bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a cryogenic hydrogen microjet for high-intensity, high-repetition rate experiments
Authors: Kim J. B. , Göde S. , Glenzer S. H.
Published: August 2016

The advent of high-intensity, high-repetition-rate lasers has led to the need for replenishing targets of interest for high energy density sciences. We describe the design and characterization of a cryogenic microjet source, which can deliver a continuous stream of liquid hydrogen with a diameter of a few microns. The jet has been imaged at 1 μm resolution by shadowgraphy with a short pulse laser. The pointing stability has been measured at well below a mrad, for a stable free-standing filament of solid-density hydrogen.
Modified electron acoustic field and energy applied to observation data
Authors: Abdelwahed H. G. , El-Shewy E. K.
Published: August 2016

Improved electrostatic acoustic field and energy have been debated in vortex trapped hot electrons and fluid of cold electrons with pressure term plasmas. The perturbed higher-order modified-Korteweg-de Vries equation (PhomKdV) has been worked out. The effect of trapping and electron temperatures on the electro-field and energy properties in auroral plasmas has been inspected.
Prediction of salt transport in different soil textures under drip irrigation in an arid zone using the SWAGMAN Destiny model
Authors: Yang Haichang , Chen Yun , Zhang Fenghua , Xu Tingbao , Cai Xu
Published: August 2016

In recent years, Xinjiang Oasis has faced a major challenge of increasing risk of secondary salinization caused by drip irrigation under plastic mulch. Predicting the salt balance is therefore essential for understanding how to sustain the use of salinized land in this arid area. This research validated the SWAGMAN (Salt, Water And Groundwater MANagement) Destiny model to simulate and forecast the movement of salt in different soil textures based on field experiments. The results were verified with extensive field work in Shihutan, Xinjiang, China. They show that soil salinity decreases in the upper layers and increases in the bottom layers of the investigated soil profile. The desalinization rate in sand, which shows an overall steady trend throughout the soil profile, is generally higher than that in loam and clay. The depth of 60cm is critical for loam and clay; soil salinity decreases above it but increases below it. Model sensitivity analysis reveals the variation of soil salinity is independent of the initial electrical conductivity setting of SWAGMAN Destiny simulations. This study indicates that numerical modelling is a useful approach for efficiently estimating the salt balance under drip irrigation. The result provides a scientific basis for making adaptive strategies to manage salinised farmlands in arid zones.
Sulfur-enriched biochar as a potential soil amendment and fertiliser
Authors: Zhang Hongjie , Voroney R. Paul , Price G. W. , White Andrew J.
Published: August 2016

Hydrogen sulfide (H2S) is a highly toxic and corrosive contaminant gas co-generated during anaerobic digestion. Studies have shown that biochars have the potential to adsorb H2S and to promote its oxidisation. To date, no studies have investigated the bioavailabilty to plants of the sulfur (S) contained in biochar when used as an S fertiliser.
Biochar was packed into the biogas emissions stream to adsorb the H2S being generated. The resulting sulfur-enriched biochar (SulfaChar) and synthetic S fertiliser (control treatment) were amended to potting soils and the growth response of corn (Zea mays L.) and soybeans [Glycine max (L.) Merr.] and nutrient uptake were measured after a 90-day greenhouse study.
SulfaChar contained 36.5% S (S element and SO42–), confirming it adsorbed significant amounts of H2S. Compared with the control treatment, SulfaChar amendment significantly increased corn plant biomass, ranging from 31% to 49% but only a slight increase in soybean biomass (4 to 14%). SulfaChar also increased corn plant uptake of S and other macro- (N, P, K, Ca, and Mg) and micro-nutrients (Zn, Mn and B).
Our results show that SulfaChar was a source of plant available S, suggesting that SulfaChar is either a supplier of these nutrients or that it promoted their uptake.
Signal transmission through the CXC chemokine receptor 4 (CXCR4) transmembrane helices
Authors: Wescott Melanie P. , Kufareva Irina , Paes Cheryl , Goodman Jason R. , Thaker Yana , Puffer Bridget A. , Berdougo Eli , Rucker Joseph B. , Handel Tracy M. , Doranz Benjamin J.
Published: August 2016

Significance

Our study helps answer the question of how G protein-coupled receptors bind an extracellular ligand and relay this signal through its transmembrane helices into an intracellular signaling event. This has been the central thesis that G protein-coupled receptor structural studies have sought to address through static snapshots of the crystallized proteins. Our functional approach using CXC chemokine receptor 4 as a model complements these structures by identifying the dynamic atomic pathway from chemokine engagement to G protein coupling.
Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency
Authors: Reid-Bayliss Kate S. , Arron Sarah T. , Loeb Lawrence A. , Bezrookove Vladimir , Cleaver James E.
Published: August 2016

Significance

Cockayne syndrome (CS) and xeroderma pigmentosum (XP) are photosensitive diseases with mutations in the nucleotide excision repair (NER) pathway. XP patients have a very high incidence of UV-induced skin cancer, but CS patients have never been reported to develop cancer. Cultured cells from both diseases have similar sensitivity to UV-induced cytotoxicity. We examined UV-induced mutagenesis in cells from XP patients with mutations in the global genome repair branch of the NER pathway (XP-C cells) and CS primary cells using duplex sequencing for high sensitivity without selection. XP-C cells showed increased UV-induced mutation frequencies compared with normal cells, consistent with their increased cancer incidence. CS cells, in contrast, showed no elevated mutagenesis. Therefore the absence of cancer in CS patients results from the absence of increased mutations following UV exposure.
Stromal uptake and transmission of acid is a pathway for venting cancer cell-generated acid
Authors: Hulikova Alzbeta , Black Nicholas , Hsia Lin-Ting , Wilding Jennifer , Bodmer Walter F. , Swietach Pawel
Published: August 2016

Significance

Metabolism energizes cancer growth, but only if its end product, acid, is removed effectively. A bottleneck for acid handling is slow diffusion across the underperfused extracellular milieu of hypoxic tumors. Here, we characterize the acid-handling mechanisms operating in stromal myofibroblasts that can improve the flow of acid through tumors. We show that myofibroblasts are high-capacity reservoirs that absorb excess extracellular acidity, via the AE2 transporter, and transmit this acid load across a syncytium fused by channels, such as connexin-43. Furthermore, the cytokine TGFβ1, which orchestrates many cancer–stromal interactions, can stimulate acid uptake and transmission in stromal cells with lower baseline activities. Because many colorectal cancer cells do not express AE2 and connexin-43, acid traffic would be routed preferentially through the stromal compartment of tumors.
The U.S. swine industry: historical milestones and the future of on-farm swine welfare assessments.
Authors: Pairis-Garcia M. D. , Johnson A. K. , Azarpajouh S. , Colpoys J. D. , Rademacher C. J. , Millman S. T. , Webb S. R.
Published: August 2016

Swine welfare has become an ever increasing area of public interest in the United States (USA) and has resulted in dramatic changes to legislation, policy and practices in swine production. Over the past decades, consumer engagement, animal protection campaigns and increase knowledge about swine welfare arising from education and research programmes have escalated swine welfare to a top industry priority. For both mainstream and niche pork marketing streams, science based and culturally relevant programmes have been developed to assess swine welfare, articulate standards of care and verify compliance to assure purchasers and consumers of pork about on-farm husbandry practices that impact animal welfare. This response has transitioned primarily from education of producers and/or consumers, to outcome-based animal welfare assessment programmes with independent third party verification audits. This review paper will evaluate some factors that have influenced the development of swine welfare standards in the USA and describe programmes developed to improve and evolve on-farm swine welfare for the future.
IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization
Authors: Yoon Juhan , Leyva-Castillo Juan Manuel , Wang Guoxing , Galand Claire , Oyoshi Michiko K. , Kumar Lalit , Hoff Sabine , He Rui , Chervonsky Alexander , Oppenheim Joost J. , Kuchroo Vijay K. , van den Brink Marcel R.M. , Malefyt Rene De Waal , Tessier Philippe A. , Fuhlbrigge Robert , Rosenstiel Philip , Terhorst Cox , Murphy George , Geha Raif S.
Published: August 2016

Atopic dermatitis (AD) is a Th2-dominated inflammatory skin disease characterized by epidermal thickening. Serum levels of IL-22, a cytokine known to induce keratinocyte proliferation, are elevated in AD, and Th22 cells infiltrate AD skin lesions. We show that application of antigen to mouse skin subjected to tape stripping, a surrogate for scratching, induces an IL-22 response that drives epidermal hyperplasia and keratinocyte proliferation in a mouse model of skin inflammation that shares many features of AD. DC-derived IL-23 is known to act on CD4+ T cells to induce IL-22 production. However, the mechanisms that drive IL-23 production by skin DCs in response to cutaneous sensitization are not well understood. We demonstrate that IL-23 released by keratinocytes in response to endogenous TLR4 ligands causes skin DCs, which selectively express IL-23R, to up-regulate their endogenous IL-23 production and drive an IL-22 response in naive CD4+ T cells that mediates epidermal thickening. We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD.
MHC II+ resident peritoneal and pleural macrophages rely on IRF4 for development from circulating monocytes
Authors: Kim Ki-Wook , Williams Jesse W. , Wang Ya-Ting , Ivanov Stoyan , Gilfillan Susan , Colonna Marco , Virgin Herbert W. , Gautier Emmanuel L. , Randolph Gwendalyn J.
Published: August 2016

Peritoneal and pleural resident macrophages in the mouse share common features and in each compartment exist as two distinct subpopulations: F4/80+ macrophages and MHC II+ CD11c+ macrophages. F4/80+ macrophages derive from embryonic precursors, and their maintenance is controlled by Gata6. However, the origin and regulatory factors that maintain MHC II+ macrophages remain unknown. Here, we show that the MHC II+ macrophages arise postnatally from CCR2-dependent precursors that resemble monocytes. Monocytes continuously replenish this subset through adulthood. Gene expression analysis identified distinct surface markers like CD226 and revealed that the transcription factor IRF4 was selectively expressed in these macrophages relative to other organs. Monocytes first entered peritoneal or pleural cavities to become MHC II+ cells that up-regulated CD226 and CD11c later as they continued to mature. In the absence of IRF4 or after administration of oral antibiotics, MHC II+CD226−CD11c− monocyte-derived cells accumulated in peritoneal and pleural cavities, but CD11c+ CD226+ macrophages were lost. Thus, MHC II+ resident peritoneal and pleural macrophages are continuously replenished by blood monocytes recruited to the peritoneal and pleural cavities constitutively, starting after birth, where they require IRF4 and signals likely derived from the microbiome to fully differentiate.
Let's all get home safely: a commentary on NICE and SCIE guidelines (NG27) transition between inpatient hospital settings and community or care home settings
Authors: Winfield Anna , Burns Eileen
Published: August 2016

Safe and appropriate transition between inpatient settings and the community is one of the major challenges facing the modern NHS. The National Institute for Health and Care Excellence in conjunction with the Social Care Institute for Excellence published guidance on this challenging area in December 2015. This commentary provides context, summary and discussion of the key areas covered. The guidance particularly emphasises the importance of a person-centred approach in which patients are individuals and equal partners in the multidisciplinary team who should be treated with dignity and respect. Additionally, communication and information sharing is crucial both on admission and when taking a proactive approach to discharge, including the role of the discharge coordinator in liaising with community teams and arranging follow-up post-discharge. Self-care and the significance of carers are also highlighted as valuable in facilitating safe discharge and reducing readmissions. It is clear that in older people with complex needs, safe appropriate transition between hospital and community settings has a positive impact on patients and their carers. Given the financial and capacity pressures facing the NHS, strategies to reduce readmissions and prevent delays in discharge are increasingly important. These guidelines are therefore both timely and advocated to improve care for older people.
Effect of salt stress on ion concentration, proline content, antioxidant enzyme activities and gene expression in tomato cultivars
Authors: Gharsallah Charfeddine , Fakhfakh Hatem , Grubb Douglas , Gorsane Faten
Published: August 2016

Salinity is a constraint limiting plant growth and productivity of crops throughout the world. Understanding the mechanism underlying plant response to salinity provides new insights into the improvement of salt tolerance-crops of importance. In the present study, we report on the responses of twenty cultivars of tomato. We have clustered genotypes into scale classes according to their response to increased NaCl levels. Three local tomato genotypes, representative of different saline scale classes, were selected for further investigation. During early (0 h, 6 h and 12 h) and later (7 days) stages of the response to salt treatment, ion concentrations (Na + , K +  and Ca 2+ ), proline content, enzyme activities (catalase, ascorbate peroxidase and guiacol peroxidase) were recorded. qPCR analysis of candidate genes WRKY (8, 31and 39), ERF (9, 16 and 80), LeNHX (1, 3 and 4) and HKT (class I) were performed. A high K + , Ca 2 + and proline accumulation as well as a decrease of Na +  concentration-mediated salt tolerance. Concomitant with a pattern of high-antioxidant enzyme activities, tolerant genotypes also displayed differential patterns of gene expression during the response to salt stress.
MSIdV: a versatile tool to visualize biological indices from mass spectrometry imaging data
Authors: Hayakawa Eisuke , Fujimura Yoshinori , Miura Daisuke
Published: August 2016

Summary: Mass spectrometry imaging (MSI) visualizes the simultaneous lateral distribution of multiple compounds on sample surface. However, it is still difficult to visualize biological indices such as energy charge index from multiple compounds because of the lack of publicly available tools. Here we present MSIdV, a visualization tool for biological indices calculated from mass spectrometry imaging data, which can effectively scan a series of mass spectra and process, calculate and visualize user-defined index measures accurately with a number of signal processing features.

Availability and Implementation: MSIdV is implemented in Python 2.7 and is freely available on the web at https://sourceforge.net/projects/msidv/.

Contact:  eisuke.hayakawa@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Performance of bycatch reduction devices varies for chondrichthyan, reptile, and cetacean mitigation in demersal fish trawls: assimilating subsurface interactions and unaccounted mortality
Authors: Wakefield Corey B. , Santana-Garcon Julia , Dorman Stacey R. , Blight Stuart , Denham Ainslie , Wakeford John , Molony Brett W. , Newman Stephen J.
Published: August 2016

To improve bycatch mitigation of chondrichthyans, reptiles and cetaceans for a tropical demersal fish-trawl fishery, species-specific responses to bycatch reduction devices (BRDs) were investigated using both in situ subsurface and onboard observations. There are few, if any, studies that have determined mitigation performances of BRDs from subsurface interactions for these species, as most are rarely encountered and thus require substantial levels of observer coverage for robust assessments. This study combined in-net and onboard (774 day trawls and 1320 day trawl hours of subsurface observer coverage) electronic monitoring on all fish-trawl vessels (n = 3) to compare bycatch mitigation performances among nine megafauna groups, based on escape rates and interaction durations for three BRDs over 6 months (June to December 2012). Overall, 26.9% of day trawls had no megafauna interactions and 38.3% of the 1826 interactions escaped, with most in rapid time (91.4% in ≤ 5 min). The upward inclined exclusion grid significantly improved the escape proportions for most chondrichthyans by 20–30%. All BRDs were highly effective in reducing reptile (turtles and seasnakes) bycatch, but irrelevant for the few sawfish (n = 13) that readily entangled in the anterior of the net. Cetacean (bottlenose dolphins only) interactions with BRDs were very rare (n = 7) despite high levels of attendance and depredation during trawling. Loss of targeted teleosts through the BRD hatch was rare (1.3% of day trawls). This relatively cost-effective method of electronic monitoring achieved very high levels of subsurface observer coverage (60% of day trawls or 56% of day trawl hours), and provided evidence that the subsurface expulsion of megafauna in poor condition is negligible. Furthermore, this study provides species-specific improvements toward bycatch mitigation strategies for demersal fish trawling.
Albino Leaf 2is involved in the splicing of chloroplast group I and II introns in rice
Authors: Liu Changhong , Zhu Haitao , Xing Yi , Tan Jianjie , Chen Xionghui , Zhang Jianjun , Peng Haifeng , Xie Qingjun , Zhang Zemin
Published: August 2016

Chloroplasts play an essential role in plant growth and development through manipulating photosynthesis and the production of hormones and metabolites. Although many genes or regulators involved in chloroplast biogenesis and development have been isolated and characterized, identification of novel components is still lacking. We isolated a rice ( Oryza sativa ) mutant, termed albino leaf 2 ( al2 ), using genetic screening. Phenotypic analysis revealed that the al2 mutation caused obvious albino leaves at the early developmental stage, eventually leading to al2 seedling death. Electron microscopy investigations indicated that the chloroplast structure was disrupted in the al2 mutants at an early developmental stage and subsequently resulted in the breakdown of the entire chloroplast. Molecular cloning illustrated that AL2 encodes a chloroplast group IIA intron splicing facilitator (CRS1) in rice, which was confirmed by a genetic complementation experiment. Moreover, our results demonstrated that AL2 was constitutively expressed in various tissues, including green and non-green tissues. Interestingly, we found that the expression levels of a subset of chloroplast genes that contain group IIA and IIB introns were significantly reduced in the al2 mutant compared to that in the wild type, suggesting that AL2 is a functional CRS1 in rice. Differing from the orthologous CRS1 in maize and Arabidopsis that only regulates splicing of the chloroplast group II intron, our results demonstrated that the AL2 gene is also likely to be involved in the splicing of the chloroplast group I intron. They also showed that disruption of AL2 results in the altered expression of chloroplast-associated genes, including chlorophyll biosynthetic genes, plastid-encoded polymerases and nuclear-encoded chloroplast genes. Taken together, these findings shed new light on the function of nuclear-encoded chloroplast group I and II intron splicing factors in rice.
Allergic Diseases
Authors: Volcheck Gerald W.
Published: August 2016

Standard allergy testing relies on identifying the immunoglobulin (Ig) E antibody specific for the allergen in question. Two classic methods of doing this are the immediate wheal-and-flare skin prick tests (in which a small amount of antigen is introduced into the skin and the site is evaluated after 15 minutes for the presence of an immediate wheal-and-flare reaction) and in vitro (blood) testing. Methods of allergy testing that do not have a clear scientific basis include cytotoxic testing, provocation-neutralization testing or treatment, and “yeast allergy” testing.
Heart Failure and Cardiomyopathies
Authors: Timimi Farris K.
Published: August 2016

Heart failure is a clinical syndrome characterized by inability of the heart to maintain adequate cardiac output to meet the metabolic demands of the body while still maintaining normal or near-normal ventricular filling pressures. Heart failure may be present at rest, but often it is symptomatic only during exertion due to the dynamic nature of cardiac demands. For the optimal treatment of heart failure, the mechanism, underlying cause, and any reversible precipitating factors must be identified. Typical manifestations of heart failure are dyspnea and fatigue limiting activity tolerance and fluid retention leading to pulmonary or peripheral edema.
Ischemic Heart Disease
Authors: Anavekar Nandan S.
Published: August 2016

Ischemic heart disease is cardiac disease that results in diminished myocardial blood supply and its attendant clinicopathologic manifestations. It may be clinically silent or present with syndromes categorized as stable angina, unstable angina, non–ST-elevation acute coronary syndrome, ST-elevation myocardial infarction (MI), or sudden death. Ischemic heart disease causes nearly 800,000 deaths annually. Notably, about a third of deaths annually in the United States are due to MI. Primary prevention and new treatments have led to a substantial decrease in death from acute MI since 1970.
Pericardial Disease and Cardiac Tumors
Authors: Klarich Kyle W.
Published: August 2016

The space between the visceral and parietal pericardium normally contains 15 to 25 mL of clear fluid. The pericardium functions to prevent cardiac distention, limit cardiac displacement (by its attachment to neighboring structures), and protect the heart from inflammation. The chest pain of pericarditis is aggravated by movement of the trunk, inspiration, and coughing. The pain can be relieved by sitting up. Low-grade fever and malaise may occur.
Valvular and Congenital Heart Diseases
Authors: Klarich Kyle W. , Blauwet Lori A. , Phillips Sabrina D.
Published: August 2016

The pathophysiologic effect of aortic stenosis on the heart is pressure overload, leading to left ventricular hypertrophy. The vast majority of cases of aortic stenosis are due to valvular stenosis. The classic symptoms of the valvular type of aortic stenosis (regardless of type) include exertional dyspnea, syncope, angina, and sudden cardiac death. The onset of symptoms is an ominous sign and portends a very poor prognosis. Patients with symptomatic aortic stenosis need rapid surgical intervention.
Dermatology
Authors: Wieland Carilyn N.
Published: August 2016

Nonmelanoma skin cancers (basal cell carcinoma, squamous cell carcinoma) are the most common malignancies in the United States. Both basal cell and squamous cell carcinomas commonly occur on sun-exposed skin areas. The strongest risk factors for melanoma are a family history of melanoma, multiple benign or atypical nevi, and a previous melanoma. Cutaneous T-cell lymphoma is a non-Hodgkin lymphoma characterized by expansion of malignant T cells within the skin. The most common clinical presentations are mycosis fungoides and Sézary syndrome.
Acid-Base Disorders
Authors: Qian Qi
Published: August 2016

Specific skin and soft tissue infections can be characterized by their visual appearance, including vesicles, bullae, folliculitis, crusted lesions, papular lesions, ulcerations, and cellulitis. Nonpurulent cellulitis is an acute, spreading infection of the dermis and subcutaneous tissue. Cellulitis is most common in tissue damaged by trauma and in extremities with impaired venous or lymphatic drainage (eg, the arm after mastectomy, the leg after saphenous vein harvest for coronary artery bypass grafting).
Renal Parenchymal Diseases
Authors: Norby Suzanne M. , Fervenza Fernando C.
Published: August 2016

Volume expansion can be general (as in patients with congestive heart failure, cirrhosis, or nephrotic syndrome) or regional (as in patients with regional capillary leak, venous insufficiency, or lymphatic obstruction). Volume depletion is associated primarily with gastrointestinal tract (GI) fluid loss, excessive sweating, and renal sodium loss related to diuretic use or, rarely, renal salt wasting. The cause of a volume disorder can be determined by physical examination.
Headache, Facial Pain, and “Dizziness”
Authors: Vargas Bert B.
Published: August 2016

The causes of ischemic cerebrovascular disorders, including transient ischemic attack (TIA) and cerebral infarction, can be classified according to the site of the source for the arterial blockage within the vascular system, from most proximal to distal: cardiac source, large-vessel disorders, small-vessel occlusive disease, and hematologic disorders. Notably, illicit drug use is a common cause of stroke in young persons; it may cause arrhythmia, inflammatory arteriopathies, and a relative hypercoagulable state.
Movement Disorders
Authors: Hassan Anhar , Benarroch Eduardo E.
Published: August 2016

The most common inflammatory demyelinating disease of the central nervous system is multiple sclerosis, a disabling disorder that affects predominantly young adults between 20 and 50 years old. It affects women twice as often as men. Multiple sclerosis has a complex immunopathogenesis, variable prognosis, and an unpredictable course. Polygenic and environmental (possibly viral) factors probably have a substantial effect on susceptibility to multiple sclerosis.
Colorectal Cancer
Authors: Hubbard Joleen M.
Published: August 2016

Globally, cervical cancer is the second most common type of cancer and the second leading cause of cancer death among women. The incidence varies geographically because of differences in the availability of screening programs and access to them. For example, in Africa, cervical cancer is the leading cause of cancer deaths among women, but in the United States, where screening is more prevalent, cervical cancer is not among the top 10 causes of cancer deaths. In recent decades, the incidence of cervical cancer, as well as the mortality associated with the disease, has markedly decreased.
Vasculitis
Authors: Koster Matthew J. , Warrington Kenneth J.
Published: August 2016

Rheumatoid arthritis is a chronic systemic inflammatory disease characterized by joint destruction. It affects 0.03% to 1.5% of the population worldwide. Women are affected 3 times more frequently than men. Its incidence peaks between the ages of 35 and 45 years; however, the age-related prevalence of the disease increases even after age 65 years. Conditions in the spondyloarthritis spectrum include ankylosing spondylitis, reactive arthritis (Reiter syndrome), arthritis related to inflammatory bowel disease, and psoriatic arthritis.
Questions and Answers
Authors: Schwenk Nina M.
Published: August 2016

This section consist of question and answers for the section
Questions and Answers
Authors: Wang Amy T.
Published: August 2016

This section consist of question and answers for the section
Questions and Answers
Authors: Beckman Thomas J. , Collins Nerissa M. , Wang Amy T.
Published: August 2016

This section consist of question and answers for the section
Manual of Neurological Signs
Authors: Morris John G. , Grattan-Smith Padraic J.
Published: August 2016

Neurology is the most visual of the medical specialties, and videos have an ability to illustrate physical signs in a way that cannot be matched by written descriptions. The Manual of Neurological Signs comprises over 900 videos of adults and children with neurologic disorders with sections including: Higher Functions, Movement Disorders, Eyes/Eye Movement, Head and Neck, Epilepsy, Reflexes, Gait, Cerebellar Disorders, Upper Motor Neuron Disorders, Lower Motor Neuron Disorders, Faces, Psychogenic Disorders, Skin Disorders, and Miscellaneous Signs.
Discordance Between Cobas BRAF V600 Testing and VE1 Immunohistochemistry in a Melanoma Patient With Bone Marrow Metastases
Authors: Rapisuwon Suthee , Busam Klaus J. , Parks Kellie , Chapman Paul B. , Lee Elsie , Atkins Michael B.
Published: August 2016

False negative result remains an ongoing problem in direct gene sequencing of cancers. It is important to use the appropriate mutation detection method most appropriate to each circumstance and the available tissue. Here, we report a patient with melanoma of unknown primary with metastases to spleen and bone marrow, who was tested negative for Cobas BRAF V600E mutation, whose cancer progressed on antiprogrammed death 1 (PD1) receptor monoclonal antibody therapy. Subsequent VE1 immunohistochemistry was positive for BRAF V600E mutation, and the tumor responded dramatically to v-Raf murine sarcoma viral oncogene homolog B (BRAF)/Mitogen-activated protein kinase inhibitor combination therapy. This demonstrates how alternative BRAF testing methodology could produce results that can influence treatment choice and the outcome.
HIV Trafficking Between Blood and Semen During Early Untreated HIV Infection
Authors: Chaillon Antoine , Smith Davey M. , Vanpouille Christophe , Lisco Andrea , Jordan Parris , Caballero Gemma , Vargas Milenka , Gianella Sara , Mehta Sanjay R.
Published: August 2016

Background:

Understanding the dynamics of HIV across anatomic compartments is important to design effective eradication strategies. In this study, we evaluated viral trafficking between blood and semen during primary HIV infection in 6 antiretroviral-naive men who have sex with men.

Methods:

Deep sequencing data of HIV env were generated from longitudinal blood plasma, peripheral blood mononuclear cells, and seminal plasma samples. The presence or absence of viral compartmentalization was assessed using tree-based Slatkin–Maddison and distance-based Fst methods. Phylogeographic analyses were performed using a discrete Bayesian asymmetric approach of diffusion with Markov jump count estimation to evaluate the gene flow between blood and semen during primary HIV infection. Levels of DNA from human herpesviruses and selected inflammatory cytokines were also measured on genital secretions collected at baseline to evaluate potential correlates of increased viral migration between anatomic compartments.

Results:

We detected varying degrees of compartmentalization in all 6 individuals evaluated. None of them maintained viral compartmentalization between blood and seminal plasma throughout the analyzed time points. Phylogeographic analyses revealed that the HIV population circulating in blood plasma populated the seminal compartment during the earliest stages of infection. In our limited data set, we found no association between local inflammation or herpesvirus shedding at baseline and viral trafficking between semen and blood.

Conclusions:

The early spread of virus from blood plasma to genital tract and the complex viral interplay between these compartments suggest that viral eradication efforts will require monitoring viral subpopulations in anatomic sites and viral trafficking during the course of infection.
Targeted re-sequencing reveals the genomic signatures of multiple barley domestications
Authors: Pankin Artem , Altmüller Janine , Becker Christian , von Korff Maria
Published: August 2016

Barley (Hordeum vulgareL.) is an established model to study domestication of the Fertile Crescent cereals. Recent molecular data suggested that domesticated barley genomes consist of the ancestral blocks descending from multiple wild barley populations. However, the relationship between the mosaic ancestry patterns and the process of domestication itself remained unclear.

To address this knowledge gap, we identified candidate domestication genes using selection scans based on targeted resequencing of 433 wild and domesticated barley accessions. We conducted phylogenetic, population structure, and ancestry analyses to investigate the origin of the domesticated barley haplotypes separately at the neutral and candidate domestication loci.

We discovered multiple selective sweeps that occurred on all barley chromosomes during domestication in the background of several ancestral wild populations. The ancestry analyses demonstrated that, although the ancestral blocks of the domesticated barley genomes descended from all over the Fertile Crescent, the candidate domestication loci originated specifically in its eastern and western parts.

These findings provided first molecular evidence in favor of multiple barley domestications in the Levantine and Zagros clusters of the origin of agriculture.
Widespread Historical Contingency in Influenza Viruses
Authors: Nshogozabahizi Jean Claude , Dench Jonathan , Aris-Brosou Stéphane
Published: August 2016

In systems biology and genomics, epistasis characterizes the impact that a substitution at a particular location in a genome can have on a substitution at another location. This phenomenon is often implicated in the evolution of drug resistance or to explain why particular ‘disease-causing’ mutations do not have the same outcome in all individuals. Hence, uncovering these mutations and their locations in a genome is a central question in biology. However, epistasis is notoriously difficult to uncover, especially in fast-evolving organisms. Here, we present a novel statistical approach that replies on a model developed in ecology and that we adapt to analyze genetic data in fast-evolving systems such as the influenza A virus. We validate the approach using a two-pronged strategy: extensive simulations demonstrate a low-to-moderate sensitivity with excellent specificity and precision, while analyses of experimentally-validated data recover known interactions, including in a eukaryotic system. We further evaluate the ability of our approach to detect correlated evolution during antigenic shifts or at the emergence of drug resistance. We show that in all cases, correlated evolution is prevalent in influenza A viruses, involving many pairs of sites linked together in chains, a hallmark of historical contingency. Strikingly, interacting sites are separated by large physical distances, which entails either long-range conformational changes or functional tradeoffs, for which we find support with the emergence of drug resistance. Our work paves a new way for the unbiased detection of epistasis in a wide range of organisms by performing whole-genome scans.
Microbial Signatures of Oral Dysbiosis, Periodontitis and Edentulism Revealed by Gene Meter Methodology
Authors: Hunter M. Colby , Pozhitkov Alex E. , Noble Peter A.
Published: August 2016

Conceptual models suggest certain microorganisms (e.g., the red complex) are indicative of a specific disease state (e.g., periodontitis); however, recent studies have questioned the validity of these models. Here, the abundances of 500+ microbial species were determined in 16 patients with clinical signs of one of the following oral conditions: periodontitis, established caries, edentulism, and oral health. Our goal was to determine if the abundances of certain microorganisms reflect dysbiosis or a specific clinical condition that could be used as a signature for dental research. Microbial abundances were determined by the analysis of 138,718 calibrated probes using Gene Meter methodology. Each 16S rRNA gene was targeted by an average of 194 unique probes (n=25 nt). The calibration involved diluting pooled gene target samples, hybridizing each dilution to a DNA microarray, and fitting the probe intensities to adsorption models. The fit of the model to the experimental data was used to assess individual and aggregate probe behavior; good fits (R2>0.90) were retained for back-calculating microbial abundances from patient samples. The abundance of a gene was determined from the median of all calibrated individual probes or from the calibrated abundance of all aggregated probes. With the exception of genes with low abundances (< 2 arbitrary units), the abundances determined by the different calibrations were highly correlated (r ∼1.0). Seventeen genera were classified as signatures of dysbiosis because they had significantly higher abundances in patients with periodontitis and edentulism when contrasted with health. Similarly, 13 genera were classified as signatures of periodontitis, and 14 genera were classified as signatures of edentulism. The signatures could be used, individually or in combination, to assess the clinical status of a patient (e.g., evaluating treatments such as antibiotic therapies). Comparisons of the same patient samples revealed high false negatives (45%) for next-generation-sequencing results and low false positives (7%) for Gene Meter results.
Association ofAKAP6andMIR2113with cognitive performance in a population based sample of older adults
Authors: Andrews Shea J. , Das Debjani , Anstey Kaarin J. , Easteal Simon
Published: August 2016

Genetic factors make a substantial contribution to inter-individual variability in cognitive function. A recent meta-analysis of genome-wide association studies identified two loci,AKAP6andMIR2113that are associated with general cognitive function. Here, we extend this previous research by investigating the association ofMIR2113andAKAP6with baseline and longitudinal nonlinear change across a broad spectrum of cognitive domains in community-based cohort of 1,570 older adults without dementia. Two SNPs,MIR211-rs10457441 andAKAP6-rs17522122 were genotyped in 1,570 non-demented older Australians of European ancestry, who were examined up to 4 times over 12 years. Linear mixed effects models were used to examine the association betweenAKAP6andMIR2113with cognitive performance in episodic memory, working memory, vocabulary, perceptual speed and reaction time at baseline and with linear and quadratic rates of change.AKAP6-rs17522122*T was associated with worse baseline performance in episodic memory, working memory, vocabulary and perceptual speed, but it was not associated with cognitive change in any domain.MIR2113-rs10457441*T was associated with accelerated decline in episodic memory. No other associations with baseline cognitive performance or with linear or quadratic rate or cognitive changes was observed for this SNP. These results confirm the previous finding that,AKAP6is associated with performance across multiple cognitive domains at baseline but not with cognitive decline, whileMIR2113primarily affects the rate at which memory declines over time.
ANU-ADRI and not Genetic Risk score predicts MCI in a cohort of older adults followed for 12 years
Authors: Andrews Shea J. , Eramudugolla Ranmalee , Velez Jorge I. , Cherbuin Nicolas , Easteal Simon , Anstey Kaarin J.
Published: August 2016

INTRODUCTION

We evaluated a risk score comprising lifestyle, medical and demographic factors (ANU-ADRI), and a genetic risk score (GRS) as predictors of Mild Cognitive Impairment (MCI).

METHODS

ANU-ADRI risk scores were computed for the baseline assessment of 2,078 participants from the PATH project. Participants were assessed for clinically diagnosed MCI/Dementia and psychometric test-based MCI (MCI-TB) at 12 years of follow-up. Multi-state models estimated the odds of transitioning from cognitively normal (CN) to MCI/Dementia and MCI-TB over 12 years according to baseline ANU-ADRI and GRS.

RESULTS

Higher ANU-ADRI score predicted transitioning from CN to either MCI/Dementia and MCI-TB (Hazard ratio [HR] = 1.06, 95% CI:1.04-1.09; HR = 1.06, 95% CI: 1.03-1.09), and a reduced likelihood of cognitive recovery from MCITB to CN (HR = 0.69, 95% CI: 0.49-0.98). GRS was not associated with transition to MCI/Dementia, or MCI-TB.

DISCUSSION

The ANU-ADRI may be used for population-level risk assessment and screening.

Research in Context

Systematic Review

The authors reviewed the literature using online databases e.g. (PubMed). We consulted mild cognitive impairment (MCI) and Alzheimer’s disease (AD) research detailing the use of risk factors for predicting progression from MCI and AD; and the appropriate statistical models for modelling transitions between cognitive states. These publications are appropriately cited.

Interpretation

In the general population, the ANU-ADRI comprising lifestyle, medical and demographic factors is predictive of progression from normal cognition to MCI/Dementia whereas a Genetic Risk Score comprising the main Alzheimer’s risk genes is not predictive.

Future Directions

Further evaluation of the ANU-ADRI as a predictor of specific MCI and dementia subtypes is required. The ANU-ADRI may be used to identify individuals indicated for risk reduction intervention and to assist clinical management and cognitive health promotion. Genetic risk scores contribute to understanding dementia etiology but apart from APOE are unlikely to be useful in screening or prevention trials.
Quantifying uncertainty of taxonomic placement in DNA barcoding and metabarcoding
Authors: Somervuo Panu , Yu Douglas , Xu Charles , Ji Yinqiu , Hultman Jenni , Wirta Helena , Ovaskainen Otso
Published: August 2016

A crucial step in the use of DNA markers for biodiversity surveys is the assignment of Linnaean taxonomies (species, genus, etc.) to sequence reads. This allows the use of all the information known based on the taxonomic names. Taxonomic placement of DNA barcoding sequences is inherently probabilistic because DNA sequences contain errors, because there is natural variation among sequences within a species, and because reference databases are incomplete and can have false annotations. However, most existing bioinformatics methods for taxonomic placement either exclude uncertainty, or quantify it using metrics other than probability.

In this paper we evaluate the performance of a recently proposed probabilistic taxonomic placement method PROTAX by applying it to both annotated reference sequence data as well as unknown environmental data. Our four case studies include contrasting taxonomic groups (fungi, bacteria, mammals, and insects), variation in the length and quality of the barcoding sequences (from individually Sanger-sequenced sequences to short Illumina reads), variation in the structures and sizes of the taxonomies (from 800 to 130 000 species), and variation in the completeness of the reference databases (representing 15% to 100% of the species).

Our results demonstrate that PROTAX yields essentially unbiased assessment of probabilities of taxonomic placement, and thus that its quantification of species identification uncertainty is reliable. As expected, the accuracy of taxonomic placement increases with increasing coverage of taxonomic and reference sequence databases, and with increasing ratio of genetic variation among taxonomic levels over within taxonomic levels.

Our results show that reliable species-level identification from environmental samples is still challenging, and thus neglecting identification uncertainty can lead to spurious inference. A key aim for future research is the completion and pruning of taxonomic and reference sequence databases, and making these two types of data compatible.
School autonomy and 21st century learning: the Canadian context
Authors: Newton Paul , da Costa Jose
Published: August 2016

Purpose

The purpose of this paper is to report on the policy and practice contexts for school autonomy and twenty-first century learning in Canadian provinces.

Design/methodology/approach

This paper reports on an analysis of policies in Canadian provinces (particularly the provinces of Alberta and Saskatchewan). The authors review policies related to school autonomy and twenty-first century learning initiatives.

Findings

In this paper, the authors argue that autonomy is a complicated and multi-levelled phenomena with a measure of autonomy devolved from the state to local school divisions, and yet other elements of autonomy devolved to the school and to individual teachers. The link between autonomy and twenty-first century learning are unclear as yet. This paper attempts to establish the policy contexts for school autonomy and twenty-first century learning without making claims about a causal relation between the two.

Originality/value

The originality of this paper lies in its description of autonomy beyond the school level. Autonomy, as a construct, is rarely examined as a dynamic process among multiple layers of the educational system.
The role of emotions and social influences on consumer loyalty towards online travel communities
Authors: Ruiz-Mafe Carla , Tronch Jose , Sanz-Blas Silvia
Published: August 2016

Purpose

The purpose of this paper is to analyse the role of emotions and social influences on loyalty formation towards online travel communities.

Design/methodology/approach

The individual (perceived risk) and social (subjective norm and social presence) antecedents of emotions as well as the impact of emotions on attitude and loyalty towards online travel communities are tested through structural equation modelling techniques. The sample consists of 385 active users of online travel communities in Spain.

Findings

Data analysis shows that perceived privacy and security risk elicit negative emotions such as stress, frustration and fear towards the online travel community. Normative influences (subjective norm) and feeling the presence of other community members (social presence) boost positive emotions towards the online travel community. Interpersonal influences have a positive effect on subjective norm but not external influences. Positive and negative emotions affect preferences towards the online travel community (attitudes) as proposed by social impact theory. Subjective norm and attitude have a direct influence on loyalty towards an online travel community, confirming previous research grounded on theory of reasoned action models.

Originality/value

Despite the crucial impact of consumers’ affective states on loyalty formation, research on social media is mainly focused on the technological nature of consumer information exchanges, neglecting other drivers of consumer behaviour beyond the technology employed. This paper develops a model that integrates the relationships between consumer emotions and their individual (perceived risk) and social (social presence and subjective norm) antecedents and outcome variables (attitude and loyalty). The role of social influences is analysed, assessing the conjoint impact of one-way communication (interpersonal influences and mass media) and Web 2.0 communications (social presence) on positive emotions and loyalty formation towards the online travel community.