bluuebunny/crossref_metadata_2025 huggingface dataset:
Slowing Amazon deforestation through public policy and interventions in beef and soy supply chains
Authors: Nepstad Daniel , McGrath David , Stickler Claudia , Alencar Ane , Azevedo Andrea , Swette Briana , Bezerra Tathiana , DiGiano Maria , Shimada João , Seroa da Motta Ronaldo , Armijo Eric , Castello Leandro , Brando Paulo , Hansen Matt C. , McGrath-Horn Max , Carvalho Oswaldo , Hess Laura
Published: June 2014

The recent 70% decline in deforestation in the Brazilian Amazon suggests that it is possible to manage the advance of a vast agricultural frontier. Enforcement of laws, interventions in soy and beef supply chains, restrictions on access to credit, and expansion of protected areas appear to have contributed to this decline, as did a decline in the demand for new deforestation. The supply chain interventions that fed into this deceleration are precariously dependent on corporate risk management, and public policies have relied excessively on punitive measures. Systems for delivering positive incentives for farmers to forgo deforestation have been designed but not fully implemented. Territorial approaches to deforestation have been effective and could consolidate progress in slowing deforestation while providing a framework for addressing other important dimensions of sustainable development.
Defining an essential transcription factor program for naïve pluripotency
Authors: Dunn S.-J. , Martello G. , Yordanov B. , Emmott S. , Smith A. G.
Published: June 2014

Predicting stem cell renewal or differentiation

Predicting complex mammalian cell behavior is extremely challenging. Dunn
et al.
developed a computational model that predicts when embryonic stem cells will self-renew or differentiate. The model revealed an essential program governing pluripotency and identifies a minimal set of components and interactions that accurately predict responses to genetic perturbation.

Science
, this issue p.
1156
Sleep promotes branch-specific formation of dendritic spines after learning
Authors: Yang Guang , Lai Cora Sau Wan , Cichon Joseph , Ma Lei , Li Wei , Gan Wen-Biao
Published: June 2014

To sleep, perchance to remember

Many researchers believe sleep helps us consolidate our memories, but no one knows quite how. Yang
et al.
investigated the precise role of sleep in changing mouse brain structures (see the Perspective by Euston and Steenland). When mice learned motor tasks, small protuberances—or “spines”—formed on some of the dendritic branches of specific brain neurons. These spines represent the physical correlate of a memory. But the neurons grew and retained these spines better when the mice slept after learning the task. Neurons that fired during learning fired again during subsequent slow-wave sleep, allowing the mice to conserve the newly formed spines—and memories.

Science
, this issue p.
1173
; see also p.
1087
A mutually assured destruction mechanism attenuates light signaling in
Arabidopsis
Authors: Ni Weimin , Xu Shou-Ling , Tepperman James M. , Stanley David J. , Maltby Dave A. , Gross John D. , Burlingame Alma L. , Wang Zhi-Yong , Quail Peter H.
Published: June 2014

Emerging from the shade into the light

As a growing seedling emerges into the light, it needs to shift its developmental program to grow toward the light. Signaling components that flip the switch from growth in the shade to growth in the light include phytochromes, which are sensitive to red light, and transcription factors that drive the shade-adapted pattern of development. Ni
et al.
now show how phosphorylation sets these signaling partners up for destruction. The signaling established by red light invokes photomorphogenesis by promoting the destruction of the photoreceptor and its signaling partner.

Science
, this issue p.
1160
The sheep genome illuminates biology of the rumen and lipid metabolism
Authors: Jiang Yu , Xie Min , Chen Wenbin , Talbot Richard , Maddox Jillian F. , Faraut Thomas , Wu Chunhua , Muzny Donna M. , Li Yuxiang , Zhang Wenguang , Stanton Jo-Ann , Brauning Rudiger , Barris Wesley C. , Hourlier Thibaut , Aken Bronwen L. , Searle Stephen M. J. , Adelson David L. , Bian Chao , Cam Graham R. , Chen Yulin , Cheng Shifeng , DeSilva Udaya , Dixen Karen , Dong Yang , Fan Guangyi , Franklin Ian R. , Fu Shaoyin , Fuentes-Utrilla Pablo , Guan Rui , Highland Margaret A. , Holder Michael E. , Huang Guodong , Ingham Aaron B. , Jhangiani Shalini N. , Kalra Divya , Kovar Christie L. , Lee Sandra L. , Liu Weiqing , Liu Xin , Lu Changxin , Lv Tian , Mathew Tittu , McWilliam Sean , Menzies Moira , Pan Shengkai , Robelin David , Servin Bertrand , Townley David , Wang Wenliang , Wei Bin , White Stephen N. , Yang Xinhua , Ye Chen , Yue Yaojing , Zeng Peng , Zhou Qing , Hansen Jacob B. , Kristiansen Karsten , Gibbs Richard A. , Flicek Paul , Warkup Christopher C. , Jones Huw E. , Oddy V. Hutton , Nicholas Frank W. , McEwan John C. , Kijas James W. , Wang Jun , Worley Kim C. , Archibald Alan L. , Cockett Noelle , Xu Xun , Wang Wen , Dalrymple Brian P.
Published: June 2014

A genome for ewe and ewe

Sheep-specific genetic changes underlie differences in lipid metabolism between sheep and other mammals, and may have contributed to the production of wool. Jiang et al. sequenced the genome of two Texel sheep, a breed that produces high-value meat, milk, and wool. The genome information will provide an important resource for livestock production and aid in the understanding of mammalian evolution.

Science
, this issue p.
1168
Liquid flow along a solid surface reversibly alters interfacial chemistry
Authors: Lis Dan , Backus Ellen H. G. , Hunger Johannes , Parekh Sapun H. , Bonn Mischa
Published: June 2014

Monitoring water interfaces in motion

Water behaves differently at interfaces—where it meets the air, or a solid surface—than it does in the middle of the liquid. Past laboratory studies of this phenomenon have mainly focused on still samples, despite the fact that in natural settings such as rivers and rain, the water moves along the surfaces. Lis
et al.
used a microfluidics apparatus and a spectroscopy technique called sum frequency generation to study the effects of flow on aqueous chemistry at silica and fluorite surfaces (see the Perspective by Waychunas). The flow of fresh water along the surfaces disrupts the equilibrium of dissolved ions, substantially changing the surface charge and the molecular orientation of the water at the interface.

Science
, this issue p.
1138
; see also p.
1094
Specific disruption of thalamic inputs to the auditory cortex in schizophrenia models
Authors: Chun Sungkun , Westmoreland Joby J. , Bayazitov Ildar T. , Eddins Donnie , Pani Amar K. , Smeyne Richard J. , Yu Jing , Blundon Jay A. , Zakharenko Stanislav S.
Published: June 2014

Genes, synapses, and hallucinations

In a schizophrenia mouse model, Chun
et al.
found that an abnormal increase of dopamine D2 receptors in the brain's thalamic nuclei caused thalamocortical synapse deficits owing to reduced glutamate release. Antipsychotic agents or a dopamine receptor antagonist reversed this down-regulation. The defect was associated with the loss of a component of the microRNA processing machinery encoded by the
dgcr8
gene.

Science
, this issue p.
1178
Best practices for biofuels
Authors: Youngs Heather , Somerville Chris
Published: June 2014

Data-based standards should guide biofuel production
The whole chain
Authors: Dooley Kevin J.
Published: June 2014

A commercial port town on the East China Sea, a bustling manufacturing city in Ireland, and a scenic city on the Mediterranean coast—what ties together these regions and their people, economies, and environments? They could be part of a product's supply chain. Because the global economy rests on the maintenance of such chains, there needs to be a shift in perspective, from considering supply chains as isolated parts to optimizing them as sustainable wholes. The good news is that academia, industry, government, and civil society organizations recognize this and are seeking ways to work together to achieve sustainability across supply chains.
Kickoff looms for demo of brain-controlled machine
Authors: Servick Kelly
Published: June 2014

Brazilian neuroscientist Miguel Nicolelis defends his plans to show off a thought-directed exoskeleton at the World Cup.
A bold baby step on emissions
Authors: Kintisch Eli
Published: June 2014

But U.S. curbs alone won't slow warming.
Gearing up for a closer look at the human placenta
Authors: Kaiser Jocelyn
Published: June 2014

Workshop participants build an agenda for research on this oft-ignored bridge between mother and fetus.
Solid tumors reveal their secrets: predictive and prognostic evidence from copy number analysis
Authors: Boutros Paul C. , Pandita Ajay
Published: June 2014

Recent research has revealed the importance of copy number analysis in the study of solid tumors. New evidence argues that tumors can be classified in those driven by either mutations (M class) or copy number aberrations (C class). C class tumors include breast, ovarian, and squamous cell lung cancers as well as, some believe, prostate cancer. Other publications have noted that predictive copy number changes are more frequent than predictive somatic mutation changes in solid tumor samples. These results seem to indicate that there is some risk to limiting tumor profiling to somatic mutations, and emphasize the importance of whole genome copy number analysis in identifying clinically relevant prognostic and predictive markers. This process is technically challenging, especially when using formalin-fixed, paraffin-embedded (FFPE) tissue or heterogeneous samples where only a small fraction of cells may be aberrant. Next generation sequencing technologies have limited ability to detect clinically relevant lower level amplifications, copy neutral loss of heterozygosity, and homozygous deletions, even at significant depth of coverage. This webinar will explore the importance of copy number analysis and highlight new technologies that are making this process more accessible, especially in solid tumor samples.
Simple Objective Detection of Human Lyme Disease Infection Using Immuno-PCR and a Single Recombinant Hybrid Antigen
Authors: Halpern Micah D. , Molins Claudia R. , Schriefer Martin , Jewett Mollie W.
Published: June 2014

A serology-based tiered approach has, to date, provided the most effective means of laboratory confirmation of clinically suspected cases of Lyme disease, but it lacks sensitivity in the early stages of disease and is often dependent on subjectively scored immunoblots. We recently demonstrated the use of immuno-PCR (iPCR) for detectingBorrelia burgdorferiantibodies in patient serum samples that were positive for Lyme disease. To better understand the performance of the Lyme disease iPCR assay, the repeatability and variability of the background of the assay across samples from a healthy population (n= 36) were analyzed. Both of these parameters were found to have coefficients of variation of <3%. Using eight antigen-specific iPCR assays and positive call thresholds established for each assay, iPCR IgM and/or IgG diagnosis from Lyme disease patient serum samples (n= 12) demonstrated a strong correlation with that of 2-tier testing. Furthermore, a simplified iPCR approach using a single hybrid antigen and detecting only IgG antibodies confirmed the 2-tier diagnosis in the Lyme disease patient serum samples (n= 12). Validation of the hybrid antigen IgG iPCR assay using a blinded panel of Lyme disease and non-Lyme disease patient serum samples (n= 92) resulted in a sensitivity of 69% (95% confidence interval [CI], 50% to 84%), compared to that of the 2-tier analysis at 59% (95% CI, 41% to 76%), and a specificity of 98% (95% CI, 91% to 100%) compared to that of the 2-tier analysis at 97% (95% CI, 88% to 100%). A single-tier hybrid antigen iPCR assay has the potential to be an improved method for detecting host-generated antibodies againstB. burgdorferi.
Immunogenicity of Peanut Proteins Containing Poly(Anhydride) Nanoparticles
Authors: De S. Rebouças Juliana , Irache Juan M. , Camacho Ana I. , Gastaminza Gabriel , Sanz María L. , Ferrer Marta , Gamazo Carlos
Published: June 2014

In the last decade, peanut allergy has increased substantially. Significant differences in the prevalence among different countries are attributed to the type of thermal processing. In spite of the high prevalence and the severe reaction induced by peanuts, there is no immunotherapy available. The aim of this work was to evaluate the potential application of poly(anhydride) nanoparticles (NPs) as immunoadjuvants for peanut oral immunotherapy. NPs loaded with raw or roasted peanut proteins were prepared by a solvent displacement method and dried by either lyophilization or spray-drying. After physicochemical characterization, their adjuvant capacity was evaluated after oral immunization of C57BL/6 mice. All nanoparticle formulations induced a balanced TH1 and TH2 antibody response, accompanied by low specific IgE induction. In addition, oral immunization with spray-dried NPs loaded with peanut proteins was associated with a significant decrease in splenic TH2 cytokines (interleukin 4 [IL-4], IL-5, and IL-6) and enhancement of both TH1 (gamma interferon [IFN-γ]) and regulatory (IL-10) cytokines. In conclusion, oral immunization with poly(anhydride) NPs, particularly spray-dried formulations, led to a pro-TH1 immune response.
Performance of the Verigene Gram-Negative Blood Culture Assay for Rapid Detection of Bacteria and Resistance Determinants
Authors: Dodémont Magali , De Mendonça Ricardo , Nonhoff Claire , Roisin Sandrine , Denis Olivier
Published: June 2014

Nonduplicate blood cultures that were positive for Gram-negative bacilli (
n
= 125) were tested by the Verigene Gram-negative blood culture (BC-GN) assay; 117 (90.7%) isolates were members of the panel. For identification and resistance markers, the agreements with routine methods were 97.4% (114/117) and 92.3% (12/13). The BC-GN assay is a rapid and accurate tool for the detection of pathogens from blood cultures and could be integrated alongside conventional systems to enable faster patient management, but the clinical benefits should be further evaluated.
Molecular Characterization of Methicillin-Resistant Staphylococcus aureus Clinical Isolates Obtained from the Rikers Island Jail System from 2009 to 2013
Authors: Tanner Joshua , Lin Ying , Kornblum John , Herzig Carolyn T. A. , Bystritsky Rachel , Uhlemann Anne-Catrin , Lowy Franklin D.
Published: June 2014

Inmates of Rikers Island jail potentially introduce
Staphylococcus aureus
into New York State prisons upon transfer. In this study, methicillin-resistant
Staphylococcus aureus
isolates (
n
= 452), collected from infected inmates (2009 to 2013), were characterized.
spa
type t008 was the predominant clone identified, accounting for 82.3% of the isolates, with no evidence of mupirocin or chlorhexidine resistance.
Zoonotic Anatrichosomiasis in a Mother and Daughter
Authors: Eberhard Mark L. , Hellstein John W. , Lanzel Emily A.
Published: June 2014

Zoonotic anatrichosomiasis in a mother and daughter is reported. Both presented with a 10-week history of multiple painful oral ulcers. Biopsy specimens revealed the presence of small, coiled trichuroid nematodes with distinctive morphological features, including stichocytes and paired bacillary bands. This represents an unusual infection by a zoonotic
Anatrichosoma
species.
Unexpected Blastomyces dermatitidis Etiology of Fungal Sinusitis and Erosive Palatal Infection in a Diabetic Patient
Authors: Thomas Jane , Munson Erik , Christianson John C.
Published: June 2014

We present what is believed to be the initial report of hard-palate infection caused byBlastomyces dermatitidis. The organism was cultivated from biopsy material obtained from a diabetic patient presenting with complaints of headache and malaise. Radiologic findings revealed a malignant-appearing soft-tissue mass with paranasal sinus base destruction.
Analytic and Clinical Performance of cobas HPV Testing in Anal Specimens from HIV-Positive Men Who Have Sex with Men
Authors: Wentzensen Nicolas , Follansbee Stephen , Borgonovo Sylvia , Tokugawa Diane , Sahasrabuddhe Vikrant V. , Chen Jie , Lorey Thomas S. , Gage Julia C. , Fetterman Barbara , Boyle Sean , Sadorra Mark , Tang Scott Dahai , Darragh Teresa M. , Castle Philip E.
Published: June 2014

Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (
P
trend
< 0.001), HPV18 (
P
trend
= 0.07), and other carcinogenic types (
P
trend
< 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV.
PB2 Mutations D701N and S714R Promote Adaptation of an Influenza H5N1 Virus to a Mammalian Host
Authors: Czudai-Matwich Volker , Otte Anna , Matrosovich Mikhail , Gabriel Gülsah , Klenk Hans-Dieter
Published: June 2014

Mutation D701N in the PB2 protein is known to play a prominent role in the adaptation of avian influenza A viruses to mammalian hosts. In contrast, little is known about the nearby mutations S714I and S714R, which have been observed in some avian influenza viruses highly pathogenic for mammals. We have generated recombinant H5N1 viruses with PB2 displaying the avian signature 701D or the mammalian signature 701N and serine, isoleucine, and arginine at position 714 and compared them for polymerase activity and virus growth in avian and mammalian cells, as well as for pathogenicity in mice. Mutation D701N led to an increase in polymerase activity and replication efficiency in mammalian cells and in mouse pathogenicity, and this increase was significantly enhanced when mutation D701N was combined with mutation S714R. Stimulation by mutation S714I was less distinct. These observations indicate that PB2 mutation S714R, in combination with the mammalian signature at position 701, has the potential to promote the adaptation of an H5N1 virus to a mammalian host.

IMPORTANCE
Influenza A/H5N1 viruses are avian pathogens that have pandemic potential, since they are spread over large parts of Asia, Africa, and Europe and are occasionally transmitted to humans. It is therefore of high scientific interest to understand the mechanisms that determine the host specificity and pathogenicity of these viruses. It is well known that the PB2 subunit of the viral polymerase is an important host range determinant and that PB2 mutation D701N plays an important role in virus adaptation to mammalian cells. In the present study, we show that mutation S714R is also involved in adaptation and that it cooperates with D701N in exposing a nuclear localization signal that mediates importin-α binding and entry of PB2 into the nucleus, where virus replication and transcription take place.
HIV-1 Vpr Redirects Host Ubiquitination Pathway
Authors: Arora Sakshi , Verma Sachin , Banerjea Akhil C.
Published: June 2014

HIV-1 modulates key host cellular pathways for successful replication and pathogenesis through viral proteins. By evaluating the hijacking of the host ubiquitination pathway by HIV-1 at the whole-cell level, we now show major perturbations in the ubiquitinated pool of the host proteins post-HIV-1 infection. Our overexpression- and infection-based studies of T cells with wild-type and mutant HIV-1 proviral constructs showed that Vpr is necessary and sufficient for reducing whole-cell ubiquitination. Mutagenic analysis revealed that the three leucine-rich helical regions of Vpr are critical for this novel function of Vpr, which was independent of its other known cellular functions. We also validated that this effect of Vpr was conserved among different subtypes (subtypes B and C) and circulating recombinants from Northern India. Finally, we establish that this phenomenon is involved in HIV-1-mediated diversion of host ubiquitination machinery specifically toward the degradation of various restriction factors during viral pathogenesis.

IMPORTANCEHIV-1 is known to rely heavily on modulation of the host ubiquitin pathway, particularly for counteraction of antiretroviral restriction factors, i.e., APOBEC3G, UNG2, and BST-2, etc.; viral assembly; and release. Reports to date have focused on the molecular hijacking of the ubiquitin machinery by HIV-1 at the level of E3 ligases. Interaction of a viral protein with an E3 ligase alters its specificity to bring about selective protein ubiquitination. However, in the case of infection, multiple viral proteins can interact with this multienzyme pathway at various levels, making it much more complicated. Here, we have addressed the manipulation of ubiquitination at the whole-cell level post-HIV-1 infection. Our results show that HIV-1 Vpr is necessary and sufficient to bring about the redirection of the host ubiquitin pathway toward HIV-1-specific outcomes. We also show that the three leucine-rich helical regions of Vpr are critical for this effect and that this ability of Vpr is conserved across circulating recombinants. Our work, the first of its kind, provides novel insight into the regulation of the ubiquitin system at the whole-cell level by HIV-1.
Isolation and Characterization of the DNA and Protein Binding Activities of Adenovirus Core Protein V
Authors: Pérez-Vargas Jimena , Vaughan Robert C. , Houser Carolyn , Hastie Kathryn M. , Kao C. Cheng , Nemerow Glen R.
Published: June 2014

The structure of adenovirus outer capsid was revealed recently at 3- to 4-Å resolution (V. Reddy, S. Natchiar, P. Stewart, and G. Nemerow, Science 329:1071–1075, 2010,
http://dx.doi.org/10.1126/science.1187292
); however, precise details on the function and biochemical and structural features for the inner core still are lacking. Protein V is one the most important components of the adenovirus core, as it links the outer capsid via association with protein VI with the inner DNA core. Protein V is a highly basic protein that strongly binds to DNA in a nonspecific manner. We report the expression of a soluble protein V that exists in monomer-dimer equilibrium. Using reversible cross-linking affinity purification in combination with mass spectrometry, we found that protein V contains multiple DNA binding sites. The binding sites from protein V mediate heat-stable nucleic acid associations, with some of the binding sites possibly masked in the virus by other core proteins. We also demonstrate direct interaction between soluble proteins V and VI, thereby revealing the bridging of the inner DNA core with the outer capsid proteins. These findings are consistent with a model of nucleosome-like structures proposed for the adenovirus core and encapsidated DNA. They also suggest an additional role for protein V in linking the inner nucleic acid core with protein VI on the inner capsid shell.

IMPORTANCE
Scant knowledge exists of how the inner core of adenovirus containing its double-stranded DNA (dsDNA) genome and associated proteins is organized. Here, we report a purification scheme for a recombinant form of protein V that allowed analysis of its interactions with the nucleic acid core region. We demonstrate that protein V exhibits stable associations with dsDNA due to the presence of multiple nucleic acid binding sites identified both in the isolated recombinant protein and in virus particles. As protein V also binds to the membrane lytic protein VI molecules, this core protein may serve as a bridge from the inner dsDNA core to the inner capsid shell.
Functional Analyses of the Three Simian Hemorrhagic Fever Virus Nonstructural Protein 1 Papain-Like Proteases
Authors: Vatter Heather A. , Di Han , Donaldson Eric F. , Radu Gertrud U. , Maines Taronna R. , Brinton Margo A.
Published: June 2014

The N-terminal region of simian hemorrhagic fever virus (SHFV) nonstructural polyprotein 1a is predicted to encode three papain-like proteases (PLP1α, PLP1β, and PLP1γ). Catalytic residues and cleavage sites for each of the SHFV PLP1s were predicted by alignment of the SHFV PLP1 region sequences with each other as well as with those of other arteriviruses, and the predicted catalytic residues were shown to be proximal by homology modeling of the SHFV nsp1s on porcine respiratory and reproductive syndrome virus (PRRSV) nsp1 crystal structures. The functionality of the predicted catalytic Cys residues and cleavage sites was tested by analysis of the autoproteolytic products generated in
in vitro
transcription/translation reactions done with wild-type or mutant SHFV nsp1 constructs. Cleavage sites were also analyzed by mass spectroscopy analysis of selected immunoprecipitated cleavage products. The data showed that each of the three SHFV PLP1s is an active protease. Cys63 was identified as the catalytic Cys of SHFV PLP1α and is adjacent to an Ala instead of the canonical Tyr observed in other arterivirus PLP1s. SHFV PLP1γ is able to cleave at both downstream and upstream nsp1 junction sites. Although intermediate precursor polyproteins as well as alternative products generated by each of the SHFV PLP1s cleaving at sites within the N-terminal region of nsp1β were produced in the
in vitro
reactions, Western blotting of SHFV-infected, MA104 cell lysates with SHFV nsp1 protein-specific antibodies detected only the three mature nsp1 proteins.

IMPORTANCE
SHFV is unique among arteriviruses in having three N-terminal papain-like protease 1 (PLP1) domains. Other arteriviruses encode one or two active PLP1s. This is the first functional study of the SHFV PLP1s. Analysis of the products of
in vitro
autoprocessing of an N-terminal SHFV nonstructural 1a polypeptide fragment showed that each of the three SHFV PLP1s is active, and the predicted catalytic Cys residues and cleavage sites for each PLP1 were confirmed by testing mutant constructs. Several unique features of the SHFV PLP1s were discovered. The SHFV PLP1α catalytic Cys63 is unique among arterivirus PLP1s in being adjacent to an Ala instead of a Trp. Other arterivirus PLP1s cleave only in
cis
at a single downstream site, but SHFV PLP1γ can cleave at both the downstream nsp1γ-nsp2 and upstream nsp1β-nsp1γ junctions. The three mature nsp1 proteins were produced both in the
in vitro
reactions and in infected cells.
Avian Influenza H7N9/13 and H7N7/13: a Comparative Virulence Study in Chickens, Pigeons, and Ferrets
Authors: Kalthoff Donata , Bogs Jessica , Grund Christian , Tauscher Kerstin , Teifke Jens P. , Starick Elke , Harder Timm , Beer Martin
Published: June 2014

Human influenza cases caused by a novel avian H7N9 virus in China emphasize the zoonotic potential of that subtype. We compared the infectivity and pathogenicity of the novel H7N9 virus with those of a recent European avian H7N7 strain in chickens, pigeons, and ferrets. Neither virus induced signs of disease despite substantial replication in inoculated chickens and rapid transmission to contact chickens. Evidence of the replication of both viruses in pigeons, albeit at lower levels of RNA excretion, was also detected. No clear-cut differences between the two H7 isolates emerged regarding replication and antibody development in avian hosts. In ferrets, in contrast, greater replication of the avian H7N9 virus than of the H7N7 strain was observed with significant differences in viral presence, e.g., in nasal wash, lung, and cerebellum samples. Importantly, both viruses showed the potential to spread to the mammal brain. We conclude that efficient asymptomatic viral replication and shedding, as shown in chickens, facilitate the spread of H7 viruses that may harbor zoonotic potential. Biosafety measures are required for the handling of poultry infected with avian influenza viruses of the H7 subtype, independently of their pathogenicity for gallinaceous poultry.

IMPORTANCE
This study is important to the field since it provides data about the behavior of the novel H7N9 avian influenza virus in chickens, pigeons, and ferrets in comparison with that of a recent low-pathogenicity H7N7 strain isolated from poultry. We clearly show that chickens, but not pigeons, are highly permissive hosts of both H7 viruses, allowing high-titer replication and virus shedding without any relevant clinical signs. In the ferret model, the potential of both viruses to infect mammals could be demonstrated, including infection of the brain. However, the replication efficiency of the H7N9 virus in ferrets was higher than that of the H7N7 strain. In conclusion, valuable data for the risk analysis of low-pathogenicity avian influenza viruses of the H7 subtype are provided that could also be used for the risk assessment of zoonotic potentials and necessary biosafety measures.
Hepatitis C Virus Entry Is Impaired by Claudin-1 Downregulation in Diacylglycerol Acyltransferase-1-Deficient Cells
Authors: Sung Pil Soo , Murayama Asako , Kang Wonseok , Kim Myung-Sun , Yoon Seung Kew , Fukasawa Masayoshi , Kondoh Masuo , Kim Jin-Soo , Kim Hyongbum , Kato Takanobu , Shin Eui-Cheol
Published: June 2014

Diacylglycerol acyltransferase-1 (DGAT1) is involved in the assembly of hepatitis C virus (HCV) by facilitating the trafficking of the HCV core protein to the lipid droplet. Here, we abrogated DGAT1 expression in Huh-7.5 cells by using either the transcription activator-like effector nuclease (TALEN) or lentivirus vector short hairpin RNA (shRNA) and achieved complete long-term silencing of DGAT1. HCV entry was severely impaired in DGAT1-silenced Huh-7.5 cell lines, which showed markedly diminished claudin-1 (CLDN1) expression. In DGAT1-silenced cell lines, the forced expression of CLDN1 restored HCV entry, implying that the downregulation of CLDN1 is a critical factor underlying defective HCV entry. The expression of the gene coding for hepatocyte nuclear factor 4α (HNF4α) and other hepatocyte-specific genes was also reduced in DGAT1-silenced cell lines. After
DGAT1
gene rescue, CLDN1 expression was preserved, and HCV entry was restored. Strikingly, after DGAT1 silencing, CLDN1 expression and HCV entry were also restored by low-dose palmitic acid treatment, indicating that the downregulation of CLDN1 was associated with altered fatty acid homeostasis in the absence of DGAT1. Our findings provide novel insight into the role of DGAT1 in the life cycle of HCV.

IMPORTANCE
In this study, we report the novel effect of complete silencing of DGAT1 on the entry of HCV. DGAT1 was recently reported as a host factor of HCV, involved in the assembly of HCV by facilitating the trafficking of the HCV core protein to lipid droplets. We achieved complete and long-term silencing of DGAT1 by either TALEN or repeated transduction of lentivirus shRNA. We found that HCV entry was severely impaired in DGAT1-silenced cell lines. The impairment of HCV entry was caused by CLDN1 downregulation, and the expression of HNF4α and other hepatocyte-specific genes was also downregulated in DGAT1-silenced cell lines. Our results suggest new roles of DGAT1 in human liver-derived cells: maintaining intracellular lipid homeostasis and affecting HCV entry by modulating CLDN1 expression.
Isolated renal zygomycosis in an immunocompetent patient
Authors: Singh Ajay Kr , Goel Madhu Mati , Gupta Chani , Kumar Suresh
Published: June 2014

Zygomycosis is a rare opportunistic fungal infection in immunocompetent patients. Isolated renal involvement by zygomycosis is extremely rare and diagnosed mainly during postmortem study. We report a case of a 22-year-old man with right upper quadrant pain and fever. The CT of the abdomen revealed renal cell carcinoma and subsequent nephrectomy was performed. The histopathological diagnosis of nephrectomy established zygomycosis. After that patient was given 2 months antifungal therapy and is living well even after her 1 year follow-up.
Urachal cancer with direct caecal invasion: differential diagnosis from primary colon cancer
Authors: Park Ji Young , Jeon Tae Joo , Ryu Mi Jin , Shin Won Chang
Published: June 2014

A 56-year-old man who had a history of repeated previous treatment for cystitis was admitted with abdominal distension, dysuria, pollakiuria, nocturia and sensation of urine retention after emptying the bladder. A CT scan showed a 10 cm irregularly shaped soft tissue mass abutting the anterosuperior aspect of the urinary bladder with wall thickening and a soft tissue component in the caecum. Colonoscopy revealed an encircling huge fungating mass on the caecum. The tumour was removed surgically. Histological examination showed moderately differentiated adenocarcinoma extending to the caecal wall and the bladder mucosa, the origin of the mass was consistent with that of a urachal cyst. The epicentre of the tumour was located in the bladder wall, with a distinct margin as a pathological feature. The patient was diagnosed with urachal cancer and concurrent direct caecal invasion.
Older men with unexplained hepatitis
Authors: Lim Kok Haw Jonathan , Howard Mark , Jackson Neil , Verma Sumita
Published: June 2014

A 59-year-old Caucasian man presented with painless jaundice for 6 weeks. He drank 70 units of alcohol per week. Examination revealed jaundice, spider angiomata and a 3 cm firm hepatomegaly. Initial bloods: bilirubin 152 µmol/L, alanine aminotransferase 1484 IU/L, alkaline phosphatase 130 IU/L, γ-glutamyl-transpeptidase 1224 IU/L and International Normalised Ratio 1.1. A standard liver screen was normal, and an abdominal ultrasound/CT scan suggested cirrhosis, confirmed by liver biopsy on day 5. Hepatitis E virus (HEV) serology on day 6 indicated acute infection. He developed severe hepatic decompensation characterised by worsening jaundice, ascites and variceal bleeding. On day 33 ribavirin 600 mg was initiated though discontinued after 2 weeks on receipt of a negative HEV RNA. At the last follow-up he had recovered, and remains abstinent from alcohol. We describe a case of autochthonously (locally) acquired HEV infection with life-threatening hepatic decompensation in the presence of undiagnosed alcohol-related cirrhosis.
Changes in addressing inequalities in access to hospital care in Andhra Pradesh and Maharashtra states of India: a difference-in-differences study using repeated cross-sectional surveys
Authors: Rao Mala , Katyal Anuradha , Singh Prabal V , Samarth Amit , Bergkvist Sofi , Kancharla Manjusha , Wagstaff Adam , Netuveli Gopalakrishnan , Renton Adrian
Published: June 2014

Objectives

To compare the effects of the Rajiv Aarogyasri Health Insurance Scheme of Andhra Pradesh (AP) with health financing innovations including the Rashtriya Swasthya Bima Yojana (RSBY) in Maharashtra (MH) over time on access to and out-of-pocket expenditure (OOPE) on hospital inpatient care.

Study design

A difference-in-differences (DID) study using repeated cross-sectional surveys with parallel control.

Setting

National Sample Survey Organisation of India (NSSO) urban and rural ‘first stratum units’, 863 in AP and 1008 in MH.

Methods

We used two cross-sectional surveys: as a baseline, the data from the NSSO 2004 survey collected before the Aarogyasri and RSBY schemes were launched; and as postintervention, a survey using the same methodology conducted in 2012.

Participants

8623 households in AP and 10 073 in MH.

Main outcome measures

Average OOPE, large OOPE and large borrowing per household per year for inpatient care, hospitalisation rate per 1000 population per year.

Results

Average expenditure, large expenditures and large borrowings on inpatient care had increased in MH and AP, but the increase was smaller in AP across these three measures. DIDs for average expenditure and large borrowings were significant and in favour of AP for the rural and the poorest households. Hospitalisation rates also increased in both states but more so in AP, although the DID was not significant and the subgroup analysis presented a mixed picture.

Conclusions

Health innovations in AP had a greater beneficial effect on inpatient care-related expenditures than innovations in MH. The Aarogyasri scheme is likely to have contributed to these impacts in AP, at least in part. However, OOPE increased in both states over time. Schemes such as the Aarogyasri and RSBY may result in some positive outcomes, but additional interventions may be required to improve access to care for the most vulnerable sections of the population.
From harm to hope and purposeful action: what could we do after Francis?
Authors: Woodhead Tricia , Lachman Peter , Mountford James , Botwinick Laura , Peden Carol , Stewart Kevin
Published: June 2014

Responses to the reports on the inquiry into Mid Staffordshire have resulted in calls from politicians, NHS leaders and the public to improve care across the NHS in England. However, the substance of what needs to be done remains unclear. In this paper, we offer seven key ‘ingredients’ required to sustain improvement of care, supported by evidence drawn from published literature. We believe that empowering and upskilling the front-line workforce in understanding and implementing improvement techniques, supported by changes at system and policy level and reinforced by what leaders say and do, will result in sustainable benefit for patients and families, as well as greater satisfaction for staff.
Network model of bilateral power markets based on complex networks
Authors: Wu Yang , Liu Junyong , Li Furong , Yan Zhanxin , Zhang Li
Published: June 2014

The bilateral power transaction (BPT) mode becomes a typical market organization with the restructuring of electric power industry, the proper model which could capture its characteristics is in urgent need. However, the model is lacking because of this market organization's complexity. As a promising approach to modeling complex systems, complex networks could provide a sound theoretical framework for developing proper simulation model. In this paper, a complex network model of the BPT market is proposed. In this model, price advantage mechanism is a precondition. Unlike other general commodity transactions, both of the financial layer and the physical layer are considered in the model. Through simulation analysis, the feasibility and validity of the model are verified. At same time, some typical statistical features of BPT network are identified. Namely, the degree distribution follows the power law, the clustering coefficient is low and the average path length is a bit long. Moreover, the topological stability of the BPT network is tested. The results show that the network displays a topological robustness to random market member's failures while it is fragile against deliberate attacks, and the network could resist cascading failure to some extent. These features are helpful for making decisions and risk management in BPT markets.
STATISTICAL MODELING AND CONTROL OF SELF-ESTEEM AND SELF-LIKING
Authors: YATSENKO O.
Published: June 2014

The paper discusses the existing theories and measurement tools of self-esteem and self-liking and analyzes certain non-clinical ways for improving them. Statistical modeling is used to confirm the effect of receiving compliments on self-liking. The experimental part of the paper is based on a questionnaire about self-perceived attractiveness completed by a group of young adults, half of whom received a compliment immediately before. The modeling outcomes demonstrate that compliments lead to increased self-perceived attractiveness in both genders.
DEVELOPING AGE-SIZE RELATIONSHIPS FOR LONG LIVED TREE SPECIES
Authors: BOLAND JOHN , SINCLAIR RUSSELL
Published: June 2014

Calculating the age of trees is often desirable in vegetation studies, but is sometimes difficult. In arid areas in particular, tree rings may not be annual, and growth may be related more to rainfall than annual cycles. A relationship between age and trunk circumference was developed for two species, Acacia aneura and Myoporum platycarpum, based on measurements of trees of known age (<80 years) growing on permanent quadrats on the Koonamore Reserve, in semi-arid South Australia. Extrapolation beyond the known ages was made by finding the maximum girth of mature trees in a larger population and using this to estimate an asymptote to which the curve is constrained to approach. We envisage that the techniques developed here could be applied to other species of a similar nature, those for which there is no relationship between number of tree rings and age.
ON THE VISUAL COMPLEXITY OF BUILT AND NATURAL LANDSCAPES
Authors: BOURCHTEIN ANDREI , BOURCHTEIN LUDMILA , NAOUMOVA NATALIA
Published: June 2014

In this study, we analyze some critical points of the application of the box-counting method to the evaluation of the fractal dimensions of the natural and built landscapes. A brief theoretical discussion of the eventual drawbacks of the method is supported by experimental results of two box-counting programs applied to classical fractals. The optimized version of the algorithm, based on the results of computations for the classical fractal images, is proposed and employed for the evaluation of the complexity level of the chosen historical buildings and surrounding environment in the well-known case of Amasya city. The hypothesis of the relationship between the visual complexity of built and natural settings is analyzed for the Amasya case and for two historical Brazilian cities.
USER EQUILIBRIUM ROUTE ASSIGNMENT FOR MICROSCOPIC PEDESTRIAN SIMULATION
Authors: KRETZ TOBIAS , LEHMANN KARSTEN , HOFSÄß INGMAR
Published: June 2014

For the simulation of pedestrians, a method is introduced to find routing alternatives from any origin position to a given destination area in a given geometry composed of walking areas and obstacles. The method includes a parameter which sets a threshold for the approximate minimum size of obstacles to generate routing alternatives. The resulting data structure for navigation is constructed such that it does not introduce artifacts to the movement of simulated pedestrians and locally pedestrians prefer to walk on the shortest path. The generated set of routes can be used with iterating static or dynamic assignment methods.
Spin Transitions in Mantle Minerals
Authors: Badro James
Published: June 2014

Mantle minerals at shallow depths contain iron in the high-spin electronic state. The crystal-field splitting energy increases with increasing pressure, which can favor the low-spin state. Hence, pressure-driven transitions from the high-spin to the low-spin state were proposed as early as the 1960s, and minerals in the lower mantle were suggested to contain iron in the low-spin state. Only in the past 10 years did experiments and calculations prove that iron in mantle minerals transforms from high-spin to low-spin at lower-mantle pressures. This transition has important consequences for volume, thermodynamics, and bonding. In a geophysical framework, the transition would affect the dynamics and thermochemical state of the lower mantle, through combined effects on density, elasticity, element partitioning, and transport properties. These observations provide the basis for a new paradigm of the physics and chemistry in Earth's lower(most) mantle.
Organosulfur Compounds: Molecular and Isotopic Evolution from Biota to Oil and Gas
Authors: Amrani Alon
Published: June 2014

Organosulfur compounds (OSCs) play important roles in the formation, preservation, and thermal degradation of sedimentary organic matter and the associated petroleum generation. Improved analytical techniques for S isotope analysis have recently enhanced our understanding of the mechanisms for OSC formation and maturation and their associated S isotope distributions. The close interaction of OSCs with inorganic S species throughout their formation and maturation affects their 34S/32S isotopic ratio (δ34S), forming specific signatures for distinct sources and processes. Ultimately, thermal maturation homogenizes the δ34S values of different fractions and individual compounds. Reservoir processes such as thermochemical sulfate reduction (TSR) introduce exogenous and isotopically distinct S into hydrocarbons and can significantly change the δ34S of petroleum or kerogen. Specific OSCs react at different rates and thus can be used to evaluate the extent of processes such as TSR. This article reviews factors that affect the 34S/32S isotopic distribution of OSCs along pathways of formation, diagenesis, and thermal alteration.
On Dinosaur Growth
Authors: Erickson Gregory M.
Published: June 2014

Despite nearly two centuries of investigation, a comprehensive understanding of dinosaur biology has proven intractable. The recent development of means to study tissue-level growth, age these animals, and make growth curves has revolutionized our knowledge of dinosaur lives. From such data it is now understood that dinosaurs grew both disruptively and determinately; that they rarely if ever exceeded a century in age; that they became giants through accelerated growth and dwarfed through truncated development; that they were likely endothermic, sexually matured like crocodiles, and showed survivorship like populations of large mammals; and that basal birds retained dinosaurian physiology.
The Pivotal Regulatory Landscape of RNA Modifications
Authors: Li Sheng , Mason Christopher E.
Published: June 2014

Posttranscriptionally modified nucleosides in RNA play integral roles in the cellular control of biological information that is encoded in DNA. The modifications of RNA span all three phylogenetic domains (Archaea, Bacteria, and Eukarya) and are pervasive across RNA types, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and (less frequently) small nuclear RNA (snRNA) and microRNA (miRNA). Nucleotide modifications are also one of the most evolutionarily conserved properties of RNAs, and the sites of modification are under strong selective pressure. However, many of these modifications, as well as their prevalence and impact, have only recently been discovered. Here, we examine both labile and permanent modifications, from simple methylation to complex transcript alteration (RNA editing and intron retention); detail the models for their processing; and highlight remaining questions in the field of the epitranscriptome.
Acid-sensing ion channels are involved in epithelial Na+ uptake in the rainbow trout Oncorhynchus mykiss
Authors: Dymowska Agnieszka K. , Schultz Aaron G. , Blair Salvatore D. , Chamot Danuta , Goss Greg G.
Published: June 2014

A role for acid-sensing ion channels (ASICs) to serve as epithelial channels for Na+ uptake by the gill of freshwater rainbow trout was investigated. We found that the ASIC inhibitors 4′,6-diamidino-2-phenylindole and diminazene decreased Na+ uptake in adult rainbow trout in a dose-dependent manner, with IC50 values of 0.12 and 0.96 μM, respectively. Furthermore, we cloned the trout ASIC1 and ASIC4 homologs and demonstrated that they are expressed differentially in the tissues of the rainbow trout, including gills and isolated mitochondrion-rich cells. Immunohistochemical analysis using custom-made anti-zASIC4.2 antibody and the Na+-K+-ATPase (α5-subunit) antibody demonstrated that the trout ASIC localizes to Na+/K+-ATPase-rich cells in the gill. Moreover, three-dimensional rendering of confocal micrographs demonstrated that ASIC is found in the apical region of mitochondrion-rich cells. We present a revised model whereby ASIC4 is proposed as one mechanism for Na+ uptake from dilute freshwater in the gill of rainbow trout.