bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Cytomegalovirus IE2 Protein Disturbs Brain Development by the Dysregulation of Neural Stem Cell Maintenance and the Polarization of Migrating Neurons
Authors: Han Dasol , Byun Sung-Hyun , Kim Juwan , Kwon Mookwang , Pleasure Samuel J. , Ahn Jin-Hyun , Yoon Keejung 
Published: June 2017

ABSTRACT

Despite the high incidence of severe defects in the central nervous system caused by human cytomegalovirus (HCMV) congenital infection, the mechanism of HCMV neuropathogenesis and the roles of individual viral genes have not yet been fully determined. In this study, we show that the immediate-early 2 (IE2) protein may play a key role in HCMV-caused neurodevelopmental disorders. IE2-transduced neural progenitor cells gave rise to neurospheres with a lower frequency and produced smaller neurospheres than control cells
in vitro
, indicating reduction of self-renewal and expansion of neural progenitors by IE2. At 2 days after
in utero
electroporation into the ventricle of the developing brain, a dramatically lower percentage of IE2-expressing cells was detected in the ventricular zone (VZ) and cortical plate (CP) compared to control cells, suggesting that IE2 concurrently dysregulates neural stem cell maintenance in the VZ and neuronal migration to the CP. In addition, most IE2
+
cells in the lower intermediate zone either showed multipolar morphology with short neurites or possessed nonradially oriented processes, whereas control cells had long, radially oriented monopolar or bipolar neurites. IE2
+
callosal axons also failed to cross the midline to form the corpus callosum. Furthermore, we provide molecular evidence that the cell cycle arrest and DNA binding activities of IE2 appear to be responsible for the increased neural stem cell exit from the VZ and cortical migrational defects, respectively. Collectively, our results demonstrate that IE2 disrupts the orderly process of brain development in a stepwise manner to further our understanding of neurodevelopmental HCMV pathogenesis.

IMPORTANCE
HCMV brain pathogenesis has been studied in limited experimental settings, such as
in vitro
HCMV infection of neural progenitor cells or
in vivo
murine CMV infection of the mouse brain. Here, we show that IE2 is a pivotal factor that contributes to HCMV-induced abnormalities in the context of the embryonic brain using an
in utero
gene transfer tool. Surprisingly, IE2, but not HCMV IE1 or murine CMV ie3, interferes pleiotropically with key neurodevelopmental processes, including neural stem cell regulation, proper positioning of migrating neurons, and the callosal axon projections important for communication between the hemispheres. Our data suggest that the wide spectrum of clinical outcomes, ranging from mental retardation to microcephaly, caused by congenital HCMV infection can be sufficiently explained in terms of IE2 action alone.
Inhibition of Avian Influenza A Virus Replication in Human Cells by Host Restriction Factor TUFM Is Correlated with Autophagy
Authors: Kuo Shu-Ming , Chen Chi-Jene , Chang Shih-Cheng , Liu Tzu-Jou , Chen Yi-Hsiang , Huang Sheng-Yu , Shih Shin-Ru 
Published: June 2017

ABSTRACT

Avian influenza A viruses generally do not replicate efficiently in human cells, but substitution of glutamic acid (Glu, E) for lysine (Lys, K) at residue 627 of avian influenza virus polymerase basic protein 2 (PB2) can serve to overcome host restriction and facilitate human infectivity. Although PB2 residue 627 is regarded as a species-specific signature of influenza A viruses, host restriction factors associated with PB2
627
E have yet to be fully investigated. We conducted immunoprecipitation, followed by differential proteomic analysis, to identify proteins associating with PB2
627
K (human signature) and PB2
627
E (avian signature) of influenza A/WSN/1933(H1N1) virus, and the results indicated that Tu elongation factor, mitochondrial (TUFM), had a higher binding affinity for PB2
627
E than PB2
627
K in transfected human cells. Stronger binding of TUFM to avian-signature PB2
590
G/
591
Q and PB2
627
E in the 2009 swine-origin pandemic H1N1 and 2013 avian-origin H7N9 influenza A viruses was similarly observed. Viruses carrying avian-signature PB2
627
E demonstrated increased replication in TUFM-deficient cells, but viral replication decreased in cells overexpressing TUFM. Interestingly, the presence of TUFM specifically inhibited the replication of PB2
627
E viruses, but not PB2
627
K viruses. In addition, enhanced levels of interaction between TUFM and PB2
627
E were noted in the mitochondrial fraction of infected cells. Furthermore, TUFM-dependent autophagy was reduced in TUFM-deficient cells infected with PB2
627
E virus; however, autophagy remained consistent in PB2
627
K virus-infected cells. The results suggest that TUFM acts as a host restriction factor that impedes avian-signature influenza A virus replication in human cells in a manner that correlates with autophagy.

IMPORTANCE
An understanding of the mechanisms that influenza A viruses utilize to shift host tropism and the identification of host restriction factors that can limit infection are both critical to the prevention and control of emerging viruses that cross species barriers to target new hosts. Using a proteomic approach, we revealed a novel role for TUFM as a host restriction factor that exerts an inhibitory effect on avian-signature PB2
627
E influenza virus propagation in human cells. We further found that increased TUFM-dependent autophagy correlates with the inhibitory effect on avian-signature influenza virus replication and may serve as a key intrinsic mechanism to restrict avian influenza virus infection in humans. These findings provide new insight regarding the TUFM mitochondrial protein and may have important implications for the development of novel antiviral strategies.
Acute massive gastric dilatation causing ischaemic necrosis and perforation of the stomach
Authors: Moslim Maitham A , Mittal Jay , Falk Gavin A , Ustin Jeffrey S , Morris-Stiff Gareth 
Published: June 2017

Acute massive gastric dilatation (AMGD) is a rare distinctive condition but associates with high morbidity and mortality. Though usually seen in patients with eating disorders, many aetiologies of AMGD have been described. The distension has been reported to cause gastric necrosis with or without perforation, usually within 1–2 days of an inciting event of AMGD.We report the case of a 58-year-old male who presented with gastric perforation associated with AMGD 11 days after surgical relief of a proximal small bowel obstruction. The AMGD arose from a closed loop obstruction between a tumour at the gastro-oesophageal junction and a small bowel obstruction as a result of volvulus around a jejunal feeding tube.To our knowledge, this is the first case of a closed loop obstruction of this aetiology reported in the literature, and the presentation of this patient’s AMGD was notable for the delayed onset of gastric necrosis. The patient underwent an exploratory laparotomy and a partial gastrectomy to excise a portion of his perforated stomach. Surgeons should be aware of the possibility of delayed ischaemic gastric perforation in cases of AMGD.
Infectious crystalline keratopathy after Descemetâ€™s stripping endothelial keratoplasty
Authors: Porter Ashley J , Lee Graham A , Whitehead Kevin 
Published: June 2017

A 68-year-old woman presented with infectious crystalline keratopathy 4 months after she underwent a combined phacoemulsification and Descemet’s stripping endothelial keratoplasty for Fuch’s endothelial dystrophy in her left eye. After 5 months of topical moxifloxacin 1%, the infiltrate responded well but had not completely resolved, with the resulting endothelial failure requiring a penetrating keratoplasty 9 months after the initial operation. Microbiology identifiedEnterococcus faecaliswith the histopathology demonstrating bacterial colonies within the graft interface. Postoperatively she developed endophthalmitis, needing vitrectomy and intravitreal antibiotics. The infection settled with no recurrence, with topical and oral antibiotics continued for 2 months. A sutured toric piggyback intraocular lens was performed 18 months postvitrectomy for graft astigmatism, achieving a best-corrected vision of 6/15.Infectious crystalline keratopathy can occur following Descemet’s stripping endothelial keratoplasty, requiring long-term topical therapy and potentially leading to graft failure with the necessity for further keratoplasty.
Posterior chamber phakic intraocular lens implantation: comparative, multicentre study in 351 eyes with low-to-moderate or high myopia
Authors: Kamiya Kazutaka , Shimizu Kimiya , Igarashi Akihito , Kitazawa Yoshihiro , Kojima Takashi , Nakamura Tomoaki , Oka Yoshitaka , Matsumoto Rei 
Published: June 2017

AimTo compare the clinical outcomes of posterior chamber phakic intraocular lens implantation with a central hole (Hole Implantable Collamer Lens (ICL), STAAR Surgical) for low-to-moderate myopia and for high myopia.MethodsThis multicentre retrospective case series comprised 351 eyes of 351 consecutive patients undergoing ICL implantation. Eyes were divided into groups based on preoperative degree of myopia: group 1; 57 eyes, manifest spherical equivalent less than −6 dioptres (D), and group 2; 294 eyes, −6 D or more. Safety, efficacy, predictability, stability and adverse events were compared preoperatively; and at 1 day, 1 week and 1, 3, 6 and 12 months postoperatively,ResultsUncorrected and corrected visual acuities were −0.17±0.14 and −0.21±0.10 logMAR in group 1, and −0.16±0.09 and −0.21±0.08 logMAR in group 2, 1 year postoperatively. In groups 1 and 2, 98% and 99% of eyes were within 1.0 D of the targeted correction. Manifest refraction changes of −0.12±0.34 D (group 1) and −0.18±0.43 D (group 2) occurred from 1 day to 1 year. ICL exchanges were necessary in two eyes (0.7%) in group 2. No vision-threatening complications occurred at any time.ConclusionsThe ICL performed well for the correction of both low-to-moderate myopia and high myopia throughout the 1-year observation period. The clinical outcomes of ICL implantation for low-to-moderate myopia are essentially equivalent to those for high myopia.
Changes in risk factors and their contribution to reduction of mortality risk following gastric bypass surgery among obese individuals with type 2 diabetes: a nationwide, matched, observational cohort study
Authors: Liakopoulos Vasileios , Franzén Stefan , Svensson Ann-Marie , Zethelius Björn , Ottosson Johan , Näslund Ingmar , Gudbjörnsdottir Soffia , Eliasson Björn 
Published: June 2017

ObjectiveWe recently showed that Roux-en-Y gastric bypass (RYGB) reduces risks of mortality, cardiovascular death and myocardial infarction in obese individuals compared with matched patients with diabetes mellitus (DM). We have examined changes in risk factors after RYGB, with the aim of explaining these effects.Research design and methodsWe matched (1:1) 6132 RYGB patients with DM reported to the Scandinavian Obesity Surgery Register with patients who had not undergone RYGB, based on sex, age, body mass index (BMI) and time, and assessed effects 2007–2014. We used causal mediation analysis to study effects mediated through changes to BMI and risk factors at 1 year based on Cox proportional hazards models.ResultsBaseline BMI was 42 kg/m2. Following RYGB, the lowest BMI was observed after 2 years (mean 31.9 kg/m2), and hemoglobin A1c (HbA1c) after 1 year (mean 6.32% (45.6 mmol/mol)). Maximum high-density lipoprotein (HDL) cholesterol was observed after 3–5 years (mean 1.46 mmol/L). Differences in BMI, HbA1c and HDL between the groups were statistically significant up to 6 years, and 2–3 years for low-density lipoprotein (LDL) and blood pressure, despite fewer glucose-lowering, hypertensive and lipid-lowering treatments. The causal mediation analysis suggested that RYGB has a positive effect on mortality risk, mainly by means of weight reduction (as opposed to changes to the risk factors analyzed).ConclusionsImprovements in risk factors might contribute to the reduction of mortality risk after RYGB in obese individuals with type 2 diabetes, but the main effect seems to be mediated through a decrease in BMI, which could serve as a proxy for several mechanisms.
Irf4-dependent CD103+CD11b+dendritic cells and the intestinal microbiome regulate monocyte and macrophage activation and intestinal peristalsis in postoperative ileus
Authors: Pohl Judith-Mira , Gutweiler Sebastian , Thiebes Stephanie , Volke Julia K , Klein-Hitpass Ludger , Zwanziger Denise , Gunzer Matthias , Jung Steffen , Agace William W , Kurts Christian , Engel Daniel Robert 
Published: June 2017

ObjectivePostoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. Here, we have investigated the mechanism that activates these cells and the contribution of the intestinal microbiota for POI induction.DesignPOI was induced by manipulating the intestine of mice, which selectively lack DCs, monocytes or macrophages. The disease severity in the small and large intestine was analysed by determining the distribution of orally applied fluorescein isothiocyanate-dextran and by measuring the excretion time of a retrogradely inserted glass ball. The impact of the microbiota on intestinal peristalsis was evaluated after oral antibiotic treatment.ResultsWe found thatCd11c-Cre+Irf4flox/floxmice lack CD103+CD11b+DCs, a DC subset unique to the intestine whose function is poorly understood. Their absence in the intestinal muscularis reduced pathogenic inducible nitric oxide synthase (iNOS) production by monocytes and macrophages and ameliorated POI. Pathogenic iNOS was produced in the jejunum by resident Ly6C–macrophages and infiltrating chemokine receptor 2-dependent Ly6C+monocytes, but in the colon only by the latter demonstrating differential tolerance mechanisms along the intestinal tract. Consistently, depletion of both cell subsets reduced small intestinal POI, whereas the depletion of Ly6C+monocytes alone was sufficient to prevent large intestinal POI. The differential role of monocytes and macrophages in small and large intestinal POI suggested a potential role of the intestinal microbiota. Indeed, antibiotic treatment reduced iNOS levels and ameliorated POI.ConclusionsOur findings reveal that CD103+CD11b+DCs and the intestinal microbiome are a prerequisite for the activation of intestinal monocytes and macrophages and for dysregulating intestinal motility in POI.
An evaluation of a coagulation system (Xprecia Stride) for utilisation in anticoagulation management
Authors: McCahon Deborah , Roalfe Andrea , Fitzmaurice David A 
Published: June 2017

AimTo evaluate the reliability and performance of the Xprecia Stride coagulometer under the conditions in which it is most likely to be used.MethodsThe performance of the Xprecia Stride coagulometer was compared with a local laboratory and the CoaguChek systems routinely used for international normalised ratio (INR) estimation within one primary and one secondary care based anticoagulation clinic in Birmingham. Anticoagulation clinic personnel were trained to use the Xprecia Stride. Patients attending the clinics were eligible if aged ≥18 years and had received warfarin for at least 3 months. Consenting participants provided capillary blood samples for parallel testing on the Xprecia Stride and CoaguChek systems. At the secondary care clinic, a venous blood sample was also collected for laboratory INR estimation. INR results were compared using linear regression analysis and Bland–Altman plots.ResultsA total of 102 laboratory and 205 parallel coagulometer INR tests were performed. Linear regression revealed strong correlation between the Xprecia Stride and the laboratory (r=0.83) and between the Xprecia Stride and CoaguChek systems (r=0.92). Within the therapeutic range, agreement between the systems was very good with 87% of the Xprecia Stride and laboratory INR results and 93% of the Xprecia Stride and CoaguChek INR results being within 0.5 INR units of each other.ConclusionINRs tested using the Xprecia Stride system showed good agreement with the laboratory and CoaguChek systems. Findings indicate that in the hands of the intended users the Xprecia Stride is accurate, reliable and acceptable for use in a routine clinical setting.
Electronic properties and lattice configurations of Au/CH3NH3PbI3 interface
Authors: Si F. J. , Hu W. , Tang F. L. , Cheng Y. W. , Xue H. T. 
Published: June 2017

The lattice structure, interface binding energy, density of states, charge density difference and Bader charges of Au (100)/CH3NH3PbI3 (MAPbI3) (100) interface were studied with the first-principles calculations. The lattice mismatch of the Au (100)/MAPbI3 (100) interface is 3.48%. The interface binding energy is −0.124 J/m2. There is a small amount of electronic states nearby the interface through analyzing the density of states of the interface. In addition, the atom orbital has hybridizations nearby the interface. Through analyzing charge density difference and Bader charges, it is found that there is obvious charge transfer at the interface.
Institutional Tipping Points in Organizational Climate Change Adaptation Processes
Authors: Fünfgeld Hartmut 
Published: June 2017

Despite increasing awareness of the urgency to respond to climate change through adaptation, progress with climate change adaptation differs considerably across social contexts, even within seemingly uniform institutional environments. Only a part of these differences in engaging in adaptation can be explained by differentiated exposure or sensitivity to climate change hazards. Institutions, and institutional change, play important roles in enabling or constraining adaptation at the social group scale. This paper borrows the concept of tipping points from the natural sciences (Lenton et al. 2008; Lenton 2013) and applies it to social processes of climate change adaptation by focusing on processes of institutional change towards and beyond ‘institutional’ tipping points. Different stages of institutional change, where social groups switch from one dominant attractor regime to another, are discussed and illustrated. Empirical research conducted in two organizations in the local government and primary health care sector in Australia are used as examples for how institutional adaptation occurs and how institutional tipping points can be identified. Reflecting on these examples, the paper reviews the conceptual value-add of the institutional tipping points concept, while also discussing its epistemological and methodological limitations.
Controls on the reservoir quality of Late Cretaceous Springar Formation deep-water fan systems in the Vøring Basin
Authors: Finlayson Alana , Melvin Angela , Guise Alex , Churchill James 
Published: June 2017

Abstract
A new reservoir quality model is proposed for the Late Cretaceous Springar Formation sandstones of the Vøring Basin. Instead of a depth-related compactional control on reservoir quality, distinct high- and low-permeability trends are observed. Fan sequences which sit on the high-permeability trend are characterized by coarse-grained facies with a low matrix clay content. These facies represent the highest energy sandy turbidite facies within the depositional system, and were deposited in channelized or proximal lobe settings. Fan sequences on the low-permeability trend are characterized by their finer grain size and the presence of detrital clay, which has been diagenetically altered to a highly microporous, illitic, pore-filling clay. These fan sequences are interpreted to have been deposited in proximal–distal lobe environments. Original depositional facies determines the sorting, grain size and detrital clay content, and is the fundamental control on reservoir quality, as the illitization of detrital clay is the main mechanism for reductions in permeability. Core-scale depositional facies were linked to seismic-scale fan elements in order to better predict porosity and permeability within each fan system, allowing calibrated risking and ranking of prospects within the Springar Formation play.
Tectonics of the Laptev Shelf, Siberian Arctic
Authors: Drachev Sergey S. , Shkarubo Sergey I. 
Published: June 2017

Abstract
The Laptev Sea in the Siberian Arctic represents a unique tectonic junction of an active spreading ridge, the Gakkel Ridge in the Eurasian oceanic basin, with the Siberian Arctic continental margin. New long-offset seismic profiles acquired in recent years provide a reliable basis for deciphering the structural and seismic stratigraphic characteristics of the Laptev Rift System. The tectonic development of the Laptev Shelf represents a sequence of four phases controlled by relative plate movements: (1) intense brittle normal faulting (an initial rifting or stretching phase) affected the entire shelf in the Late Cretaceous(?)–Paleocene(?); (2) a thinning/exhumation phase resulted in exhumation of the lower continental crust and probably upper mantle in the western part of the rift system – this phase is inferred to have occurred during the Late Paleocene to Early Eocene, preceding and accompanying continental break-up in the Eurasia Basin; (3) a stalled rift phase characterized by either a dramatically reduced rate of extension, or a non-extension/compression regime controlled by major reorganization of the plate movements – the onset of this fourth phase is inferred to coincide with the initiation of seafloor spreading in the southern Eurasia Basin at around 53–50 Ma; and (4) reactivation of the rifting in the mid-Miocene (a second rift phase).
Was South Georgia covered by an ice cap during the Last Glacial Maximum?
Authors: White Duanne A. , Bennike Ole , Melles Martin , Berg Sonja , Binnie Steven A. 
Published: June 2017

Abstract
The behaviour of ice caps and glaciers on sub-Antarctic islands during previous periods of warming provide key empirical evidence for understanding the behaviour of marine ice sheets in the future. However, the extent of ice on sub-Antarctic islands during the last 100 kyr is poorly constrained. Here, we investigate the past glacial extents on South Georgia, where previous Last Glacial Maximum (LGM) reconstructions vary between small fjord-terminating glaciers and a large marine-based ice sheet. To help resolve this uncertainty, we apply Schmidt hammer relative-age dating to measure rock hardness and, thus, exposure age of a range of glacial deposits. Applying a hardness–age calibration curve constructed from well-dated Holocene, late-glacial deposits and terminal LGM deposits, we determine that deglaciation of the approximately 600 m-high peaks on the outer Lewin Peninsula occurred during the latter half of the last glacial stage, and probably the end of the LGM. We infer that South Georgia was covered by a marine-based ice cap during the latter part of the last glacial stage.