeius Trogus’ story, who apparently wanted to convince his readers that Attalos III, who was insane, accused his relatives of poisoning Berenike and Stratonike. Before he died he had bequeathed his kingdom to Rome. Sallust adduced the words of Mithridates VI, who considered Attalos’ testament a Roman forgery. What we know from Justin’s version is the Roman version, which was produced to justify the annexation of a foreign country and the seizure of the Attalids’ immense treasures. Attalos was one of the best educated Hellenistic monarchs, a lover and patron of the arts and sciences, a sculptor and a man of letters. With the slaying of Attalos III and his closest relatives the Roman senators also terminated the last great project of patronage over the Hellenic arts, letters and sciences.
The ‘Ephesian’ Terracotta Oil Lamps from the Agora of Nea Paphos
Authors: Kajzer Małgorzata
Published: October 2014

Ephesian terracotta oil lamps are a group of Hellenistic lamps used during the last two centuries BC and probably also in the 1st century AD. This very interesting mould-made type has very characteristic form, clay and ornamentation. Widespread across the whole Mediterranean, they were present in Cyprus and examples were discovered during the Paphos Agora Project. From certain findings it is even possible to suggest that Nea Paphos was a place where they were produced.
Magical Amulet from Paphos with the ιαεω- Palindrome
Authors: Śliwa Joachim
Published: October 2014

During the first excavation campaign of the Paphos Agora Project (3rd July – 6th August 2011), an interesting object was discovered. In Trench II, Area 2 (Room 5), in the upper, late Roman layer, an oval amulet was found (siltstone, 39.41 x 41.32 x 4.81mm). The layer is dated to the 6th century AD, partially due to the presence of ceramic objects of the Cypriot Red Slip Ware type (Hayes form 2, AD 450-550). The obverse of the amulet contains a schematic, simplified figure of a sitting Harpocrates and below the mummy of Osiris in a boat, as well as depictions of animals (a crocodile, a rooster and a snake) and symbolic astrals (a half-moon and a star). On the reverse, however, an eight-line text of the so-called ιαεω- palindrome, consisting of 59 letters of the Greek alphabet, was carved. According to the current state of knowledge, it was translated in the following way: “Yahweh is the bearer of the secret name, the lion of Re secure in his shrine”. Both the depiction and the text carved into the surface of the amulet clearly indicate the influence of the Orient and the context of solar ideas; the object may be dated to the 5th-6th century AD.
A Find of an Istrian Cast ‘Wheel Coin’ at Koshary (Ukraine)
Authors: Bodzek Jarosław , Redina Evgenia F.
Published: October 2014

This article’s aim is to publish a cast Istrian ‘wheel coin’ found at the Koshary site. The site is located on the northern shore of the Black Sea on the right bank of the Tiligulskii Liman and consists of a settlement, a sacral zone around an open air altar (eschara) and a necropolis. The settlement existed between the end of the 5th and the middle of the 3rd centuries BC. Among other artifacts, 55 coins have been found at the site during regular archaeological excavations. Apart from a bronze coin of Tyras and the discussed Istrian piece, all the other coins found at Koshary are Olbian. The ‘wheel coin’ was discovered in a dugout located in the southern part of the sacral area around the eschara. The cast ‘wheel coins’ were produced in the 5th-4th centuries BC in Istros and were in circulation in a wide area covering a great part of the western and northwestern Black Sea shore. The find at Koshary, when combined with other finds in Luzanivka and Ochakov, marks a trade route between Istros, Nikonion and Olbia. As it was found in the eschara area, one can suppose that the Istrian coin was not used as currency, but possessed a sacral nature instead.
The Fortifications of the Entrance Gate in the Western Defense Wall of Western Tanais
Authors: Scholl Tomasz
Published: October 2014

Since 1999 the Polish Archaeological Expedition has been working in Western Tanais. One of the important structures recovered in Trench XXV is the entrance gate.
Callatis as a Seaport
Authors: Stanecka Ewa
Published: October 2014

The task of the following paper is to give some details of the ancient harbour of Callatis. Over the course of archaeological investigations, a reconstruction of the shoreline has been put together and many architectural and portable sources have been discovered. The archaeological coastal sites of the Black Sea are partially submerged and the research carried out within the port area of Callatis is therefore of great importance.
A Lost Ivory Diptych Panel in an Indian Painting
Authors: Vickers Michael
Published: October 2014

It is argued that the composition of part of an Indian miniature painting in a private collection in Los Angeles is ultimately based on a late Roman ivory diptych panel, although the mechanism of transmission is uncertain.
Major Leon Franciszek Ulatowski – a Legionary and an Officer of the Second Republic of Poland: A Contribution to Biography
Authors: Rafalski Piotr Tadeusz
Published: October 2014

Leon Franciszek Ulatowski (1889-1973) was an officer of the Polish Army in the rank of major. He was a son of Jan, a farmer, and Maria (née Sokołowska). After he completed his education at a teachers’ college and then at the Business Academy [Akademia Handlowa] in Kraków, he studied agriculture in the Department of Philosophy of the Jagiellonian University and also in the Szkoła Główna Gospodarstwa Wiejskiego in Warsaw. Since 6 August 1914 he was a soldier of the Polish Legions which later became the 1st Infantry Regiment. He participated in the battle of Kostiuchnówka as the commander of the machinegun division of the VI battalion of the seventh infantry regiment. After the dissolution of the Legions he became the commanding officer of the Polish Military Organisation [Polska Organizacja Wojskowa] in the Borysław area. On 1 November 1918 he entered the Polish Army in Kraków by joining the 5th infantry regiment of the Legions. In 1919 he assumed command of the machinegun department of the 1st infantry regiment of the Legions in the rank of captain and the command of the 4th machinegun company. He participated in the Polish-Soviet war with the 1st infantry regiment in 1920. In 1929 he became the executive officer of the 36th infantry regiment of the Academic League. In the years 1930-1932 he worked as the director of the Office of Military Training and Physical Education [Urząd Przysposobienia Wojskowego i Wychowania Fizycznego] in the Command of the Area of Corpus No. IV in Łódź. From 1932 to 1937 he was a staff officer in the Ministry of Military Affairs in Warsaw. Then, until the outbreak of World War II, he was delegated to the Ministry of Religious Denominations and Public Education [Ministerstwo Wyznań Religijnych i Oświecenia Publicznego]. In September 1939 he performed the function of the executive Quartermaster of the Defense of Warsaw. After the capitulation he was put into a POW camp in Murnau. In 1945 he returned to Poland and took employement in a dairy cooperative.
Non-Military Activities of the Border Defence Corps in the Light of the Reports and Literary Output of the Soldiers Who Belonged to This Formation (1924-1939)
Authors: Werner Mateusz
Published: October 2014

The article attempts to describe the operations of the Border Defence Corps. These operations can be seen as a civilizing mission led by the army in the eastern borderlands. After presenting an overview of the state of research and the origin of the formation, the author elaborates upon the activity of BDC dividing it into two types. Indirect actions were connected with the military presence in the border zone. Direct actions were the initiatives of the soldiers deliberately directed at the local population. These actions concerned such spheres as: education, culture, sports or charity. The value of this text lies in the fact that the non-military activity of the BDC is shown through the eyes of the officers of this formation. The latter usually evaluated their work highly in official reports, poems and songs. This, however, is a more complex issue, which, due to methodological and source problems, could not be resolved in this article.
It Was Worth It...
Authors: Lewandowski Mirosław
Published: October 2014

Mirosław Lewandowski’s conversation with Marek Bik
Antipsychotics in the treatment of psychosis: risks and benefits
Authors: Mutsatsa Stanley , Bressington Daniel
Published: October 2014

Antipsychotics are important in the treatment and recovery of people with psychosis but current evidence suggests that mental health nurses are not always conversant with the risks and benefits of these drugs. This inadequate knowledge has important ramifications for the provision of safe and effective care. This article outlines the risks and benefit profiles associated with contemporary antipsychotic drugs to enhance mental health nurses' knowledge of medicines. Ultimately, comprehensive knowledge of medication, their actions, risk and benefits should promote mental health nurses' effectiveness in medicines
Completing a Yellow Card report following an adverse reaction
Authors: Goddard Rachel
Published: October 2014

Even the most experienced practitioners can come across moderate or severe complications when treating patients with toxins and fillers. Any adverse reactions to a therapeutic agent should be reported using the Medicines and Healthcare Products Regulatory Agency's Yellow Card scheme. Rachel Goddard summarises the process of adverse incident reporting and addresses key questions
Tratamiento de la colusión en la contratación pública: una visión del caso colombiano
Authors: Ossa Bocanegra Camilo Ernesto
Published: October 2014

La colusión, entendida como un pacto ilícito en daño a tercero, la cual se da en los procesos de contratación pública, es un acuerdo anticompetitivo sancionado por el artículo 47 numeral 9° del decreto 2153 de 1992 y más recientemente por la ley 1480 de 2011 –Estatuto Anticorrupción- en la cual, por medio de esta última ley, se elevó a categoría de delito lo que antes solo era sancionable desde el punto de vista administrativo. Sin embargo, el modelo de sanción establecido en la normativa colombiana, es un modelo de sanción que si bien es bastante alto, sobre todo después de la categorización de delito de esta conducta, el verdadero problema radica en la aplicación de la misma o mejor, en el organismo encargado de su aplicación. Así, como todo acuerdo anticompetitivo, la colusión es una conducta que genera grandes efectos en el mercado creado por el Estado, teniendo en cuenta que en la contratación pública, la competencia se traslada a otro estadio del proceso competitivo, ya que aquí se compite por el mercado, encontrándonos ante un resultado similar al que obtendrían en situación de monopolio, toda vez que es ese el resultado que maximiza los beneficios totales que los productores pueden obtener del mercado.
La crisis de la Comunidad Andina
Authors: Blanco Alvarado Carolina
Published: October 2014

A pesar de que la Comunidad Andina se ha constituido en el proceso de integración más antiguo de Suramérica; reiteradamente se ha manifestado la crisis del mismo. En este sentido, mediante estas páginas se desarrollan las principales causales por las cuales el proceso andino de integración no produce los efectos deseados. Para efectos de lo anterior se considera que a pesar de que el núcleo esencial de cualquier proceso de integración es económico, las causales que bstaculizan a la CAN son de carácter jurídico y político. Dicha afirmación supone que la crisis de la citada organización internacional obedece a la falta de capacidad jurídica y política de los países miembros de comportarse en el ambiente propio de un proceso de integración. En la primera parte de este artículo estableceremos por qué consideramos que la crisis de la CAN obedece a factores de orden jurídico y político, y con posterioridad desarrollaremos las principales causales que obstaculizan el proceso andino de integración, descartando un análisis económico sobre el particular. Este articulo es producto de un trabajo de análisis que pretende examinar un tema o aspecto concreto del proceso de integracion andino, como lo es la crisis que dicho proceso ha evidenciado. El tipo de trabajo de investigación empleado para estas páginas es sintético, esto es, trata de poner de manifiestola totalidad del contenido de una materia o tema exponiendo sus partes principales y esenciales. A su vez y en el marco del citada modalidad de trabajo de investigación, estas páginas se circunscriben en un trabajo científico tipificado en la modalidad de “Los estados de la cuestión”, esto es, en un trabajo de investigación que recoge la situación científica de una determinada materia en un determinado momento. Adicionalmente, el metodo empleado para esta investigación es analítico, esto es, aquel que parte de lo complejo, llegando a lo más simple
La protección internacional de los refugiados víctimas de trata de personas
Authors: Llain Arenilla Shirley , Guzmán Suárez Sara Patricia
Published: October 2014

En el delito de trata de personas, la víctima, con miras a ser explotada por un tercero, es obligada o engañada para trasladarla a un lugar diferente al de su origen, bien sea a nivel interno o internacional. En este último caso, de acuerdo con los instrumentos internacionales en la materia, las víctimas del mencionado delito pueden llegar a ser sujetos de protección por el Estado receptor mediante la figura del refugio. En ese orden de ideas, con esta investigación nos proponemos, en primer lugar, analizar la concepción del refugio en la actualidad y la ubicación del delito de trata a nivel trasnacional y, en segundo lugar, revisar la situación del cuestionamiento que respecto de su estatus migratorio sufren quienes siendo víctimas de trata solicitan refugio
Modeling College Graduation GPA Considering Equity in Admissions: Evidence from the University of Puerto Rico
Authors: Matos-Diaz Horacio , Garcia Dwight
Published: October 2014

Over concerns about private school students’ advantages in standardized tests, beginning in 1995–96 the University of Puerto Rico (UPR) implemented a new admissions formula that reduced the weight they previously had in the General Admissions Index (GAI), on which its admissions decisions are based. This study seeks to determine the possible effects of the new GAI regarding both its objective of promoting equity in the student body composition and as a measure of academic aptitude capable of predicting student success. With these aims, the study compares the old and new GAI averages of 11 consecutive entering cohorts at the Bayamón campus of the UPR, and models the graduation GPA (GGPA) of 6 of these cohorts. Evidence shows that (a) the new GAI eliminated private school students’ advantage over those from public schools and reduced to a minimum the gap between genders; (b) female students obtain significantly higher GGPAs and exhibit other advantages when compared to males, while public and private school students’ academic outcomes are broadly similar; (c) the probability of accessing a determined boundary in the GGPA distribution is significantly and nonlinearly related to the GAI; (d) GGPAs exhibit an uptrend that varies inversely and significantly with the GAI, and (e) the probability of being in the lower bounds of the GGPA distribution increases to the extent that graduates exceed graduation required time.
Meeting report: present state of molecular genetics in clinical laboratories. Report on the VII European Symposium on Clinical Laboratory and In Vitro Diagnostic Industry in Barcelona
Authors: Padró-Miquel Ariadna , Candás-Estébanez Beatriz
Published: October 2014

The VII European Symposium of the Clinical Laboratory and In Vitro Diagnostic Industry, co-organized between the Catalan Association for Clinical Laboratory Sciences (ACCLC) and the Catalan Society of Biology, was held on May 28th–29th, 2013 in Barcelona (Catalonia, Spain) under the IFCC auspices and the IUPAC sponsorship. The subject of the present Symposium was “Molecular Genetics in the Clinical Laboratory” and began with an opening conference that was a stroll through the history of molecular genetics in the context of the clinical laboratory. The scientific program was structured in several 2-h length roundtables that dealt with the following topics: recent advances in molecular genetics for clinical microbiology, latest evidences and real applicability of pharmacogenetics in the clinical practice, quality assurance of a molecular genetics laboratory, and latest trends in prenatal genetic diagnosis. The aim of the Symposium was the discussion of the transformation that molecular genetics has generated on clinical laboratories in terms of organization, specialization, interpretation of results and fast technical and knowledge evolution. High-qualified professionals from several countries together with in-country experts formed the roundtables. Attendants participated actively in the debates, increasing the overall interest.
When two turn into one: evolution of membrane transporters from half modules
Authors: Keller Rebecca , Ziegler Christine , Schneider Dirk
Published: October 2014

The recently increasing number of atomic structures for active transporters has not only revealed strong conservation in the architecture of sequence-unrelated transporter families, but also identified a unifying element called the ‘inverted repeat topology,’ which is found in nearly all transporter folds to date. Indeed, most membrane transporters consist of two or more domains with similar structure, so-called repeats. It is tempting to speculate that transporters have evolved by duplication of one repeat followed by gene fusion and modification events. An intriguing question is, whether recent genes encoding such a ‘half-transporter’ still exist as independent folding units. Although it seems likely that the evolution of membrane transport proteins, which harbor internal repeats, is linked to these minimal structural building blocks, their identification in the absence of structural data represents a major challenge, as sequence homology is not an issue. In this review we discuss two protein families, the DedA family and the SWEET family, being potential half-transporters and putative ancestors for two of the most abundant secondary transporter families, the MFS family and the LeuT-fold family.
Delivery outcomes after day and night onset of labour
Authors: Kanwar Sandeep , Rabindran Ranjit , Lindow Stephen W.
Published: October 2014

To describe the outcome of night onset of labour as compared with the day onset of labour to investigate if labour that begins at night is more efficient.

Retrospective review of labour and delivery data.

A large United Kingdom maternity service.

Over the period of 10 years, there were 30,022 deliveries, of which 19,842 were studied.

A United Kingdom maternity department database was used to identify deliveries over a 10-year period, and the delivery outcomes were retrieved from these records. The 19,842 labours were divided into two categories: night onset (22.00–06.00 h) and day onset (10.00–18.00 h).

Rates of operative intervention, augmentation, epidural usage and labour duration.

A significant difference in delivery outcome was noted (P=0.004) with the night-onset labours having more normal deliveries (83.6% vs. 82.5%), fewer caesarean sections (8.7% vs. 10.1%), fewer labour augmentations with syntocinon (14.9% vs. 19.5%, P<0.001), fewer artificial rupture of membranes (14.1% vs. 15.6% P<0.001) and a significantly shorter mean first stage duration (4 h 58 min vs. 5 h 7 min, P<0.05). The proportion of women from each group who delivered between 09.00 and 17.00 h was 3660 (31.1%) in the night-onset group and 2414 (30%) in the day-onset group (χ

Labours that start at night appear to be more efficient than labours that start during the day.
Spectroscopic characterization and microbial degradation of engineered bio-elastomers from linseed oil
Authors: Das Rakesh , Pramanik Nilkamal , Kundu Patit P.
Published: October 2014

The microbial degradation of elastomers synthesized through the cationic polymerization reaction of linseed oil, styrene, and divinylbenzene was investigated by using the Alkaliphilus oremlandii OhILAs strain. In Fourier transform infrared (FTIR) analysis, the bound oil content in the elastomers was found to vary from 29.63 to 45.5 wt%, whereas the percentage of unreacted oil in the elastomers were in the range of 12.9–38 wt%. In 1H nuclear magnetic resonance spectrum analysis, the unreacted oil and unreacted aromatic components in the elastomers were obtained in the ranges of 13.2–39 wt% and 6.8–16 wt%, respectively. The amount of unreacted oil in the elastomers enhanced the percentage of biodegradation, which varied from 26 to 51 wt%. The biodegradation of elastomers was also confirmed by FTIR and scanning electron micrograph analyses.
Nanostructural characterization of poly (vinylidene fluoride)-clay nanocomposites prepared by a one-step reactive extrusion process
Authors: Benabid Fatma-Zohra , Rong Lixia , Benachour Djafer , Cagiao M. Esperanza , Ponçot Marc , Zouai Foued , Bouhelal Said , Baltá Calleja Francisco J.
Published: October 2014

Poly (vinylidene fluoride) (PVDF)-untreated clay nanocomposites were successfully prepared using an innovative one-step reactive melt extrusion process. Through specific temperature and shear conditions, the chemical reactions took place between the polymer matrix, the inorganic clay particles, and three main reactive agents: an organic peroxide, sulfur, and a specific activator led finally to the PVDF-clay nanocomposites. The materials were formulated with various amounts of clay in order to identify the best conditions, enabling to obtain the optimal particle exfoliation in the polymer matrix at the nanometric scale. The microstructure and nanostructure modifications were characterized by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and wide- and small-angle X-ray scattering (WAXS and SAXS). The relationship between nanostructure and mechanical behavior was investigated by tensile experiments, impact tests, and microhardness measurements. The FTIR results suggest that there is a chemical interaction between the clay and the polymer. Furthermore, the WAXS study shows that no intercalation step takes place in any composition. In addition to this, the sample with 2.5 wt.% clay could present a total exfoliation of the clay particles. The PVDF matrix is found to be exclusively of the α-form in all compositions. The final microhardness slightly increases with both nanoclay content and degree of crystallinity.
Effects of added phthalate plasticizers on photodegradation of irradiated poly (α-methylstyrene) films
Authors: Ramadhan Afrah E.
Published: October 2014

The effects of UV irradiation and blending on the stability of poly (α-methylstyrene) (PαMS) in solid films were studied at different intervals of irradiation time in the presence of air, by absorption, emission and Fourier transform infrared (FT-IR) spectroscopy. The increase in irradiation time caused an increase in the intensity of the absorption band of the polymer, and an increase in the intensity of absorption of a new broad band at a longer wavelength, thus indicating the possibility of photodegradation of polymeric chains. The influence of added plasticizers, dimethyl terephthalate (DMT), diethyl terephthalate (DET), dibutyl phthalate (DBP), dioctyl phthalate (DOP) and dioctyl terephthalate (DOT) on photoquenching of the polymer fluorescence band was also investigated, and found to increase the photoquenching processes with increase in the amount of added plasticizers. By contrast, the intensity of excimer and monomer fluorescence bands was also found to decrease with increase in irradiation times. These changes may be attributed to the formation of new photoproducts which resulted from the photodegradation and photooxidation of irradiated polymeric chains. In addition, the observed increase in the intensities of the carbonyl and hydroxyl regions of the FT-IR spectra provides evidence for the photooxidation of polymeric chains. The increase in the intensity of some bands and the disappearance of new bands indicate the photodegradation of polymeric chains.
Mechanical properties and toughening mechanisms of epoxy/graphene nanocomposites
Authors: Eqra Rahim , Janghorban Kamal , Daneshmanesh Habib
Published: October 2014

Because of extraordinary physical, chemical and mechanical properties, graphene nanosheets (GNS) are suitable fillers for optimizing the properties of different polymers. In this research, the effect of GNS content (up to 1 wt.%) on tensile and flexural properties, morphology of fracture surface, and toughening mechanism of epoxy were investigated. Results of mechanical tests showed a peak for tensile and flexural strength of samples with 0.1 wt.% GNS such that the tensile and flexural strength improved by 13% and 3.3%, respectively. The Young’s modulus and flexural modulus increased linearly with GNS content, although the behavior of the Young’s modulus was more remarkable. Morphological investigations confirmed this behavior because the GNS dispersion in the epoxy matrix was uniform at lower contents and agglomerated at higher contents. Finally, microscopical observation showed that the major toughening mechanism of graphene-epoxy nanocomposites was crack path deflection, which changed the mirror fracture surface of the pure epoxy to rough surface.
Zeno's Paradox
Authors: Kong Jieyoung
Published: October 2014

Scholars have noted the increase in “Eastern movement forms” (e.g., non-sporting martial arts, yoga, meditation, and Tai Chi), which have been penetrating into social-cultural spaces and institutions outside their native contexts. The practice halls and studios where such movement forms are trained are intercorporeal communicative spaces where practitioners are not only grappling with the specificity of movements, but enmeshed in an assemblage of moving bodies and cultural resources. By plunging into the practice of aikido, a martial art style originating from Japan, this study explores how practitioners in the United States understand their martial art practice through their bodies. Three themes emerged: practicing, ki, and mastering. Listening to the voices of martial art bodies revealed that skillfulness is a ceaseless endeavor that uses movement to draw new relationalities between one's own corporeal assemblage and those of others rather than the internationalization of movement techniques. In the case of aikido practice, the on-site learning and practice open the way for new relationship-making across multiple lines of difference, suggesting cultural appropriation as a transformational process that exceeds the simple use and borrowing of cultural elements.
OPA1‐dependent cristae modulation is essential for cellular adaptation to metabolic demand
Authors: Patten David A , Wong Jacob , Khacho Mireille , Soubannier Vincent , Mailloux Ryan J , Pilon‐Larose Karine , MacLaurin Jason G , Park David S , McBride Heidi M , Trinkle‐Mulcahy Laura , Harper Mary‐Ellen , Germain Marc , Slack Ruth S
Published: October 2014

Cristae, the organized invaginations of the mitochondrial inner membrane, respond structurally to the energetic demands of the cell. The mechanism by which these dynamic changes are regulated and the consequences thereof are largely unknown. Optic atrophy 1 (OPA1) is the mitochondrial GTPase responsible for inner membrane fusion and maintenance of cristae structure. Here, we report that OPA1 responds dynamically to changes in energetic conditions to regulate cristae structure. This cristae regulation is independent of OPA1's role in mitochondrial fusion, since an OPA1 mutant that can still oligomerize but has no fusion activity was able to maintain cristae structure. Importantly, OPA1 was required for resistance to starvation‐induced cell death, for mitochondrial respiration, for growth in galactose media and for maintenance of ATP synthase assembly, independently of its fusion activity. We identified mitochondrial solute carriers (SLC25A) as OPA1 interactors and show that their pharmacological and genetic blockade inhibited OPA1 oligomerization and function. Thus, we propose a novel way in which OPA1 senses energy substrate availability, which modulates its function in the regulation of mitochondrial architecture in a SLC25A protein‐dependent manner.
Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells
Authors: Korzelius Jerome , Naumann Svenja K , Loza‐Coll Mariano A , Chan Jessica SK , Dutta Devanjali , Oberheim Jessica , Gläßer Christine , Southall Tony D , Brand Andrea H , Jones D Leanne , Edgar Bruce A
Published: October 2014

Snail family transcription factors are expressed in various stem cell types, but their function in maintaining stem cell identity is unclear. In the adult Drosophila midgut, the Snail homolog Esg is expressed in intestinal stem cells (ISCs) and their transient undifferentiated daughters, termed enteroblasts (EB). We demonstrate here that loss of esg in these progenitor cells causes their rapid differentiation into enterocytes (EC) or entero‐endocrine cells (EE). Conversely, forced expression of Esg in intestinal progenitor cells blocks differentiation, locking ISCs in a stem cell state. Cell type‐specific transcriptome analysis combined with Dam‐ID binding studies identified Esg as a major repressor of differentiation genes in stem and progenitor cells. One critical target of Esg was found to be the POU‐domain transcription factor, Pdm1, which is normally expressed specifically in differentiated ECs. Ectopic expression of Pdm1 in progenitor cells was sufficient to drive their differentiation into ECs. Hence, Esg is a critical stem cell determinant that maintains stemness by repressing differentiation‐promoting factors, such as Pdm1.
Iro/IRX transcription factors negatively regulate Dpp/TGF‐β pathway activity during intestinal tumorigenesis
Authors: Martorell Òscar , Barriga Francisco M , Merlos‐Suárez Anna , Stephan‐Otto Attolini Camille , Casanova Jordi , Batlle Eduard , Sancho Elena , Casali Andreu
Published: October 2014

Activating mutations in Wnt and EGFR/Ras signaling pathways are common in colorectal cancer (CRC). Remarkably, clonal co‐activation of these pathways in the adult Drosophila midgut induces “tumor‐like” overgrowths. Here, we show that, in these clones and in CRC cell lines, Dpp/TGF‐β acts as a tumor suppressor. Moreover, we discover that the Iroquois/IRX‐family‐protein Mirror downregulates the transcription of core components of the Dpp pathway, reducing its tumor suppressor activity. We also show that this genetic interaction is conserved in human CRC cells, where the Iro/IRX proteins IRX3 and IRX5 diminish the response to TGF‐β. IRX3 and IRX5 are upregulated in human adenomas, and their levels correlate inversely with the gene expression signature of response to TGF‐β. In addition, Irx5 expression confers a growth advantage in the presence of TGF‐β, but is selected against in its absence. Together, our results identify a set of Iro/IRX proteins as conserved negative regulators of Dpp/TGF‐β activity. We propose that during the characteristic adenoma‐to‐carcinoma transition of human CRC, the activity of IRX proteins could reduce the sensitivity to the cytostatic effect of TGF‐β, conferring a growth advantage to tumor cells prior to the acquisition of mutations in TGF‐β pathway components.
External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals
Authors: Cuthbertson Daniel J , Weickert Martin O , Lythgoe Daniel , Sprung Victoria S , Dobson Rebecca , Shoajee-Moradie Fariba , Umpleby Margot , Pfeiffer Andreas F H , Thomas E Louise , Bell Jimmy D , Jones Helen , Kemp Graham J
Published: October 2014

Background and aims

Simple clinical algorithms including the fatty liver index (FLI) and lipid accumulation product (LAP) have been developed as surrogate markers for non-alcoholic fatty liver disease (NAFLD), constructed using (semi-quantitative) ultrasonography. This study aimed to validate FLI and LAP as measures of hepatic steatosis, as determined quantitatively by proton magnetic resonance spectroscopy (1H-MRS).

Methods

Data were collected from 168 patients with NAFLD and 168 controls who had undergone clinical, biochemical and anthropometric assessment. Values of FLI and LAP were determined and assessed both as predictors of the presence of hepatic steatosis (liver fat >5.5%) and of actual liver fat content, as measured by 1H-MRS. The discriminative ability of FLI and LAP was estimated using the area under the receiver operator characteristic curve (AUROC). As FLI can also be interpreted as a predictive probability of hepatic steatosis, we assessed how well calibrated it was in our cohort. Linear regression with prediction intervals was used to assess the ability of FLI and LAP to predict liver fat content. Further validation was provided in 54 patients with type 2 diabetes mellitus.

Results

FLI, LAP and alanine transferase discriminated between patients with and without steatosis with an AUROC of 0.79 (IQR=0.74, 0.84), 0.78 (IQR=0.72, 0.83) and 0.83 (IQR=0.79, 0.88) respectively although could not quantitatively predict liver fat. Additionally, the algorithms accurately matched the observed percentages of patients with hepatic steatosis in our cohort.

Conclusions

FLI and LAP may be used to identify patients with hepatic steatosis clinically or for research purposes but could not predict liver fat content.
Hallmarks of gastrointestinal neuroendocrine tumours: implications for treatment
Authors: Walenkamp Annemiek , Crespo Guillermo , Fierro Maya Felipe , Fossmark Reidar , Igaz Peter , Rinke Anja , Tamagno Gianluca , Vitale Giovanni , Öberg Kjell , Meyer Tim
Published: October 2014

In the past few years, there have been advances in the treatment of neuroendocrine tumours (NETs) and improvements in our understanding of NET biology. However, the benefits to patients have been relatively modest and much remains yet to be done. The ‘Hallmarks of Cancer’, as defined by Hanahan and Weinberg, provide a conceptual framework for understanding the aberrations that underlie tumourigenesis and to help identify potential targets for therapy. In this study, our objective is to review the major molecular characteristics of NETs, based on the recently modified ‘Hallmarks of Cancer’, and highlight areas that require further research.
Quantitative Genetic Analysis Indicates Natural Selection on Leaf Phenotypes Across Wild Tomato Species (Solanumsect.Lycopersicon; Solanaceae)
Authors: Muir Christopher D , Pease James B , Moyle Leonie C
Published: October 2014

Adaptive evolution requires both raw genetic material and an accessible path of high fitness from one fitness peak to another. In this study, we used an introgression line (IL) population to map quantitative trait loci (QTL) for leaf traits thought to be associated with adaptation to precipitation in wild tomatoes (Solanum sect. Lycopersicon; Solanaceae). A QTL sign test showed that several traits likely evolved under directional natural selection. Leaf traits correlated across species do not share a common genetic basis, consistent with a scenario in which selection maintains trait covariation unconstrained by pleiotropy or linkage disequilibrium. Two large effect QTL for stomatal distribution colocalized with key genes in the stomatal development pathway, suggesting promising candidates for the molecular bases of adaptation in these species. Furthermore, macroevolutionary transitions between vastly different stomatal distributions may not be constrained when such large-effect mutations are available. Finally, genetic correlations between stomatal traits measured in this study and data on carbon isotope discrimination from the same ILs support a functional hypothesis that the distribution of stomata affects the resistance to CO2 diffusion inside the leaf, a trait implicated in climatic adaptation in wild tomatoes. Along with evidence from previous comparative and experimental studies, this analysis indicates that leaf traits are an important component of climatic niche adaptation in wild tomatoes and demonstrates that some trait transitions between species could have involved few, large-effect genetic changes, allowing rapid responses to new environmental conditions.