bluuebunny/crossref_metadata_2025 huggingface dataset:
The Potyvirus Silencing Suppressor Protein VPg Mediates Degradation of SGS3 via Ubiquitination and Autophagy Pathways
Authors: Cheng Xiaofei , Wang Aiming
Published: October 2016

RNA silencing is an innate antiviral immunity response of plants and animals. To counteract this host immune response, viruses have evolved an effective strategy to protect themselves by the expression of viral suppressors of RNA silencing (VSRs). Most potyviruses encode two VSRs, helper component-proteinase (HC-Pro) and viral genome-linked protein (VPg). The molecular biology of the former has been well characterized, whereas how VPg exerts its function in the suppression of RNA silencing is yet to be understood. In this study, we show that infection by
Turnip mosaic virus
(TuMV) causes reduced levels of suppressor of gene silencing 3 (SGS3), a key component of the RNA silencing pathway that functions in double-stranded RNA synthesis for virus-derived small interfering RNA (vsiRNA) production. We also demonstrate that among 11 TuMV-encoded viral proteins, VPg is the only one that interacts with SGS3. We furthermore present evidence that the expression of VPg alone, independent of viral infection, is sufficient to induce the degradation of SGS3 and its intimate partner RNA-dependent RNA polymerase 6 (RDR6). Moreover, we discover that the VPg-mediated degradation of SGS3 occurs via both the 20S ubiquitin-proteasome and autophagy pathways. Taken together, our data suggest a role for VPg-mediated degradation of SGS3 in suppression of silencing by VPg.

IMPORTANCE
Potyviruses represent the largest group of known plant viruses and cause significant losses of many agriculturally important crops in the world. In order to establish infection, potyviruses must overcome the host antiviral silencing response. A viral protein called VPg has been shown to play a role in this process, but how it works is unclear. In this paper, we found that the VPg protein of
Turnip mosaic virus
(TuMV), which is a potyvirus, interacts with a host protein named SGS3, a key protein in the RNA silencing pathway. Moreover, this interaction leads to the degradation of SGS3 and its interacting and functional partner RDR6, which is another essential component of the RNA silencing pathway. We also identified the cellular pathways that are recruited for the VPg-mediated degradation of SGS3. Therefore, this work reveals a possible mechanism by which VPg sabotages host antiviral RNA silencing to promote virus infection.
Efficient Transformation of Primary Human Mesenchymal Stromal Cells by Adenovirus Early Region 1 Oncogenes
Authors: Speiseder Thomas , Hofmann-Sieber Helga , Rodríguez Estefanía , Schellenberg Anna , Akyüz Nuray , Dierlamm Judith , Spruss Thilo , Lange Claudia , Dobner Thomas
Published: October 2016

Previous observations that human amniotic fluid cells (AFC) can be transformed by human adenovirus type 5 (HAdV-5) E1A/E1B oncogenes prompted us to identify the target cells in the AFC population that are susceptible to transformation. Our results demonstrate that one cell type corresponding to mesenchymal stem/stroma cells (hMSCs) can be reproducibly transformed by HAdV-5 E1A/E1B oncogenes as efficiently as primary rodent cultures. HAdV-5 E1-transformed hMSCs exhibit all properties commonly associated with a high grade of oncogenic transformation, including enhanced cell proliferation, anchorage-independent growth, increased growth rate, and high telomerase activity as well as numerical and structural chromosomal aberrations. These data confirm previous work showing that HAdV preferentially transforms cells of mesenchymal origin in rodents. More importantly, they demonstrate for the first time that human cells with stem cell characteristics can be completely transformed by HAdV oncogenes in tissue culture with high efficiency. Our findings strongly support the hypothesis that undifferentiated progenitor cells or cells with stem cell-like properties are highly susceptible targets for HAdV-mediated cell transformation and suggest that virus-associated tumors in humans may originate, at least in part, from infections of these cell types. We expect that primary hMSCs will replace the primary rodent cultures in HAdV viral transformation studies and are confident that these investigations will continue to uncover general principles of viral oncogenesis that can be extended to human DNA tumor viruses as well.

IMPORTANCE
It is generally believed that transformation of primary human cells with HAdV-5 E1 oncogenes is very inefficient. However, a few cell lines have been successfully transformed with HAdV-5 E1A and E1B, indicating that there is a certain cell type which is susceptible to HAdV-mediated transformation. Interestingly, all those cell lines have been derived from human embryonic tissue, albeit the exact cell type is not known yet. We show for the first time the successful transformation of primary human mesenchymal stromal cells (hMSCs) by HAdV-5 E1A and E1B. Further, we show upon HAdV-5 E1A and E1B expression that these primary progenitor cells exhibit features of tumor cells and can no longer be differentiated into the adipogenic, chondrogenic, or osteogenic lineage. Hence, primary hMSCs represent a robust and novel model system to elucidate the underlying molecular mechanisms of adenovirus-mediated transformation of multipotent human progenitor cells.
Mycosins Are Required for the Stabilization of the ESX-1 and ESX-5 Type VII Secretion Membrane Complexes
Authors: van Winden Vincent J. C. , Ummels Roy , Piersma Sander R. , Jiménez Connie R. , Korotkov Konstantin V. , Bitter Wilbert , Houben Edith N. G.
Published: October 2016

Pathogenic mycobacteria contain up to five type VII secretion (T7S) systems, ESX-1 to ESX-5. One of the conserved T7S components is the serine protease mycosin (MycP). Strikingly, whereas MycP is essential for secretion, the protease activity of MycP
1
in
Mycobacterium tuberculosis
has been shown to be dispensable for secretion. The essential role of MycP therefore remains unclear. Here we show that MycP
1
and MycP
5
of
M. marinum
have similar phenotypes, confirming that MycP has a second unknown function that is essential for its T7S system. To investigate whether this role is related to proper functioning of the T7S membrane complex, we first analyzed the composition of the ESX-1 membrane complex and showed that this complex consists of EccBCDE
1
, similarly to what was previously shown for ESX-5. Surprisingly, while mycosins are not an integral part of these purified core complexes, we noticed that the stability of both the ESX-1 complex and the ESX-5 complex is compromised in the absence of their MycP subunit. Additional interaction studies showed that, although mycosins are not part of the central ESX membrane complex, they loosely associate with this complex. We hypothesize that this MycP association with the core membrane complex is crucial for the integrity and functioning of the T7S machinery.

IMPORTANCE
Among the major virulence factors of pathogenic mycobacteria are the type VII secretion (T7S) systems. Three of these systems, ESX-1, ESX-3, and ESX-5, have been shown to be crucial for virulence or viability. Here we describe the function of mycosin proteases, which are conserved components within these systems. We show that MycP
1
and MycP
5
have a second, proteolytic-independent function which is essential for the T7S system. We additionally found that this second essential role is related to the stabilization and proper functioning of their respective ESX membrane core complexes. Finally, we found that this is mediated by a loose association of MycP with the complex. Understanding the essential role of mycosins in type VII secretion systems, which play central roles in the virulence and viability of pathogenic mycobacteria, may provide new intervention strategies to treat tuberculosis.
Exported Epoxide Hydrolases Modulate Erythrocyte Vasoactive Lipids during Plasmodium falciparum Infection
Authors: Spillman Natalie J. , Dalmia Varun K. , Goldberg Daniel E.
Published: October 2016

Erythrocytes are reservoirs of important epoxide-containing lipid signaling molecules, including epoxyeicosatrienoic acids (EETs). EETs function as vasodilators and anti-inflammatory modulators in the bloodstream. Bioactive EETs are hydrolyzed to less active diols (dihydroxyeicosatrienoic acids) by epoxide hydrolases (EHs). The malaria parasite
Plasmodium falciparum
infects host red blood cells (RBCs) and exports hundreds of proteins into the RBC compartment. In this study, we show that two parasite epoxide hydrolases,
P. falciparum
epoxide hydrolases 1 (PfEH1) and 2 (PfEH2), both with noncanonical serine nucleophiles, are exported to the periphery of infected RBCs. PfEH1 and PfEH2 were successfully expressed in
Escherichia coli
, and they hydrolyzed physiologically relevant erythrocyte EETs. Mutations in active site residues of PfEH1 ablated the ability of the enzyme to hydrolyze an epoxide substrate. Overexpression of PfEH1 or PfEH2 in parasite-infected RBCs resulted in a significant alteration in the epoxide fatty acids stored in RBC phospholipids. We hypothesize that the parasite disruption of epoxide-containing signaling lipids leads to perturbed vascular function, creating favorable conditions for binding and sequestration of infected RBCs to the microvascular endothelium.

IMPORTANCE
The malaria parasite exports hundreds of proteins into the erythrocyte compartment. However, for most of these proteins, their physiological function is unknown. In this study, we investigate two “hypothetical” proteins of the α/β-hydrolase fold family that share sequence similarity with epoxide hydrolases (EHs)—enzymes that destroy bioactive epoxides. Altering EH expression in parasite-infected erythrocytes resulted in a significant change in the epoxide fatty acids stored in the host cell. We propose that these EH enzymes may help the parasite to manipulate host blood vessel opening and inflame the vessel walls as they pass through the circulation system. Understanding how the malaria parasite interacts with its host RBCs will aid in our ability to combat this deadly disease.
A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts
Authors: Gerwien Franziska , Safyan Abu , Wisgott Stephanie , Hille Fabrice , Kaemmer Philipp , Linde Jörg , Brunke Sascha , Kasper Lydia , Hube Bernhard
Published: October 2016

Iron is an essential micronutrient for both pathogens and their hosts, which restrict iron availability during infections in an effort to prevent microbial growth. Successful human pathogens like the yeast
Candida glabrata
have thus developed effective iron acquisition strategies. Their regulation has been investigated well for some pathogenic fungi and in the model organism
Saccharomyces cerevisiae
, which employs an evolutionarily derived system. Here, we show that
C. glabrata
uses a regulation network largely consisting of components of the
S. cerevisiae
regulon but also of elements of other pathogenic fungi. Specifically, similarly to baker’s yeast, Aft1 is the main positive regulator under iron starvation conditions, while Cth2 degrades mRNAs encoding iron-requiring enzymes. However, unlike the case with
S. cerevisiae
, a Sef1 ortholog is required for full growth under iron limitation conditions, making
C. glabrata
an evolutionary intermediate to
SEF1
-dependent fungal pathogens. Therefore,
C. glabrata
has evolved an iron homeostasis system which seems to be unique within the pathogenic fungi.

IMPORTANCE
The fungus
Candida glabrata
represents an evolutionarily close relative of the well-studied and benign baker’s yeast and model organism
Saccharomyces cerevisiae
. On the other hand,
C. glabrata
is an important opportunistic human pathogen causing both superficial and systemic infections. The ability to acquire trace metals, in particular, iron, and to tightly regulate this process during infection is considered an important virulence attribute of a variety of pathogens. Importantly,
S. cerevisiae
uses a highly derivative regulatory system distinct from those of other fungi. Until now, the regulatory mechanism of iron homeostasis in
C. glabrata
has been mostly unknown. Our study revealed a hybrid iron regulation network that is unique to
C. glabrata
and is placed at an evolutionary midpoint between those of
S. cerevisiae
and related fungal pathogens. We thereby show that, in the host, even a successful human pathogen can rely largely on a strategy normally found in nonpathogenic fungi from a terrestrial environment.
Shewanella baltica Ecotypes Have Wide Transcriptional Variation under the Same Growth Conditions
Authors: Hambright W. S. , Deng Jie , Tiedje James M. , Brettar Ingrid , Rodrigues Jorge L. M.
Published: October 2016

Eukaryotic studies have shown considerable transcriptional variation among individuals from the same population. It has been suggested that natural variation in eukaryotic gene expression may have significant evolutionary consequences and may explain large-scale phenotypic divergence of closely related species, such as humans and chimpanzees (M.-C. King and A. C. Wilson, Science 188:107–116, 1975,http://dx.doi.org/10.1126/science.1090005; M. F. Oleksiak, G. A. Churchill, and D. L. Crawford, Nat Genet 32:261–266, 2002,http://dx.doi.org/10.1038/ng983). However, natural variation in gene expression is much less well understood in prokaryotic organisms. In this study, we used four sequenced strains of the marine bacteriumShewanella balticato better understand the natural transcriptional divergence of a stratified prokaryotic population. We found substantial low-magnitude expressional variation among the fourS. balticastrains cultivated under identical laboratory conditions. Collectively, our results indicate that transcriptional variation is an important factor for ecological speciation.
Volunteering and overseas placements in the NHS: a survey of current activity
Authors: Chatwin John , Ackers Louise
Published: October 2016

Objective

The study aimed to establish current levels of overseas volunteering and placement activity across all staff grades within the National Health Service (NHS) in the North West of England.

Design

Cross-sectional survey.

Instrument

Descriptive statistics.

Setting

4 main regional hospitals in the North West of England, and additional NHS staff training events.

Participants

Convenience sample of NHS staff (n=911).

Results

911 NHS staff took part in the survey. The medical and dental staff group returned the highest number of responses (32.1%). 42% of staff reported some form of overseas volunteering or placement experience. Most staff took an international placement as students (33.6% men; 40.6% women). Medium-term placements were undertaken by 46.7% of men, and 52.5% of women. Settlement stays (ie, over 1 year) were reported by 7.6% men, and 8.3% women). The majority of respondents engaged in international placement were from the age groups incorporating ‘below 25’ to ‘41–50’ (74%). Multiple placement experiences were uncommon: 2.5% of respondents reported three periods of overseas activity, and 1.5% reported four. All those with multiple placement experience came from the staff groups incorporating midwife/nurse/health visitor, and medical and dental.

Conclusions

This survey captured a snapshot of current levels of volunteering and overseas placement activity across NHS staff grades in the North West. Owing to relatively homogenous organisational structures, findings are likely to broadly represent the position across the organisation as a whole. Although some degree of overseas placement activity is undertaken by a relatively high proportion of NHS staff, such activity is currently heavily skewed towards higher clinical staff grades. Significant numbers of allied health professionals and equivalent non-clinical cadres also report overseas experience, and we anticipate that the numbers will continue to rise if current policy initiatives gain momentum.
Ethics knowledge of recent paediatric residency graduates: the role of residency ethics curricula
Authors: Kesselheim Jennifer C , Najita Julie , Morley Debra , Bair Elizabeth , Joffe Steven
Published: October 2016

Objective

To evaluate the relationship between recently trained paediatricians' ethics knowledge and exposure to a formal ethics or professionalism curriculum during residency.

Methods

We conducted a cross-sectional survey of recently trained paediatricians which included a validated 23-item instrument called the Test of Residents' Ethics Knowledge for Pediatrics. The sample included paediatricians who completed medical school in 2006–2008, whose primary specialty was paediatrics or a paediatric subspecialty, and who completed paediatric residency training in 2010–2011. This sample was stratified based on residency programme variables: presence of a formal curriculum in ethics or professionalism, programme size and American Board of Pediatrics certifying exam passage rate. Paediatricians were randomly selected from each stratum for survey participation.

Results

Among the 370 responding paediatricians (55%), the mean knowledge score was 17.3 (SD 2.2) out of a possible 23. Presence of a formal curriculum in ethics and/or professionalism was not significantly associated with knowledge. Knowledge was lowest on items about parental requests for a child to undergo genetic testing (2 items, 44% and 85% incorrect), preserving patient confidentiality over email (55% incorrect), decision-making regarding life-sustaining technologies (61% incorrect), and decision-making principles such as assent and parental permission (2 items, 47% and 49% incorrect).

Conclusions

This study highlights several areas in which paediatricians' knowledge may be low and that are amenable to targeted educational interventions. These findings should prompt discussion and research among ethicists and educators about how ethics and professionalism curricula can more consistently influence paediatricians' knowledge.
Some analytic models of plane symmetric radiating collapse
Authors: Abbas G. , Shah Hassan , Ahmad Zahid
Published: October 2016

This paper deals with the analytical solutions of the field equations in the presence of radiating plane symmetric source. For this purpose we have solved the field equations as well as junction conditions by imposing the conformal flatness conditions. The effective adiabatic index (that determines the stability of the system) has been calculated for the present radiating source. It has been found that effective adiabatic index remains invariant throughout the matter distribution. To study the thermal behavior of the source, we have discussed the thermal profile of the source and found that in the absence of dissipation from the system the temperature of the system remains constant.
Perinatal hypothyroidism modulates antioxidant defence status in the developing rat liver and heart
Authors: Zhang Hongmei , Dong Yan , Su Qing
Published: October 2016

In the present study, we investigated oxidative stress parameters and antioxidant defence status in perinatal hypothyroid rat liver and heart. We found that the proteincarbonyl content did not differ significantly between the three groups both in the pup liver and in the heart. The OH˙ level was significantly decreased in the hypothyroid heart but not in the liver compared with controls. A slight but not significant decrease in SOD activity was observed in both perinatal hypothyroid liver and heart. A significantly increased activity of CAT was observed in the liver but not in the heart of hypothyroid pups. The GPx activity was considerably increased compared with controls in the perinatal hypothyroid heart and was unaltered in the liver of hypothyroid pups. We also found that vitamin E levels in the liver decreased significantly in hypothyroidism and were unaltered in the heart of perinatal hypothyroid rats. The GSH content was elevated significantly in both hypothyroid liver and heart. The total antioxidant capacity was higher in the liver of the hypothyroid group but not in the hypothyroid heart. Thyroxine replacement could not repair the above changes to normal. In conclusion, perinatal hypothyroidism modulates the oxidative stress status of the perinatal liver and heart.
Triple gauge couplings at future hadron and lepton colliders
Authors: Bian Ligong , Shu Jing , Zhang Yongchao
Published: October 2016

The [Formula: see text] production is the primary channel to directly probe the triple gauge couplings (TGCs). We analyze the [Formula: see text] process at the proposed circular electron–positron collider (CEPC), and find that the anomalous TGCs and relevant dimension six operators can be probed up to the order of [Formula: see text]. We also estimate constraints at the 14 TeV (LHC), with both 300 fb[Formula: see text] and 3000 fb[Formula: see text] integrated luminosity from the leading lepton [Formula: see text] and azimuthal angle difference [Formula: see text] in the di-lepton channel. The constrain is somewhat weaker, up to the order of [Formula: see text]. The limits on the TGCs are complementary to those on the electroweak precision observables and Higgs couplings.
Dynamic Response of a Defected Periodic Viaduct to a Moving Point Load
Authors: Sha Xuan , Lu Jian-Fei , Lan Tian , Jeng Dong-Sheng
Published: October 2016

A defected periodic viaduct (DPV) is an infinite viaduct consisting of a left and a right semi-infinite ordered periodic viaducts (OPV) and one or several in-between defected spans different from the standard span of the OPV. Currently, no methodology is available in the literature for assessing the dynamic response of a DPV to a moving load, as the presence of the defected spans breaks the periodicity of the OPV. In this study, a new FEM model for estimating the dynamic response of a DPV with one defected span to a moving load is proposed. To establish the model, the time-space domain (TSD) moving load is decomposed into the sum of its constituent frequency wavenumber domain (FWD) load components first. For the DPV subjected to the FWD load component, the response of the left and right semi-infinite OPVs of the DPV can be divided into two parts, namely, the free wave field and the scattered wave field. To determine the free wave field of the left and right semi-infinite OPVs of the DPV, the FEM equations for an individual span of the viaduct are established and applied to the two OPVs. The scattered wave field in the two semi-infinite OPVs consists of the characteristic waves of the OPV and can be determined using the FEM eigenvalue equations for the OPV free of external loads. Applying the span FEM equations to the defected span and using the expressions for the free wave field and the scattered wave field yield the FWD response of the DPV. The time-space domain response of the DPV can then be retrieved by superposing all the FWD responses of the DPV. Numerical simulations are conducted to investigate the influence of the defected span on the dynamic response of the DPV. For the DPV, there are two kinds of the resonant frequencies, namely, the resonant frequencies common to the corresponding OPV and the additional resonant frequencies due to the presence of the defected span. In some cases, the magnitudes of the responses at the additional resonant frequencies may be larger than those at the common resonance frequencies. Therefore, when conducting the design for a periodic viaduct, it is important to account for the influence of the defected span on the dynamic response of the periodic viaduct.
Inflammation drives renal scarring in experimental pyelonephritis
Authors: Li Birong , Haridas Babitha , Jackson Ashley R. , Cortado Hanna , Mayne Nicholas , Kohnken Rebecca , Bolon Brad , McHugh Kirk M. , Schwaderer Andrew L. , Spencer John David , Ching Christina B. , Hains David S. , Justice Sheryl S. , Partida-Sanchez Santiago , Becknell Brian
Published: October 2016

Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment, and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis. The extent of fibrosis correlates most significantly with inflammation at 7 and 28 days postinfection. The recruitment of neutrophils and inflammatory macrophages to infected kidneys is proportional to renal bacterial burden. Transcriptome analysis reveals molecular signatures associated with renal ischemia-reperfusion injury, immune cell chemotaxis, and leukocyte activation. This murine model recapitulates the cardinal histopathological features observed in humans with acquired renal scarring following pyelonephritis. The integration of histopathology, quantification of cellular immune influx, and unbiased transcriptional profiling begins to define potential mechanisms of tissue injury during pyelonephritis in the context of an intact immune response. The clear relationship between inflammatory cell recruitment and fibrosis supports the hypothesis that acquired renal scarring arises as a consequence of excessive host inflammation and suggests that immunomodulatory therapies should be investigated to reduce renal scarring in patients with pyelonephritis.
Skeletal muscle and resistance exercise training; the role of protein synthesis in recovery and remodeling
Authors: McGlory Chris , Devries Michaela C. , Phillips Stuart M.
Published: October 2016

Exercise results in the rapid remodeling of skeletal muscle. This process is underpinned by acute and chronic changes in both gene and protein synthesis. In this short review we provide a brief summary of our current understanding regarding how exercise influences these processes as well as the subsequent impact on muscle protein turnover and resultant shift in muscle phenotype. We explore concepts of ribosomal biogenesis and the potential role of increased translational capacity vs. translational efficiency in contributing to muscular hypertrophy. We also examine whether high-intensity sprinting-type exercise promotes changes in protein turnover that lead to hypertrophy or merely a change in mitochondrial content. Finally, we propose novel areas for future study that will fill existing knowledge gaps in the fields of translational research and exercise science.
Independent coding of absolute duration and distance magnitudes in the prefrontal cortex
Authors: Marcos Encarni , Tsujimoto Satoshi , Genovesio Aldo
Published: October 2016

The estimation of space and time can interfere with each other, and neuroimaging studies have shown overlapping activation in the parietal and prefrontal cortical areas. We used duration and distance discrimination tasks to determine whether space and time share resources in prefrontal cortex (PF) neurons. Monkeys were required to report which of two stimuli, a red circle or blue square, presented sequentially, were longer and farther, respectively, in the duration and distance tasks. In a previous study, we showed that relative duration and distance are coded by different populations of neurons and that the only common representation is related to goal coding. Here, we examined the coding of absolute duration and distance. Our results support a model of independent coding of absolute duration and distance metrics by demonstrating that not only relative magnitude but also absolute magnitude are independently coded in the PF.

NEW & NOTEWORTHY Human behavioral studies have shown that spatial and duration judgments can interfere with each other. We investigated the neural representation of such magnitudes in the prefrontal cortex. We found that the two magnitudes are independently coded by prefrontal neurons. We suggest that the interference among magnitude judgments might depend on the goal rather than the perceptual resource sharing.
Effects of ion channel noise on neural circuits: an application to the respiratory pattern generator to investigate breathing variability
Authors: Yu Haitao , Dhingra Rishi R. , Dick Thomas E. , Galán Roberto F.
Published: October 2016

Neural activity generally displays irregular firing patterns even in circuits with apparently regular outputs, such as motor pattern generators, in which the output frequency fluctuates randomly around a mean value. This “circuit noise” is inherited from the random firing of single neurons, which emerges from stochastic ion channel gating (channel noise), spontaneous neurotransmitter release, and its diffusion and binding to synaptic receptors. Here we demonstrate how to expand conductance-based network models that are originally deterministic to include realistic, physiological noise, focusing on stochastic ion channel gating. We illustrate this procedure with a well-established conductance-based model of the respiratory pattern generator, which allows us to investigate how channel noise affects neural dynamics at the circuit level and, in particular, to understand the relationship between the respiratory pattern and its breath-to-breath variability. We show that as the channel number increases, the duration of inspiration and expiration varies, and so does the coefficient of variation of the breath-to-breath interval, which attains a minimum when the mean duration of expiration slightly exceeds that of inspiration. For small channel numbers, the variability of the expiratory phase dominates over that of the inspiratory phase, and vice versa for large channel numbers. Among the four different cell types in the respiratory pattern generator, pacemaker cells exhibit the highest sensitivity to channel noise. The model shows that suppressing input from the pons leads to longer inspiratory phases, a reduction in breathing frequency, and larger breath-to-breath variability, whereas enhanced input from the raphe nucleus increases breathing frequency without changing its pattern.

NEW & NOTEWORTHY A major source of noise in neuronal circuits is the “flickering” of ion currents passing through the neurons' membranes (channel noise), which cannot be suppressed experimentally. Computational simulations are therefore the best way to investigate the effects of this physiological noise by manipulating its level at will. We investigate the role of noise in the respiratory pattern generator and show that endogenous, breath-to-breath variability is tightly linked to the respiratory pattern.
Vestibular implants studied in animal models: clinical and scientific implications
Authors: Lewis Richard F.
Published: October 2016

Damage to the peripheral vestibular system can result in debilitating postural, perceptual, and visual symptoms. A potential new treatment for this clinical problem is to replace some aspects of peripheral vestibular function with an implant that senses head motion and provides this information to the brain by stimulating branches of the vestibular nerve. In this review I consider animal studies performed at our institution over the past 15 years, which have helped elucidate how the brain processes information provided by a vestibular (semicircular canal) implant and how this information could be used to improve the problems experienced by patients with peripheral vestibular damage.
Adalimumab Induced or Provoked MS in Patient with Autoimmune Uveitis: A Case Report and Review of the Literature
Authors: Alnasser Alsukhni Rana , Jriekh Ziena , Aboras Yasmin
Published: October 2016

Anti-tumor necrosis factorα(anti-TNF-α) agents have been widely used in the field of autoimmune diseases and have proved decisive efficacy and relative safety. Data concerning their adverse effects has been lately describing central nervous system (CNS) demyelination process at escalating basis.Case Presentation. A 23-year-old male with autoimmune uveitis and a family history of multiple sclerosis (MS) developed two neurological attacks, after Adalimumab infusion, simultaneously with several cerebral lesions on magnetic resonance imaging (MRI). Hence the diagnosis of Adalimumab induced MS was suspected.Conclusion. This case is reported to tell physicians to be cautious when using anti-TNF-αin patients with family history of MS and to reconsider the risk of MS in patients with autoimmune diseases.
Atypical Diabetic Foot Ulcer Keratinocyte Protein Signaling Correlates with Impaired Wound Healing
Authors: Hoke Glenn D. , Ramos Corrine , Hoke Nicholas N. , Crossland Mary C. , Shawler Lisa G. , Boykin Joseph V.
Published: October 2016

Diabetes mellitus is associated with chronic diabetic foot ulcers (DFUs) and wound infections often resulting in lower extremity amputations. The protein signaling architecture of the mechanisms responsible for impaired DFU healing has not been characterized. In this preliminary clinical study, the intracellular levels of proteins involved in signal transduction networks relevant to wound healing were non-biasedly measured using reverse-phase protein arrays (RPPA) in keratinocytes isolated from DFU wound biopsies. RPPA allows for the simultaneous documentation and assessment of the signaling pathways active in each DFU. Thus, RPPA provides for the accurate mapping of wound healing pathways associated with apoptosis, proliferation, senescence, survival, and angiogenesis. From the study data, we have identified potential diagnostic, or predictive, biomarkers for DFU wound healing derived from the ratios of quantified signaling protein expressions within interconnected pathways. These biomarkers may allow physicians to personalize therapeutic strategies for DFU management on an individual basis based upon the signaling architecture present in each wound. Additionally, we have identified altered, interconnected signaling pathways within DFU keratinocytes that may help guide the development of therapeutics to modulate these dysregulated pathways, many of which parallel the therapeutic targets which are the hallmarks of molecular therapies for treating cancer.
An Explanation of the Underlying Mechanisms for the In Vitro and In Vivo Antiurolithic Activity of Glechoma longituba
Authors: Liang Qiang , Li Xiaoran , Zhou Wangning , Su Yu , He Shenbao , Cheng Shuanglei , Lu Jianzhong , Cao Wenjuan , Yan Yuke , Pei Xiaxia , Qi Jin , Xu Guangli , Yue Zhongjin
Published: October 2016

Purpose. To use in vitro and in vivo models to evaluate Glechoma longituba extract to provide scientific evidence for this extract’s antiurolithic activity. Materials and Methods. Potassium citrate was used as a positive control group. Oxidative stress (OS) markers and the expression of osteopontin (OPN) and kidney injury molecule‐1 (KIM‐1) were measured to assess the protective effects of Glechoma longituba. Multiple urolithiasis‐related biochemical parameters were evaluated in urine and serum. Kidneys were harvested for histological examination and the assessment of crystal deposits. Results. In vitro and in vivo experiments demonstrated that treatment with Glechoma longituba extract significantly decreased calcium oxalate‐ (CaOx‐) induced OPN expression, KIM‐1 expression, and OS compared with the positive control group (P < 0.05). Additionally, in vivo rats that received Glechoma longituba extract exhibited significantly decreased CaOx deposits and pathological alterations (P < 0.05) compared with urolithic rats. Significantly lower levels of oxalate, creatinine, and urea and increased citrate levels were observed among rats that received Glechoma longituba (P < 0.05) compared with urolithic rats. Conclusion. Glechoma longituba has antiurolithic effects due to its possible combined effects of increasing antioxidant levels, decreasing urinary stone‐forming constituents and urolithiasis‐related protein expression, and elevating urinary citrate levels.
Fixed Points and Exponential Stability for Impulsive Time-Delays BAM Neural Networks via LMI Approach and Contraction Mapping Principle
Authors: Rao Ruofeng , Pu Zhilin , Zhong Shouming , Li Xinggui
Published: October 2016

The fixed point technique has been employed in the stability analysis of time-delays bidirectional associative memory (BAM) neural networks with impulse. By formulating a contraction mapping in a product space, a new LMI-based exponential stability criterion was derived. Lately, fixed point methods have educed various good results inspiring this work, but those criteria cannot be programmed by a computer. In this paper, LMI conditions of the obtained result can be applicable to computer Matlab LMI toolbox which meets the need of the large-scale calculation in real engineering. Moreover, a numerical example and a comparable table are presented to illustrate the effectiveness of the proposed methods.
A Rare Case of an Irreducible Patella Dislocation
Authors: Delagrammaticas Dimitri E. , Cordes Scott D.
Published: October 2016

Reports of irreducible patellar dislocations are exceedingly sparse throughout the literature. Obvious radiographic or physical exam findings including fracture or inversion of the patella are often present to explain the block to reduction. Not described previously in the literature is the instance of an irreducible patella dislocation in the setting of innocuous appearing injury imaging. We present a case of a healthy thirty-two-year-old female who sustained an irreducible lateral patella dislocation while participating in a dance aerobics class. Closed means of reduction were unsuccessful, necessitating open reduction. Intraoperative findings suggest incarceration of a nondisplaced fracture and a chondral defect as the block to reduction. Following open reduction, the patient has had no further episodes of pain or instability related to the patella at one-year follow-up. Irreducible patellar dislocations are exceedingly rare injuries, where associated osseous or chondral lesions may necessitate open reduction despite innocuous appearing initial imaging. A high index of suspicion to proceed with open reduction may limit repeated attempts at closed reduction and further injury.
Assessment of Heat Hazard during the Polymerization of Selected Light-Sensitive Dental Materials
Authors: Janeczek Maciej , Herman Katarzyna , Fita Katarzyna , Dudek Krzysztof , Kowalczyk-Zając Małgorzata , Czajczyńska-Waszkiewicz Agnieszka , Piesiak-Pańczyszyn Dagmara , Kosior Piotr , Dobrzyński Maciej
Published: October 2016

Introduction.Polymerization of light-cured dental materials used for restoration of hard tooth tissue may lead to an increase in temperature that may have negative consequence for pulp vitality.Aim.The aim of this study was to determine maximum temperatures reached during the polymerization of selected dental materials, as well as the time that is needed for samples of sizes similar to those used in clinical practice to reach these temperatures.Materials and Methods.The study involved four composite restorative materials, one lining material and a dentine bonding agent. The polymerization was conducted with the use of a diode light-curing unit. The measurements of the external surface temperature of the samples were carried out using the Thermovision®550 thermal camera.Results.The examined materials significantly differed in terms of the maximum temperatures values they reached, as well as the time required for reaching the temperatures. A statistically significant positive correlation of the maximum temperature and the sample weight was observed.Conclusions.In clinical practice, it is crucial to bear in mind the risk of thermal damage involved in the application of light-cured materials. It can be reduced by using thin increments of composite materials.
Notes on the Wild Tomistoma Populations in Western Sarawak, Malaysian Borneo
Authors: Hassan Ruhana , Ahmad Rambli , Md Adzhar Muhammad Amirul Arib , Abdul Gani Mohd Izwan Zulaini , Ayob Anuar , Zainudin Ramlah
Published: October 2016

Tomistoma schlegelii, the Freshwater Malayan Gharial or Tomistoma (local name: buaya jejulong), is secretive in nature; thus, very limited information is currently available on its wild population, especially in Sarawak. The objective of this study is to describe effort in assessing the Tomistoma wild populations in Ulu Sebuyau, Samarahan, and Serian, western Sarawak. Despite many challenges faced, this research has been successful at different levels. There was no Tomistoma seen during day surveys (2014-2015) in tributary of Samarahan River (Samarahan), Bunga-Baki River (Serian), and Kepayang River (Ulu Sebuyau). However, the research team came across two incidents of Tomistoma captured by the local people: (i) an adult male Tomistoma, captured in February 2015 in peat swamp area of Samarahan River tributary, and (ii) a hatchling, caught in Bunga-Baki River in March 2015. The sightings of Tomistoma in Kepayang River were reported by local people in February 2016; however, no individual was captured. The presence of hatchling in Bunga-Baki River indicates that a breeding population is most likely to occur in the area, and this gives hope for future conservation of Tomistoma in Sarawak. All sampling sites recorded almost similar water quality parameters and landscape of peat swamp areas, which previous studies claimed to be the potential Tomistoma habitats. The findings of this study should help relevant state agencies to step up efforts related to conservation of Tomistoma in Sarawak.
Hermite-Hadamard Type Inequalities Obtained via Fractional Integral for Differentiable m-Convex and α,m-Convex Functions
Authors: Set Erhan , Karataş Süleyman Sami , Khan Muhammad Adil
Published: October 2016

Some Hermite-Hadamard type inequalities involving fractional integrals for m-convex and (α,m)-convex functions are obtained.
Retrospective Case Reports of Anemic Pregnant Women Receiving Intravenous Ferric Carboxymaltose: Experience from a Tertiary Hospital in Spain
Authors: Aporta Rodriguez Rafael , García Montero Mariola , Lorente Aporta Jose Pablo , Gallego Luque Carolina , Chacón Mayor Alfonso , Aragón Ruiz Jose , Torres Degayón Virginia , García Jimenez Claudia , Sanchez Sanchez Guadalupe
Published: October 2016

Iron deficiency and iron deficiency anemia during pregnancy call for safe treatment options that raise maternal hemoglobin levels and counterbalance iron demand and blood volume expansion while minimizing risks for the growing fetus. This retrospective study describes experience with intravenous ferric carboxymaltose given to pregnant women in a tertiary hospital in Spain. In a 5-year period, 95 pregnant women who had pretreatment hemoglobin <10 g/dL and at least one time of ferric carboxymaltose administration during pregnancy were included. Main outcome measures were week of pregnancy at iron administration, Hb levels before and after treatment, neonatal 5-minute Apgar scores, and birth weight. The majority received one dose of ferric carboxymaltose (1000 mg iron) during advanced pregnancy (median 31 weeks; interquartile range [IQR]: 27; 37 weeks) with minor to no adverse outcomes. Overall, median Hb increased from 8.5 g/dL (8.1; 8.9 g/dL) before treatment to 11.0 g/dL (9.9; 11.7 g/dL) after treatment. Normal Apgar scores were observed in all 97 infants (median birth weights 3560 g, 3270, and 3798 g). Four women received ferric carboxymaltose in the first trimester and twenty-eight during the second trimester without adverse outcomes for mother or child. These cases add to the evidence that ferric carboxymaltose administration during pregnancy is effective and safe.
Bowel Ischemia from Heat Stroke: A Rare Presentation of an Uncommon Complication
Authors: Masood Umair , Sharma Anuj , Syed Wajihuddin , Manocha Divey
Published: October 2016

A healthy 27-year-old female presented to the hospital after she collapsed an hour into her first marathon run on a hot humid day. On presentation, she was hyperthermic, encephalopathic, tachycardic, and hypotensive. On admission, she was found to have lactic acidosis, rhabdomyolysis, and acute kidney injury and was treated with cold normal saline and cooling blankets. She subsequently started having abdominal pain and bloody bowel movements. Computed tomography of the abdomen revealed ascending colon thickening. Furthermore, her lab findings showed transaminitis and elevated coagulation parameters. Due to the acute hypotensive state from the heat stroke, patient had developed bowel ischemia, ischemic hepatitis, and disseminated intravascular coagulation, all of which are uncommon complications of heat stroke. She was managed aggressively with intravenous fluid hydration with resolution of her symptoms over the course of 4 days. In addition to the uncommon complications, early presentation of this bowel ischemia despite adequate hydration in such a healthy individual is another unique aspect of the case.
Qualitative and Quantitative Determination of Phytochemical Contents of Indigenous Nigerian Softwoods
Authors: Ezeonu Chukwuma S. , Ejikeme Chigozie M.
Published: October 2016

The phytochemical contents of some milled Nigerian softwood chips were carried out in a quest to evaluate their potentials as sources of alternative medicine as well as uses in other industrial applications. The qualitative and quantitative analysis were ascertained. Tannin was found in all the Nigerian softwoods examined with the highest quantities obtained in Sterculia oblonga (1240 mg/100 g) and Barteria nigritiana (1230 mg/100 g). Highest quantities of alkaloid were obtained in Cordia millenii (11.2%) and Sterculia oblonga (10.4%). Barteria nigritiana (14.2%) and Moringa oleifera (12.2%) recorded more flavonoid content than other individual softwoods. Saponin was more in Anogeissus leiocarpus (12.5%) and Dichrostachys cinerea (9.8%). Oxalate was found to be higher in Combretodendron macrocarpum (5.84 g/100 g) and Glyphaea brevis (3.55 g/100 g). Pentaclethra macrophylla (890 mg/100 g) and Moringa oleifera (880 mg/100 g) contained more cyanogenic glycosides. Sacoglottis gabonensis (4.68 mg/g) and Pentaclethra macrophylla (4.04 mg/g) showed the highest contents of phenol, while more lipids (8% and 7.2%) were found in Anogeissus leiocarpus and Kaempferia galanga, respectively. The results showed that these Nigerian softwoods grains could be a source for the exploitation of these phytochemicals beneficial in the pharmaceutical and alternative medicine industries.
Robust FCM Algorithm with Local and Gray Information for Image Segmentation
Authors: Barrah Hanane , Cherkaoui Abdeljabbar , Sarsri Driss
Published: October 2016

The FCM (fuzzy c-mean) algorithm has been extended and modified in many ways in order to solve the image segmentation problem. However, almost all the extensions require the adjustment of at least one parameter that depends on the image itself. To overcome this problem and provide a robust fuzzy clustering algorithm that is fully free of the empirical parameters and noise type-independent, we propose a new factor that includes the local spatial and the gray level information. Actually, this work provides three extensions of the FCM algorithm that proved their efficiency on synthetic and real images.