bluuebunny/crossref_metadata_2025 huggingface dataset:
The 2′-5′-Oligoadenylate Synthetase 3 Enzyme Potently Synthesizes the 2′-5′-Oligoadenylates Required for RNase L Activation
Authors: Ibsen Mikkel Søes , Gad Hans Henrik , Thavachelvam Karthiga , Boesen Thomas , Desprès Philippe , Hartmann Rune
Published: October 2014

The members of the oligoadenylate synthetase (OAS) family of proteins are antiviral restriction factors that target a wide range of RNA and DNA viruses. They function as intracellular double-stranded RNA (dsRNA) sensors that, upon binding to dsRNA, undergo a conformational change and are activated to synthesize 2′-5′-linked oligoadenylates (2-5As). 2-5As of sufficient length act as second messengers to activate RNase L and thereby restrict viral replication. We expressed human OAS3 using the baculovirus system and purified it to homogeneity. We show that recombinant OAS3 is activated at a substantially lower concentration of dsRNA than OAS1, making it a potent
in vivo
sensor of dsRNA. Moreover, we find that OAS3 synthesizes considerably longer 2-5As than previously reported, and that OAS3 can activate RNase L intracellularly. The combined high affinity for dsRNA and the capability to produce 2-5As of sufficient length to activate RNase L suggests that OAS3 is a potent activator of RNase L. In addition, we provide experimental evidence to support one active site of OAS3 located in the C-terminal OAS domain and generate a low-resolution structure of OAS3 using SAXS.

IMPORTANCE
We are the first to purify the OAS3 enzyme to homogeneity, which allowed us to characterize the mechanism utilized by OAS3 and identify the active site. We provide compelling evidence that OAS3 can produce 2′-5′-oligoadenylates of sufficient length to activate RNase L. This is contrary to what is described in the current literature but agrees with recent
in vivo
data showing that OAS3 harbors an antiviral activity requiring RNase L. Thus, our work redefines our understanding of the biological role of OAS3. Furthermore, we used a combination of mutagenesis and small-angle X-ray scattering to describe the active site and low-resolution structure of OAS3.
Cooperativity among Rev-Associated Nuclear Export Signals Regulates HIV-1 Gene Expression and Is a Determinant of Virus Species Tropism
Authors: Aligeti Mounavya , Behrens Ryan T. , Pocock Ginger M. , Schindelin Johannes , Dietz Christian , Eliceiri Kevin W. , Swanson Chad M. , Malim Michael H. , Ahlquist Paul , Sherer Nathan M.
Published: October 2014

Murine cells exhibit a profound block to HIV-1 virion production that was recently mapped to a species-specific structural attribute of the murine version of the chromosomal region maintenance 1 (mCRM1) nuclear export receptor and rescued by the expression of human CRM1 (hCRM1). In human cells, the HIV-1 Rev protein recruits hCRM1 to intron-containing viral mRNAs encoding the Rev response element (RRE), thereby facilitating viral late gene expression. Here we exploited murine 3T3 fibroblasts as a gain-of-function system to study hCRM1's species-specific role in regulating Rev's effector functions. We show that Rev is rapidly exported from the nucleus by mCRM1 despite only weak contributions to HIV-1's posttranscriptional stages. Indeed, Rev preferentially accumulates in the cytoplasm of murine 3T3 cells with or without hCRM1 expression, in contrast to human HeLa cells, where Rev exhibits striking
en masse
transitions between the nuclear and cytoplasmic compartments. Efforts to bias Rev's trafficking either into or out of the nucleus revealed that Rev encoding a second CRM1 binding domain (Rev-2xNES) or Rev-dependent viral
gag-pol
mRNAs bearing tandem RREs (GP-2xRRE), rescue virus particle production in murine cells even in the absence of hCRM1. Combined, these results suggest a model wherein Rev-associated nuclear export signals cooperate to regulate the number or quality of CRM1's interactions with viral Rev/RRE ribonucleoprotein complexes in the nucleus. This mechanism regulates CRM1-dependent viral gene expression and is a determinant of HIV-1's capacity to produce virions in nonhuman cell types.

IMPORTANCE
Cells derived from mice and other nonhuman species exhibit profound blocks to HIV-1 replication. Here we elucidate a block to HIV-1 gene expression attributable to the murine version of the CRM1 (mCRM1) nuclear export receptor. In human cells, hCRM1 regulates the nuclear export of viral intron-containing mRNAs through the activity of the viral Rev adapter protein that forms a multimeric complex on these mRNAs prior to recruiting hCRM1. We demonstrate that Rev-dependent gene expression is poor in murine cells despite the finding that, surprisingly, the bulk of Rev interacts efficiently with mCRM1 and is rapidly exported from the nucleus. Instead, we map the mCRM1 defect to the apparent inability of this factor to engage Rev multimers in the context of large viral Rev/RNA ribonucleoprotein complexes. These findings shed new light on HIV-1 gene regulation and could inform the development of novel antiviral strategies that target viral gene expression.
Different Roles of the Three Loops Forming the Adhesive Interface of Nectin-4 in Measles Virus Binding and Cell Entry, Nectin-4 Homodimerization, and Heterodimerization with Nectin-1
Authors: Mateo Mathieu , Navaratnarajah Chanakha K. , Willenbring Robin C. , Maroun Justin W. , Iankov Ianko , Lopez Marc , Sinn Patrick L. , Cattaneo Roberto
Published: October 2014

Many viruses utilize cell adhesion molecules of the immunoglobulin superfamily as receptors. In particular, viruses of different classes exploit nectins. The large DNA viruses, herpes simplex and pseudorabies viruses, use ubiquitous nectins 1 and 2. The negative-strand RNA virus measles virus (MeV) uses tissue-specific nectin-4, and the positive-strand RNA virus poliovirus uses nectin-like 5 (necl-5), also known as poliovirus receptor. These viruses contact the BC, C′C″, and FG loops on the upper tip of their receptor's most membrane-distal domain. This location corresponds to the newly defined canonical adhesive interface of nectins, but how viruses utilize this interface has remained unclear. Here we show that the same key residues in the BC and FG loops of nectin-4 govern binding to the MeV attachment protein hemagglutinin (H) and cell entry, nectin-4 homodimerization, and heterodimerization with nectin-1. On the other hand, residues in the C′C″ loop necessary for homo- and heterotypic interactions are dispensable for MeV-induced fusion and cell entry. Remarkably, the C′C″ loop governs dissociation of the nectin-4 and H ectodomains. We provide formal proof that H can interfere with the formation of stable nectin-1/nectin-4 heterodimers. Finally, while developing an alternative model to study MeV spread, we observed that polarized primary pig airway epithelial sheets cannot be infected. We show that a single amino acid variant in the BC loop of pig nectin-4 fully accounts for restricted MeV entry. Thus, the three loops forming the adhesive interface of nectin-4 have different roles in supporting MeV H association and dissociation and MeV-induced fusion.

IMPORTANCE
Different viruses utilize nectins as receptors. Nectins are immunoglobulin superfamily glycoproteins that mediate cell-cell adhesion in vertebrate tissues. They interact through an adhesive interface located at the top of their membrane-distal domain. How viruses utilize the three loops forming this interface has remained unclear. We demonstrate that while nectin-nectin interactions require residues in all three loops, the association of nectin-4 with the measles virus hemagglutinin requires only the BC and FG loops. However, we discovered that residues in the C′C″ loop modulate the dissociation of nectin-4 from the viral hemagglutinin. Analogous mechanisms may support cell entry of other viruses that utilize nectins or other cell adhesion molecules of the immunoglobulin superfamily as receptors.
RNA Populations in Immunocompromised Patients as Reservoirs for Novel Norovirus Variants
Authors: Vega Everardo , Donaldson Eric , Huynh Jeremy , Barclay Leslie , Lopman Ben , Baric Ralph , Chen Luke F. , Vinjé Jan
Published: October 2014

Noroviruses are the leading cause of acute gastroenteritis outbreaks worldwide. The majority of norovirus outbreaks are caused by genogroup II.4 (GII.4). Novel GII.4 strains emerge every 2 to 4 years and replace older variants as the dominant norovirus. Novel variants emerge through a combination of recombination, genetic drift, and selection driven by population immunity, but the exact mechanism of how or where is not known. We detected two previously unknown novel GII.4 variants, termed GII.4 UNK1 and GII.4 UNK2, and a diverse norovirus population in fecal specimens from immunocompromised individuals with diarrhea after they had undergone bone marrow transplantation. We hypothesized that immunocompromised individuals can serve as reservoirs for novel norovirus variants. To test our hypothesis, metagenomic analysis of viral RNA populations was combined with a full-genome bioinformatic analysis of publicly available GII.4 norovirus sequences from 1974 to 2014 to identify converging sites. Variable sites were proportionally more likely to be within two amino acids (
P
< 0.05) of positively selected sites. Further analysis using a hypergeometric distribution indicated that polymorphic site distribution was random and its proximity to positively selected sites was dependent on the size of the norovirus genome and the number of positively selected sites.In conclusion, random mutations may have a positive impact on driving norovirus evolution, and immunocompromised individuals could serve as potential reservoirs for novel GII.4 strains.

IMPORTANCE
Norovirus is the most common cause of viral gastroenteritis in the United States. Every 2 to 3 years novel norovirus variants emerge and replace dominant strains. The continual emergence of novel noroviruses is believed to be caused by a combination of genetic drift, population immunity, and recombination, but exactly how this emergence occurs remains unknown. In this study, we identified two novel GII.4 variants in immunocompromised bone marrow transplant patients. Using metagenomic and bioinformatic analysis, we showed that most genetic polymorphisms in the novel variants occur near 0 to 2 amino acids of positively selected sites, but the distribution of mutations was random; clustering of polymorphisms with positively selected sites was a result of genome size and number of mutations and positively selected sites. This study shows that immunocompromised patients can harbor infectious novel norovirus variants, and although mutations in viruses are random, they can have a positive effect on viral evolution.
Improving handover of patient care using a new weekend proforma with a focus on ceiling of care
Authors: Akhunbay-Fudge Christopher Yusuf , Buss Imogen , Ward Abigail , Snead Charlotte , Cole Miranda , Coulter Archie
Published: October 2014

Patient handover is paramount for effective patient care and is often poorly documented or incomplete. North Bristol NHS Trust weekend handover proformas identify medical patients requiring weekend review. Many patients seen during on-call shifts are not handed over. Our aim was to develop Friday ward round proforma sheets for medical patients, to encourage clear documentation of management plans in order to improve handover of important information, particularly ceiling of care decisions.

Questionnaires were completed by F1 doctors regarding current handover systems. Baseline data collected by on-call F1s included time of understanding a patient’s ceiling of care decision, and difficulty of comprehension of medical notes. Repeat data were collected with novel proformas in situ. Multiple cycles were performed to refine the sheets and target problems arising in their use.

Ninety-three percent of F1s wanted improved patient handover, with ceiling of care (87%) and management plans (73%) being the most difficult areas to understand. Time taken to ascertain ceiling of care decisions improved with the introduction of Friday handover proformas; mean time 153 seconds before and 5 seconds after. Clarity and documentation of management plans improved, with 50% improvement in ease of understanding medical notes.

Results demonstrate that introducing Friday ward round proformas for medical patients improves communication between weekday and on-call teams, highlights current escalation of care plans, and leads to faster decision-making. Future plans include the introduction of a short educational session to the new F1 doctors and continued progress with introduction into hospital stationary.
Hydraulic conductivity of clay mixed with nanomaterials
Authors: Ng C.W.W. , Coo J.L.
Published: October 2014

The focus of this note is to investigate the hydraulic conductivity behavior of clay mixed with nanomaterials. Two different nanomaterials — namely, gamma-aluminum oxide powder (γ-Al2O3) and nano-copper oxide (CuO) — were selected and mixed with clay at different percentages (i.e., 2%, 4%, and 6%). Hydraulic conductivity tests were carried out in a flexible wall permeameter following the ASTM D5084 standard. Mercury intrusion porosimetry (MIP) tests were also carried out to determine the pore-size distribution. At 2% of γ-Al2O3 and nano-CuO, the hydraulic conductivity of clay decreased 30% and 45%, respectively. As the proportion of the nanomaterial increases, the reduction of hydraulic conductivity becomes less prominent as flow paths devoid of nanomaterials are unlikely. Reduction of hydraulic conductivity is due to the pores of clay being clogged by the nanomaterial. Pore-size distribution curves show that the largest pore size reduced by 20% when clay was mixed with 4% nano-CuO.
Performance of 3D computers and 3D printed models as a fundamental means for spatial engineering information visualization
Authors: Dadi Gabriel B. , Taylor Timothy R.B. , Goodrum Paul M. , Maloney William F.
Published: October 2014

Engineering information delivery can be a source of inefficient communication of design, leading to construction rework and lower worker morale. Due to errors, omissions, and misinterpretations, there remains a great opportunity to improve the traditional documentation of engineering information that craft professionals use to complete their work. Historically, physical three dimensional (3D) models built by hand provided 3D physical representations of the project to assist in sequencing, visualization, and planning of critical construction activities. This practice has greatly diminished since the adoption of 3D computer-aided design (CAD) and building information modeling technologies. Recently, additive manufacturing (a.k.a. 3D printing) technologies have allowed for three dimensional printing of 3D CAD models. A cognitive experiment was established to measure the effectiveness of 2D drawings, a 3D computer model, and a 3D printed model in delivering engineering information to an end-user are scientifically measured. The 3D printed model outperformed the 2D drawings and 3D computer interface in productivity measures. This paper’s primary contribution to the body of knowledge is identification of how different mediums of engineering information influence the performance of a simple task execution.
New age data refine extent and duration of Paleozoic and Neoproterozoic plutonism at Ganderia–Avalonia boundary, Newfoundland
Authors: Kellett Dawn A. , Rogers Neil , McNicoll Vicki , Kerr Andrew , van Staal Cees
Published: October 2014

Devonian and younger plutonic suites of the Appalachian orogen in Newfoundland form a curvilinear belt straddling the boundary between Ganderia and Avalonia, and exhibit a general pattern of younging to the southeast. However, many individual plutonic suites within this belt remain undated or have ages that are poorly constrained. This study reports U–Pb sensitive high-resolution ion microprobe (SHRIMP) data from zircon and 40Ar–39Ar data from hornblende, biotite, and muscovite, which collectively improve definition of post-tectonic plutonic events in southeastern Newfoundland, but at the same time raise new questions for further study. U–Pb zircon SHRIMP determinations provide valuable new geochronological information for the Deadman’s Bay Granite (390 ± 4 Ma), the Gander Lake Granite (378 ± 4 Ma), the Terra Nova Granite (384 ± 4 Ma), the Old Woman stock (376 ± 4 Ma), and the easternmost unit (Tolt phase) of the composite Ackley Granite (372 ± 4 Ma). The Pass Island Granite, long considered part of this age group, gave a Silurian age of 423 ± 4 Ma and provides the first confirmation of Silurian granitoid magmatism in Avalonia of Newfoundland. The Berry Hills Granite on the Burin Peninsula, previously designated as Devonian, instead gave a Neoproterozoic age of 570 ± 6 Ma, and a similar age of 575 ± 6 Ma was obtained from granite that is intruded by the ca. 376 Ma Old Woman stock. These results indicate that regional geological context, deformation state, and (or) petrographic–geochemical data are not reliable indicators of emplacement age in this region. 40Ar–39Ar data from the Paleozoic granites provide mixed results in comparison to the U–Pb emplacement ages, and in some cases Ar systematics appear to have been disturbed by later hydrothermal alteration. In other cases, correspondence between the U–Pb and 40Ar–39Ar data sets is consistent with rapid postemplacement exhumation. Granophile-type mineralization (Mo, W, F, base metals) is present within both Ganderia and Avalonia examples, but is generally restricted to the youngest plutons, in which it is associated with high-level, near-roof, or apical settings. This age versus mineralization pattern is consistent with an interpretation in which mineralized environments within older suites have been preferentially eroded as a consequence of greater exhumation. The identification of a Silurian (ca. 423 Ma) granite in an area previously assigned to Avalonia may be important in constraining tectonic models for Ganderia–Avalonia interaction, which has generally been considered Silurian or younger. Given that many other plutonic suites in Avalonia are not well constrained by regional geology and remain undated, more work is needed to better define the extent of such magmatism and evaluate its implications for broader models of orogenic development.
Differential impacts of calcium and aluminum treatments on sugar maple and American beech growth dynamics
Authors: Halman Joshua M. , Schaberg Paul G. , Hawley Gary J. , Hansen Christopher F. , Fahey Timothy J.
Published: October 2014

Acid deposition induced losses of calcium (Ca) from northeastern forests have had negative effects on forest health for decades, including the mobilization of potentially phytotoxic aluminum (Al) from soils. To evaluate the impact of changes in Ca and Al availability on sugar maple (Acer saccharum Marsh.) and American beech (Fagus grandifolia Ehrh.) growth and forest composition following a major ice storm in 1998, we measured xylem annual increment, foliar cation concentrations, American beech root sprouting, and tree mortality at the Hubbard Brook Experimental Forest (Thornton, New Hampshire) in control plots and in plots amended with Ca or Al (treated plots) beginning in 1995. Dominant sugar maple trees were unaffected by the treatment, but nondominant sugar maple tree growth responded positively to Ca treatment. Although plots were mainly composed of sugar maple, American beech experienced the greatest growth on Al-treated plots. Increases in tree mortality on Al-treated plots may have released surviving American beech and increased their growth. The Al tolerance of American beech and the Ca:Al sensitivity of sugar maple contributed to divergent growth patterns that influenced stand productivity and composition. Given that acidic inputs are expected to continue, the growth dynamics associated with Al treatment may have direct relevance to future conditions in native forests.
Genetic control of immunity toTurnip mosaic virus(TuMV) pathotype 1 inBrassica rapa(Chinese cabbage)
Authors: Lydiate Derek J. , Pilcher Rachel L. Rusholme , Higgins Erin E. , Walsh John A.
Published: October 2014

Turnip mosaic virus (TuMV) is the major virus infecting crops of the genus Brassica worldwide. A dominant resistance gene, TuRB01b, that confers immunity to the virus isolate UK 1 (a representative pathotype 1 isolate of TuMV) on Brassica rapa was identified in the Chinese cabbage cultivar Tropical Delight. The TuRB01b locus was mapped to a 2.9-cM interval on B. rapa chromosome 6 (A6) that was flanked by RFLP markers pN101e1 and pW137e1. This mapping used a first backcross (B1) population segregating for the resistance gene at TuRB01b and sets of RFLP markers employed in previous mapping experiments in Brassica. Virus–plant interaction phenotypes were assayed in inbred progeny derived from B1individuals to allow different virus isolates to be tested. Comparative mapping confirmed that A6 of B. rapa was equivalent to chromosome 6 of Brassica napus (A6) and that the map position of TuRB01b in B. rapa could be identical to that of TuRB01 in B. napus. Detailed evaluation of plant–virus interactions showed that TuRB01 and TuRB01b had indistinguishable specificities to a range of TuMV isolates. The possibility that TuRB01 and TuRB01b represent similar or identical alleles at the same A genome resistance locus suggests that B. napus acquired TuRB01 from the B. rapa gene pool.
On the negative capacitance behavior in the forward bias of Au/n–4H–SiC (MS) and comparison between MS and Au/TiO2/n–4H–SiC (MIS) type diodes both in dark and under 200 W illumination intensity
Authors: Çetinkaya H. G. , Yıldız D. E. , Altındal Ş.
Published: October 2014

In order to see the effect of interfacial layer on electrical characteristics both Au /n–4 H – SiC (MS) and Au/TiO 2/n–4 H – SiC (MIS) type Schottky barrier diodes (SBDs) were fabricated and their main electrical parameters were investigated by using the forward and reverse bias current-voltage (I–V), capacitance/conductance-voltage (C/G–V) measurements at room temperature. The ideality factor (n), series and shunt resistances (Rs, Rsh), barrier height (BH), depletion layer width (WD) and the concentration of donor atoms (ND) were obtained before and after illumination. The energy density distribution profile of surface states (Nss) was also obtained by taking into account voltage dependent effective BH (Φe) and ideality factor (nV). All of these experimental results confirmed that the use of a high dielectric material or insulator layer ( TiO 2) between metal and semiconductor leads to improvements in the diode performance in terms of Rs, Rsh, BH, Nss and rectifier rate (RR = IF/IR for sufficiently high forward and reverse current). Another important result is the negative capacitance (NC) behavior observed in the forward bias C–V plot for the Au /n–4 H – SiC (MS) diode, but it disappears in Au/TiO 2/n–4 H – SiC (MIS) diode and also the minimum value of C–V plot corresponds to maximum value of G/ω–V plot in the accumulation region. Such behavior of NC shows that the material displays an inductive behavior.
WHAT ABOUT THE ENTREPRENEUR? HOW STATIC BUSINESS MODELS DRIVE AND HINDER THE DEVELOPMENT OF SELF-SUSTAINING LOCAL ENERGY ACCESS VENTURES
Authors: WAKKEE INGRID , BARUA RAHUL , VAN BEUKERING PIETER
Published: October 2014

The central assumption of publicly-supported market development programs is that providing resources to local entrepreneurs and strengthening the business environments fosters the emergence of self-sustaining local energy access ventures. We explore this assumption by applying a business model lens to analyze how participation in a market development program affects the development of local energy access ventures. Using the domestic biogas market development program in Rwanda as our case, we evaluate program design, the role of local entrepreneurs and interactions between participating ventures and the coordinating office to determine how market development programs contribute to a self-sustaining private energy sector. While providing a detailed framework for local ventures, the business model offers entrepreneurs few possibilities to act entrepreneurial and exploit local opportunities. Consequently, such programs will attract necessity-driven rather than opportunity- and growth-driven entrepreneurs, causing concern for the achievement of program objectives and the establishment of a self-sustaining private sector.
CASE REPORT: A DISEASE OUTBREAK OF BOVINE RESPIRATORY SYNCYTIAL VIRUS IN TAIWAN
Authors: Liu Shyh-Shyan , Shen Hsiu-Yen , Lee Jai-Wei , Lin Show-Win , Chen Hunter , Yang Chung-Da , Chu Chun-Yen
Published: October 2014

A dairy farm with 300 Holstein cattle in Hsin-Chu County, Taiwan, had an outbreak of a respiratory disease from the end of September to November, 2013. Adult animals (1–5-year-old) showed clinical symptoms of anorexia, depression, fever, and dropped milk production during the early stage of infection. In severe cases, animals suffered from dyspnea with frothy saliva at the edge of opened mouth. Samples were collected from eight sick animals, amplified in the baby hamster kidney cell-21 (BHK-21), and the cytopathic effect (CPE) was confirmed. Primers specific to Bovine respiratory syncytial virus (BRSV), Bovine viral diarrhea virus (BVDV), Bovine herpesvirus type I (BHV-I), Bovine ephemeral fever virus (BEFV) and Mannheimia haemolytica were used to identify the pathogen responsible for this respiratory disease by polymerase chain reaction (PCR). Results of sequence analysis confirmed that BRSV is the causative pathogen for the respiratory infection. This is, to the best of our knowledge, the first disease case of BRSV reported in Taiwan.
Distinguishing newforms
Authors: Chow Sam , Ghitza Alexandru
Published: October 2014

Let n0(N, k) be the number of initial Fourier coefficients necessary to distinguish newforms of level N and even weight k. We produce extensive data to support our conjecture that if N is a fixed squarefree positive integer and k is large then n0(N, k) is the least prime that does not divide N.
Neuroprotectin/protectin D1: endogenous biosynthesis and actions on diabetic macrophages in promoting wound healing and innervation impaired by diabetes
Authors: Hong Song , Tian Haibin , Lu Yan , Laborde James Monroe , Muhale Filipe A. , Wang Quansheng , Alapure Bhagwat V. , Serhan Charles N. , Bazan Nicolas G.
Published: October 2014

Dysfunction of macrophages (MΦs) in diabetic wounds impairs the healing. MΦs produce anti-inflammatory and pro-resolving neuroprotectin/protectin D1 (NPD1/PD1, 10 R,17 S-dihydroxy-docosa-4 Z,7 Z,11 E,13 E,15 Z,19 Z-hexaenoic acid); however, little is known about endogenous NPD1 biosynthesis by MΦs and the actions of NPD1 on diabetic MΦ functions in diabetic wound healing. We used an excisional skin wound model of diabetic mice, MΦ depletion, MΦs isolated from diabetic mice, and mass spectrometry-based targeted lipidomics to study the time course progression of NPD1 levels in wounds, the roles of MΦs in NPD1 biosynthesis, and NPD1 action on diabetic MΦ inflammatory activities. We also investigated the healing, innervation, chronic inflammation, and oxidative stress in diabetic wounds treated with NPD1 or NPD1-modulated MΦs from diabetic mice. Injury induced endogenous NPD1 biosynthesis in wounds, but diabetes impeded NPD1 formation. NPD1 was mainly produced by MΦs. NPD1 enhanced wound healing and innervation in diabetic mice and promoted MΦs functions that accelerated these processes. The underlying mechanisms for these actions of NPD1 or NPD1-modulated MΦs involved 1) attenuating MΦ inflammatory activities and chronic inflammation and oxidative stress after acute inflammation in diabetic wound, and 2) increasing MΦ production of IL10 and hepatocyte growth factor. Taken together, NPD1 appears to be a MΦs-produced factor that accelerates diabetic wound healing and promotes MΦ pro-healing functions in diabetic wounds. Decreased NPD1 production in diabetic wound is associated with impaired healing. This study identifies a new molecular target that might be useful in development of more effective therapeutics based on NPD1 and syngeneic diabetic MΦs for treatment of diabetic wounds.
Inhibitory control of the cough reflex by galanin receptors in the caudal nucleus tractus solitarii of the rabbit
Authors: Mutolo Donatella , Cinelli Elenia , Bongianni Fulvia , Pantaleo Tito
Published: October 2014

The caudal nucleus tractus solitarii (NTS) is the main central station of cough-related afferents and a strategic site for the modulation of the cough reflex. The similarities between the characteristics of central processing of nociceptive and cough-related inputs led us to hypothesize that galanin, a neuropeptide implicated in the control of pain, could also be involved in the regulation of the cough reflex at the level of the NTS, where galanin receptors have been found. We investigated the effects of galanin and galnon, a nonpeptide agonist at galanin receptors, on cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. Drugs were microinjected (30–50 nl) into the caudal NTS of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Galnon antitussive effects on cough responses to the mechanical stimulation of the airway mucosa via a custom-built device were also investigated. Bilateral microinjections of 1 mM galanin markedly decreased cough number, peak abdominal activity, and increased cough-related total cycle duration. Bilateral microinjections of 1 mM galnon induced mild depressant effects on cough, whereas bilateral microinjections of 10 mM galnon caused marked antitussive effects consistent with those produced by galanin. Galnon effects were confirmed by using the cough-inducing device. The results indicate that galanin receptors play a role in the inhibitory control of the cough reflex at the level of the caudal NTS and provide hints for the development of novel antitussive strategies.
Contribution of the autophagy-lysosomal and ubiquitin-proteasomal proteolytic systems to total proteolysis in rainbow trout (Oncorhynchus mykiss) myotubes
Authors: Seiliez Iban , Dias Karine , Cleveland Beth M.
Published: October 2014

The ubiquitin-proteasome system (UPS) is recognized as the major contributor to total proteolysis in mammalian skeletal muscle, responsible for 50% or more of total protein degradation in skeletal muscle, whereas the autophagic-lysosome system (ALS) plays a more minor role. While the relative contribution of these systems to muscle loss is well documented in mammals, little is known in fish species. The current study uses myotubes derived from rainbow trout myogenic precursor cells as an in vitro model of white muscle tissue. Cells were incubated in complete or serum-deprived media or media supplemented with insulin-like growth factor-1 (IGF-1) and exposed to selective proteolytic inhibitors to determine the relative contribution of the ALS and UPS to total protein degradation in myotubes in different culture conditions. Results indicate that the ALS is responsible for 30–34% and 50% of total protein degradation in myotubes in complete and serum-deprived media, respectively. The UPS appears to contribute much less to total protein degradation at almost 4% in cells in complete media to nearly 17% in serum-deprived cells. IGF-1 decreases activity of both systems, as it inhibited the upregulation of both proteolytic systems induced by serum deprivation. The combined inhibition of both the ALS and UPS reduced degradation by a maximum of 55% in serum-deprived cells, suggesting an important contribution of other proteolytic systems to total protein degradation. Collectively, these data identify the ALS as a potential target for strategies aimed at improving muscle protein retention and fillet yield through reductions in protein degradation.
Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome
Authors: Medow Marvin S. , Sood Shilpa , Messer Zachary , Dzogbeta Seli , Terilli Courtney , Stewart Julian M.
Published: October 2014

Chronic fatigue syndrome (CFS) with orthostatic intolerance is characterized by neurocognitive deficits and impaired working memory, concentration, and information processing. In CFS, upright tilting [head-up tilt (HUT)] caused decreased cerebral blood flow velocity (CBFv) related to hyperventilation/hypocapnia and impaired cerebral autoregulation; increasing orthostatic stress resulted in decreased neurocognition. We loaded the baroreflex with phenylephrine to prevent hyperventilation and performed n-back neurocognition testing in 11 control subjects and 15 CFS patients. HUT caused a significant increase in heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decrease in end-tidal CO2 (ETCO2; 42.8 ± 1.2 vs. 33.9 ± 1.1 Torr, P < 0.05) in CFS vs. control. HUT caused CBFv to decrease 8.7% in control subjects but fell 22.5% in CFS. In CFS, phenylephrine prevented the HUT-induced hyperventilation/hypocapnia and the significant drop in CBFv with HUT (−8.1% vs. −22.5% untreated). There was no difference in control subject n-back normalized response time (nRT) comparing supine to HUT (106.1 ± 6.9 vs. 97.6 ± 7.1 ms at n = 4), and no difference comparing control to CFS while supine (97.1 ± 7.1 vs 96.5 ± 3.9 ms at n = 4). However, HUT of CFS subjects caused a significant increase in nRT (148.0 ± 9.3 vs. 96.4 ± 6.0 ms at n = 4) compared with supine. Phenylephrine significantly reduced the HUT-induced increase in nRT in CFS to levels similar to supine (114.6 ± 7.1 vs. 114.6 ± 9.3 ms at n = 4). Compared with control subjects, CFS subjects are more sensitive both to orthostatic challenge and to baroreflex/chemoreflex-mediated interventions. Increasing blood pressure with phenylephrine can alter CBFv. In CFS subjects, mitigation of the HUT-induced CBFv decrease with phenylephrine has a beneficial effect on n-back outcome.
Context-dependent inhibition of unloaded muscles during the long-latency epoch
Authors: Nashed Joseph Y. , Kurtzer Isaac L. , Scott Stephen H.
Published: October 2014

A number of studies have highlighted the sophistication of corrective responses in lengthened muscles during the long-latency epoch. However, in various contexts, unloading can occur, which requires corrective actions from a shortened muscle. Here, we investigate the sophistication of inhibitory responses in shortened muscles due to unloading. Our first experiment quantified the inhibitory responses following an unloading torque that displaced the hand either into or away from a peripheral target. We observed larger long-latency inhibitory responses when perturbed into the peripheral target compared with away from the target. In our second experiment, we characterized the degree of inhibition following unloading with respect to different levels of preperturbation muscle activity. We initially observed that the inhibitory activity during the short-latency epoch scaled with increased levels of preperturbation muscle activity. However, this scaling peaked early in the R2 epoch (∼50 ms) but then quickly diminished through the rest of the long-latency epoch. Finally, in experiment 3, we investigated whether inhibitory perturbation responses consider intersegmental dynamics of the limb. We quantified unloading responses for either pure shoulder or pure elbow torques that evoked similar motion at the shoulder but different elbow motion. The long-latency inhibitory response in the shoulder, unlike the short-latency, was greater for the shoulder torque compared with the response following an elbow torque, as previously observed for a loading response. Taken together, these results illustrate that the long-latency unloading response is capable of a similar level of complexity as observed when loads are applied to the limb.
The power of the mind: the cortex as a critical determinant of muscle strength/weakness
Authors: Clark Brian C. , Mahato Niladri K. , Nakazawa Masato , Law Timothy D. , Thomas James S.
Published: October 2014

We tested the hypothesis that the nervous system, and the cortex in particular, is a critical determinant of muscle strength/weakness and that a high level of corticospinal inhibition is an important neurophysiological factor regulating force generation. A group of healthy individuals underwent 4 wk of wrist-hand immobilization to induce weakness. Another group also underwent 4 wk of immobilization, but they also performed mental imagery of strong muscle contractions 5 days/wk. Mental imagery has been shown to activate several cortical areas that are involved with actual motor behaviors, including premotor and M1 regions. A control group, who underwent no interventions, also participated in this study. Before, immediately after, and 1 wk following immobilization, we measured wrist flexor strength, voluntary activation (VA), and the cortical silent period (SP; a measure that reflect corticospinal inhibition quantified via transcranial magnetic stimulation). Immobilization decreased strength 45.1 ± 5.0%, impaired VA 23.2 ± 5.8%, and prolonged the SP 13.5 ± 2.6%. Mental imagery training, however, attenuated the loss of strength and VA by ∼50% (23.8 ± 5.6% and 12.9 ± 3.2% reductions, respectively) and eliminated prolongation of the SP (4.8 ± 2.8% reduction). Significant associations were observed between the changes in muscle strength and VA ( r = 0.56) and SP ( r = −0.39). These findings suggest neurological mechanisms, most likely at the cortical level, contribute significantly to disuse-induced weakness, and that regular activation of the cortical regions via imagery attenuates weakness and VA by maintaining normal levels of inhibition.
Evolution of SILS Cholecystectomy in the Caribbean: The Direct Transfascial Puncture Technique Using Conventional Instruments without Working Ports
Authors: Cawich Shamir O. , Thomas Dexter , Hassranah Dale , Naraynsingh Vijay
Published: October 2014

Introduction.Single incision laparoscopic cholecystectomy (SILC) has become accepted as an alternative to conventional multiport cholecystectomy. However, SILC is still limited in applicability in low resource centres due to the expense associated with specialized access platforms, curved instruments, and flexible scopes.Presentation of Case.We present three cases where a modified SILC technique was used with conventional instruments and no working ports. The evolution of this technique is described.Discussion.In order to contain cost, we used conventional instruments and three transfascial ports placed in an umbilical incision, but we noted significant instrument clashes that originated at the port platforms. Therefore, we modified our technique by omitting ports for the working instruments. The technique allowed us to exchange instruments as necessary, maximized ergonomics, and prevented collisions from the bulky port platforms. Finally, the puncture left by the instrument alone did not require fascial closure at the termination of the procedure.Conclusion.The direct transfascial puncture using conventional laparoscopic instruments without working ports is a feasible option that minimizes cost and increases ergonomics.
Langerhans Cell Histiocytosis of the Thyroid with Multiple Cervical Lymph Node Involvement Accompanying Metastatic Thyroid Papillary Carcinoma
Authors: Ceyran A. Bahar , Şenol Serkan , Bayraktar Barış , Özkanlı Şeyma , Cinel Z. Leyla , Aydın Abdullah
Published: October 2014

A 37-year-old male case was admitted with goiter. Ultrasonography of thyroid showed a 5 cm cystic nodule in the left lobe with a 1.5 cm solid component. Fine needle aspiration biopsy revealed atypia of undetermined significance or follicular lesion. The patient was operated on. The pathological diagnosis was reported as papillary thyroid carcinoma. The immunohistochemical examination showed multiple foci of Langerhans cell histiocytosis involving both lobes. The patient died due to cardiac arrest with respiratory causes in the early postoperative period. Langerhans cell histiocytosis is a rare primary condition which involves abnormal clonal proliferation of Langerhans cells in various tissues and organs. Thyroid involvement is infrequently seen. Although the etiology is unknown, genetic components may be linked to the disease. It is also associated with a family history of thyroid disease. Papillary thyroid carcinoma is the most common malignant epithelial tumor of the thyroid gland. Langerhans cell histiocytosis presenting with papillary thyroid carcinoma is rare. The privilege of our case is langerhans cell histiocytosis of the thyroid with multiple cervical lymph node involvement accompanying cervical lymph node metastatic thyroid papillary carcinoma.
Screening of Pearl Millet F1Hybrids for Heat Tolerance at Early Seedling Stage
Authors: Yadav Ashok Kumar , Arya Rajesh Kumar , Narwal M. S.
Published: October 2014

Ten pearl millet genotypes selected on the basis of response to supra-optimal temperature tolerance were crossed in a half-diallel mating system. The 45F1hybrids produced were tested along with parents for heat tolerance and related traits at seedling stage. Field screening and laboratory screening techniques were simultaneously used for the evaluation ofF1hybrids and their parents. Heat tolerance was measured as seedling thermotolerance index (STI) and seed to seedling thermotolerance index (SSTI) under field conditions, but membrane thermostability (MTS) in the laboratory. The hybrid H77/29-2×CVJ-2-5-3-1-3 showed highest STI value followed by H77/833-2×96AC-93. The genotype H77/833-2×96AC-93 had the highest worth for SSTI. These three indices were highly correlated among themselves. STI values were invariably high, whereas SSTI has lower values, as it also covers the effect of under soil mortality (USM). It was seen that the heat tolerance indices STI and SSTI were not showing any perceptible pooled correlation with developmental traits except germination and emergence rate. Based on our results, it could be suggested that membrane thermostability (MTS) may be used for screening large number of genotypes. Field based indices STI and SSTI may be used for evaluation of hybrids and varieties before they are released.
Kawasaki Disease with Retropharyngeal Edema following a Blackfly Bite
Authors: Watanabe Toru
Published: October 2014

We describe a patient with Kawasaki disease (KD) and retropharyngeal edema following a blackfly bite. An 8-year-old boy was referred to our hospital because of a 3-day-history of fever and left neck swelling and redness after a blackfly bite. Computed tomography of the neck revealed left cervical lymph nodes swelling with edema, increased density of the adjacent subcutaneous tissue layer, and low density of the retropharyngeum. The patient was initially presumed to have cervical cellulitis, lymphadenitis, and retropharyngeal abscess. He was administered antibiotics intravenously, which did not improve his condition. The patient subsequently exhibited other signs of KD and was diagnosed with KD and retropharyngeal edema. Intravenous immunoglobulin therapy and oral flurbiprofen completely resolved the symptoms and signs. A blackfly bite sometimes incites a systemic reaction in humans due to a hypersensitive reaction to salivary secretions, which may have contributed to the development of KD in our patient.
Design of Iterative Learning Control Method with Global Convergence Property for Nonlinear Systems
Authors: Xu Guang-Wei , Shao Cheng , Han Yu
Published: October 2014

We address an iterative learning control (ILC) method for overcoming initial value problem caused by local convergence methods. Introducing a feedback recursive form of tracking errors into iterative learning law, this algorithm can avoid a crude linear approximation to nonlinear plants to reach global convergence property. The algorithm’s structure is entirely illustrated. Under assumptions, it is guaranteed that tracking errors of the closed-loop system converge to zero. Besides, we discuss the roles of parameters in iterative learning law for algorithm realization, and a nonlinear case study is presented to demonstrate the effectiveness and tracking performance of the proposed algorithm.
Aluminum-Induced Entropy in Biological Systems: Implications for Neurological Disease
Authors: Shaw Christopher A. , Seneff Stephanie , Kette Stephen D. , Tomljenovic Lucija , Oller John W. , Davidson Robert M.
Published: October 2014

Over the last 200 years, mining, smelting, and refining of aluminum (Al) in various forms have increasingly exposed living species to this naturally abundant metal. Because of its prevalence in the earth’s crust, prior to its recent uses it was regarded as inert and therefore harmless. However, Al is invariably toxic to living systems and has no known beneficial role in any biological systems. Humans are increasingly exposed to Al from food, water, medicinals, vaccines, and cosmetics, as well as from industrial occupational exposure. Al disrupts biological self-ordering, energy transduction, and signaling systems, thus increasing biosemiotic entropy. Beginning with the biophysics of water, disruption progresses through the macromolecules that are crucial to living processes (DNAs, RNAs, proteoglycans, and proteins). It injures cells, circuits, and subsystems and can cause catastrophic failures ending in death. Al forms toxic complexes with other elements, such as fluorine, and interacts negatively with mercury, lead, and glyphosate. Al negatively impacts the central nervous system in all species that have been studied, including humans. Because of the global impacts of Al on water dynamics and biosemiotic systems, CNS disorders in humans are sensitive indicators of the Al toxicants to which we are being exposed.
Barriers to Lose Weight from the Perspective of Children with Overweight/Obesity and Their Parents: A Sociocultural Approach
Authors: Rodríguez-Ventura Ana Lilia , Pelaez-Ballestas Ingris , Sámano-Sámano Reyna , Jimenez-Gutierrez Carlos , Aguilar-Salinas Carlos
Published: October 2014

Introduction.There are not enough studies about the barriers to lose weight from the perspective of children and their parents.Methods.Children and adolescents diagnosed with overweight/obesity in the Department of Endocrinology and their parents were invited to participate in a series of focus group discussions (FGD). Twenty-nine children 10–16 years old and 22 parents participated in 7 focus groups; 2 mothers and 2 adolescents participated in depth interviews. All interviews were recorded, transcribed, and analyzed through grounded theory.Results.Parents went to the hospital only when their children presented any obesity complication; for them, overweight was not a health problem. Parents referred to lack of time to supervise about a healthy diet and exercise; besides, the same parents, relatives, friends, and the mass media encourage the consumption of junk food. Children accepted eating a lot, not doing exercise, skipping meals, and not understanding overweight consequences. Both, parents and children, demanded support to do the time recommended for exercise inside the schools. They also suggested getting information from schools and mass media (TV) about overweight consequences, exercise, and healthy food by health workers; they recommended prohibiting announcements about junk food and its sale.Conclusions.The barriers detected were lack of perception of being overweight, its identification as a disease and its consequences, lack of time to supervise a healthy lifestyle, and a big social influence to eat junk food.
Hepatic Lesions with Secondary Syphilis in an HIV-Infected Patient
Authors: Solari Paola R. , Jones Christopher , Wallace Mark R.
Published: October 2014

Syphilis among HIV-infected patients continues to be a public health concern, especially in men who have sex with men. The clinical manifestations of syphilis are protean; syphilitic hepatitis is an unusual complication that can occur at any stage of the disease. We report a case of an HIV-infected male who presented with systemic symptoms and liver lesions highly suggestive of lymphoma and was proven to have syphilitic hepatitis by liver biopsy. Our case reinforces the importance of recognizing syphilis as a possible cause of unexplained abnormal liver enzymes and/or hepatic lesions in HIV-infected patients.