bluuebunny/crossref_metadata_2025 huggingface dataset:
The Autographa californica Multiple Nucleopolyhedrovirus
ac54
Gene Is Crucial for Localization of the Major Capsid Protein VP39 at the Site of Nucleocapsid Assembly
Authors: Guan Zhanwen , Zhong Ling , Li Chunyan , Wu Wenbi , Yuan Meijin , Yang Kai
Published: February 2016

Baculovirus DNAs are synthesized and inserted into preformed capsids to form nucleocapsids at a site in the infected cell nucleus, termed the virogenic stroma. Nucleocapsid assembly of
Autographa californica
multiple nucleopolyhedrovirus (AcMNPV) requires the major capsid protein VP39 and nine minor capsid proteins, including VP1054. However, how VP1054 participates in nucleocapsid assembly remains elusive. In this study, the VP1054-encoding gene (
ac54
) was deleted to generate the
ac54
-knockout AcMNPV (vAc54KO). In vAc54KO-transfected cells, nucleocapsid assembly was disrupted, leading to the formation of abnormally elongated capsid structures. Interestingly, unlike cells transfected with AcMNPV mutants lacking other minor capsid proteins, in which capsid structures were distributed within the virogenic stroma,
ac54
ablation resulted in a distinctive location of capsid structures and VP39 at the periphery of the nucleus. The altered distribution pattern of capsid structures was also observed in cells transfected with AcMNPV lacking BV/ODV-C42 or in cytochalasin
d
-treated AcMNPV-infected cells. BV/ODV-C42, along with PP78/83, has been shown to promote nuclear filamentous actin (F-actin) formation, which is another requisite for nucleocapsid assembly. Immunofluorescence using phalloidin indicated that the formation and distribution of nuclear F-actin were not affected by
ac54
deletion. However, immunoelectron microscopy revealed that BV/ODV-C42, PP78/83, and 38K failed to integrate into capsid structures in the absence of VP1054, and immunoprecipitation further demonstrated that in transient expression assays, VP1054 interacted with BV/ODV-C42 and VP80 but not VP39. Our findings suggest that VP1054 plays an important role in the transport of capsid proteins to the nucleocapsid assembly site prior to the process of nucleocapsid assembly.

IMPORTANCE
Baculoviruses are large DNA viruses whose replication occurs within the host nucleus. The localization of capsids into the capsid assembly site requires virus-induced nuclear F-actin; the inhibition of nuclear F-actin formation results in the retention of capsid structures at the periphery of the nucleus. In this paper, we note that the minor capsid protein VP1054 is essential for the localization of capsid structures, the major capsid protein VP39, and the minor capsid protein 38K into the capsid assembly site. Moreover, VP1054 is crucial for correct targeting of the nuclear F-actin factors BV/ODV-C42 and PP78/83 for capsid maturation. However, the formation and distribution of nuclear F-actin are not affected by the lack of VP1054. We further reveal that VP1054 interacts with BV/ODV-C42 and a capsid transport-related protein, VP80. Taken together, our findings suggest that VP1054 plays a unique role in the pathway(s) for transport of capsid proteins.
Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses
Authors: Meyer Bjoern , Ly Hinh
Published: February 2016

Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.
Effects of an In-Frame Deletion of the
6k
Gene Locus from the Genome of Ross River Virus
Authors: Taylor Adam , Melton Julian V. , Herrero Lara J. , Thaa Bastian , Karo-Astover Liis , Gage Peter W. , Nelson Michelle A. , Sheng Kuo-Ching , Lidbury Brett A. , Ewart Gary D. , McInerney Gerald M. , Merits Andres , Mahalingam Suresh
Published: February 2016

The alphaviral
6k
gene region encodes the two structural proteins 6K protein and, due to a ribosomal frameshift event, the transframe protein (TF). Here, we characterized the role of the
6k
proteins in the arthritogenic alphavirus Ross River virus (RRV) in infected cells and in mice, using a novel
6k
in-frame deletion mutant. Comprehensive microscopic analysis revealed that the
6k
proteins were predominantly localized at the endoplasmic reticulum of RRV-infected cells. RRV virions that lack the
6k
proteins 6K and TF [RRV-(Δ6K)] were more vulnerable to changes in pH, and the corresponding virus had increased sensitivity to a higher temperature. While the
6k
deletion did not reduce RRV particle production in BHK-21 cells, it affected virion release from the host cell. Subsequent
in vivo
studies demonstrated that RRV-(Δ6K) caused a milder disease than wild-type virus, with viral titers being reduced in infected mice. Immunization of mice with RRV-(Δ6K) resulted in a reduced viral load and accelerated viral elimination upon secondary infection with wild-type RRV or another alphavirus, chikungunya virus (CHIKV). Our results show that the
6k
proteins may contribute to alphaviral disease manifestations and suggest that manipulation of the
6k
gene may be a potential strategy to facilitate viral vaccine development.

IMPORTANCE
Arthritogenic alphaviruses, such as chikungunya virus (CHIKV) and Ross River virus (RRV), cause epidemics of debilitating rheumatic disease in areas where they are endemic and can emerge in new regions worldwide. RRV is of considerable medical significance in Australia, where it is the leading cause of arboviral disease. The mechanisms by which alphaviruses persist and cause disease in the host are ill defined. This paper describes the phenotypic properties of an RRV
6k
deletion mutant. The absence of the
6k
gene reduced virion release from infected cells and also reduced the severity of disease and viral titers in infected mice. Immunization with the mutant virus protected mice against viremia not only upon exposure to RRV but also upon challenge with CHIKV. These findings could lead to the development of safer and more immunogenic alphavirus vectors for vaccine delivery.
Staying in Shape: the Impact of Cell Shape on Bacterial Survival in Diverse Environments
Authors: Yang Desirée C. , Blair Kris M. , Salama Nina R.
Published: February 2016

Bacteria display an abundance of cellular forms and can change shape during their life cycle. Many plausible models regarding the functional significance of cell morphology have emerged. A greater understanding of the genetic programs underpinning morphological variation in diverse bacterial groups, combined with assays of bacteria under conditions that mimic their varied natural environments, from flowing freshwater streams to diverse human body sites, provides new opportunities to probe the functional significance of cell shape. Here we explore shape diversity among bacteria, at the levels of cell geometry, size, and surface appendages (both placement and number), as it relates to survival in diverse environments. Cell shape in most bacteria is determined by the cell wall. A major challenge in this field has been deconvoluting the effects of differences in the chemical properties of the cell wall and the resulting cell shape perturbations on observed fitness changes. Still, such studies have begun to reveal the selective pressures that drive the diverse forms (or cell wall compositions) observed in mammalian pathogens and bacteria more generally, including efficient adherence to biotic and abiotic surfaces, survival under low-nutrient or stressful conditions, evasion of mammalian complement deposition, efficient dispersal through mucous barriers and tissues, and efficient nutrient acquisition.
Unusual presentation of a familiar pathology: chronic appendicitis
Authors: Sierakowski Kyra , Pattichis Andrew , Russell Patrick , Wattchow David
Published: February 2016

We present a case of a man who experienced night sweats, abdominal pain and fever for over 3 months, with incomplete response to broad-spectrum intravenous antibiotics. Although CT imaging was insufficient to identify the cause for his chronic abdominal pain, the abnormality of a ‘misty mesentery’ was crucial in guiding further investigation. The final diagnosis of chronic appendicitis was made through laparoscopic and pathological examination. This case highlights the utility of a collaborative diagnostic effort between disciplines. Chronic appendicitis can cause lingering abdominal pain. Early recognition and appropriate referral can save patients months and even years of unnecessary suffering.
Ectopic pregnancy in an undescended fallopian tube: a diagnostic challenge
Authors: Pardal Catarina , Braga Luís , Vides Belisa
Published: February 2016

Uterine malformations are the most frequent anomalies of the Müllerian ducts, but undescended ovaries and fallopian tubes are very rare congenital defects. Pregnancy in these misplaced organs may occur, frequently posing a diagnostic challenge. A case of a ruptured ectopic pregnancy in an undescended fallopian tube associated with other genital malformations is presented. This case provides evidence for the recognised phenomenon of peritoneal gametes or embryo transmigration.
Vitamin D for the treatment of painful diabetic neuropathy
Authors: Basit Abdul , Basit Khalid Abdul , Fawwad Asher , Shaheen Fariha , Fatima Nimra , Petropoulos Ioannis N , Alam Uazman , Malik Rayaz A
Published: February 2016

Objective

To assess the effect of high-dose vitamin D in patients with painful diabetic neuropathy.

Methods

A single intramuscular dose of 600 000 IU vitamin D was administered, and the effects on metabolic parameters and neuropathic pain assessed over 20 weeks.

Results

143 participants with predominantly type 2 diabetes, aged 52.31±11.48 years, with a Douleur Neuropathique 4 (DN4) score (3.0±1.8), total McGill pain score (21.2±14.9), and Short Form McGill Pain Questionnaire (SFMPQ) score (2.1±0.9), were enrolled. The baseline 25-hydroxyvitamin D (25(OH)D) level was 31.7±23.3 ng/mL and 58 (40.5%) patients showed evidence of vitamin D deficiency (25(OH)D<20 ng/mL). Intramuscular administration of vitamin D resulted in a significant increase in 25(OH)D (46.2±10.2 ng/mL, p<0.0001) and a reduction in positive symptoms on the DN4 (p<0.0001), total pain score (p<0.0001), and SFMPQ (p<0.0001).

Conclusions

Treatment with a single intramuscular dose of 600 000 IU of vitamin D in patients with painful diabetic neuropathy is associated with a significant decrease in the symptoms of painful diabetic neuropathy.

Trial registration number

BIDE-12/2014.
Are adolescent orphans more likely to be HIV-positive? A pooled data analyses across 19 countries in sub-Saharan Africa
Authors: Kidman Rachel , Anglewicz Philip
Published: February 2016

Background

Despite extensive resources and numerous programmes directed towards orphans in sub-Saharan Africa, evidence of their disadvantage is surprisingly limited. While initial research suggests that orphans are at greater risk of being HIV-positive, the evidence is limited in geographic scope.

Methods

To rigorously test disparities in HIV prevalence related to orphanhood and parental HIV status in sub-Saharan Africa, we used Demographic and Health Survey data from 19 countries in sub-Saharan Africa. We conducted pooled multilevel logistic regression on adolescents aged 15–17 years with HIV test results (N=22 837 girls and 20 452 boys).

Results

Regardless of their gender, orphans who lost their mother, lost both parents or had an HIV-infected mother were two to three times more likely to test positive for HIV infection (ORs 1.87–3.17). The loss of a father was also associated with HIV infection risk for females, but of slightly lower magnitude (OR 1.63).

Conclusions

To better inform interventions, future research is needed to quantify the relative contribution of perinatally-acquired and sexually-acquired infections, and to investigate the specific mechanisms that may account for disparities in the latter. In the meantime, programmes serving HIV-infect adults as well as those serving orphaned and vulnerable children should invest in family-based HIV testing in order to identify adolescents in need of treatment.
Comparison of commercial type 1 and type 2 PRRSV vaccines against heterologous dual challenge
Authors: Choi K. , Park C. , Jeong J. , Kang I. , Park S.‐J. , Chae C.
Published: February 2016

This study was to compare the effect of vaccination of pigs with either type 1 or type 2 porcine reproductive and respiratory syndrome virus (PRRSV) against heterologous dual challenge of both genotypes. Pigs were administered type 1 (UNISTRAIN PRRS) or type 2 (Fostera PRRS) PRRSV vaccine at 28 days of age and inoculated intranasally with both genotypes at 63 days of age. Vaccination of pigs with type 1 PRRSV was able to reduce the levels of type 1 but not type 2 PRRSV viraemia, whereas vaccination of pigs with type 2 PRRSV was able to reduce the levels of type 1 and type 2 PRRSV viraemia against a dual challenge. Vaccination of pigs with type 2 PRRSV significantly reduced lung lesions after dual challenge compared with vaccination of pigs with type 1 PRRSV. Vaccination of pigs with type 2 PRRSV induced higher numbers of type 1 and type 2 PRRSV‐specific interferon‐γ secreting cells compared with vaccination of pigs with type 1 PRRSV after dual challenge. The results of this study demonstrated that vaccination of pigs with type 2 PRRSV is efficacious in protecting growing pigs from respiratory disease after heterologous dual type 1 and type 2 PRRSV challenge compared with vaccination of pigs with type 1 PRRSV.
Surface soil organic carbon in temperate and subtropical oriental oak stands of East China
Authors: Yu Wenjuan , Fahey Timothy J. , Kang Hongzhang , Zhou Pisheng
Published: February 2016

Forest ecosystems contain large amounts of soil organic carbon (SOC), which is a major component of biogeochemical cycles that may be sensitive to environmental change. We used a combination of nuclear magnetic resonance (NMR) spectroscopy and elemental and isotopic composition to examine the influence of soil properties and climatic factors on the quantity and degree of decomposition of SOC for organic and surface mineral horizons in seven oriental oak (Quercus variabilis Blume) forest sites arranged across a 11o latitudinal gradient in East China. Lacking Oa horizons, the two southernmost sites contained lower amounts of SOC in the forest floor horizon, but otherwise, latitudinal trends were not consistent. The SOC stock in the 0–10 cm mineral horizon exhibited no clear trend along the gradient and had a negative association with clay + silt content. Based on a higher alkyl/O-alkyl (A/O) ratio and alkyl/methoxyl (A/M) ratio, the SOC at the 0–10 cm depth appeared to be relatively more decomposed in three of the four southern subtropical sites. However, the degree of SOC degradation also decreased strongly with increasing soil pH (R2 = 0.90, P = 0.001). Soil organic carbon exhibited increases in δ13C and δ15N and decreases in the C/N ratio with depth for all the seven sites, indicating an increase in its extent of decomposition. Our analysis indicated that the A/M ratio from NMR provided the best indication of the extent of SOC degradation along the latitudinal transect, whereas the elemental and isotopic composition better reflected patterns with soil depth.
A power moment reformulation of the Nikiforov–Uvarov method for exactly solvable systems
Authors: Handy Carlos R. , Vrinceanu Daniel
Published: February 2016

Exactly solvable (ES) systems are those for which the full, discrete spectrum can be solved in closed form. In this work, we argue that a moment’s representation analysis can generate these closed-form expressions for the energy in a more direct and transparent manner than the popular Nikiforov–Uvarov (NU) procedure. NU analysis strips the asymptotic form of the physical states. We retain these to generate appropriate moment equations. We show how the form of these moment equations leads to closed-form energy expressions. The wave functions can then be generated as well. Our analysis is extendable to quasi-exactly solvable systems (QES; those for which a subset of the discrete spectrum can be generated in closed form). Two formulations are presented. One of these affirms that a previously developed, general, moment quantization procedure is exact for ES and QES states. This method is referred to as the orthogonal polynomial projection quantization method. It combines moment equation representations for physical states with weighted polynomial expansions (Handy and Vrinceanu. J. Phys. A: Math. Theor. 46, 135202 (2013). doi:10.1088/1751-8113/46/13/135202 ). We also show that in implementing any numerical search procedure to determine the quantum parameter regimes corresponding to ES or QES states, our procedure is more reliable (i.e., numerically stable) than using a Hill determinant formulation. We develop our formalism, demonstrate its effectiveness, and prove its equivalence to the NU approach for ES systems.
Thermodynamic stability of a regular black hole in nonlinear electrodynamics
Authors: López L.A. , Matias A. Eunice
Published: February 2016

By the turning point method, we study the thermodynamic stability of the a regular black hole in nonlinear electrodynamics. The microcanonical, canonical, and grand canonical ensembles are analyzed; the phase diagrams (m, βm) and (q, βq) (microcanonical ensemble) show that the regular black hole is stable at all the equilibrium sequence, but for the phase diagram (βm, –m) (canonical and grand canonical ensembles) the black hole shows a turning point. This means that the black hole is thermodynamically unstable. The temperature of the regular black hole has behavior that resembling Reissner–Nordstrom behavior: the temperature grows with the mass as in an ordinary thermodynamical system, but there is a maximum value of mass beyond which the temperature diminishes. The heat capacity displays a divergence with a change of sign that occurs precisely at the turning point obtained by the turning point method in the canonical ensemble.
Interactions between alluvial fans and axial rivers in Yukon, Canada and Alaska, USA
Authors: Giles Philip T. , Whitehouse Bryce M. , Karymbalis Efthimios
Published: February 2016

In contrast with the archetypal definition of an alluvial fan, this study shows that fans interacting with axial rivers in Yukon and Alaska commonly exhibit asymmetrical morphology in planform. Hypothesis tests relating to the geomorphological characteristics of these alluvial fans were conducted on a dataset of 63 fluvial-dominated fans. A significant relationship existed between fan asymmetry and the direction of axial river flow, which was attributed to two factors supported by examples: (1) axial rivers have a propensity to trim the toes on the up-valley sides of fans; and (2) axial river channels are deflected across the broad valley floors, which allows the profiles on the down-valley sides of fans to be longer than on the up-valley sides. However, an asymmetrical planform morphology does not lead to a significant bias in the spatial distribution of surface streams towards the up-valley sides of fans, which typically have shorter profiles from apex to boundary. If the asymmetry in fan morphology is preserved in the sedimentary record, then the interpretation of fan deposits that developed in broad valleys and that interacted with axial rivers would be improved by understanding this modern analogue.
The Costs of Photorespiration to Food Production Now and in the Future
Authors: Walker Berkley J. , VanLoocke Andy , Bernacchi Carl J. , Ort Donald R.
Published: February 2016

Photorespiration is essential for C3 plants but operates at the massive expense of fixed carbon dioxide and energy. Photorespiration is initiated when the initial enzyme of photosynthesis, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), reacts with oxygen instead of carbon dioxide and produces a toxic compound that is then recycled by photorespiration. Photorespiration can be modeled at the canopy and regional scales to determine its cost under current and future atmospheres. A regional-scale model reveals that photorespiration currently decreases US soybean and wheat yields by 36% and 20%, respectively, and a 5% decrease in the losses due to photorespiration would be worth approximately $500 million annually in the United States. Furthermore, photorespiration will continue to impact yield under future climates despite increases in carbon dioxide, with models suggesting a 12–55% improvement in gross photosynthesis in the absence of photorespiration, even under climate change scenarios predicting the largest increases in atmospheric carbon dioxide concentration. Although photorespiration is tied to other important metabolic functions, the benefit of improving its efficiency appears to outweigh any potential secondary disadvantages.
The Conservation and Function of RNA Secondary Structure in Plants
Authors: Vandivier Lee E. , Anderson Stephen J. , Foley Shawn W. , Gregory Brian D.
Published: February 2016

RNA transcripts fold into secondary structures via intricate patterns of base pairing. These secondary structures impart catalytic, ligand binding, and scaffolding functions to a wide array of RNAs, forming a critical node of biological regulation. Among their many functions, RNA structural elements modulate epigenetic marks, alter mRNA stability and translation, regulate alternative splicing, transduce signals, and scaffold large macromolecular complexes. Thus, the study of RNA secondary structure is critical to understanding the function and regulation of RNA transcripts. Here, we review the origins, form, and function of RNA secondary structure, focusing on plants. We then provide an overview of methods for probing secondary structure, from physical methods such as X-ray crystallography and nuclear magnetic resonance (NMR) imaging to chemical and nuclease probing methods. Combining these latter methods with high-throughput sequencing has enabled them to scale across whole transcriptomes, yielding tremendous new insights into the form and function of RNA secondary structure.
The Plant Polyester Cutin: Biosynthesis, Structure, and Biological Roles
Authors: Fich Eric A. , Segerson Nicholas A. , Rose Jocelyn K.C.
Published: February 2016

Cutin, a polyester composed mostly of oxygenated fatty acids, serves as the framework of the plant cuticle. The same types of cutin monomers occur across most plant lineages, although some evolutionary trends are evident. Additionally, cutins from some species have monomer profiles that are characteristic of the related polymer suberin. Compositional differences likely have profound structural consequences, but little is known about cutin's molecular organization and architectural heterogeneity. Its biological importance is suggested by the wide variety of associated mutants and gene-silencing lines that show a disruption of cuticular integrity, giving rise to numerous physiological and developmental abnormalities. Mapping and characterization of these mutants, along with suppression of gene paralogs through RNA interference, have revealed much of the biosynthetic pathway and several regulatory factors; however, the mechanisms of cutin polymerization and its interactions with other cuticle and cell wall components are only now beginning to be resolved.
The Lymphatic System in Disease Processes and Cancer Progression
Authors: Padera Timothy P. , Meijer Eelco F.J. , Munn Lance L.
Published: February 2016

Advances in our understanding of the structure and function of the lymphatic system have made it possible to identify its role in a variety of disease processes. Because it is involved not only in fluid homeostasis but also in immune cell trafficking, the lymphatic system can mediate and ultimately alter immune responses. Our rapidly increasing knowledge of the molecular control of the lymphatic system will inevitably lead to new and effective therapies for patients with lymphatic dysfunction. In this review, we discuss the molecular and physiological control of lymphatic vessel function and explore how the lymphatic system contributes to many disease processes, including cancer and lymphedema.
Charisma: An Ill-Defined and Ill-Measured Gift
Authors: Antonakis John , Bastardoz Nicolas , Jacquart Philippe , Shamir Boas
Published: February 2016

We take historical stock of charisma, tracing its origins and how it has been conceptualized in the sociological and organizational sciences literatures. Although charisma has been intensely studied, the concept is still not well understood and much of the research undertaken cannot inform policy. We show that the major obstacles to advancing our understanding of charisma have included issues with its definition, its confusion with transformational leadership, the use of questionnaire measures, and that it has not been studied using correctly specified causal models. To help spawn a new genre of research on charisma, we use signaling theory to provide a general definition of charisma, and make suggestions about how charisma should be conceptualized, operationalized, and modeled. We also describe trends and patterns in articles we reviewed, using cocitation as well as bibliometric analyses, and discuss the practical implications of our findings.
Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats
Authors: Kieffer Dorothy A. , Piccolo Brian D. , Vaziri Nosratola D. , Liu Shuman , Lau Wei L. , Khazaeli Mahyar , Nazertehrani Sohrab , Moore Mary E. , Marco Maria L. , Martin Roy J. , Adams Sean H.
Published: February 2016

Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk ( n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function.
Response reliability observed with voltage-sensitive dye imaging of cortical layer 2/3: the probability of activation hypothesis
Authors: Gollnick Clare A. , Millard Daniel C. , Ortiz Alexander D. , Bellamkonda Ravi V. , Stanley Garrett B.
Published: February 2016

A central assertion in the study of neural processing is that our perception of the environment directly reflects the activity of our sensory neurons. This assertion reinforces the intuition that the strength of a sensory input directly modulates the amount of neural activity observed in response to that sensory feature: an increase in the strength of the input yields a graded increase in the amount of neural activity. However, cortical activity across a range of sensory pathways can be sparse, with individual neurons having remarkably low firing rates, often exhibiting suprathreshold activity on only a fraction of experimental trials. To compensate for this observed apparent unreliability, it is assumed that instead the local population of neurons, although not explicitly measured, does reliably represent the strength of the sensory input. This assumption, however, is largely untested. In this study, using wide-field voltage-sensitive dye (VSD) imaging of the somatosensory cortex in the anesthetized rat, we show that whisker deflection velocity, or stimulus strength, is not encoded by the magnitude of the population response at the level of cortex. Instead, modulation of whisker deflection velocity affects the likelihood of the cortical response, impacting the magnitude, rate of change, and spatial extent of the cortical response. An ideal observer analysis of the cortical response points to a probabilistic code based on repeated sampling across cortical columns and/or time, which we refer to as the probability of activation hypothesis. This hypothesis motivates a range of testable predictions for both future electrophysiological and future behavioral studies.
Frontal and motor cortex contributions to response inhibition: evidence from electrocorticography
Authors: Fonken Yvonne M. , Rieger Jochem W. , Tzvi Elinor , Crone Nathan E. , Chang Edward , Parvizi Josef , Knight Robert T. , Krämer Ulrike M.
Published: February 2016

Changes in the environment require rapid modification or inhibition of ongoing behavior. We used the stop-signal paradigm and intracranial recordings to investigate response preparation, inhibition, and monitoring of task-relevant information. Electrocorticographic data were recorded in eight patients with electrodes covering frontal, temporal, and parietal cortex, and time-frequency analysis was used to examine power differences in the beta (13–30 Hz) and high-gamma bands (60–180 Hz). Over motor cortex, beta power decreased, and high-gamma power increased during motor preparation for both go trials (Go) and unsuccessful stops (US). For successful stops (SS), beta increased, and high-gamma was reduced, indexing the cancellation of the prepared response. In the middle frontal gyrus (MFG), stop signals elicited a transient high-gamma increase. The MFG response occurred before the estimated stop-signal reaction time but did not distinguish between SS and US trials, likely signaling attention to the salient stop stimulus. A postresponse high-gamma increase in MFG was stronger for US compared with SS and absent in Go, supporting a role in behavior monitoring. These results provide evidence for differential contributions of frontal subregions to response inhibition, including motor preparation and inhibitory control in motor cortex and cognitive control and action evaluation in lateral prefrontal cortex.
Associative plasticity in the human motor cortex is enhanced by concurrently targeting separate muscle representations with excitatory and inhibitory protocols
Authors: Kamke Marc R. , Nydam Abbey S. , Sale Martin V. , Mattingley Jason B.
Published: February 2016

Paired associative stimulation (PAS) induces changes in the excitability of human sensorimotor cortex that outlast the procedure. PAS typically involves repeatedly pairing stimulation of a peripheral nerve that innervates an intrinsic hand muscle with transcranial magnetic stimulation over the representation of that muscle in the primary motor cortex. Depending on the timing of the stimuli (interstimulus interval of 25 or 10 ms), PAS leads to either an increase (PAS25) or a decrease (PAS10) in excitability. Both protocols, however, have been associated with an increase in excitability of nearby muscle representations not specifically targeted by PAS. Based on these spillover effects, we hypothesized that an additive, excitability-enhancing effect of PAS25 applied to one muscle representation may be produced by simultaneously applying PAS25 or PAS10 to a nearby representation. In different experiments prototypical PAS25 targeting the left thumb representation [abductor pollicis brevis (APB)] was combined with either PAS25 or PAS10 applied to the left little finger representation [abductor digiti minimi (ADM)] or, in a control experiment, with PAS10 also targeting the APB. In an additional control experiment PAS10 targeted both representations. The plasticity effects were quantified by measuring the amplitude of motor evoked potentials (MEPs) recorded before and after PAS. As expected, prototypical PAS25 was associated with an increase in MEP amplitude in the APB muscle. This effect was enhanced when PAS also targeted the ADM representation but only when a different interstimulus timing (PAS10) was used. These results suggest that PAS-induced plasticity is modified by concurrently targeting separate motor cortical representations with excitatory and inhibitory protocols.
Arm posture-dependent changes in corticospinal excitability are largely spinal in origin
Authors: Nuzzo James L. , Trajano Gabriel S. , Barry Benjamin K. , Gandevia Simon C. , Taylor Janet L.
Published: February 2016

Biceps brachii motor evoked potentials (MEPs) from cortical stimulation are influenced by arm posture. We used subcortical stimulation of corticospinal axons to determine whether this postural effect is spinal in origin. While seated at rest, 12 subjects assumed several static arm postures, which varied in upper-arm (shoulder flexed, shoulder abducted, arm hanging to side) and forearm orientation (pronated, neutral, supinated). Transcranial magnetic stimulation over the contralateral motor cortex elicited MEPs in resting biceps and triceps brachii, and electrical stimulation of corticospinal tract axons at the cervicomedullary junction elicited cervicomedullary motor evoked potentials (CMEPs). MEPs and CMEPs were normalized to the maximal compound muscle action potential (Mmax). Responses in biceps were influenced by upper-arm and forearm orientation. For upper-arm orientation, biceps CMEPs were 68% smaller ( P = 0.001), and biceps MEPs 31% smaller ( P = 0.012), with the arm hanging to the side compared with when the shoulder was flexed. For forearm orientation, both biceps CMEPs and MEPs were 34% smaller (both P < 0.046) in pronation compared with supination. Responses in triceps were influenced by upper-arm, but not forearm, orientation. Triceps CMEPs were 46% smaller ( P = 0.007) with the arm hanging to the side compared with when the shoulder was flexed. Triceps MEPs and biceps and triceps MEP/CMEP ratios were unaffected by arm posture. The novel finding is that arm posture-dependent changes in corticospinal excitability in humans are largely spinal in origin. An interplay of multiple reflex inputs to motoneurons likely explains the results.
Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex
Authors: Pathak Dhruba , Guan Dongxu , Foehring Robert C.
Published: February 2016

The action potential (AP) is a fundamental feature of excitable cells that serves as the basis for long-distance signaling in the nervous system. There is considerable diversity in the appearance of APs and the underlying repolarization mechanisms in different neuronal types (reviewed in Bean BP. Nat Rev Neurosci 8: 451–465, 2007), including among pyramidal cell subtypes. In the present work, we used specific pharmacological blockers to test for contributions of Kv1, Kv2, or Kv4 channels to repolarization of single APs in two genetically defined subpopulations of pyramidal cells in layer 5 of mouse somatosensory cortex ( etv1 and glt) as well as pyramidal cells from layer 2/3. These three subtypes differ in AP properties (Groh A, Meyer HS, Schmidt EF, Heintz N, Sakmann B, Krieger P. Cereb Cortex 20: 826–836, 2010; Guan D, Armstrong WE, Foehring RC. J Neurophysiol 113: 2014–2032, 2015) as well as laminar position, morphology, and projection targets. We asked what the roles of Kv1, Kv2, and Kv4 channels are in AP repolarization and whether the underlying mechanisms are pyramidal cell subtype dependent. We found that Kv4 channels are critically involved in repolarizing neocortical pyramidal cells. There are also pyramidal cell subtype-specific differences in the role for Kv1 channels. Only Kv4 channels were involved in repolarizing the narrow APs of glt cells. In contrast, in etv1 cells and layer 2/3 cells, the broader APs are partially repolarized by Kv1 channels in addition to Kv4 channels. Consistent with their activation in the subthreshold range, Kv1 channels also regulate AP voltage threshold in all pyramidal cell subtypes.
Electroencephalographic detection of respiratory-related cortical activity in humans: from event-related approaches to continuous connectivity evaluation
Authors: Hudson Anna L. , Navarro-Sune Xavier , Martinerie Jacques , Pouget Pierre , Raux Mathieu , Chavez Mario , Similowski Thomas
Published: February 2016

The presence of a respiratory-related cortical activity during tidal breathing is abnormal and a hallmark of respiratory difficulties, but its detection requires superior discrimination and temporal resolution. The aim of this study was to validate a computational method using EEG covariance (or connectivity) matrices to detect a change in brain activity related to breathing. In 17 healthy subjects, EEG was recorded during resting unloaded breathing (RB), voluntary sniffs, and breathing against an inspiratory threshold load (ITL). EEG were analyzed by the specially developed covariance-based classifier, event-related potentials, and time-frequency (T-F) distributions. Nine subjects repeated the protocol. The classifier could accurately detect ITL and sniffs compared with the reference period of RB. For ITL, EEG-based detection was superior to airflow-based detection ( P < 0.05). A coincident improvement in EEG-airflow correlation in ITL compared with RB ( P < 0.05) confirmed that EEG detection relates to breathing. Premotor potential incidence was significantly higher before inspiration in sniffs and ITL compared with RB ( P < 0.05), but T-F distributions revealed a significant difference between sniffs and RB only ( P < 0.05). Intraclass correlation values ranged from poor (−0.2) to excellent (1.0). Thus, as for conventional event-related potential analysis, the covariance-based classifier can accurately predict a change in brain state related to a change in respiratory state, and given its capacity for near “real-time” detection, it is suitable to monitor the respiratory state in respiratory and critically ill patients in the development of a brain-ventilator interface.
Ear Infection and Its Associated Risk Factors in First Nations and Rural School-Aged Canadian Children
Authors: Karunanayake Chandima P. , Albritton William , Rennie Donna C. , Lawson Joshua A. , McCallum Laura , Gardipy P. Jenny , Seeseequasis Jeremy , Naytowhow Arnold , Hagel Louise , McMullin Kathleen , Ramsden Vivian , Abonyi Sylvia , Episkenew Jo-Ann , Dosman James A. , Pahwa Punam , Project Research Team The First Nations Lung Health , Study Team The Saskatchewan Rural Health
Published: February 2016

Background.Ear infections in children are a major health problem and may be associated with hearing impairment and delayed language development.Objective.To determine the prevalence and the associated risk factors of ear infections in children 6–17 years old residing on two reserves and rural areas in the province of Saskatchewan.Methodology.Data were provided from two rural cross-sectional children studies. Outcome variable of interest was presence/absence of an ear infection. Logistic regression analysis was conducted to examine the relationship between ear infection and the other covariates.Results.The prevalence of ear infection was 57.8% for rural Caucasian children and 43.6% for First Nations children living on-reserve. First Nations children had a lower risk of ear infection. Ear infection prevalence was positively associated with younger age; first born in the family; self-reported physician-diagnosed tonsillitis; self-reported physician-diagnosed asthma; and any respiratory related allergy. Protective effect of breastfeeding longer than three months was observed on the prevalence of ear infection.Conclusions.While ear infection is a prevalent condition of childhood, First Nations children were less likely to have a history of ear infections when compared to their rural Caucasian counterparts.
Prospects on Time-Domain Diffuse Optical Tomography Based on Time-Correlated Single Photon Counting for Small Animal Imaging
Authors: Bérubé-Lauzière Yves , Crotti Matteo , Boucher Simon , Ettehadi Seyedrohollah , Pichette Julien , Rech Ivan
Published: February 2016

This paper discusses instrumentation based on multiview parallel high temporal resolution (<50 ps) time-domain (TD) measurements for diffuse optical tomography (DOT) and a prospective view on the steps to undertake as regards such instrumentation to make TD-DOT a viable technology for small animal molecular imaging. TD measurements provide information-richest data, and we briefly review the interaction of light with biological tissues to provide an understanding of this. This data richness is yet to be exploited to its full potential to increase the spatial resolution of DOT imaging and to allow probing, via the fluorescence lifetime, tissue biochemical parameters, and processes that are otherwise not accessible in fluorescence DOT. TD data acquisition time is, however, the main factor that currently compromises the viability of TD-DOT. Current high temporal resolution TD-DOT scanners simply do not integrate sufficient detection channels. Based on our past experience in developing TD-DOT instrumentation, we review and discuss promising technologies to overcome this difficulty. These are single photon avalanche diode (SPAD) detectors and fully parallel highly integrated electronics for time-correlated single photon counting (TCSPC). We present experimental results obtained with such technologies demonstrating the feasibility of next-generation multiview TD-DOT therewith.
Substance P Receptor Signaling Mediates Doxorubicin-Induced Cardiomyocyte Apoptosis and Triple-Negative Breast Cancer Chemoresistance
Authors: Robinson Prema , Kasembeli Moses , Bharadwaj Uddalak , Engineer Nikita , Eckols Kris T. , Tweardy David J.
Published: February 2016

Doxorubicin (DOX), an anthracycline, is broadly considered the most active single agent available for treating breast cancer but has been known to induce cardiotoxicity. Although DOX is highly effective in treating triple-negative breast cancer (TNBC), DOX can have poor outcomes owing to induction of chemoresistance. There is an urgent need to develop new therapies for TNBC aimed at improving DOX outcome and DOX-induced cardiotoxicity. Substance P (SP), a neuropeptide involved in pain transmission is known to stimulate production of reactive oxygen species (ROS). Elevated cardiac ROS is linked with heart injury and failure. We investigated the role of SP in chemotherapy-associated death of cardiomyocytes and chemoresistance. We showed that pretreating a cardiomyocyte cell line (H9C2) and a TNBC cell line (MDA-MB 231) with aprepitant, a SP receptor antagonist that is routinely used to treat chemotherapy-associated associated nausea, decreased DOX-induced reduction of cell viability, apoptotic cell death, and ROS production in cardiomyocytes and increased DOX-induced reduction of cell viability, apoptotic cell death, and ROS production in TNBC cells compared with cells treated with DOX alone. Our findings demonstrate the ability of aprepitant to decrease DOX-induced killing of cardiomyocytes and to increase cancer cell sensitivity to DOX, which has tremendous clinical significance.
An Unconventional Inchworm Actuator Based on PZT/ERFs Control Technology
Authors: Liu Guojun , Zhang Yanyan , Liu Jianfang , Li Jianqiao , Tang Chunxiu , Wang Tengfei , Yang Xuhao
Published: February 2016

An unconventional inchworm actuator for precision positioning based on piezoelectric (PZT) actuation and electrorheological fluids (ERFs) control technology is presented. The actuator consists of actuation unit (PZT stack pump), fluid control unit (ERFs valve), and execution unit (hydraulic actuator). In view of smaller deformation of PZT stack, a new structure is designed for actuation unit, which integrates the advantages of two modes (namely, diaphragm type and piston type) of the volume changing of pump chamber. In order to improve the static shear yield strength of ERFs, a composite ERFs valve is designed, which adopts the series-parallel plate compound structure. The prototype of the inchworm actuator has been designed and manufactured in the lab. Systematic test results indicate that the displacement resolution of the unconventional inchworm actuator reaches 0.038 μm, and the maximum driving force and velocity are 42 N, 14.8 mm/s, respectively. The optimal working frequency for the maximum driving velocity is 120 Hz. The complete research and development processes further confirm the feasibility of developing a new type of inchworm actuator with high performance based on PZT actuation and ERFs control technology, which provides a reference for the future development of a new type of actuator.
Schizophrenia and Suicide Attempts: Findings from a Representative Community-Based Canadian Sample
Authors: Fuller-Thomson Esme , Hollister Bailey
Published: February 2016

This study examined factors associated with suicide attempts among those with schizophrenia (n=101) versus those without (n=21,643) in a representative sample of noninstitutionalized Canadians. The lifetime prevalence of suicide attempts among persons with schizophrenia was 39.2% versus 2.8% of nonafflicted individuals. After adjusting for sociodemographics, childhood adversities, substance abuse/dependence, depression/anxiety, and chronic pain, those with schizophrenia had 6 times the odds (OR = 6.47) of attempting suicide. Among persons with schizophrenia, suicide attempts were associated with female gender (OR = 4.59), substance abuse/dependence (OR = 6.31), depression (OR = 4.93), and childhood physical abuse (OR = 5.75). Community-dwelling persons with schizophrenia appear to be at high risk for suicide attempts.
Synthesis and Evaluation of Mannitol-Based Inhibitors for Lipopolysaccharide Biosynthesis
Authors: Johnsson Richard E.
Published: February 2016

Antibiotic resistance is a serious threat against humankind and the need for new therapeutics is crucial. Without working antibiotics, diseases that we thought were extinct will come back. In this paper two new mannitol bisphosphate analogs, 1,6-dideoxy-1,6-diphosphoramidate mannitol and 1,6-dideoxy-1,6-dimethansulfonamide mannitol, have been synthesized and evaluated as potential inhibitors of the enzyme GmhB in the biosynthesis of lipopolysaccharides. 1,6-Dideoxy-1,6-diphosphoramidate mannitol showed promising result in computational docking experiments, but neither phosphate analog showed activity in the Kirby-Bauer antibiotic susceptibility test.