bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin A deficiency and xerophthalmia in children of a developed country
Authors: Chiu Mimi , Dillon Alexander , Watson Stephanie
Published: July 2016

Aim

We aim (i) to characterise the clinical features of vitamin A deficiency (VAD) in a small cohort of Australian children; (ii) to determine the effects of VAD; and (iii) to quantify the prevalence of ophthalmic review in this group.

Methods

Data collected from the charts incorporated patient demographics, laboratory results, past medical history, ophthalmic symptoms and dietary history. Outcome measures were (i) occurrence of VAD in our study population; (ii) presence of associated systemic effects and ocular manifestations in those diagnosed with VAD; and (iii) determination of whether children with VAD had an ophthalmology review.

Results

Fifty‐two of the 146 children had VAD; their average age was 8.4 years (range 11 days to 18 years old). In this Australian cohort, the most common pre‐existing medical conditions in those children whose vitamin A status was investigated were cystic fibrosis, gastro‐oesophageal reflux disease, micronutrient deficiency and short gut syndrome. The most common medical conditions affecting children with measured VAD in this cohort include autism, coeliac disease and cystic fibrosis. A significant association was found between VAD and anaemia and serum iron levels. Of the 146 children, 28 had ophthalmology review, of whom 13 had VAD. The most common reason for ophthalmology review was retinopathy of prematurity; there was only one referral for review for xerophthalmia. There was one case of xerophthalmia referred due to microbial keratitis.

Conclusion

Vitamin A deficiency and xerophthalmia do exist in children of developed country. The potential for xerophthalmia should be considered, and there should be a consideration of an ophthalmology review.
Chlorophyll f distribution and dynamics in cyanobacterial beachrock biofilms
Authors: Trampe Erik , Kühl Michael
Published: July 2016

Chlorophyll (Chl) f, the most far‐red (720–740 nm) absorbing Chl species, was discovered in cyanobacterial isolates from stromatolites and subsequently in other habitats as well. However, the spatial distribution and temporal dynamics of Chl f in a natural habitat have so far not been documented. Here, we report the presence of Chl f in cyanobacterial beachrock biofilms. Hyperspectral imaging on cross‐sections of beachrock from Heron Island (Great Barrier Reef, Australia), showed a strong and widely distributed signature of Chl f absorption in an endolithic layer below the dense cyanobacterial surface biofilm that could be localized to aggregates of Chroococcidiopsis‐like unicellular cyanobacteria packed within a thick common sheath. High‐pressure liquid chromatography‐based pigment analyses showed in situ ratios of Chl f to Chl a of 5% in brown‐pigmented zones of the beachrock, with lower ratios of ~0.5% in the black‐ and pink‐pigmented biofilm zones. Enrichment experiments with black beachrock biofilm showed stimulated synthesis of Chl f and Chl d when grown under near‐infrared radiation (NIR; 740 nm), with a Chl f to Chl a ratio increasing 4‐fold to 2%, whereas the Chl d to Chl a ratio went from 0% to 0.8%. Enrichments grown under white light (400–700 nm) produced no detectable amounts of either Chl d or Chl f. Beachrock cyanobacteria thus exhibited characteristics of far‐red light photoacclimation, enabling Chl f ‐containing cyanobacteria to thrive in optical niches deprived of visible light when sufficient NIR is prevalent.
Effect of different drug classes on reverse remodeling of intramural coronary arterioles in the spontaneously hypertensive rat
Authors: Mancini Massimiliano , Scavone Angela , Sartorio Carmem Luiza , Baccaro Rocco , Kleinert Christina , Pernazza Angelina , Buia Veronica , Leopizzi Martina , d'Amati Giulia , Camici Paolo G.
Published: July 2016

Background

Symptoms and signs of myocardial ischemia in the absence of obstructive coronary disease are common in hypertensive patients. This can be explained by CMD due to adverse remodeling of coronary arterioles which have also been reported in the SHR.

Objective

The aim of this study was to compare the effects of ramipril, perindopril, candesartan, atenolol, amlodipine, indapamide, and HMR1766 on CMD in the SHR.

Methods

Eight groups of 24‐wk‐old SHR were treated for 8 wk. BP was measured invasively at the end of the treatment. After sacrifice, hearts were mounted on a Langendorff apparatus for the measurement of hyperemic CF. Hearts were then processed for histomorphometric analysis.

Results

All compounds, except HMR1766, induced a significant reduction in BP. Perindopril and candesartan increased hyperemic CF, whereas the other compounds had no significant effect. Perindopril, ramipril, atenolol, indapamide, and HMR1766 induced significant reverse arteriolar remodeling, whereas candesartan and amlodipine did not.

Conclusions

The effect of antihypertensive treatment on CMD is not exclusively dependent on BP reduction. Compounds with comparable antihypertensive efficacy may exert different effects on CF and induce different degrees of reverse arteriolar remodeling.
Short‐Term Traffic Speed Prediction for an Urban Corridor
Authors: Yao Baozhen , Chen Chao , Cao Qingda , Jin Lu , Zhang Mingheng , Zhu Hanbing , Yu Bin
Published: July 2016

Short‐term traffic speed prediction is one of the most critical components of an intelligent transportation system (ITS). The accurate and real‐time prediction of traffic speeds can support travellers’ route choices and traffic guidance/control. In this article, a support vector machine model (single‐step prediction model) composed of spatial and temporal parameters is proposed. Furthermore, a short‐term traffic speed prediction model is developed based on the single‐step prediction model. To test the accuracy of the proposed short‐term traffic speed prediction model, its application is illustrated using GPS data from taxis in Foshan city, China. The results indicate that the error of the short‐term traffic speed prediction varies from 3.31% to 15.35%. The support vector machine model with spatial‐temporal parameters exhibits good performance compared with an artificial neural network, a k‐nearest neighbor model, a historical data‐based model, and a moving average data‐based model.
Airway stenting in the management of iatrogenic tracheal injuries: 10‐Year experience
Authors: Tazi‐Mezalek Rachid , Musani Ali I. , Laroumagne Sophie , Astoul Philippe J. , D'Journo Xavier B. , Thomas Pascal A. , Dutau Hervé
Published: July 2016

Background and objective

Iatrogenic tracheal injury (ITI) is a rare yet severe complication of endotracheal tube (ETT) placement or tracheostomy. ITI is suspected in patients with clinical and/or radiographic signs or inefficient mechanical ventilation (MV) following these procedures. Bronchoscopy is used to establish a definitive diagnosis.

Methods

We conducted a retrospective, single‐centre chart review of 35 patients between 2004 and 2014. Depending on the nature and location of ITI and need for MV, patients were triaged to surgical repair, endoscopic management with airway stents or conservative treatment consisting of ETT or tracheotomy cannula (TC) placement distal to the wound and bronchoscopic surveillance.

Results

Three of the four patients (11.43%) presenting with tracheoesophageal fistula (TEF) underwent surgery. Seven patients (20%) who did not require MV underwent endoscopic surveillance. Of the 24 ventilated patients (68.57%), 7 with ITI in the lower trachea were treated with silicone Y‐stent (ETT or TC was placed inside the stent) and 17 patients with ITI in the upper trachea were managed by placing ETT or TC cuff distal to the injury. Overall management success, defined as complete healing of the ITI, was seen in 88.57% of patients. Four patients (11.43%) died of non‐ITI‐related comorbidities.

Conclusion

Conservative management should be considered in non‐ventilated patients with ITI and when ITI is located in the upper trachea of ventilated patients where ETT or TC bypasses the injury. Airway stenting should be considered in ventilated patients with ITI located in the lower trachea. Surgery should be reserved for TEF and conservative and endoscopic management failure.
Prognostic value of right ventricular ejection/filling parameters in IPAH using cardiac magnetic resonance: A prospective pilot study
Authors: Li Wen , Yang Tao , Zhang Yan , Gu Qing , Liu Zhi‐Hong , Ni Xin‐Hai , Luo Qin , Xiong Chang‐Ming , He Jian‐Guo
Published: July 2016

Background and objective

The potential prognostic value of cardiovascular magnetic resonance (CMR)‐derived right ventricular (RV) ejection/filling parameters in the assessment of RV function remains to be fully established. The goal of this study was to explore the prognostic value of these parameters in idiopathic pulmonary arterial hypertension (IPAH) patients.

Methods

In this prospective investigation, newly diagnosed IPAH patients without targeted therapy were recruited. Patients underwent right heart catheterization (RHC), 6‐min walk test and CMR imaging within 1 week. Cardiopulmonary haemodynamics derived from RHC, and RV ejection/filling parameters derived from CMR were collected.

Results

A total of 41 IPAH patients were recruited with the median follow‐up time of 824 days. During this period, 13 patients significantly deteriorated and among them, 7 patients died. CMR‐derived RV peak ejection rate (PER) correlated significantly with CMR‐derived RV stroke volume index (r = 0.574, P < 0.001) and RV cardiac index (r = 0.611, P < 0.001), but had no significant correlation with RV end diastolic volume index (EDVI, r = 0.201, P = 0.208) and pulmonary vascular resistance (r = −0.134, P = 0.403). Multivariate Cox regression analysis showed that RV time to PER (TPER, hazard ratio (HR) = 1.010, 95% CI: 1.003–1.017, P = 0.005) and RV TPER/time of a cardiac cycle (TPER/TCC, HR = 1.085, 95% CI: 1.031–1.141, P = 0.002) were predictors of clinical deterioration after adjusting for N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and RV EDVI. Kaplan–Meier survival analyses showed that patients with RV TPER ≥ 199.01 ms (log rank: P = 0.036) or RV TPER/TCC ≥ 20.02% (log rank: P = 0.007) had worse prognosis.

Conclusion

CMR‐derived RV TPER and TPER/TCC can reflect RV early systolic function, and may be promising predictors for long‐term prognosis in IPAH patients.
Survivors' quality of life after cardiopulmonary resuscitation: an integrative review of the literature
Authors: Haydon Gunilla , van der Riet Pamela , Maguire Jane
Published: July 2016

Background

The incidence of cardiac arrest and cardiopulmonary resuscitation continues to increase worldwide largely due to greater awareness of the symptoms of cardiac events and increased attention to cardiopulmonary resuscitation training in the community. Globally, predicted survival rates after cardiopulmonary resuscitation have remained at 10% for decades and although patient outcome remains unpredictable, there is a positive trend in life expectancy. For a resuscitation attempt to be classed as successful, not only survival but also quality of life has to be evaluated.

Aim

The aim of this review was to examine literature that explores the quality of life (QOL) for survivors' after CPR and the influence cognitive impairment, anxiety, depression and post‐traumatic stress disorder (PTSD) has had on their QOL.

Review methods

This review follows Whittemore and Knafl's framework for an integrative literature review. Electronic databases EBSCO, Ovid, PubMed and EMBASE were searched. After application of the inclusion and exclusion criteria, thirty‐six papers published from January 2000 to June 2015 were included in this review.

Results

These papers represent a broad spectrum of research evaluating quality of life for survivors of cardiopulmonary resuscitation. The heterogeneous research methods and vast number of different research tools make it challenging to compare the findings. The majority of papers concluded that quality of life for survivors of cardiac arrest and cardiopulmonary resuscitation was generally acceptable. However, studies also described survivors' experience of anxiety, depression, post‐traumatic stress and cognitive dysfunction.

Conclusion

A majority of papers reported an acceptable quality of life if the patient survived to hospital discharge. The heterogeneity in quantitative papers was noticeable and indicates a marked variance in patient outcomes. This review highlights the absence of specialized tools used to investigate survivors' experience of the event. Further exploration of the impact cardiopulmonary resuscitation has on the individual may improve ongoing rehabilitation and quality of life levels for survivors.
Classical momentum gap for electron transport in vacuum and consequences for space charge in thermionic converters with a grid electrode
Authors: Khoshaman Amir H. , Nojeh Alireza
Published: July 2016

Quantum mechanics tells us that the bound states of a potential well are quantized—a phenomenon that is easily understandable based on wave properties and resonance. Here, the authors demonstrate a classical mechanism for the formation of a momentum gap in the phase space of electrons traveling as particles in a potential well in vacuum. This effect is caused by the reflection of electrons from at least two potential maxima, which may, for instance, exist due to space-charge distribution in a triode configuration. This gap plays a critical role in space-charge-mitigated electron transport in vacuum, such as in a thermionic energy converter with a positively biased grid, where it is shown that the current density can be increased by 1–3 orders of magnitude depending on the severity of space charge in the absence of the grid.
High hardness in the biocompatible intermetallic compound β-Ti
3
Au
Authors: Svanidze Eteri , Besara Tiglet , Ozaydin M. Fevsi , Tiwary Chandra Sekhar , Wang Jiakui K. , Radhakrishnan Sruthi , Mani Sendurai , Xin Yan , Han Ke , Liang Hong , Siegrist Theo , Ajayan Pulickel M. , Morosan E.
Published: July 2016

A remarkable fourfold increase in hardness of titanium is achieved by the addition of gold, yielding a novel biocompatible material.
MORC3, a Component of PML Nuclear Bodies, Has a Role in Restricting Herpes Simplex Virus 1 and Human Cytomegalovirus
Authors: Sloan Elizabeth , Orr Anne , Everett Roger D.
Published: July 2016

We previously reported that MORC3, a protein associated with promyelocytic leukemia nuclear bodies (PML NBs), is a target of herpes simplex virus 1 (HSV-1) ICP0-mediated degradation (E. Sloan, et al., PLoS Pathog
11:
e1005059, 2015,
http://dx.doi.org/10.1371/journal.ppat.1005059
). Since it is well known that certain other components of the PML NB complex play an important role during an intrinsic immune response to HSV-1 and are also degraded or inactivated by ICP0, here we further investigate the role of MORC3 during HSV-1 infection. We demonstrate that MORC3 has antiviral activity during HSV-1 infection and that this antiviral role is counteracted by ICP0. In addition, MORC3's antiviral role extends to wild-type (wt) human cytomegalovirus (HCMV) infection, as its plaque-forming efficiency increased in MORC3-depleted cells. We found that MORC3 is recruited to sites associated with HSV-1 genomes after their entry into the nucleus of an infected cell, and in wt infections this is followed by its association with ICP0 foci prior to its degradation. The RING finger domain of ICP0 was required for degradation of MORC3, and we confirmed that no other HSV-1 protein is required for the loss of MORC3. We also found that MORC3 is required for fully efficient recruitment of PML, Sp100, hDaxx, and γH2AX to sites associated with HSV-1 genomes entering the host cell nucleus. This study further unravels the intricate ways in which HSV-1 has evolved to counteract the host immune response and reveals a novel function for MORC3 during the host intrinsic immune response.

IMPORTANCE
Herpesviruses have devised ways to manipulate the host intrinsic immune response to promote their own survival and persistence within the human population. One way in which this is achieved is through degradation or functional inactivation of PML NB proteins, which are recruited to viral genomes in order to repress viral transcription. Because MORC3 associates with PML NBs in uninfected cells and is a target for HSV-1-mediated degradation, we investigated the role of MORC3 during HSV-1 infection. We found that MORC3 is also recruited to viral HSV-1 genomes, and importantly it contributes to the fully efficient recruitment of PML, hDaxx, Sp100, and γH2AX to these sites. Depletion of MORC3 resulted in an increase in ICP0-null HSV-1 and wt HCMV replication and plaque formation; therefore, this study reveals that MORC3 is an antiviral factor which plays an important role during HSV-1 and HCMV infection.
The Interferon-Stimulated Gene IFITM3 Restricts Infection and Pathogenesis of Arthritogenic and Encephalitic Alphaviruses
Authors: Poddar Subhajit , Hyde Jennifer L. , Gorman Matthew J. , Farzan Michael , Diamond Michael S.
Published: July 2016

Host cells respond to viral infections by producing type I interferon (IFN), which induces the expression of hundreds of interferon-stimulated genes (ISGs). Although ISGs mediate a protective state against many pathogens, the antiviral functions of the majority of these genes have not been identified. IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses. Here, we show that alphavirus infection is increased in
Ifitm3
−/−
and
Ifitm
locus deletion (
Ifitm-del
) fibroblasts and, reciprocally, reduced in fibroblasts transcomplemented with Ifitm3. Mechanistic studies showed that Ifitm3 did not affect viral binding or entry but inhibited pH-dependent fusion. In a murine model of chikungunya virus arthritis,
Ifitm3
−/−
mice sustained greater joint swelling in the ipsilateral ankle at days 3 and 7 postinfection, and this correlated with higher levels of proinflammatory cytokines and viral burden. Flow cytometric analysis suggested that
Ifitm3
−/−
macrophages from the spleen were infected at greater levels than observed in wild-type (WT) mice, results that were supported by experiments with
Ifitm3
−/−
bone marrow-derived macrophages.
Ifitm3
−/−
mice also were more susceptible than WT mice to lethal alphavirus infection with Venezuelan equine encephalitis virus, and this was associated with greater viral burden in multiple organs. Collectively, our data define an antiviral role for Ifitm3 in restricting infection of multiple alphaviruses.

IMPORTANCE
The interferon-induced transmembrane protein 3 (IFITM3) inhibits infection of multiple families of viruses in cell culture. Compared to other viruses, much less is known about the antiviral effect of IFITM3 on alphaviruses. In this study, we characterized the antiviral activity of mouse Ifitm3 against arthritogenic and encephalitic alphaviruses using cells and animals with a targeted gene deletion of
Ifitm3
as well as deficient cells transcomplemented with Ifitm3. Based on extensive virological analysis, we demonstrate greater levels of alphavirus infection and disease pathogenesis when Ifitm3 expression is absent. Our data establish an inhibitory role for Ifitm3 in controlling infection of alphaviruses.
Exocytosis of Varicella-Zoster Virus Virions Involves a Convergence of Endosomal and Autophagy Pathways
Authors: Buckingham Erin M. , Jarosinski Keith W. , Jackson Wallen , Carpenter John E. , Grose Charles
Published: July 2016

Varicella-zoster virus (VZV) is an extremely cell-associated herpesvirus with limited egress of viral particles. The induction of autophagy in VZV-infected monolayers is easily detectable; inhibition of autophagy leads to decreased VZV glycoprotein biosynthesis and diminished viral titers. To explain how autophagic flux could exert a proviral effect on the VZV infectious cycle, we postulated that the VZV exocytosis pathway following secondary envelopment may converge with the autophagy pathway. This hypothesis depended on known similarities between VZV gE and autophagy-related (Atg) Atg9/Atg16L1 trafficking pathways. Investigations were carried out with highly purified fractions of VZV virions. When the virion fraction was tested for the presence of autophagy and endosomal proteins, microtubule-associated protein 1 light chain (MAP1LC3B) and Ras-like GTPase 11 (Rab11) were detected. By two-dimensional (2D) and 3D imaging after immunolabeling, both proteins also colocalized with VZV gE in a proportion of cytoplasmic vesicles. When purified VZV virions were enumerated after immunoelectron microscopy, gold beads were detected on viruses following incubation with antibodies to VZV gE (∼100%), Rab11 (50%), and LC3B (30%). Examination of numerous electron micrographs demonstrated that enveloped virions were housed in single-membraned vesicles; viral particles were not observed in autophagosomes. Taken together, our data suggested that some viral particles after secondary envelopment accumulated in a heterogeneous population of single-membraned vesicular compartments, which were decorated with components from both the endocytic pathway (Rab11) and the autophagy pathway (LC3B). The latter cytoplasmic viral vesicles resembled an amphisome.

IMPORTANCE
VZV infection leads to increased autophagic flux, while inhibition of autophagy leads to a marked reduction in virus spread. In this investigation of the proviral role of autophagy, we found evidence for an intersection of viral exocytosis and autophagy pathways. Specifically, both LC3-II and Rab11 proteins copurified with some infectious VZV particles. The results suggested that a subpopulation of VZV particles were carried to the cell surface in single-walled vesicles with attributes of an amphisome, an organelle formed from the fusion of an endosome and an autophagosome. Our results also addressed the interpretation of autophagy/xenophagy results with mutated herpes simplex virus lacking its ICP34.5 neurovirulence gene (HSVΔ34.5). The VZV genome lacks an ICP34.5 ortholog, yet we found no evidence of VZV particles housed in a double-membraned autophagosome. In other words, xenophagy, a degradative process documented after infection with HSVΔ34.5, was not observed in VZV-infected cells.
Deep Sequencing of Distinct Preparations of the Live Attenuated Varicella-Zoster Virus Vaccine Reveals a Conserved Core of Attenuating Single-Nucleotide Polymorphisms
Authors: Depledge Daniel P. , Yamanishi Koichi , Gomi Yasuyuki , Gershon Anne A. , Breuer Judith
Published: July 2016

The continued success of the live attenuated varicella-zoster virus vaccine in preventing varicella-zoster and herpes zoster is well documented, as are many of the mutations that contribute to the attenuation of the vOka virus for replication in skin. At least three different preparations of vOka are marketed. Here, we show using deep sequencing of seven batches of vOka vaccine (including ZostaVax, VariVax, VarilRix, and the Oka/Biken working seed) from three different manufacturers (VariVax, GSK, and Biken) that 137 single-nucleotide polymorphism (SNP) mutations are present in all vaccine batches. This includes six sites at which the vaccine allele is fixed or near fixation, which we speculate are likely to be important for attenuation. We also show that despite differences in the vaccine populations between preparations, batch-to-batch variation is minimal, as is the number and frequency of mutations unique to individual batches. This suggests that the vaccine manufacturing processes are not introducing new mutations and that, notwithstanding the mixture of variants present, VZV live vaccines are extremely stable.

IMPORTANCE
The continued success of vaccinations to prevent chickenpox and shingles, combined with the extremely low incidence of adverse reactions, indicates the quality of these vaccines. The vaccine itself is comprised of a heterogeneous live attenuated virus population and thus requires deep-sequencing technologies to explore the differences and similarities in the virus populations between different preparations and batches of the vaccines. Our data demonstrate minimal variation between batches, an important safety feature, and provide new insights into the extent of the mutations present in this attenuated virus.
Epstein-Barr Virus Oncoprotein LMP1 Mediates Epigenetic Changes in Host Gene Expression through PARP1
Authors: Martin Kayla A. , Lupey Lena N. , Tempera Italo
Published: July 2016

The latent infection of Epstein-Barr virus (EBV) is associated with 1% of human cancer incidence. Poly(ADP-ribosyl)ation (PARylation) is a posttranslational modification catalyzed by poly(ADP-ribose) polymerases (PARPs) that mediate EBV replication during latency. In this study, we detail the mechanisms that drive cellular PARylation during latent EBV infection and the effects of PARylation on host gene expression and cellular function. EBV-infected B cells had higher PAR levels than EBV-negative B cells. Moreover, cellular PAR levels were up to 2-fold greater in type III than type I latently infected EBV B cells. We identified a positive association between expression of the EBV genome-encoded latency membrane protein 1 (LMP1) and PAR levels that was dependent upon PARP1. PARP1 regulates gene expression by numerous mechanisms, including modifying chromatin structure and altering the function of chromatin-modifying enzymes. Since LMP1 is essential in establishing EBV latency and promoting tumorigenesis, we explored the model that disruption in cellular PARylation, driven by LMP1 expression, subsequently promotes epigenetic alterations to elicit changes in host gene expression. PARP1 inhibition resulted in the accumulation of the repressive histone mark H3K27me3 at a subset of LMP1-regulated genes. Inhibition of PARP1, or abrogation of PARP1 expression, also suppressed the expression of LMP1-activated genes and LMP1-mediated cellular transformation, demonstrating an essential role for PARP1 activity in LMP1-induced gene expression and cellular transformation associated with LMP1. In summary, we identified a novel mechanism by which LMP1 drives expression of host tumor-promoting genes by blocking generation of the inhibitory histone modification H3K27me3 through PARP1 activation.

IMPORTANCE
EBV is causally linked to several malignancies and is responsible for 1% of cancer incidence worldwide. The EBV-encoded protein LMP1 is essential for promoting viral tumorigenesis by aberrant activation of several well-known intracellular signaling pathways. We have identified and defined an additional novel molecular mechanism by which LMP1 regulates the expression of tumor-promoting host genes. We found that LMP1 activates the cellular protein PARP1, leading to a decrease in a repressive histone modification, accompanied by induction in expression of multiple cancer-related genes. PARP1 inhibition or depletion led to a decrease in LMP1-induced cellular transformation. Therefore, targeting PARP1 activity may be an effective treatment for EBV-associated malignancies.
Concurrence of Iridovirus, Polyomavirus, and a Unique Member of a New Group of Fish Papillomaviruses in Lymphocystis Disease-Affected Gilthead Sea Bream
Authors: López-Bueno Alberto , Mavian Carla , Labella Alejandro M. , Castro Dolores , Borrego Juan J. , Alcami Antonio , Alejo Alí
Published: July 2016

Lymphocystis disease is a geographically widespread disease affecting more than 150 different species of marine and freshwater fish. The disease, provoked by the iridovirus lymphocystis disease virus (LCDV), is characterized by the appearance of papillomalike lesions on the skin of affected animals that usually self-resolve over time. Development of the disease is usually associated with several environmental factors and, more frequently, with stress conditions provoked by the intensive culture conditions present in fish farms. In gilthead sea bream (
Sparus aurata
), an economically important cultured fish species in the Mediterranean area, a distinct LCDV has been identified but not yet completely characterized. We have used direct sequencing of the virome of lymphocystis lesions from affected
S. aurata
fish to obtain the complete genome of a new LCDV-Sa species that is the largest vertebrate iridovirus sequenced to date. Importantly, this approach allowed us to assemble the full-length circular genome sequence of two previously unknown viruses belonging to the papillomaviruses and polyomaviruses, termed Sparus aurata papillomavirus 1 (SaPV1) and Sparus aurata polyomavirus 1 (SaPyV1), respectively. Epidemiological surveys showed that lymphocystis disease was frequently associated with the concurrent appearance of one or both of the new viruses. SaPV1 has unique characteristics, such as an intron within the L1 gene, and as the first member of the
Papillomaviridae
family described in fish, provides evidence for a more ancient origin of this family than previously thought.

IMPORTANCE
Lymphocystis disease affects marine and freshwater fish species worldwide. It is characterized by the appearance of papillomalike lesions on the skin that contain heavily enlarged cells (lymphocysts). The causative agent is the lymphocystis disease virus (LCDV), a large icosahedral virus of the family
Iridoviridae
. In the Mediterranean area, the gilthead sea bream (
Sparus aurata
), an important farmed fish, is frequently affected. Using next-generation sequencing, we have identified within
S. aurata
lymphocystis lesions the concurrent presence of an additional LCDV species (LCDV-Sa) as well as two novel viruses. These are members of polyomavirus and papillomavirus families, and here we report them to be frequently associated with the presence of lymphocysts in affected fish. Because papillomaviruses have not been described in fish before, these findings support a more ancient origin of this virus family than previously thought and evolutionary implications are discussed.
The PB2 Subunit of the Influenza A Virus RNA Polymerase Is Imported into the Mitochondrial Matrix
Authors: Long Joshua C. D. , Fodor Ervin
Published: July 2016

The polymerase basic 2 (PB2) subunit of the RNA polymerase complex of seasonal human influenza A viruses has been shown to localize to the mitochondria. Various roles, including the regulation of apoptosis and innate immune responses to viral infection, have been proposed for mitochondrial PB2. In particular, PB2 has been shown to inhibit interferon expression by associating with the mitochondrial antiviral signaling (MAVS) protein, which acts downstream of RIG-I and MDA-5 in the interferon induction pathway. However, in spite of a growing body of literature on the potential roles of mitochondrial PB2, the exact location of PB2 in mitochondria has not been determined. Here, we used enhanced
a
scorbate
pe
ro
x
idase (APEX)-tagged PB2 proteins and electron microscopy to study the localization of PB2 in mitochondria. We found that PB2 is imported into mitochondria, where it localizes to the mitochondrial matrix. We also demonstrated that MAVS is not required for the import of PB2 into mitochondria by showing that PB2 associates with mitochondria in MAVS knockout mouse embryo fibroblasts. Instead, we found that amino acid residue 9 in the N-terminal mitochondrial targeting sequence is a determinant of the mitochondrial import of PB2, differentiating the localization of PB2 of human from that of avian influenza A virus strains. We also showed that a virus encoding nonmitochondrial PB2 is attenuated in mouse embryonic fibroblasts (MEFs) compared with an isogenic virus encoding mitochondrial PB2, in a MAVS-independent manner, suggesting a role for PB2 within the mitochondrial matrix. This work extends our understanding of the interplay between influenza virus and mitochondria.

IMPORTANCE
The PB2 subunit of the influenza virus RNA polymerase is a major determinant of viral pathogenicity. However, the molecular mechanisms of how PB2 determines pathogenicity remain poorly understood. PB2 associates with mitochondria and inhibits the function of the mitochondrial antiviral signaling protein MAVS, implicating PB2 in the regulation of innate immune responses. We found that PB2 is imported into the mitochondrial matrix and showed that amino acid residue 9 is a determinant of mitochondrial import. The presence of asparagine or threonine in over 99% of all human seasonal influenza virus pre-2009 H1N1, H2N2, and H3N2 strains is compatible with mitochondrial import, whereas the presence of an aspartic acid in over 95% of all avian influenza viruses is not, resulting in a clear distinction between human-adapted and avian influenza viruses. These findings provide insights into the interplay between influenza virus and mitochondria and suggest mechanisms by which PB2 could affect pathogenicity.
Historical and Critical Review on Biophysical Economics
Authors: Adigüzel Yekbun
Published: July 2016

Biophysical economics is initiated with the long history of the relation of economics with ecological basis and biophysical perspectives of the physiocrats. It inherently has social, economic, biological, environmental, natural, physical, and scientific grounds. Biological entities in economy like the resources, consumers, populations, and parts of production systems, etc. could all be dealt by biophysical economics. Considering this wide scope, current work is a “biophysical economics at a glance” rather than a comprehensive review of the full range of topics that may just be adequately covered in a book-length work. However, the sense of its wide range of applications is aimed to be provided to the reader in this work. Here, modern approaches and biophysical growth theory are presented after the long history and an overview of the concepts in biophysical economics. Examples of the recent studies are provided at the end with discussions. This review is also related to the work by Cleveland, “Biophysical Economics: From Physiocracy to Ecological Economics and Industrial Ecology” [C. J. Cleveland, in Advances in Bioeconomics and Sustainability: Essay in Honor of Nicholas Gerogescu-Roegen, eds. J. Gowdy and K. Mayumi (Edward Elgar Publishing, Cheltenham, England, 1999), pp. 125–154.]. Relevant parts include critics and comments on the presented concepts in a parallelized fashion with the Cleveland’s work.
Paralic reservoirs
Authors: Reynolds Antony D.
Published: July 2016

Paralic environments, deltas, estuaries and shoreline-shelf systems respond sensitively to changes in sea-level and sediment supply, commonly by shifts in facies belts across sequence stratigraphic surfaces. As a result, they are often interleaved in highly layered successions. Layering and a wide range of associated sandbody types control the distinctive nature of paralic oil and gas fields. Layering results in stacked reservoirs. Thick extensive sandstones have structurally defined spill points, large aquifers and good reservoir properties. Such sands have high recovery, good reservoir performance and form primary completion targets. By contrast, thin, laterally restricted, isolated sandstones have low recovery factors and poor performance. Each isolated sand may have its own hydrocarbon contacts and a distinct outline that reflects both structural and stratigraphic trapping. Such sands form secondary completion targets. Fault compartmentalization is a recurring risk. Sealing faults increase the number of reservoir compartments and may decrease performance and recovery. They can also generate traps. Sedimentology is pivotal in describing heterogeneity in paralic reservoirs at all scales. Established techniques are likely to be complemented in the future by forward stratigraphic modelling, integration with palynology and more studies of surveillance data to show how sedimentological variability controls fluid movement in real reservoirs.
Rift–drift transition in a magma-rich system: the Gop Rift–Laxmi Basin case study, West India
Authors: Nemčok M. , Rybár S.
Published: July 2016

This paper studies the magma-rich Gop Rift–Laxmi Basin, West India, which underwent the mantle first–crust second break-up mode. It draws from reflection seismic and gravity data from this abandoned system. Seismic images document that the crustal necking was associated with the development of seawards-dipping reflector wedges deformed by landwards-dipping detachment faults. A wide crustal necking zone indicates that the ductile lower crust was still present during necking. Observed uneven detachment fault spacing indicates the effect of upper-crustal anisotropy. Comparison of the seismic images through progressively more mature stages of the rift–drift transition documents that the final stages of thinning represented the time period when the upper-crustal wide and symmetrical rift architecture changed to the asymmetrical one, and the decoupled system to the coupled one. It further indicates that the last crustal layer was broken with a convex-up fault that was associated with an excess magmatic event. The fault propagation represented the first spontaneous deformation unaffected by the pre-existing anisotropy. Subsequent drift of the two plates was associated with melt-assisted spreading and spontaneous faulting. The faulting geometry and sequence controlled which of the conjugate margins ended up with a volcanic outer high, representing the record of the break-up-locating excess magmatism.
Transfer Learning for Semisupervised Collaborative Recommendation
Authors: Pan Weike , Yang Qiang , Duan Yuchao , Ming Zhong
Published: July 2016

Users’ online behaviors such as ratings and examination of items are recognized as one of the most valuable sources of information for learning users’ preferences in order to make personalized recommendations. But most previous works focus on modeling only one type of users’ behaviors such as numerical ratings or browsing records, which are referred to as explicit feedback and implicit feedback, respectively. In this article, we study a Semisupervised Collaborative Recommendation (SSCR) problem with labeled feedback (for explicit feedback) and unlabeled feedback (for implicit feedback), in analogy to the well-known Semisupervised Learning (SSL) setting with labeled instances and unlabeled instances. SSCR is associated with two fundamental challenges, that is, heterogeneity of two types of users’ feedback and uncertainty of the unlabeled feedback. As a response, we design a novel Self-Transfer Learning (sTL) algorithm to iteratively identify and integrate likely positive unlabeled feedback, which is inspired by the general forward/backward process in machine learning. The merit of sTL is its ability to learn users’ preferences from heterogeneous behaviors in a joint and selective manner. We conduct extensive empirical studies of sTL and several very competitive baselines on three large datasets. The experimental results show that our sTL is significantly better than the state-of-the-art methods.
3-D Maps and Compasses in the Brain
Authors: Finkelstein Arseny , Las Liora , Ulanovsky Nachum
Published: July 2016

The world has a complex, three-dimensional (3-D) spatial structure, but until recently the neural representation of space was studied primarily in planar horizontal environments. Here we review the emerging literature on allocentric spatial representations in 3-D and discuss the relations between 3-D spatial perception and the underlying neural codes. We suggest that the statistics of movements through space determine the topology and the dimensionality of the neural representation, across species and different behavioral modes. We argue that hippocampal place-cell maps are metric in all three dimensions, and might be composed of 2-D and 3-D fragments that are stitched together into a global 3-D metric representation via the 3-D head-direction cells. Finally, we propose that the hippocampal formation might implement a neural analogue of a Kalman filter, a standard engineering algorithm used for 3-D navigation.
The role of prostate inflammation and fibrosis in lower urinary tract symptoms
Authors: Bushman Wade A. , Jerde Travis J.
Published: July 2016

Lower urinary tract symptoms (LUTS) in aging men are extremely common. They have historically been attributed to benign prostatic hyperplasia (BPH), enlargement of the prostate, and bladder outlet obstruction. However, recent studies have revealed acute and chronic inflammation to be highly associated with LUTS, correlated with prostatic enlargement, and implicated as a cause of prostatic fibrosis that contributes to bladder outlet obstruction. This review examines the evidence implicating inflammation and fibrosis in BPH/LUTS. It identifies potential mechanisms by which inflammation may drive nociceptive signaling as well as hyperplastic growth and fibrosis and identifies targets for pharmacological intervention. This is a promising area for research and development of novel therapies to prevent or more effectively treat LUTS in aging men.
Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling
Authors: Dean Andrew , Byrne Aisling , Marinova Mira , Hayden Ingrid
Published: July 2016

Patients with heavily pretreated advanced cancer or with rare tumors are difficult to treat. Molecular profiling (MP) of tumors to identify biomarkers that predict potential outcomes with individual therapies is an emerging strategy to guide treatment decisions. Patients with rare tumors for which standard-of-care therapy was unavailable or more common tumors for which standard-of-care options had been exhausted underwent MP at a single Australian center. Data regarding treating physicians’ choice of therapy, MP results and recommendations, and patient outcomes were collected. Seven patients had received prior standard first-line therapy (PST), 16 had rare tumors, and 31 had been heavily pretreated (HPT; ≥2 prior lines). Most treatments suggested by MP (541/594; 91.1%) were common chemotherapy drugs available in generic formulations. MP-guided therapy recommendations differed from physician’s recommendations in 48 patients (88.9%). MP-guided therapy produced clinical benefit (improved QOL and/or performance status, symptoms, bodyweight, or RECIST) in 19/31 (61.3%), 11/16 (68.8%), and 3/7 (42.9%) patients with HPTs, rare tumors, and PSTs, respectively, and had a PFS ratio ≥1.3 in 22/37 evaluable patients (59.5%; 95% confidence interval 44–76%). The null hypothesis that ≤15% of these patients would have a PFS ratio ≥1.3 was rejected (one-sidedp<0.0001). In conclusion, using MP to guide therapy selection is feasible in clinical practice and may improve patient outcomes.
Numerical Simulation and Optimization of Enhanced Oil Recovery by the In Situ Generated CO2Huff-n-Puff Process with Compound Surfactant
Authors: Tang Yong , Su Zhengyuan , He Jibo , Yang Fulin
Published: July 2016

This paper presents the numerical investigation and optimization of the operating parameters of the in situ generated CO2Huff-n-Puff method with compound surfactant on the performance of enhanced oil recovery. First, we conducted experiments of in situ generated CO2and surfactant flooding. Next, we constructed a single-well radial 3D numerical model using a thermal recovery chemical flooding simulator to simulate the process of CO2Huff-n-Puff. The activation energy and reaction enthalpy were calculated based on the reaction kinetics and thermodynamic models. The interpolation parameters were determined through history matching a series of surfactant core flooding results with the simulation model. The effect of compound surfactant on the Huff-n-Puff CO2process was demonstrated via a series of sensitivity studies to quantify the effects of a number of operation parameters including the injection volume and mole concentration of the reagent, the injection rate, the well shut-in time, and the oil withdrawal rate. Based on the daily production rate during the period of Huff-n-Puff, a desirable agreement was shown between the field applications and simulated results.
Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication
Authors: Wang Gefei , Li Rui , Jiang Zhiwu , Gu Liming , Chen Yanxia , Dai Jianping , Li Kangsheng
Published: July 2016

Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i.) but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.
A Rare Case ofStreptococcus alactolyticusInfective Endocarditis Complicated by Septic Emboli and Mycotic Left Middle Cerebral Artery Aneurysm
Authors: Almeida Patricia , Railsback Jaclyn , Gleason James Benjamin
Published: July 2016

To date,S. alactolyticusendocarditis complicated by middle cerebral artery aneurysm has not been reported. We describe the case of a 65-year-old female with a history of hypertrophic cardiomyopathy with left ventricular outflow tract obstruction presenting with confusion and a apical holosystolic murmur. Angiography of the brain identified new bilobed left middle cerebral artery aneurysm. Serial blood cultures grewS. alactolyticus, and aortic and mitral valve vegetation were discovered on transesophageal echocardiography. The patient was treated with antimicrobial therapy, mitral and aortic valve replacements, and microsurgical clipping of cerebral aneurysm. This case serves to highlight the pathogenicity of a sparsely described bacterium belonging to the heterogenousS. boviscomplex.
Immune Architecture of Colorectal Lung Metastases and Implications for Patient Survival
Authors: Brunner Stefan M. , Hahn Ulrich , Jeiter Tonia , Kesselring Rebecca , Rubner Christoph , Ruemmele Petra , Sziklavari Zsolt , Hofmann Hans S. , Schlitt Hans J. , Fichtner-Feigl Stefan
Published: July 2016

Background: Pulmonary metastases occur in 10-20% of patients with colorectal cancer and significantly influence long-term survival. In this study, the immunological architecture of colorectal lung in comparison to liver metastases and its impact on patient survival were examined. Methods: Specimens of patients with colorectal lung and liver metastases were stained for HE, CD4, CD8, CD20, CD68 and CD45RO. Besides histomorphological evaluation, immunohistochemical stainings were analyzed for the respective cell numbers separately for tumor area, infiltrative margin and distant lung or liver stroma. These findings were correlated with clinical data and patient outcome. Results: In colorectal lung (n = 69) in comparison to liver (n = 222) metastases, the immunological focus is located in the tumor region. A high CD4+ cell infiltration of this area is associated with prolonged survival of patients after resection of colorectal lung metastases [103 ± 33 (high) vs. 37 ± 6 months (low); p = 0.0246]. Patients who were treated with preoperative chemotherapy did not show differences in immune infiltrates compared to chemotherapy-naïve patients. Conclusion: Colorectal lung and liver metastases showed a distinct immunological architecture. A dense cell infiltration of colorectal lung metastases by CD4+ cells was related to prolonged patient survival. Preoperative chemotherapy did not influence cellular immune infiltrates.