bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of major histocompatibility complex class I allele polymorphisms in common marmosets
Authors: Li T. , Xu Y. , Yin S. , Liu B. , Zhu S. , Wang W. , Wang Y. , Liu F. , Allain J.‐P. , Li C.
Published: October 2014

Currently, little information is available for major histocompatibility complex (MHC)‐I that conditions the T‐cell response of marmosets. In this study, 471 clones of MHC‐I cDNA sequences were isolated from 12 marmosets. Twenty full‐length sequences of class I G (Caja‐G) alleles were obtained from these marmosets, 15 of them were novel. Among these 20 Caja‐G alleles, 10 were found in individual animals while the rests were in two to four marmosets, but none was common to all animals. Ten marmosets possessed one to three Caja‐G alleles, and two marmosets carried five or six alleles, which suggested that the Caja‐G locus was duplicated in marmoset's genome. The high polymorphisms of Caja‐G sequences provided important information helpful for understanding the cellular immune response in virus‐infected marmosets.
The Medical Research Council (UK)/Uganda Virus Research Institute Uganda Research Unit on AIDS – ‘25 years of research through partnerships’
Authors: Kaleebu P. , Kamali A. , Seeley J. , Elliott A. M. , Katongole‐Mbidde E.
Published: October 2014

For the past 25 years, the Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS has conducted research on HIV‐1, coinfections and, more recently, on non‐communicable diseases. Working with various partners, the research findings of the Unit have contributed to the understanding and control of the HIV epidemic both in Uganda and globally, and informed the future development of biomedical HIV interventions, health policy and practice. In this report, as we celebrate our silver jubilee, we describe some of these achievements and the Unit's multidisciplinary approach to research. We also discuss the future direction of the Unit; an exemplar of a partnership that has been largely funded from the north but led in the south.
Extracorporeal photopheresis for graft‐versus‐host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome—results from a large single‐center study
Authors: Berger Massimo , Albiani Roberto , Sini Bruno , Fagioli Franca
Published: October 2014

Background

Extracorporeal photopheresis (ECP) has been shown as active therapy for graft‐versus‐host disease (GVHD).

Study Design and Methods

The aim was to ascertain the role of ECP in 71 patients with steroid‐refractory or ‐dependent acute and chronic GVHD (aGVHD and cGVHD) with special focus on hematologic variables and GVHD staging classification. A total of 34 patients were treated for aGVHD and 37 for cGVHD.

Results

The overall response rate (ORR) for aGVHD was 65% and the complete aGVHD‐free survival was 50% (95% confidence interval [CI], 36%‐70%). The ORR for cGVHD response was 81% while the complete cGVHD‐free survival was 50% (95% CI, 34%‐73%). The aGVHD‐free survival was associated with aGVHD grading (Grade II 81%, Grade III 33%, and Grade IV 0%, p ≤ 0.00) and the absence of visceral involvement (77% vs. 33%, p = 0.03). The cGVHD‐free survival was associated with the female sex (67% vs. 25%, p = 0.01) and with the limited form according to the Seattle classification (67% vs. 20%, p = 0.003). No role for hematologic values or apheresis cell count was found, except for the cGVHD ORR (p = 0.037). Transplant‐related mortality and overall survival were associated with ECP response 0% versus 54% (p = 0.0001) and 77% versus 45% (p = 0.03) for aGVHD patients and 7% versus 14% (p = 0.02) and 73% versus 20% (p = 0.0003) for cGVHD patients, respectively.

Conclusions

While confirming a higher probability of GVHD responses for early GVHD, our study shows no role of hematologic values or apheresis cell count on GVHD response.
Physical Activity, Life Events Stress, Cortisol, and DHEA: Preliminary Findings That Physical Activity May Buffer Against the Negative Effects of Stress
Authors: Heaney Jennifer L.J. , Carroll Douglas , Phillips Anna C.
Published: October 2014

The present study examined the relationship between habitual physical activity, life events stress, the diurnal rhythms of cortisol and DHEA, and the cortisol:dehydroepiandrosterone (DHEA) ratio in older adults. Thirty-six participants aged ≥ 65 reported their habitual physical activity, and indicated if a particular event happened to them in the past year (stress incidence) and how stressful they perceived the event to be (stress severity). Older adults with higher stress severity demonstrated a significantly higher cortisol:DHEA ratio. Individuals with higher stress incidence scores and who did not participate in aerobic exercise had a significantly higher cortisol:DHEA ratio and flatter DHEA diurnal rhythm compared with those who regularly participated in aerobic exercise. In conclusion, life events stress may have a negative impact on the cortisol:DHEA ratio in older adults. Under conditions of high stress exposure, exercise may protect older adults from an increased cortisol:DHEA ratio and flatter DHEA diurnal rhythm.
Dual-task Performance in Young and Older Adults: Speed-Accuracy Tradeoffs in Choice Responding While Treadmill Walking
Authors: Tomporowski Phillip D. , Audiffren Michel
Published: October 2014

Thirty-one young (mean age = 20.8 years) and 30 older (mean age = 71.5 years) men and women categorized as physically active (n = 30) or inactive (n = 31) performed an executive processing task while standing, treadmill walking at a preferred pace, and treadmill walking at a faster pace. Dual-task interference was predicted to negatively impact older adults’ cognitive flexibility as measured by an auditory switch task more than younger adults; further, participants’ level of physical activity was predicted to mitigate the relation. For older adults, treadmill walking was accompanied by significantly more rapid response times and reductions in local- and mixed-switch costs. A speed-accuracy tradeoff was observed in which response errors increased linearly as walking speed increased, suggesting that locomotion under dual-task conditions degrades the quality of older adults’ cognitive flexibility. Participants’ level of physical activity did not influence cognitive test performance.
Kinesiophobia After Anterior Cruciate Ligament Reconstruction in Physically Active Individuals
Authors: Cozzi Arika L. , Dunn Kristina L. , Harding Josie L. , McLeod Tamara C. Valovich , Bacon Cailee E. Welch
Published: October 2014

Clinical Scenario:

There are approximately 200,000 anterior cruciate ligament (ACL) tears reported annually in the United States. Patients who undergo ACL reconstruction followed by an aggressive rehabilitation protocol can often structurally and functionally progress to a preinjury level. Despite physical improvements with ACL-rehabilitation protocols, however, there are still a substantial number of individuals who do not return to preinjury level, particularly physically active individuals, of whom only 63% return to their full potential preinjury level. This may be due to continued pain, swelling, stiffness, and weakness in the knee. In addition, research concerning the topic of kinesiophobia (ie, fear of reinjury), which may prevent individuals from returning to their activities, has increased over the past several years. Kinesiophobia is defined as the irrational or debilitating movement of physical activity resulting in the feeling of vulnerability to painful injury or reinjury. Kinesiophobia may have a significant impact on physically active individuals, considering the proportion of patients who do not return to their sport. However, it is unknown whether kinesiophobia is associated with patients’ perceived physical-impairment levels after ACL reconstruction.

Focused Clinical Question:

Is kinesiophobia associated with self-perceived levels of knee function after ACL reconstruction?
The Impact of Adding an Eccentric-Exercise Component to the Rehabilitation Program of Patients With Shoulder Impingement: A Critically Appraised Topic
Authors: Valier Alison R. , Averett Ryan S. , Anderson Barton E. , Bacon Cailee E. Welch
Published: October 2014

Clinical Scenario:

Shoulder pain is a common musculoskeletal complaint and is often associated with shoulder impingement. The annual incidence of shoulder pain is estimated to be 7% of all injuries, and is the third-most-common type of musculoskeletal pain. Initial treatment of shoulder impingement follows a conservative plan and emphasizes rehabilitation programs as opposed to surgical interventions. Shoulder rehabilitation programs commonly focus on strengthening the muscles of the shoulder complex and, more specifically, the rotator cuff. The rotator cuff is a primary dynamic stabilizer of the glenohumeral joint, using both eccentric and concentric contractions. The posterior rotator cuff, including teres minor and infraspinatus, works eccentrically to decelerate the arm during overhead throwing. Exercises to strengthen the rotator cuff and the surrounding dynamic stabilizers of the shoulder girdle vary and include activities such as internal and external rotation, full-can lifts, and rhythmic stabilizations. Traditionally, shoulder rehabilitation programs have focused on isotonic concentric contractions. Common strengthening exercises typically involve movements that result in shortening the muscle length while simultaneously loading the muscles. However, recent attention has been given to eccentric exercises, which involve lengthening of the muscle during loading, for the treatment of a variety of different tendinopathies including those of the Achilles and patellar tendons. The eccentric, or lengthening, motion is thought to be beneficial for people who are involved in activities that place eccentric stress on their shoulder, such as overhead throwers. Based on studies related to the Achilles tendon, eccentric exercise may positively influence the tendon structure by increasing collagen production and decreasing neovascularization. The changes that occur as a result of eccentric exercises may improve function, strength, and performance and decrease pain more than concentric programs, producing better patient outcomes. Although eccentric strength training has been shown to provide strength gains, there are no clear guidelines as to the inclusion of this form of exercise training in shoulder rehabilitation programs for the purposes of improving function and decreasing pain.

Focused Clinical Question:

Does adding an eccentric-exercise component to the rehabilitation program of patients with shoulder impingement improve shoulder function and/or decrease pain?
Economic and social implications of aging societies
Authors: Harper Sarah
Published: October 2014

The challenge of global population aging has been brought into sharper focus by the financial crisis of 2008. In particular, growing national debt has drawn government attention to two apparently conflicting priorities: the need to sustain public spending on pensions and health care versus the need to reduce budget deficits. A number of countries are consequently reconsidering their pension and health care provisions, which account for up to 40% of all government spending in advanced economies. Yet population aging is a global phenomenon that will continue to affect all regions of the world. By 2050 there will be the same number of old as young in the world, with 2 billion people aged 60 or over and another 2 billion under age 15, each group accounting for 21% of the world’s population.
Plasticity of the aging brain: New directions in cognitive neuroscience
Authors: Gutchess Angela
Published: October 2014

Cognitive neuroscience has revealed aging of the human brain to be rich in reorganization and change. Neuroimaging results have recast our framework around cognitive aging from one of decline to one emphasizing plasticity. Current methods use neurostimulation approaches to manipulate brain function, providing a direct test of the ways that the brain differently contributes to task performance for younger and older adults. Emerging research into emotional, social, and motivational domains provides some evidence for preservation with age, suggesting potential avenues of plasticity, alongside additional evidence for reorganization. Thus, we begin to see that aging of the brain, amidst interrelated behavioral and biological changes, is as complex and idiosyncratic as the brain itself, qualitatively changing over the life span.
The specificity of vesicle traffic to the Golgi is encoded in the golgin coiled-coil proteins
Authors: Wong Mie , Munro Sean
Published: October 2014

You've got to pick a Golgi tether or two

The inside of the cell contains a large variety of different membrane transport vesicles, each of which needs to find and fuse with its correct target destination. The detailed mechanism specifying which vesicle can fuse with which target membrane has been the subject of an enormous amount of research. An additional layer of specificity in intracellular membrane trafficking across the Golgi complex is thought to involve particular membrane “tethers.” However, the importance of these tethers has been unclear. Wong and Munro used a clever trick to reveal how specific tethers can indeed ensure correct vesicle destination. Tether proteins experimentally expressed on mitochondria hijacked different transport vesicles and diverted them from their normal destination to the mitochondria.

Science
, this issue
10.1126/science.1256898
Recent introduction of a chytrid fungus endangers Western Palearctic salamanders
Authors: Martel A. , Blooi M. , Adriaensen C. , Van Rooij P. , Beukema W. , Fisher M. C. , Farrer R. A. , Schmidt B. R. , Tobler U. , Goka K. , Lips K. R. , Muletz C. , Zamudio K. R. , Bosch J. , Lötters S. , Wombwell E. , Garner T. W. J. , Cunningham A. A. , Spitzen-van der Sluijs A. , Salvidio S. , Ducatelle R. , Nishikawa K. , Nguyen T. T. , Kolby J. E. , Van Bocxlaer I. , Bossuyt F. , Pasmans F.
Published: October 2014

A new, yet old, threat to amphibians

Globally, populations of amphibians have been severely affected by a disease caused by the fungus
Batrachochytrium dendrobatidis
. Recently, some European salamander populations were decimated by the emergence of a new, related chytrid fungus,
B. salamandrivorans
. Martel
et al.
screened amphibians across continents. This newly emerging threat seems to have originated in Asia and traveled to Europe with salamanders transported as part of the pet trade. Asian salamanders have evolved resistance to the pathogen, but salamanders from other parts of the world are highly susceptible.

Science
, this issue p.
630
A Spaetzle-like role for nerve growth factor β in vertebrate immunity to
Staphylococcus aureus
Authors: Hepburn Lucy , Prajsnar Tomasz K. , Klapholz Catherine , Moreno Pablo , Loynes Catherine A. , Ogryzko Nikolay V. , Brown Karen , Schiebler Mark , Hegyi Krisztina , Antrobus Robin , Hammond Katherine L. , Connolly John , Ochoa Bernardo , Bryant Clare , Otto Michael , Surewaard Bas , Seneviratne Suranjith L. , Grogono Dorothy M. , Cachat Julien , Ny Tor , Kaser Arthur , Török M. Estée , Peacock Sharon J. , Holden Matthew , Blundell Tom , Wang Lihui , Ligoxygakis Petros , Minichiello Liliana , Woods C. Geoff , Foster Simon J. , Renshaw Stephen A. , Floto R. Andres
Published: October 2014

Overcoming staph infections is hardwired

Several evolutionarily conserved components of antistaphylococcal immunity have been identified, using
Drosophila
as a model organism. However, no vertebrate ortholog has been identified for the Toll ligand Spaetzle, which plays a key role in controlling gram-positive infection in flies. Hepburn
et al.
have now identified NGF-β as a functional equivalent to Spaetzle in vertebrates. NGF-β acts as a paracrine “alarmin” orchestrating macrophage and neutrophil responses to
S. aureus
infection. People with deleterious mutations in genes encoding NGF-β or its high-affinity receptor TRKA are predisposed to recurrent and severe staph infections.
S. aureus
proteins selectively trigger macrophage production of NGF-β, which enhances uptake and superoxide-dependent killing of
S. aureus
, stimulates proinflammatory cytokine production, and promotes neutrophil recruitment. Moreover, TrkA silencing in vivo increases susceptibility to
S. aureus
. Thus, the NGF-β–TRKA pathway is a critical, evolutionarily conserved component of vertebrate immunity to
S. aureus
infection.

Science
, this issue p.
641
Dendrite morphogenesis depends on relative levels of NT-3/TrkC signaling
Authors: Joo William , Hippenmeyer Simon , Luo Liqun
Published: October 2014

Making dendritic arbors during development

Developing axons are known to compete for limiting, target-derived neurotrophins for survival and growth in the peripheral nervous system. Joo
et al.
suggest that an additional, reciprocal model is involved in the development of dendritic arbors of cerebellar Purkinje cells. Working in mice, the authors show that growing dendrites of Purkinje neurons require presynaptic partner-derived neurotrophins during competitive dendritic growth in the central nervous system.

Science
, this issue p.
626
The atoms of neural computation
Authors: Marcus Gary , Marblestone Adam , Dean Thomas
Published: October 2014

Does the brain depend on a set of elementary, reusable computations?
Stepping on the gas
Authors: Service Robert F.
Published: October 2014

What would it take to put you behind the wheel of a methane-powered vehicle? Researchers are determined to find out.
A Eukaryotic Expression Plasmid Carrying Chicken Interleukin-18 Enhances the Response to Newcastle Disease Virus Vaccine
Authors: Wang Chen , Li Xiaokang , Zhang Chunjie , Wu Tingcai , Li Yinju , Cheng Xiangchao
Published: October 2014

Interleukin-18 (IL-18) is an important cytokine involved in innate and acquired immunity. In this study, we cloned the full-length chicken IL-18 (ChIL-18) gene from specific-pathogen-free (SPF) chicken embryo spleen cells and provided evidence that the ChIL-18 gene in a recombinant plasmid was successfully expressed in chicken DT40 cells. ChIL-18 significantly enhanced gamma interferon (IFN-γ) mRNA expression in chicken splenocytes, which increased IFN-γ-induced nitric oxide (NO) synthesis by macrophages. The potential genetic adjuvant activity of the ChIL-18 plasmid was examined in chickens by coinjecting ChIL-18 plasmid and inactivated Newcastle disease virus (NDV) vaccine. ChIL-18 markedly elevated serum hemagglutination inhibition (HI) titers and anti-hemagglutinin-neuraminidase (anti-HN)-specific antibody levels, induced the secretion of both Th1- (IFN-γ) and Th2- (interleukin-4) type cytokines, promoted the proliferation of T and B lymphocytes, and increased the populations of CD3+T cells and their subsets, CD3+CD4+and CD3+CD8+T cells. Furthermore, a virus challenge revealed that ChIL-18 contributed to protection against Newcastle disease virus challenge. Taken together, our data indicate that the coadministration of ChIL-18 plasmid and NDV vaccine induces a strong immune response at both the humoral and cellular levels and that ChIL-18 is a novel immunoadjuvant suitable for NDV vaccination.
Harmonization of Bordetella pertussis Real-Time PCR Diagnostics in the United States in 2012
Authors: Williams Margaret M. , Taylor Thomas H. , Warshauer David M. , Martin Monte D. , Valley Ann M. , Tondella M. Lucia
Published: October 2014

Real-time PCR (rt-PCR) is an important diagnostic tool for the identification of
Bordetella pertussis
,
Bordetella holmesii
, and
Bordetella parapertussis
. Most U.S. public health laboratories (USPHLs) target IS
481
, present in 218 to 238 copies in the
B. pertussis
genome and 32 to 65 copies in
B. holmesii
. The CDC developed a multitarget PCR assay to differentiate
B. pertussis
,
B. holmesii
, and
B. parapertussis
and provided protocols and training to 19 USPHLs. The 2012 performance exercise (PE) assessed the capability of USPHLs to detect these three
Bordetella
species in clinical samples. Laboratories were recruited by the Wisconsin State Proficiency Testing program through the Association of Public Health Laboratories, in partnership with the CDC. Spring and fall PE panels contained 12 samples each of viable
Bordetella
and non-
Bordetella
species in saline. Fifty and 53 USPHLs participated in the spring and fall PEs, respectively, using a variety of nucleic acid extraction methods, PCR platforms, and assays. Ninety-six percent and 94% of laboratories targeted IS
481
in spring and fall, respectively, in either singleplex or multiplex assays. In spring and fall, respectively, 72% and 79% of USPHLs differentiated
B. pertussis
and
B. holmesii
and 68% and 72% identified
B. parapertussis
. IS
481
cycle threshold (

C
T

) values for
B. pertussis
samples had coefficients of variation (CV) ranging from 10% to 28%. Of the USPHLs that differentiated
B. pertussis
and
B. holmesii
, sensitivity was 96% and specificity was 95% for the combined panels. The 2012 PE demonstrated increased harmonization of rt-PCR
Bordetella
diagnostic protocols in USPHLs compared to that of the previous survey.
Rapid Identification of Major Escherichia coli Sequence Types Causing Urinary Tract and Bloodstream Infections
Authors: Doumith M. , Day M. , Ciesielczuk H. , Hope R. , Underwood A. , Reynolds R. , Wain J. , Livermore D. M. , Woodford N.
Published: October 2014

Escherichia coli
sequence types (STs) 69, 73, 95, and 131 are collectively responsible for a large proportion of
E. coli
urinary tract and bloodstream infections, and they differ markedly in their antibiotic susceptibilities. Here, we describe a novel PCR method to rapidly detect and distinguish these lineages. Three hundred eighteen published
E. coli
genomes were compared in order to identify signature sequences unique to each of the four major STs. The specificities of these sequences were assessed
in silico
by seeking them in an additional 98 genomes. A PCR assay was designed to amplify size-distinguishable fragments unique to the four lineages and was validated using 515
E. coli
isolates of known STs. Genome comparisons identified 22 regions ranging in size from 335 bp to 26.5 kb that are unique to one or more of the four predominant
E. coli
STs, with two to 10 specific regions per ST. These regions predominantly harbor genes encoding hypothetical proteins and are within or adjacent to prophage sequences. Most (13/22) were highly conserved (>96.5% identity) in the genomes of their respective ST. The new assay correctly identified all 142 representatives of the four major STs in the validation set (
n
= 515), with only two ST12 isolates misidentified as ST95. Compared with MLST, the assay has 100% sensitivity and 99.5% specificity. The rapid identification of major extraintestinal
E. coli
STs will benefit future epidemiological studies and could be developed to tailor antibiotic therapy to the different susceptibilities of these dominant lineages.
Interaction of Infectious Spleen and Kidney Necrosis Virus ORF119L with PINCH Leads to Dominant-Negative Inhibition of Integrin-Linked Kinase and Cardiovascular Defects in Zebrafish
Authors: Yuan Ji-Min , He Bai-Liang , Yang Lu-Yun , Guo Chang-Jun , Weng Shao-Ping , Li Shengwen Calvin , He Jian-Guo
Published: October 2014

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the
Megalocytivirus
genus,
Iridoviridae
family, causing a severe systemic disease with high mortality in mandarin fish (
Siniperca chuatsi
) in China and Southeast Asia. At present, the pathogenesis of ISKNV infection is still not fully understood. Based on a genome-wide bioinformatics analysis of ISKNV-encoded proteins, we found that ISKNV open reading frame 119L (ORF119L) is predicted to encode a three-ankyrin-repeat (3ANK)-domain-containing protein, which shows high similarity to the dominant negative form of integrin-linked kinase (ILK); i.e., viral ORF119L lacks the ILK kinase domain. Thus, we speculated that viral ORF119L might affect the host ILK complex. Here, we demonstrated that viral ORF119L directly interacts with particularly interesting Cys-His-rich protein (PINCH) and affects the host ILK-PINCH interaction
in vitro
in fathead minnow (FHM) cells.
In vivo
ORF119L overexpression in zebrafish (
Danio rerio
) embryos resulted in myocardial dysfunctions with disintegration of the sarcomeric Z disk. Importantly, ORF119L overexpression in zebrafish highly resembles the phenotype of endogenous ILK inhibition, either by overexpressing a dominant negative form of ILK or by injecting an ILK antisense morpholino oligonucleotide. Intriguingly, ISKNV-infected mandarin fish develop disorganized sarcomeric Z disks in cardiomyocytes. Furthermore, phosphorylation of AKT, a downstream effector of ILK, was remarkably decreased in ORF119L-overexpressing zebrafish embryos. With these results, we show that ISKNV ORF119L acts as a domain-negative inhibitor of the host ILK, providing a novel mechanism for the megalocytivirus pathogenesis.

IMPORTANCE
Our work is the first to show the role of a dominant negative inhibitor of the host ILK from ISKNV (an iridovirus). Mechanistically, the viral ORF119L directly binds to the host PINCH, attenuates the host PINCH-ILK interaction, and thus impairs ILK signaling. Intriguingly, ORF119L-overexpressing zebrafish embryos and ISKNV-infected mandarin fish develop similar disordered sarcomeric Z disks in cardiomyocytes. These findings provide a novel mechanism for megalocytivirus pathogenesis.
The Megavirus Chilensis Cu,Zn-Superoxide Dismutase: the First Viral Structure of a Typical Cellular Copper Chaperone-Independent Hyperstable Dimeric Enzyme
Authors: Lartigue Audrey , Burlat Bénédicte , Coutard Bruno , Chaspoul Florence , Claverie Jean-Michel , Abergel Chantal
Published: October 2014

Giant viruses able to replicate in
Acanthamoeba castellanii
penetrate their host through phagocytosis. After capsid opening, a fusion between the internal membranes of the virion and the phagocytic vacuole triggers the transfer in the cytoplasm of the viral DNA together with the DNA repair enzymes and the transcription machinery present in the particles. In addition, the proteome analysis of purified mimivirus virions revealed the presence of many enzymes meant to resist oxidative stress and conserved in the
Mimiviridae
. Megavirus chilensis encodes a predicted copper, zinc superoxide dismutase (Cu,Zn-SOD), an enzyme known to detoxify reactive oxygen species released in the course of host defense reactions. While it was thought that the metal ions are required for the formation of the active-site lid and dimer stabilization, megavirus chilensis SOD forms a very stable metal-free dimer. We used electron paramagnetic resonance (EPR) analysis and activity measurements to show that the supplementation of the bacterial culture with copper and zinc during the recombinant expression of Mg277 is sufficient to restore a fully active holoenzyme. These results demonstrate that the viral enzyme's activation is independent of a chaperone both for disulfide bridge formation and for copper incorporation and suggest that its assembly may not be as regulated as that of its cellular counterparts. A SOD protein is encoded by a variety of DNA viruses but is absent from mimivirus. As in poxviruses, the enzyme might be dispensable when the virus infects
Acanthamoeba
cells but may allow megavirus chilensis to infect a broad range of eukaryotic hosts.

IMPORTANCE
Mimiviridae
are giant viruses encoding more than 1,000 proteins. The virion particles are loaded with proteins used by the virus to resist the vacuole's oxidative stress. The megavirus chilensis virion contains a predicted copper, zinc superoxide dismutase (Cu,Zn-SOD). The corresponding gene is present in some megavirus chilensis relatives but is absent from mimivirus. This first crystallographic structure of a viral Cu,Zn-SOD highlights the features that it has in common with and its differences from cellular SODs. It corresponds to a very stable dimer of the apo form of the enzyme. We demonstrate that upon supplementation of the growth medium with Cu and Zn, the recombinant protein is fully active, suggesting that the virus's SOD activation is independent of a copper chaperone for SOD generally used by eukaryotic SODs.
Hallucinations and illusions in migraine in children and the Alice in Wonderland Syndrome
Authors: Smith R A , Wright B , Bennett Sophie
Published: October 2014

Design

A prospective observational study over 1 year.

Setting

A District General Hospital, and Child and Adolescent Mental Health Department.

Patients

Children aged 8–18 years living in the catchment area of a district hospital service with any type of unexplained hallucinations or illusions associated with or without an established diagnosis of migraine.

Results

The study identified nine children with a combination of migraine and a variety of hallucinations and illusions, including illusions of size, time, colour, body shape, movement and visual and auditory hallucination. An average of 10 symptoms (range 7–15) were reported.

Interventions

None.

Main outcome measure

None.

Conclusions

It is important to recognise these symptoms to enable appropriate history taking and diagnosis. These symptoms are common and currently seem to go unrecognised and may pose diagnostic difficulties if onset is before typical migraine headaches occur.
General response functions to silvicultural treatments in loblolly pine plantations
Authors: Gyawali Nabin , Burkhart Harold E.
Published: October 2014

Forest growth and yield models that incorporate common silvicultural practices are essential for practicing intensive forest management. We present models for growth response to a wide range of silvicultural treatments in loblolly pine (Pinus taeda L.) plantations. Baseline models for basal area, dominant height, and survival were fitted using data from across the southeastern United States. Growth models for treated stands were developed by multiplying baseline models with modifier response functions accounting for effects of thinning, fertilization, and control of competing vegetation. Response to early control of competing vegetation was incorporated into baseline models through multiplier factors that were calculated from growth differences between treated and untreated stands. The thinning response function included duration and rate parameters and was sensitive to stand age at the time of thinning, time since thinning, and intensity of thinning. Fertilization response functions were based on the Weibull distribution; the magnitude of responses varies with time since application of fertilizers, type of fertilizer, and rate of application. A difference function, derived from a differential equation with age, initial stand density, and site index as predictors, served as the baseline survival model. The survival model was adjusted for thinning treatment by including an additional independent variable that represents thinning intensity. The resulting models were able to predict growth response when single, as well as multiple, treatments were applied.
The effect of snow on space use of an alpine ungulate: recently fallen snow tells more than cumulative snow depth
Authors: Richard Julien H. , Wilmshurst John , Côté Steeve D.
Published: October 2014

Snow is one of the most limiting environmental factors for large wildlife of temperate and arctic zones during winter. Snow depth may limit space use, increase energy expenditure related to movement, limit resource availability, and ultimately affect individual survival. Most of the studies on the effect of snow on animal space use have used cumulative snow depth. The amount of recently fallen snow, however, could be more relevant for wildlife, especially in alpine and northern environments, where wind shifts and hardens the snow cover constantly. From 2011 to 2013, we studied space use of mountain goats (Oreamnos americanus (Blainville, 1816)) within Jasper National Park in Alberta, Canada. During winter, daily and weekly movements decreased with the amount of recently fallen snow, but not with cumulative snow depth. These results indicate that recently fallen snow should be included in wildlife space-use studies during winter. Limited movement and range size of mountain goats also highlight the energy-saving tactic used in winter by this species.
Acquisition of the field measurement data relating to lane change actions
Authors: Tanimoto Jun , Fujiki Takuya , Kukida Shinji , Ikegaya Naoki , Hagishima Aya
Published: October 2014

As a data set for validation of microscopic simulation models, we obtained the fundamental diagram (flux versus density relation), and the relations of velocity versus density, lane usage ratio versus density and lane-changing frequency versus density derived from a single field measurement campaign held at a Japanese urban expressway. The results were drawn from image analysis of video camera data obtained at the site.
Genetic Algorithm for a Two-Agent Scheduling Problem with Truncated Learning Consideration
Authors: Wu Wen-Hsiang , Yin Yunqiang , Cheng Shuenn-Ren , Hsu Peng-Hsiang , Wu Chin-Chia
Published: October 2014

Scheduling with learning effects has received lots of research attention lately. However, the multiple-agent setting with learning consideration is relatively limited. On the other hand, the actual processing time of a job under an uncontrolled learning effect will drop to zero precipitously as the number of the jobs already processed increases. This is rather absurd in reality. Based on these observations, this paper considers a single-machine two-agent scheduling problem in which the actual processing time of a job depends not only on the job's scheduled position, but also on a control parameter. The objective is to minimize the total weighted completion time of jobs from the first agent with the restriction that no tardy job is allowed for the second agent. A branch-and-bound algorithm incorporated with several dominance properties and lower bounds is proposed to derive the optimal solution for the problem. In addition, genetic algorithms (GAs) are also provided to obtain the near-optimal solution. Finally, a computational experiment is conducted to evaluate the performance of the proposed algorithms.
Geochemistry of a large impoundment, Part I: solute sources, mixing dynamics, and seasonal anoxia
Authors: Sun Li , Leybourne Matthew I. , Rissmann Clinton , Olariu Cornel , Sader Jamil ,   Lake Study Group
Published: October 2014

Lake Texoma is a large impoundment on the border of Texas and Oklahoma, formed from the confluence of two river systems with different salinities, the Red River (total dissolved salt, TDS, of 2700–11 900 mg/l, average of 4862 mg/l) and the Washita River (TDS of 420–915 mg/l, average of 701.4 mg/l). Systematic analyses for major and trace elements were conducted of water samples collected spatially and with depth in the lake in different seasons. Overall, Lake Texoma waters are characterized by Na-Ca-Cl-SO
4
-type waters with spatial distribution shifting from Na-Cl type to Ca-SO
4
type from the Red River arm to the main lake and to the Washita River arm. In addition, vertical and seasonal variations in major and trace elements concentrations indicate major elements in the lake are mainly controlled by different bedrock weathering from the two river systems. Trace elements that exhibit different distribution patterns to the major species are associated with variable sources such as river inflow, summer stratification effects, biological effects and anthropogenic activities. In Lake Texoma, differential inflow volumes and summer stratification are principal factors controlling the variation and geochemistry of lake waters and mixing dynamics.

Supplementary material:

Summary of major and trace element chemistry in the five zones of Lake Texoma for summer, fall and spring seasons (2003–2004) is available at
http://www.geolsoc.org.uk/SUP18771
Glucose and palmitate uncouple AMPK from autophagy in human aortic endothelial cells
Authors: Weikel Karen A. , Cacicedo José M. , Ruderman Neil B. , Ido Yasuo
Published: October 2014

Dysregulated autophagy and decreased AMP-activated protein kinase (AMPK) activity are each associated with atherogenesis. Atherogenesis is preceded by high circulating concentrations of glucose and fatty acids, yet the mechanism by which these nutrients regulate autophagy in human aortic endothelial cells (HAECs) is not known. Furthermore, whereas AMPK is recognized as an activator of autophagy in cells with few nutrients, its effects on autophagy in nutrient-rich HAECs has not been investigated. We maintained and passaged primary HAECs in media containing 25 mM glucose and incubated them subsequently with 0.4 mM palmitate. These conditions impaired basal autophagy and rendered HAECs more susceptible to apoptosis and adhesion of monocytes, outcomes attenuated by the autophagy activator rapamycin. Glucose and palmitate diminished AMPK activity and phosphorylation of the uncoordinated-51-like kinase 1 (ULK1) at Ser555, an autophagy-activating site targeted by AMPK. 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR)-mediated activation of AMPK phosphorylated acetyl-CoA carboxylase, but treatment with AICAR or other AMPK activators (A769662, phenformin) did not restore ULK1 phosphorylation or autophagosome formation. To determine whether palmitate-induced ceramide accumulation contributed to this finding, we overexpressed a ceramide-metabolizing enzyme, acid ceramidase. The increase in acid ceramidase expression ameliorated the effects of excess nutrients on ULK1 phosphorylation, without altering the effects of the AMPK activators. Thus, unlike low nutrient conditions, AMPK becomes uncoupled from autophagy in HAECs in a nutrient-rich environment, such as that found in patients with increased cardiovascular risk. These findings suggest that combinations of AMPK-independent and AMPK-dependent therapies may be more effective alternatives than either therapy alone for treating nutrient-induced cellular dysfunction.
Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines
Authors: Urushima Hayato , Nishimura Junichi , Mizushima Tsunekazu , Hayashi Noriyuki , Maeda Kazuhisa , Ito Toshinori
Published: October 2014

Anti-inflammatory effects have been reported in Perilla frutescens leaf extract (PE), which is a plant of the genus belonging to the Lamiaceae family. We examined the effect of PE on dextran sulfate sodium (DSS)-induced colitis. Preliminarily, PE was safely administered for 7 wk without any adverse effects. In the preventive protocol, mice were fed 1.5% DSS solution dissolved in distilled water (control group) or 0.54% PE solution (PE group) ad libitum for 7 days. In the therapeutic protocol, distilled water or 0.54% PE solution was given for 10 days just after administration of 1.5% DSS for 5 days. PE intake significantly improved body weight loss. The serum cytokine profile demonstrated that TNF-α, IL-17A, and IL-10 were significantly lower in the PE group than in the control group. In the therapeutic protocol, mice in the PE group showed significantly higher body weight and lower histological colitis scores compared with mice in the control group on day 15. The serum cytokine profile demonstrated that TGF-β was significantly higher in the PE group than in the control group. In distal colon mRNA expression, TNF-α, and IL-17A were significantly downregulated. In vitro analyses of biologically active ingredients, such as luteolin, apigenin, and rosmarinic acid, in PE were performed. Luteolin suppressed production of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-17A. Apigenin also suppressed secretion of IL-17A and increased the anti-inflammatory cytokine IL-10. Rosmarinic acid increased the regulatory T cell population. We conclude that PE might be useful in treatment and prevention of DSS-induced colitis.
Involvement of neutral sphingomyelinase in the angiotensin II signaling pathway
Authors: Bautista-Pérez Rocio , del Valle-Mondragón Leonardo , Cano-Martínez Agustina , Pérez-Méndez Oscar , Escalante Bruno , Franco Martha
Published: October 2014

The possibility that angiotensin II (ANG II) exerts its effects through the activation of neutral sphingomyelinase (nSMase) has not been tested in kidneys. The results of the present study provide evidence for the activity and expression of nSMase in rat kidneys. In isolated perfused rat kidney, ANG II-induced renal vasoconstriction was inhibited by GW4869, an inhibitor of nSMase. We used nSMase for investigating the signal transduction downstream of ceramide. nSMase constricted the renal vasculature. An inhibitor of ceramidase (CDase), N-oleoylethanolamine (OEA), enhanced either ANG II- or nSMase-induced renal vasoconstriction. To demonstrate the interaction between the nSMase and cytosolic phospholipase A2(cPLA2) signal transduction pathways, we evaluated the response to nSMase in the presence and absence of inhibitors of arachidonic acid (AA) metabolism: arachidonyl trifluoromethyl ketone (AACOCF3), an inhibitor of cPLA2; 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of all AA pathways; indomethacin, an inhibitor of cyclooxygenase (COX); furegrelate, a thromboxane A2(TxA2)-synthase inhibitor; and SQ29548 , a TxA2-receptor antagonist. In these experiments, the nSMase-induced renal vasoconstriction decreased. ANG II or nSMase was associated with an increase in the release of thromboxane B2(TxB2) in the renal perfusate of isolated perfused rat kidney. In addition, the coexpression of the ceramide with cPLA2, was found in the smooth muscle layer of intrarenal vessels. Our results suggest that ANG II stimulates ceramide formation via the activation of nSMase; thus ceramide may indirectly regulate vasoactive processes that modulate the activity of cPLA2and the release of TxA2.
Frequency response properties of primary afferent neurons in the posterior lateral line system of larval zebrafish
Authors: Levi Rafael , Akanyeti Otar , Ballo Aleksander , Liao James C.
Published: October 2014

The ability of fishes to detect water flow with the neuromasts of their lateral line system depends on the physiology of afferent neurons as well as the hydrodynamic environment. Using larval zebrafish ( Danio rerio), we measured the basic response properties of primary afferent neurons to mechanical deflections of individual superficial neuromasts. We used two types of stimulation protocols. First, we used sine wave stimulation to characterize the response properties of the afferent neurons. The average frequency-response curve was flat across stimulation frequencies between 0 and 100 Hz, matching the filtering properties of a displacement detector. Spike rate increased asymptotically with frequency, and phase locking was maximal between 10 and 60 Hz. Second, we used pulse train stimulation to analyze the maximum spike rate capabilities. We found that afferent neurons could generate up to 80 spikes/s and could follow a pulse train stimulation rate of up to 40 pulses/s in a reliable and precise manner. Both sine wave and pulse stimulation protocols indicate that an afferent neuron can maintain their evoked activity for longer durations at low stimulation frequencies than at high frequencies. We found one type of afferent neuron based on spontaneous activity patterns and discovered a correlation between the level of spontaneous and evoked activity. Overall, our results establish the baseline response properties of lateral line primary afferent neurons in larval zebrafish, which is a crucial step in understanding how vertebrate mechanoreceptive systems sense and subsequently process information from the environment.
Contrast-dependent phase sensitivity in V1 but not V2 of macaque visual cortex
Authors: Cloherty Shaun L. , Ibbotson Michael R.
Published: October 2014

Some neurons in early visual cortex are highly selective for the position of oriented edges in their receptive fields (simple cells), whereas others are largely position insensitive (complex cells). These characteristics are reflected in their sensitivity to the spatial phase of moving sine-wave gratings: simple cell responses oscillate at the fundamental frequency of the stimulus, whereas this is less so for complex cells. In primates, when assessed at high stimulus contrast, simple cells and complex cells are roughly equally represented in the first visual cortical area, V1, whereas in the second visual area, V2, the majority of cells are complex. Recent evidence has shown that phase sensitivity of complex cells is contrast dependent. This has led to speculation that reduced contrast may lead to changes in the spatial structure of receptive fields, perhaps due to changes in how feedforward and recurrent signals interact. Given the substantial interconnections between V1 and V2 and recent evidence for the emergence of unique functional capacity in V2, we assess the relationship between contrast and phase sensitivity in the two brain regions. We show that a substantial proportion of complex cells in macaque V1 exhibit significant increases in phase sensitivity at low contrast, whereas this is rarely observed in V2. Our results support a degree of hierarchical processing from V1 to V2 with the differences possibly relating to the fact that V1 combines both subcortical and cortical input, whereas V2 receives input purely from cortical circuits.
Study of Glove Perforation during Hip Replacement Arthroplasty: Its Frequency, Location, and Timing
Authors: Tao Li Xiao , Basnet Deepak Kumar
Published: October 2014

Objective. The aim of the study was to evaluate the location, timing, and frequency of glove perforation during hip replacement arthroplasty. Methods. Gloves worn by surgical team members in 19 primary hip replacement arthroplasties were assessed. The study was of a single gloving system. All the used gloves were collected at the end of the surgery and assessed visually and by using water inflation technique. Relevant data were collected at the time of surgery. Results. A total of one hundred and ninety-one surgical gloves were evaluated. Twenty-three glove perforations were noted in nineteen of the operations. Of these perforations 14 belonged to gloves worn by surgeon and first assistant (60.1%). Glove perforation in thumb, index finger, and palm was more common. More perforation occurred in the gloves worn in nondominant hand (52%) but was insignificant. Conclusion. Glove perforation in surgeries such as total hip arthroplasty is not uncommon. In this study of single gloving system glove perforation rate was 12.04%, whereas literature reports of glove perforation rate as low as 3.3% in elective orthopedic surgeries with double gloving system. As such emphasis should be given to wear double pair of gloves wherever this practice is uncommon.
Social Determinants of Infectious Diseases in South Asia
Authors: Bishwajit Ghose , Ide Seydou , Ghosh Sharmistha
Published: October 2014

South Asian countries have developed infectious disease control programs such as routine immunization, vaccination, and the provision of essential drugs which are operating nationwide in cooperation with many local and foreign NGOs. Most South Asian countries have a relatively low prevalence of HIV/AIDS until now, but issues like poverty, food insecurity, illiteracy, poor sanitation, and social stigma around AIDS are widespread and are creating formidable challenges to prevention of further spread of this epidemic. Besides that, resurgence of tuberculosis along with the emergence of the drug resistant (MDR-TB and XDRTB) strains and the coepidemic of TB and HIV are posing ever-growing threats to the underdeveloped healthcare infrastructure. The countries are undergoing an epidemiological transition where the disease burden is gradually shifting to noncommunicable diseases, but the infectious diseases still account for almost half of the total disease burden. Despite this huge burden of infectious diseases in South Asia, which is second only to Africa, there is yet any study on the social determinants of infectious diseases in a local context. This paper examines various issues surrounding the social determinants of infectious diseases in South Asian countries with a special reference to HIV and tuberculosis. And, by doing so, it attempts to provide a framework for formulating more efficient prevention and intervention strategies for the future.