bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of intermolecular interactions in perylene films on Au(111) by infrared spectroscopy
Authors: Ding Li , Schulz Philip , Farahzadi Azadeh , Shportko Kostiantyn V. , Wuttig Matthias
Published: February 2012

Intermolecular interactions in crystalline perylene films on Au(111) have been investigated by Fourier transform infrared spectroscopy. Dimer modes of vibrations are observed in the crystalline film, in contrast to the monomer modes found for isolated perylene molecules. These dimers are formed via hydrogen bonding in the sandwich herringbone structure of the crystalline α-phase. Davydov splitting of both the monomer and the dimer modes is observed due to resonance dynamic intermolecular interaction. The splitting of monomer modes into three distinct vibrations and the occurrence of the dimer modes confirm that the film crystallizes in the α phase, which is in line with the x-ray diffraction results. The frequency shift and band broadening at elevated temperature have been attributed to the cubic and quartic anharmonic interactions.
Stereopsis Loses Dominance over Relative Size as Target Separation Increases
Authors: Marlow Phillip , Gillam Barbara J
Published: February 2012

Binocular disparity produces less stereoscopic depth if the targets are separated by several degrees. It is thus possible that separation decreases the influence of stereopsis as a relative depth cue. Here, four experiments tested the strength of disparity in determining the direction of relative depth in the face of strongly conflicting relative size for a range of target separations. Under conditions of natural fixation—permitting sequential stereopsis—disparity dominated completely at small separations (0.42°) but gradually gave way to relative size domination at large separations. However, when brief presentations prevented changes in fixation, disparity completely dominated at a separation of 0.5° while relative size mostly dominated by 0.75° – 1° of separation. By varying target separation at different retinal eccentricities, we showed that separation per se was the critical factor in the dominance switch. Stereoacuity as a function of target separation for the same observers did not predict the switch from disparity to relative size. Stereoscopic dominance was found for the same small separations that are immune to stereoscopic reversals (Gillam, 1993 Perception22 1025 – 1036). Our results suggest that relative disparity has a compulsory influence on perceived depth at small separations, suggesting a different mechanism from the one operating at larger separations.
The Effect of Fear in the Periphery in Binocular Rivalry
Authors: Ritchie Kay L , Bannerman Rachel L , Sahraie Arash
Published: February 2012

The perceived dominance of percepts within a rival pair of images can be influenced by emotional content, with emotional images dominating over neutral images. We investigated this effect in the periphery. Rival gratings and (fearful or neutral) face/house pairs were viewed centrally and with the near edge positioned 1° and 4° from the fixation. Both fearful and neutral faces were perceived as dominant for significantly longer than houses, with fearful faces dominating for significantly longer than neutral faces at all three eccentricities. There was no difference between dominances at 1° and 4° eccentricity, and there was no difference in the dominance of the gratings at any eccentricity. Our findings show that face stimuli, and in particular fearful faces, continue to dominate perception in binocular rivalry even when viewed in the periphery.
Changes in forest structure over 60 years: tree densities continue to increase in the Pilliga forests, New South Wales, Australia
Authors: Whipp Robyn K. , Lunt Ian D. , Spooner Peter G. , Bradstock Ross A.
Published: February 2012

Studies of long-term vegetation changes are critical for enhancing our understanding of successional dynamics in natural ecosystems. By comparing forest inventory data from the 1940s against field data from 2005, we document changes in stand structure over 60 years in forests co-dominated by Callitris glaucophylla J.Thompson & L.Johnson, Allocasuarina luehmannii (R.Baker) L.Johnson and Eucalyptus crebra F.Muell., in central Pilliga, New South Wales (NSW), Australia. Sampling was stratified across two forest types and across a 1951 wildfire boundary, to assess the effects of initial stand structure and early disturbance on stand dynamics. Stems in the size range tallied in the 1940s (>8.9 cm DBH for Callitris and >11.4 cm for Allocasuarina and Eucalyptus) of each genus increased about three-fold in density and about four-fold in basal area over 60 years, with similar trends in both forest types and fire zones. On average, there were 3638 stems ha–1 in 2010, of which 86% were small Allocasuarina and Callitris (<11.4-cm and <8.9-cm diameter at breast height, DBH, respectively). These results illustrate a continuation of forest encroachment that was initially documented in the late 1800s. However, increases in Allocasuarina have received little attention compared with Callitris recruitment. In the absence of disturbance, ongoing increases in stand stocking may be expected.
Seedling growth under osmotic stress and agronomic traits in Bulgarian semi-dwarf wheat: comparison of genotypes with Rht8 and/or Rht-B1 genes
Authors: Landjeva Svetlana , Karceva Tania , Korzun Viktor , Ganeva Ganka
Published: February 2012

Early-season drought is an adverse environmental factor affecting seedling emergence and crop establishment in winter wheat grown in continental climates. The different semi-dwarfing (Rht, reduced height) genes exert various effects on seedling growth, plant height and productivity. The occurrence of the major Rht genes in 69 Bulgarian bread wheat cultivars was postulated by molecular markers. Cultivars carrying Rht-D1b+Rht8 (1), Rht-B1b/d (6), Rht-B1b/d+Rht8 (19), or Rht8 (43) were identified. The three latter groups were compared in respect to germination and seedling growth in response to polyethylene glycol-induced osmotic stress, plant height and main yield components. Cultivars carrying only Rht8 produced longer roots, coleoptiles and shoots, and had smaller root-to-shoot length ratio in non-stress and in osmotic stress conditions compared with those carrying Rht-B1b/d or Rht-B1b/d+Rht8. The same cultivars produced shorter culms, shorter spikes with fewer spikelets, reduced number and mass of grain in the main spike, and reduced 50-grain mass. The Rht genic effects were confirmed on Rht near-isogenic lines. The preferential semi-dwarfing allele selection aiming to combine the advantages of Rht8 and Rht-B1b/d alleles in specific eco-climatic conditions and to improve breeding efficiency in wheat is discussed.
Internode elongation pattern and differential response of rice genotypes to varying levels of flood water
Authors: Anandan Annamalai , Rajiv Govindrajan , Ramarao Akkisetty , Prakash Muthu
Published: February 2012

Rice plants are damaged during floods by complete or partial submergence. The pattern of expression of rice plant varies with different flood regimes. Accordingly, the morphological and physiological responses of rice genotypes were studied in field and pot experiments under different flood regimes. Wide genetic base lines of Oryza sativa and sub 1 introgressed submergence tolerant were compared in field experiments using principle component analysis. Further, based on internode elongation pattern, two genotypes – Bodikaburi and Pokkali – were selected for a pot experiment to find more on elongation pattern of internodes under different flood regimes. Short-term submergence in minimal water, elongation of blade, sheath, leaf area, DW, number of nodes in primary stem and survival present showed strong positive relationship with shoot length. Number of tillers, leaf area and DW were more affected and decreased during submergence than its non-submergence counterpart. Under different flooding regimes, cvv Bodikaburi and Pokkali exhibited different behaviour in the elongation pattern of the shoot. Partial submergence accelerated elongation of all internodes whereas complete submergence accelerated the top internode. Enhancement of shoot elongation during submergence in water is an escape strategy adopted by rice to resume aerobic metabolism and to improve carbon fixation. This escape strategy varies among genotypes with respect to different flooding regimes. Therefore, breeders should be aware of breeding of rice plants with suitable architecture for different flood- prone environments.
Pulmonary infection by
Yersinia pestis
rapidly establishes a permissive environment for microbial proliferation
Authors: Price Paul A. , Jin Jianping , Goldman William E.
Published: February 2012

Disease progression of primary pneumonic plague is biphasic, consisting of a preinflammatory and a proinflammatory phase. During the long preinflammatory phase, bacteria replicate to high levels, seemingly uninhibited by normal pulmonary defenses. In a coinfection model of pneumonic plague, it appears that
Yersinia pestis
quickly creates a localized, dominant anti-inflammatory state that allows for the survival and rapid growth of both itself and normally avirulent organisms.
Yersinia pseudotuberculosis
, the relatively recent progenitor of
Y. pestis
, shows no similar
trans
-complementation effect, which is unprecedented among other respiratory pathogens. We demonstrate that the effectors secreted by the Ysc type III secretion system are necessary but not sufficient to mediate this apparent immunosuppression. Even an unbiased negative selection screen using a vast pool of
Y. pestis
mutants revealed no selection against any known virulence genes, demonstrating the transformation of the lung from a highly restrictive to a generally permissive environment during the preinflammatory phase of pneumonic plague.
Phoneme and word recognition in the auditory ventral stream
Authors: DeWitt Iain , Rauschecker Josef P.
Published: February 2012

Spoken word recognition requires complex, invariant representations. Using a meta-analytic approach incorporating more than 100 functional imaging experiments, we show that preference for complex sounds emerges in the human auditory ventral stream in a hierarchical fashion, consistent with nonhuman primate electrophysiology. Examining speech sounds, we show that activation associated with the processing of short-timescale patterns (i.e., phonemes) is consistently localized to left mid-superior temporal gyrus (STG), whereas activation associated with the integration of phonemes into temporally complex patterns (i.e., words) is consistently localized to left anterior STG. Further, we show left mid- to anterior STG is reliably implicated in the invariant representation of phonetic forms and that this area also responds preferentially to phonetic sounds, above artificial control sounds or environmental sounds. Together, this shows increasing encoding specificity and invariance along the auditory ventral stream for temporally complex speech sounds.
High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C
Authors: Willander Hanna , Askarieh Glareh , Landreh Michael , Westermark Per , Nordling Kerstin , Keränen Henrik , Hermansson Erik , Hamvas Aaron , Nogee Lawrence M. , Bergman Tomas , Saenz Alejandra , Casals Cristina , Åqvist Johan , Jörnvall Hans , Berglund Helena , Presto Jenny , Knight Stefan D. , Johansson Jan
Published: February 2012

BRICHOS domains are encoded in > 30 human genes, which are associated with cancer, neurodegeneration, and interstitial lung disease (ILD). The BRICHOS domain from lung surfactant protein C proprotein (proSP-C) is required for membrane insertion of SP-C and has anti-amyloid activity in vitro. Here, we report the 2.1 Å crystal structure of the human proSP-C BRICHOS domain, which, together with molecular dynamics simulations and hydrogen-deuterium exchange mass spectrometry, reveals how BRICHOS domains may mediate chaperone activity. Observation of amyloid deposits composed of mature SP-C in lung tissue samples from ILD patients with mutations in the BRICHOS domain or in its peptide-binding linker region supports the in vivo relevance of the proposed mechanism. The results indicate that ILD mutations interfering with proSP-C BRICHOS activity cause amyloid disease secondary to intramolecular chaperone malfunction.
Subunit order of eukaryotic TRiC/CCT chaperonin by cross-linking, mass spectrometry, and combinatorial homology modeling
Authors: Kalisman Nir , Adams Christopher M. , Levitt Michael
Published: February 2012

The TRiC/CCT chaperonin is a 1-MDa hetero-oligomer of 16 subunits that assists the folding of proteins in eukaryotes. Low-resolution structural studies confirmed the TRiC particle to be composed of two stacked octameric rings enclosing a folding cavity. The exact arrangement of the different proteins in the rings underlies the functionality of TRiC and is likely to be conserved across all eukaryotes. Yet despite its importance it has not been determined conclusively, mainly because the different subunits appear nearly identical under low resolution. This work successfully addresses the arrangement problem by the emerging technique of cross-linking, mass spectrometry, and modeling. We cross-linked TRiC under native conditions with a cross-linker that is primarily reactive toward exposed lysine side chains that are spatially close in the context of the particle. Following digestion and mass spectrometry we were able to identify over 60 lysine pairs that underwent cross-linking, thus providing distance restraints between specific residues in the complex. Independently of the cross-link set, we constructed 40,320 (= 8 factorial) computational models of the TRiC particle, which exhaustively enumerate all the possible arrangements of the different subunits. When we assessed the compatibility of each model with the cross-link set, we discovered that one specific model is significantly more compatible than any other model. Furthermore, bootstrapping analysis confirmed that this model is 10 times more likely to result from this cross-link set than the next best-fitting model. Our subunit arrangement is very different than any of the previously reported models and changes the context of existing and future findings on TRiC.
Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity
Authors: Malley Richard , Anderson Porter W.
Published: February 2012

For prevention of
Streptococcus pneumoniae
(pneumococcus) infections in infancy, protein-conjugated capsular polysaccharide vaccines provide serotype-specific, antibody-mediated immunity but do not cover all of the 90+ capsule serotypes. Therefore, microbiologists have sought protective noncapsular antigens common to all strains. Alternatively, we investigated killed cells of a noncapsulated strain, which expose many such common antigens. Given to mice intranasally, this vaccine elicits antibody-independent, CD4+ T lymphocyte-dependent accelerated clearance of pneumococci of various serotypes from the nasopharynx mediated by the cytokine IL-17A. Such immunity may reproduce the natural resistance that develops in infants before capsular antibodies arise. Given by injection, the killed cell vaccine induces bifunctional immunity: plasma antibodies protective against fatal pneumonia challenge, as well as IL-17A–mediated nasopharyngeal clearance. Human testing of this inexpensive candidate vaccine by intramuscular injection is planned. Bacterial cellular vaccines are complex—a challenge for reproducibility. However, when several known protective antigens were deleted, the killed pneumococcal vaccine was still protective. This antigenic redundancy may prevent vaccine escape variants by recombinational loss, which is frequent in pneumococcus. Biochemically defined immunogens with bifunctional activity have also been devised. These immunogens are three-component conjugates in which cell wall teichoic acid (a common antigen capable of T cell activation) is coupled to a genetic fusion of two common pneumococcal proteins: a protective surface antigen and a derivative of pneumolysin, which provides TLR4 agonist activity and induces antitoxic immunity. Such constructs induce accelerated clearance when given intranasally and induce both immune mechanisms when injected. The defined composition permits analysis of structure-function activity.
The discourse of historical legitimization: a comparative examination of Southern Jutland and the Slovenian language area
Authors: Thaler Peter
Published: February 2012

This article analyzes the discourse of historical legitimacy in the duchy of Schleswig and in the Slovenian-speaking regions of Carniola, Styria, and especially Carinthia in the nineteenth and twentieth centuries. The question as to who had arrived in the area first was never far from the surface, because in an era of national romanticism, duration of stay seemed to allot special claims to possession. Rather than challenging this rationale, all sides tended to focus their efforts on enhancing their local genealogy. Yet the national conflicts of the period were not about political and linguistic history, but about contemporary interests and identities. In both Jutland and the southeastern Alps, national movements tended to focus on select moments in time that corresponded most closely to their modern-day political aspirations. The comparative analysis of two otherwise fairly divergent European regions reveals the pragmatic similarities of historical nation-building.
In the service of the nation: intellectuals’ articulation of the Muslim national identity1
Authors: Lucic Iva
Published: February 2012

This article explores the emerging national narratives about Muslim national identity in the period of the 1960s and 1970s. After the national recognition of a Bosnian Muslim nation, which was proposed by the members of the Central Committee of Bosnia and Herzegovina, it was the intellectuals’ task to endow the national category with cultural repertoire. Hereby affirmative as well as negating discursive practices on the national status of Muslims entered the debates, which geographically expanded the republican scope of Bosnia and Herzegovina. The author examines internal discussions of the LCY on that issue as well as the intellectuals’ engagement in the public spheres in Socialist Yugoslavia. By integrating the nation-building activities of intellectuals outside Yugoslavia, the author postulates for a trans-national dimension of nation-building processes.
The coupling between sister kinetochore directional instability and oscillations in centromere stretch in metaphase PtK1 cells
Authors: Wan Xiaohu , Cimini Daniela , Cameron Lisa A. , Salmon E. D.
Published: February 2012

Kinetochores bound to kinetochore microtubules (kMTs) exhibit directional instability in mammalian and other mitotic vertebrate cells, oscillating between poleward (P) and away-from-the-pole (AP) movements. These oscillations are coupled to changes in length of kMTs in a way that maintains a net stretch of the centromere. To understand how sister kinetochore directional instability and kMT plus-end dynamic instability are coupled to oscillations in centromere stretch, we tracked at high resolution the positions of fluorescent kinetochores and their poles for oscillating chromosomes within spindles of metaphase PtK1 cells. We found that the kinetics of P and AP movement are nonlinear and different. By subtracting contributions from the poleward flux of kMTs, we found that maximum centromere stretch occurred when the leading kinetochore switched from depolymerization to polymerization, whereas minimum centromere stretch occurred on average 7 s after the initially trailing kinetochore switched from polymerization to depolymerization. These differences produce oscillations in centromere stretch at about twice the frequency of kinetochore directional instability and at about twice the frequency of centromere oscillations back and forth across the spindle equator.
Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology
Authors: Broch Kaspar , Ueland Thor , Nymo Ståle H. , Kjekshus John , Hulthe Johannes , Muntendam Pieter , McMurray John J. , Wikstrand John , Cleland John G. , Aukrust Pål , Gullestad Lars ,   on behalf of the CORONA Study Group
Published: February 2012

Aims

In patients with ischaemic heart failure (HF), myocardial dysfunction often progresses. Elevated levels of soluble ST2 (sST2) are associated with a poor prognosis, but an association between sST2 and worsening heart failure per se has not been established. We assessed the association between sST2 and cause‐specific outcome in 1449 patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA study).

Methods and results

Soluble ST2 was measured with a highly sensitive immunoassay in 1449 patients ≥60 years of age with left ventricular ejection fraction (LVEF) ≤40% due to ischaemic heart disease. By Cox regression analyses, we found sST2 to be associated with the primary endpoint, i.e. a composite of cadiovascular (CV) death, non‐fatal myocardial infarction, or stroke, as well as all pre‐defined secondary endpoints in the CORONA study, even after adjustment for baseline clinical variables. After adjustment for N‐terminal pro brain natriuretic peptide and C‐reactive protein, the association between sST2 and the primary endpoint was attenuated and no longer statistically significant. However, sST2 remained associated with death due to worsening HF, hospitalization due to worsening HF, and hospitalization due to any CV cause, even after full adjustment.

Conclusions

Soluble ST2 is associated with adverse outcomes in older patients with systolic, ischaemic HF. In particular, sST2 is independently associated with worsening HF.
Basic knowledge
Authors: Cascarini Luke , Schilling Clare , Gurney Ben , Brennan Peter
Published: February 2012

Anatomy of the teeth 10

Anatomy of the oral cavity 12

Anatomy of the facial skeleton 16

Dental occlusion 22

Anatomy of the oral and facial muscles, nerves, and glands 26

Anatomy of the neck 30

Examination of the oral cavity 34

Examination of the face and neck ...
In the emergency department
Authors: Cascarini Luke , Schilling Clare , Gurney Ben , Brennan Peter
Published: February 2012

OMFS in the emergency department 60

The paediatric OMFS patient 62

Overview of maxillofacial trauma 64

Mandibular fractures 66

Zygomatic fractures 70

Orbital floor fractures 72

Maxillary fractures 74

Nose, naso-ethmoidal, and frontal bone fractures 76

Face and scalp soft tissue injuries 78

Penetrating injuries to the neck ...
On the ward
Authors: Cascarini Luke , Schilling Clare , Gurney Ben , Brennan Peter
Published: February 2012

OMFS on the ward 174

Trauma patients 176

Dento-alveolar patients 178

Head and neck oncology patients 180

Flap monitoring 184

The tracheostomy patient 186

Orthognathic patients 188

• Since OMFS is a small specialty with relatively few inpatients, it rarely has a dedicated ward and often shares with ENT or another small surgical specialty...
Emergencies
Authors: Cascarini Luke , Schilling Clare , Gurney Ben , Brennan Peter
Published: February 2012

The compromised airway 232

Tracheostomy tube problems 234

Massive bleeding from the face and mouth 238

Massive bleeding from the neck 240

Retrobulbar haemorrhage 242

• This is possibly the most important section in this book.

• It is written on assumption that you have ATLS training (or equivalent). We will not repeat basic facts, but give a gentle reminder that a tracheostomy is not an option in an emergency situation and you should be prepared to undertake a cricothyroidotomy from day one of an OMFS job....
People with whom you will be working
Authors: Cascarini Luke , Schilling Clare , Gurney Ben , Brennan Peter
Published: February 2012

Other surgeons 256

Dental specialists 258

Members of the multidisciplinary head and neck team 260

• ENT surgeons are probably our closest colleagues and you will often find that we share wards, junior doctors, clinics, and also patients.

• There are many occasions in OMFS when you will work with ENT surgeons and you will usually find the relationship mutually beneficial....
Efficient transmission and persistence of low‐frequency SIVmac251 variants in CD8-depleted rhesus macaques with different neuropathology
Authors: Strickland Samantha L. , Gray Rebecca R. , Lamers Susanna L. , Burdo Tricia H. , Huenink Ellen , Nolan David J. , Nowlin Brian , Alvarez Xavier , Midkiff Cecily C. , Goodenow Maureen M. , Williams Kenneth , Salemi Marco
Published: February 2012

Infection of CD8-depleted rhesus macaques with the genetically heterogeneous simian immunodeficiency virus (SIV)mac251 viral swarm provides a rapid-disease model for simian acquired immune deficiency syndrome and SIV-encephalitis (SIVE). The objective was to evaluate how the diversity of the swarm influences the initial seeding of the infection that may potentially affect disease progression. Plasma, lymphoid and non-lymphoid (brain and lung) tissues were collected from two infected macaques euthanized at 21 days post-infection (p.i.), as well as longitudinal specimens and post-mortem tissues from four macaques followed throughout the infection. About 1300 gp120 viral sequences were obtained from the infecting SIVmac251 swarm and the macaques longitudinal and post-mortem samples. Phylogenetic and amino acid signature pattern analyses were carried out to assess frequency, transmission dynamics and persistence of specific viral clusters. Although no significant reduction in viral heterogeneity was found early in infection (21 days p.i.), transmission and replication of SIV variants was not entirely random. In particular, two distinct motifs under-represented (<4 %) in the infecting swarm were found at high frequencies (up to 14 %) in all six macaques as early as 21 days p.i. Moreover, a macrophage tropic variant not detected in the viral swarm (<0.3 %) was present at high frequency (29–100 %) in sequences derived from the brain of two macaques with meningitis or severe SIVE. This study demonstrates the highly efficient transmission and persistence in vivo of multiple low frequency SIVmac251 founder variants, characterized by specific gp120 motifs that may be linked to pathogenesis in the rapid-disease model of neuroAIDS.
Bovine PrP expression levels in transgenic mice influence transmission characteristics of atypical bovine spongiform encephalopathy
Authors: Wilson Rona , Hart Patricia , Piccardo Pedro , Hunter Nora , Casalone Cristina , Baron Thierry , Barron Rona M.
Published: February 2012

Until recently, transmissible spongiform encephalopathy (TSE) disease in cattle was thought to be caused by a single agent strain, bovine spongiform encephalopathy (BSE) (classical BSE or BSE-C). However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. These atypical BSE isolates have been previously transmitted to a range of transgenic mouse models overexpressing PrP from different species at different levels, on a variety of genetic backgrounds. To control for genetic background and expression level in the analysis of these isolates, we performed here a comprehensive comparison of the neuropathological and molecular properties of all three BSE agents (BASE, BSE-C and BSE-H) upon transmission into the same gene-targeted transgenic mouse line expressing the bovine prion protein (Bov6) and a wild-type control of the same genetic background. Significantly, upon challenge with these BSE agents, we found that BASE did not produce shorter survival times in these mice compared with BSE-C, contrary to previous studies using overexpressing bovine transgenic mice. Amyloid plaques were only present in mice challenged with atypical BSE and neuropathological features, including intensity of PrP deposition in the brain and severity of vacuolar degeneration were less pronounced in BASE compared with BSE-C-challenged mice.
Promotion of viral internal ribosomal entry site-mediated translation under amino acid starvation
Authors: Licursi Maria , Komatsu Yumiko , Pongnopparat Theerawat , Hirasawa Kensuke
Published: February 2012

Cap-dependent and internal ribosomal entry site (IRES)-mediated translation are regulated differently within cells. Viral IRES-mediated translation often remains active when cellular cap-dependent translation is severely impaired under cellular stresses induced by virus infection. To investigate how cellular stresses influence the efficiency of viral IRES-mediated translation, we used a bicistronic luciferase reporter construct harbouring IRES elements from the following viruses: encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV), hepatitis C virus (HCV) or human rhinovirus (HRV). NIH3T3 cells transfected with these bicistronic reporter constructs were subjected to different cellular stresses. Increased translation initiation was only observed under amino acid starvation when EMCV or FMDV IRES elements were present. To identify cellular mechanisms that promoted viral IRES-mediated translation, we tested the involvement of eukaryotic initiation factor 4E-binding protein (4E-BP), general control non-depressed 2 (GCN2) and eukaryotic initiation factor 2B (eIF2B), as these are known to be modulated under amino acid starvation. Knockdown of 4E-BP1 impaired the promotion of EMCV and FMDV IRES-mediated translation under amino acid starvation, whereas GCN2 and eIF2B were not involved. To further investigate how 4E-BP1 regulates translation initiated by EMCV and FMDV IRES elements, we used a phosphoinositide kinase-3 inhibitor (LY294002), an mTOR inhibitor (Torin1) or leucine starvation to mimic 4E-BP1 dephosphorylation induced by amino acid starvation. 4E-BP1 dephosphorylation induced by the treatments was not sufficient to promote viral IRES-mediated translation. These results suggest that 4E-BP1 regulates EMCV and FMDV IRES-mediated translation under amino acid starvation, but not via its dephosphorylation.
Children in Vegetative State and Minimally Conscious State: Patients’ Condition and Caregivers’ Burden
Authors: Giovannetti A. M. , Pagani M. , Sattin D. , Covelli V. , Raggi A. , Strazzer S. , Castelli E. , Trabacca A. , Martinuzzi A. , Leonardi M.
Published: February 2012

Caring for children in vegetative state (VS) or minimally conscious state (MCS) challenges parents and impacts on their well-being. This study aims to evaluate caregivers’ health condition, coping, anxiety and depression levels, and how these issues relate to children’s disability. 35 children with VS and MCS were administered the disability rating scale (DRS) and 35 caregivers completed the Coping Orientations to Problem Experiences, Short Form-12, Beck Depression Inventory, and the Spielberger State-Trait Anxiety Inventory-Y. Children were mainly males (68.6%), hosted at domicile (77.1%), and diagnosed with VS (60%), with anoxic aetiology (45.7%). Caregivers were mainly mothers (85.7%), married (82.9%), and housewives (51.4%); 60% declared financial difficulties, and 82.9% provided full-time assistance. 57.2% reported depressive symptoms, poor mental health, and high level of state and trait anxiety. “Problem-oriented” (P<0.001) and “emotional-oriented” (P<0.001), were more adopted than “potentially dysfunctional” ones. DRS scores (mean = 22.0; SD = 1.9) did not significantly correlate to any psychological measure. Rehabilitative programs for children with SV and SMC should also provide interventions on surrounding systems: improving the network of psychological support and social assistance may decrease the burden of caregivers and, in turn, improve caring abilities and children quality of life.
Effects of sequence variation on differential allelic transcription factor occupancy and gene expression
Authors: Reddy Timothy E. , Gertz Jason , Pauli Florencia , Kucera Katerina S. , Varley Katherine E. , Newberry Kimberly M. , Marinov Georgi K. , Mortazavi Ali , Williams Brian A. , Song Lingyun , Crawford Gregory E. , Wold Barbara , Willard Huntington F. , Myers Richard M.
Published: February 2012

A complex interplay between transcription factors (TFs) and the genome regulates transcription. However, connecting variation in genome sequence with variation in TF binding and gene expression is challenging due to environmental differences between individuals and cell types. To address this problem, we measured genome-wide differential allelic occupancy of 24 TFs andEP300in a human lymphoblastoid cell line GM12878. Overall, 5% of human TF binding sites have an allelic imbalance in occupancy. At many sites, TFs clustered in TF-binding hubs on the same homolog in especially open chromatin. While genetic variation in core TF binding motifs generally resulted in large allelic differences in TF occupancy, most allelic differences in occupancy were subtle and associated with disruption of weak or noncanonical motifs. We also measured genome-wide differential allelic expression of genes with and without heterozygous exonic variants in the same cells. We found that genes with differential allelic expression were overall less expressed both in GM12878 cells and in unrelated human cell lines. Comparing TF occupancy with expression, we found strong association between allelic occupancy and expression within 100 bp of transcription start sites (TSSs), and weak association up to 100 kb from TSSs. Sites of differential allelic occupancy were significantly enriched for variants associated with disease, particularly autoimmune disease, suggesting that allelic differences in TF occupancy give functional insights into intergenic variants associated with disease. Our results have the potential to increase the power and interpretability of association studies by targeting functional intergenic variants in addition to protein coding sequences.
A vast collection of microbial genes that are toxic to bacteria
Authors: Kimelman Aya , Levy Asaf , Sberro Hila , Kidron Shahar , Leavitt Azita , Amitai Gil , Yoder-Himes Deborah R. , Wurtzel Omri , Zhu Yiwen , Rubin Edward M. , Sorek Rotem
Published: February 2012

In the process of clone-based genome sequencing, initial assemblies frequently contain cloning gaps that can be resolved using cloning-independent methods, but the reason for their occurrence is largely unknown. By analyzing 9,328,693 sequencing clones from 393 microbial genomes, we systematically mapped more than 15,000 genes residing in cloning gaps and experimentally showed that their expression products are toxic to the Escherichia coli host. A subset of these toxic sequences was further evaluated through a series of functional assays exploring the mechanisms of their toxicity. Among these genes, our assays revealed novel toxins and restriction enzymes, and new classes of small, non-coding toxic RNAs that reproducibly inhibit E. coli growth. Further analyses also revealed abundant, short, toxic DNA fragments that were predicted to suppress E. coli growth by interacting with the replication initiator DnaA. Our results show that cloning gaps, once considered the result of technical problems, actually serve as a rich source for the discovery of biotechnologically valuable functions, and suggest new modes of antimicrobial interventions.
Ni5-δSn4Zn (δ ∼ 0.25) from single-crystal data
Authors: Schmetterer Clemens , Effenberger Herta Silvia , Marker Martin C. J. , Flandorfer Hans
Published: February 2012

Work on the ternary Ni–Sn–Zn phase diagram revealed the existence of the title compound pentanickel tetratin zinc, Ni3.17Sn2.67Zn0.67[Schmettereret al.(2012).Intermetallics, doi:10.1016/j.intermet.2011.05.025]. It crystallizes in the Ni5Ga3Ge2structure type (orthorhombic,Cmcm) and is related to the InNi2type (hexagonal,P63/mmc) of the neighbouring Ni3Sn2high-temperature (HT) phase, but is not a superstructure. The crystal structure was determined using single-crystal X-ray diffraction. Its homogeneity range was characterized using electron microprobe analysis. Phase analysis at various temperatures indicated that the phase decomposes between 1073 and 1173 K, where a more extended ternary solid solution of the Ni3Sn2HT phase was found instead.
Pb5.0(1)In8.4(1)Bi1.6(1)S20, a new quaternary lead indium bismuth sulfide
Authors: Reis I. , Krämer V. , Seiler A. , Topa D. , Keller E.
Published: February 2012

The title phase, first detected in the early 1980s but hitherto unpublished, has been resynthesized and structurally characterized. Unambiguous determination of the chemical composition was not possible by structure analysis alone, but required additional analytical methods. The complex structure shows a close similarity to the structures of two related compounds, one known by the formula Pb1.6In8Bi4S19and the other being the ternary compound Pb6In10S21. This is despite the fact that the three phases correspond to very different Pb:Bi ratios. A geometric mechanism is described by which the three structures can be transformed into each other, provided that the heavy atoms Pb and Bi are treated as equivalent.
Multiple functions of a multi‐component mating pheromone in sea lamprey Petromyzon marinus
Authors: Johnson N. S. , Yun S.‐S. , Buchinger T. J. , Li W.
Published: February 2012

The role of the C24 sulphate in the mating pheromone component, 7α,12α,24‐trihydroxy‐5α‐cholan‐3‐one 24‐sulphate (3kPZS), to specifically induce upstream movement in ovulated female sea lampreys Petromyzon marinus was investigated. 7α,12α‐dihydroxy‐5α‐cholan‐3‐one 24‐oic acid (3kACA), a structurally similar bile acid released by spermiated males, but lacking the C24 sulphate ester, was tested in bioassays at concentrations between 10−11 and 10−14 molar (M). 3kACA did not induce upstream movement in females or additional reproductive behaviours. In contrast, spermiated male washings induced upstream movement, prolonged retention on a nest and induced an array of nesting behaviours. Differential extraction and elution by solid‐phase extraction resins showed that components other than 3kPZS + 3kACA are necessary to retain females on nests and induce nest cleaning behaviours. All pheromone components, including components in addition to 3kPZS + 3kACA that retain females and induce nest cleaning behaviours were released from the anterior region of the males, as had been reported for 3kPZS. It is concluded that the sea lamprey male mating pheromone has multiple functions and is composed of multiple components.
Identification and expression analysis of fabp2 gene from common carp Cyprinus carpio
Authors: Chen X. W. , Jiang S. , Shi Z. Y.
Published: February 2012

Two complementary (c)DNA fragments, including the complete open reading frame of fabp2 from the common carp Cyprinus carpio, were cloned by reverse‐transcription polymerase chain reaction (RT‐PCR). Both were putative intestinal‐type fabp genes, named fabp2a and fabp2b. fabp2b was mainly expressed in the intestine and the brain. This gene, however, was nearly not expressed in the liver, heart, pancreas and muscle. fabp2a was only expressed at a very low level in the intestine. Western blot also showed that Fabp2 is relatively highly expressed in the intestine and the brain. Immunohistochemical analysis revealed that Fabp2 is widely distributed in the mucosa of the intestine. These findings provide novel insights into the fabp2 gene molecular evolution, as well as its potential features in the intestine and the brain.
Lipocalin‐type prostaglandin D synthase as a marker for the proliferative potential of melanocyte‐lineage cells in the human skin
Authors: SHIMANUKI Miwa , TAKEDA Kazuhisa , KAWAGUCHI Masakazu , SUZUKI Tamio , SHIBAHARA Shigeki
Published: February 2012

Melanocytes in the human epidermis actively produce and secrete various substances, thereby contributing to the maintenance of the skin homeostasis. Lipocalin‐type prostaglandin D synthase (L‐PGDS) that catalyzes the formation of prostaglandin D2 (PGD2) may be one of such secreted molecules. Once secreted, L‐PGDS functions as a transporter for lipophilic ligands, including all‐trans retinoic acid (RA). L‐PGDS, therefore, may possess pleiotropic functions in the skin through PGD2 and RA. We aimed to identify the cell types that express L‐PGDS in human skin and to explore the role of L‐PGDS in the growth potential of melanocyte‐lineage cells. Immunohistochemical analysis for L‐PGDS expression was performed with the tissue sections that were prepared from five malignant melanomas, six nevus cell nevi and one Spitz nevus. Normal skin tissues adjacent to the excised melanoma tissues were also analyzed. L‐PGDS is expressed in epidermal melanocytes but its expression is undetectable in keratinocytes. Moreover, L‐PGDS is undetectable in most benign nevus cells, which may reflect the marginally accelerated proliferation of nevus cells. In contrast, L‐PGDS is overexpressed in malignant melanomas, although the frequency of L‐PGDS‐positive cells was variable (15–50%), depending on the specimens. Lastly, RNA interference analysis against human L‐PGDS was performed with short interfering RNA. Knockdown of L‐PGDS expression with short interfering RNA in cultured cells suggests that L‐PGDS may restrict cell proliferation through RA. In conclusion, L‐PGDS expression may contribute to the restricted proliferation of epidermal melanocytes, but conversely its overexpression may reflect the dysregulated proliferation of melanoma cells.
Effects of large sea‐level variations in connected basins: theDacian–Black Sea system of theEasternParatethys
Authors: Munteanu I. , Matenco L. , Dinu C. , Cloetingh S.
Published: February 2012

Sea‐level changes provide an important control on the interplay between accommodation space and sediment supply, in particular, for shallow‐water basins where the available space is limited. Sediment exchange between connected basins separated by a subaqueous sill (bathymetric threshold) is still not well understood. When sea‐level falls below the bathymetric level of this separating sill, the shallow‐water basin evolution is controlled by its erosion and rapid fill. Once this marginal basin is filled, the sedimentary depocenter shifts to the open marine basin (outward shift). With new accommodation space created during the subsequent sea‐level rise, sediment depocenter shifts backwards to the marginal basin (inward shift). This new conceptual model is tested here in the context of LateMiocene toQuaternary evolution of the open connection betweenDacian andBlack Sea basins. By the means of seismic sequence stratigraphic analysis of theMiocene‐Pliocene evolution of this EasternParatethys domain, this case study demonstrates these shifts in sedimentary depocenter between basins. An outward shift occurs with a delay that corresponds to the time required to fill the remaining accommodation space in theDacian Basin below the sill that separates it from the Black Sea. This study provides novel insight on the amplitude and sedimentary geometry of the Messinian Salinity Crisis (MSC) event in theBlack Sea. A large (1.3–1.7 km) sea‐level drop is demonstrated by quantifying coeval sedimentation patterns that change to mass‐flows and turbiditic deposits in the deep‐sea part of this main sink. The post‐MSCsediment routing continued into the present‐day pattern ofBlack Sea rivers discharge.
Effect of the ethinylestradiol/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women
Authors: Edelman Alison , Munar Myrna , Elman Miriam R. , Koop Dennis , Cherala Ganesh
Published: February 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Obesity is known to suppress CYP3A4/5 activity.

• Use of combined oral contraceptives (COC) has been shown to suppress CYP3A4/5 activity in non‐obese women.

• However, the effect of COC on CYP3A4/5 activity is unknown in obese women who constitute 50% of women of reproductive age.

WHAT THIS STUDY ADDS

• Although we hypothesized that obesity exposure might amplify the impact on CYP3A4/5 activity in COC users, we found that this was not the case.

• This finding is reassuring regarding potential additional drug–drug interactions in obese COC users as CYP3A4/5 is a major player in the metabolism of many marketed drugs.

AIM(S) While it is known that CYP3A4/5 activity is decreased with combined oral contraceptive (COC) use and obesity suppresses CYP expression, the combined effects of obesity and COC use on CYP3A4/5 activity are unclear. Therefore, our aim was to examine the effect of COC usage on CYP3A4/5 activity in obese women.

METHODS Thirty‐four, obese (body mass index, BMI > 30 kg m−2) women of reproductive age (18–35 years old) were placed on a COC pill containing 20 µg ethinylestradiol/100 µg levonorgestrel for 21 days starting at the onset of menses. A midazolam pharmacokinetic study was conducted prior to initiation and after 21 days of COC treatment. Serial blood samples were collected and plasma concentrations of midazolam were measured using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were estimated using a non‐compartmental method.

RESULTS Midazolam clearance, a surrogate measure of CYP3A4/5 activity, was significantly decreased upon COC use (63.3 l h−1vs. 53.9 l h−1, P < 0.05). A median decrease of 5.6 l h−1 (95% CI −4.1, 13.3 l h−1) was observed. However, the magnitude of change was similar to that reported in women with normal BMI.

CONCLUSIONS Although we hypothesized that obesity might amplify the impact on CYP3A4/5 activity in COC users, we found that this was not the case. This finding is reassuring regarding potential additional drug−drug interactions in obese COC users as CYP3A4/5 is a major enzyme in the metabolism of many marketed drugs.
Growth factor‐associated graft‐versus‐host disease and mortality 10 years after allogeneic bone marrow transplantation
Authors: Ringdén Olle , Labopin Myriam , Gorin Norbert‐Claude , Volin Liisa , Torelli Giovanni F. , Attal Michel , Jouet Jean P. , Milpied Noel , Socié Gerard , Cordonnier Catherine , Michallet Mauricette , Atienza Arturo I. , Hermine Olivier , Mohty Mohamad ,   for the Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation
Published: February 2012

This study analysed the effects of growth factor on outcome after haematopoietic stem‐cell transplantation (HSCT) with >9 years follow‐up. Of 1887 adult patients with acute leukaemia who received bone marrow from human leucocyte antigen (HLA)‐identical siblings and were treated with myeloablative conditioning, 459 (24%) were treated with growth factor. Growth factor hastened engraftment of neutrophils (P < 0·0001), but reduced platelet counts (P = 0·0002). Graft‐versus‐host disease (GVHD)‐free survival (no acute GVHD grade II–IV or chronic GVHD) at 10 years was 12 ± 2% (±SE) in the growth factor group, as opposed to 17 ± 2% in the controls [hazard ratio (HR) 0·81, P = 0·001]. Similar differences in GVHD‐free survival were seen in patients with or without conditioning with total body irradiation (TBI). Non‐relapse mortality (NRM) was higher in the growth factor group irrespective of whether or not TBI conditioning was included [HR = 1·48; 95% confidence interval (CI): 1·15–1·9; P = 0·002; HR = 1·59; 95% CI: 1·07–2·37; P = 0·02, respectively]. Both groups had similar probabilities of leukaemic relapse (HR = 0·96; 95% CI: 0·78–1·18; P = 0·71). Leukaemia‐free survival (LFS) at 10 years was 35 ± 2% in those receiving growth factor prophylaxis, as opposed to 44 ± 1% in the controls (HR = 0·70; 95% CI: 0·60–0·82; P = 0·00001). Prophylaxis with growth factor increases the risk of GVHD, does not affect relapse, increases NRM and reduces LFS > 10 years after HSCT, regardless of conditioning with TBI.