bluuebunny/crossref_metadata_2025 huggingface dataset:
Requirements for Carnitine Shuttle-Mediated Translocation of Mitochondrial Acetyl Moieties to the Yeast Cytosol
Authors: van Rossum Harmen M. , Kozak Barbara U. , Niemeijer Matthijs S. , Dykstra James C. , Luttik Marijke A. H. , Daran Jean-Marc G. , van Maris Antonius J. A. , Pronk Jack T.
Published: May 2016

In many eukaryotes, the carnitine shuttle plays a key role in intracellular transport of acyl moieties. Fatty acid-grown
Saccharomyces cerevisiae
cells employ this shuttle to translocate acetyl units into their mitochondria. Mechanistically, the carnitine shuttle should be reversible, but previous studies indicate that carnitine shuttle-mediated export of mitochondrial acetyl units to the yeast cytosol does not occur
in vivo
. This apparent unidirectionality was investigated by constitutively expressing genes encoding carnitine shuttle-related proteins in an engineered
S. cerevisiae
strain, in which cytosolic acetyl coenzyme A (acetyl-CoA) synthesis could be switched off by omitting lipoic acid from growth media. Laboratory evolution of this strain yielded mutants whose growth on glucose, in the absence of lipoic acid, was
l
-carnitine dependent, indicating that
in vivo
export of mitochondrial acetyl units to the cytosol occurred via the carnitine shuttle. The mitochondrial pyruvate dehydrogenase complex was identified as the predominant source of acetyl-CoA in the evolved strains. Whole-genome sequencing revealed mutations in genes involved in mitochondrial fatty acid synthesis (
MCT1
), nuclear-mitochondrial communication (
RTG2
), and encoding a carnitine acetyltransferase (
YAT2
). Introduction of these mutations into the nonevolved parental strain enabled
l
-carnitine-dependent growth on glucose. This study indicates intramitochondrial acetyl-CoA concentration and constitutive expression of carnitine shuttle genes as key factors in enabling
in vivo
export of mitochondrial acetyl units via the carnitine shuttle.

IMPORTANCE
This study demonstrates, for the first time, that
Saccharomyces cerevisiae
can be engineered to employ the carnitine shuttle for export of acetyl moieties from the mitochondria and, thereby, to act as the sole source of cytosolic acetyl-CoA. Further optimization of this ATP-independent mechanism for cytosolic acetyl-CoA provision can contribute to efficient, yeast-based production of industrially relevant compounds derived from this precursor. The strains constructed in this study, whose growth on glucose depends on a functional carnitine shuttle, provide valuable models for further functional analysis and engineering of this shuttle in yeast and other eukaryotes.
OsdR of Streptomyces coelicolor and the Dormancy Regulator DevR of Mycobacterium tuberculosis Control Overlapping Regulons
Authors: Urem Mia , van Rossum Teunke , Bucca Giselda , Moolenaar Geri F. , Laing Emma , Świątek-Połatyńska Magda A. , Willemse Joost , Tenconi Elodie , Rigali Sébastien , Goosen Nora , Smith Colin P. , van Wezel Gilles P.
Published: May 2016

Dormancy is a state of growth cessation that allows bacteria to escape the host defense system and antibiotic challenge. Understanding the mechanisms that control dormancy is of key importance for the treatment of latent infections, such as those fromMycobacterium tuberculosis. In mycobacteria, dormancy is controlled by the response regulator DevR, which responds to conditions of hypoxia. Here, we show that OsdR ofStreptomyces coelicolorrecognizes the same regulatory element and controls a regulon that consists of genes involved in the control of stress and development. Only the core regulon in the direct vicinity ofdosRandosdRis conserved betweenM. tuberculosisandS. coelicolor, respectively. Thus, we show how the system has diverged from allowing escape from the host defense system by mycobacteria to the control of sporulation by complex multicellular streptomycetes. This provides novel insights into how bacterial growth and development are coordinated with the environmental conditions.
Preservation Methods Differ in Fecal Microbiome Stability, Affecting Suitability for Field Studies
Authors: Song Se Jin , Amir Amnon , Metcalf Jessica L. , Amato Katherine R. , Xu Zhenjiang Zech , Humphrey Greg , Knight Rob
Published: May 2016

Our study, spanning 15 individuals and over 1,200 samples, provides our most comprehensive view to date of storage and stabilization effects on stool. We tested five methods for preserving human and dog fecal specimens for periods of up to 8 weeks, including the types of variation often encountered under field conditions, such as freeze-thaw cycles and high temperature fluctuations. We show that several cost-effective methods provide excellent microbiome stability out to 8 weeks, opening up a range of field studies with humans and wildlife that would otherwise be cost-prohibitive.
Acupuncture at Distant Myofascial Trigger Spots Enhances Endogenous Opioids in Rabbits: A Possible Mechanism for Managing Myofascial Pain
Authors: Hsieh Yueh-Ling , Hong Chang-Zern , Liu Szu-Yu , Chou Li-Wei , Yang Chen-Chia
Published: May 2016

Background and Aim

Acupuncture applied at myofascial trigger points (MTrPs) of distant anatomical regions, to reduce pain in a patient's area of primary complaint, is one strategy that is available to manage myofascial pain. However, the endogenous opioid-mediated analgesic mechanism of distant acupuncture associated with pain control is still unclear. This aims of this study were to evaluate the changes in enkephalin and β-endorphin in serum, spinal cord, dorsal root ganglion (DRG) and muscle induced by acupuncture at distant myofascial trigger spots (MTrSs, similar to human MTrPs) in rabbits, to explore its underlying remote analgesic mechanism.

Methods

Acupuncture at MTrSs of a distant muscle (gastrocnemius) was performed either for one session or five daily sessions in rabbits. The levels of enkephalin and β-endorphin in proximal muscle (biceps femoris), serum, DRGs and spinal cords (L5-S2) were then determined by immunoassay immediately and 5 days after treatment.

Results

Immediately after treatment, acupuncture comprising both one dose and five doses significantly enhanced spinal enkephalin expression and serum β-endorphin levels (p<0.05). However, only five-dose acupuncture significantly enhanced the β-endorphin levels in the biceps femoris and DRGs (p<0.05), while 1-dose acupuncture did not (p>0.05). Furthermore, 5 days after treatment, significantly increased levels of spinal enkephalin and serum β-endorphin persisted in animals that received 5-dose acupuncture (p<0.05).

Conclusions

This study demonstrates that interactions within the endogenous opioid system may be involved in the remote effects of acupuncture treatment and could be a potential analgesic mechanism underlying MTrP pain management.
The Nocturnal Serum Thyrotropin Surge is Inhibited in Patients with Adrenal Incidentaloma
Authors: Coiro Vittorio , Volpi Riccardo , Capretti Luigi , Manfredi Guido , Magotti Maria Grazia , Bianconcini Michele , Cataldo Simona , Chiodera Paolo
Published: May 2016

Background

Alterations in hypothalamic-pituitary function have been described in patients with incidentally discovered adrenal adenomas and have been attributed to their subtle hypercortisolemic status.

Methods

To establish whether the central control of the hypothalamic-pituitary-thyroid axis is altered in these endocrine conditions, the nocturnal (10:30 pm-2:00 am) serum thyroid-stimulating hormone (TSH) surge (measured by dividing the difference between nighttime and morning TSH values by the morning TSH value and then multiplying by 100), the TSH response to thyrotropin-releasing hormone (200 μg as an intravenous bolus) and serum free thyroid hormone levels were evaluated in patients with adrenal incidentaloma (experimental group) and in normal controls (control group). Urinary free cortisol concentrations were also measured.

Results

The nocturnal TSH surge was observed in the normal controls, whereas it was inhibited in the patients of the experimental group. Serum free triiodothyronine levels were similar in the two groups, whereas the TSH response to thyrotropin-releasing hormone was significantly lower in the experimental than in the control group. Urinary free cortisol levels were significantly higher in the experimental group.

Conclusion

These data indicate that even conditions of slight glucocorticoid excess may exert inhibitory effects on TSH secretion, which suggests the presence of a slight central hypothyroidism in patients with adrenal incidentaloma.
Expression of the Regenerating Gene Family in Inflammatory Bowel Disease Mucosa: Reg Iα Upregulation, Processing, and Antiapoptotic Activity
Authors: Dieckgraefe Brian K. , Crimmins Dan L. , Landt Vonnie , Houchen Courtney , Anant Shrikant , Porche-Sorbet Rhonda , Ladenson Jack H.
Published: May 2016

Background

The pathophysiology of inflammatory bowel disease (IBD) reflects a balance between mucosal injury related to an ongoing inflammatory process and mucosal reparative mechanisms. Proreparative mucosal factors may offer new therapeutic paradigms. Transcriptional profiling can be applied to identify candidate gene products involved in colonic mucosal regeneration.

Methods

Resection specimens from patients who underwent colonic resection for IBD or non-IBD indications were analyzed by performing Affymetrix GeneChip hybridization (Affymetrix, Inc., Santa Clara, Calif) and histopathologic scoring. Expression and physiologic processing of Reg Iα, the most highly expressed member of the regenerating ( Reg) gene family, was further studied by performing specific immunohistochemistry, protein sequencing, and mass spectroscopy.

Results

Foregut-derived tissues normally express human Reg proteins with minimal expression in the colon. In the setting of tissue injury associated with IBD, Reg Iα, Reg Iβ, and Reg III mRNA were highly expressed in colonic mucosa. Paired histopathologic scoring demonstrated that Reg expression was not related to the presence or the degree of mucosal inflammation. Studies of the Reg Iα protein revealed evidence of proteolytic cleavage at the N-terminus. In IBD, intact Reg Iα protein was expressed by the metaplastic Paneth granular cell population. Whereas Reg Iα cleaved at the N-terminus, it was also deposited throughout the lamina propria. Reg Iα treatment was shown to reduce epithelial apoptosis that occurred in response to treatment with hydrogen peroxide.

Conclusion

Ectopic expression, physiologic processing, and directed tissue deposition of Reg Iα are components of the colonic mucosal regenerative response in IBD. Reg Iα may serve to reduce epithelial apoptosis in inflammation.
Prednisone Induces Cognitive Dysfunction, Neuronal Degeneration, and Reactive Gliosis in Rats
Authors: Ramos-Remus César , González-Castañeda Rocio E. , González-Perez Oscar , Luquin Sonia , García-Estrada Joaquin
Published: May 2016

Background

High glucocorticoid serum levels and prednisone (PDN) therapy have been associated with depression, posttraumatic stress disorder, and some types of cognitive dysfunction in humans.

Objective

The aim of this study was to assess whether chronic (90 days) PDN administration produces disturbance in learning and memory retention associated with neuronal degeneration and cerebral glial changes.

Methods

Male Wistar rats were studied. Controls received 0.1 ml distilled water vehicle orally. The PDN group was treated orally with 5 mg/kg/d PDN, which is equivalent to moderate doses used in clinical settings. Learning and memory retention were assessed with the Morris water maze. The index of degenerated neurons as well as the number and cytoplasmic transformation of astrocytes and microglia cells were evaluated in the prefrontal cortex and the CA1 hippocampus.

Results

PDN-treated rats showed a significant delay of 20% in learning and memory retention as compared with controls. In addition, in the PDN group, the neuronal degeneration index was two times higher in the prefrontal cortex, and approximately 10 times higher in the CA1 hippocampus, than in control animals. The number and cytoplasmic transformation of astrocytes were also significantly higher in the PDN group than in control animals. In the PDN-treated group, isolectin-B4-labeled microglia cells were higher in the prefrontal cortex but not in the hippocampus.

Conclusion

These results suggest that chronic exposure to PDN produces learning and memory impairment, reduces neural viability, and increases glial reactivity in cerebral regions with these cognitive functions.
Genetic and phenotypic associations of type traits and body condition score with dry matter intake, milk yield, and number of breedings in first lactation Canadian Holstein cows
Authors: Bilal G. , Cue R.I. , Hayes J.F.
Published: May 2016

The objective of the present study was to estimate genetic parameters of milk yield (MY), intake traits, type traits, body condition score (BCS), and number of breedings (NOB) in first lactation Canadian Holsteins with a focus on the possibility of using type traits as an indicator of feed intake. Data were obtained from the Canadian Dairy Network and Valacta. A mixed linear model was fitted under REML for the statistical analysis. The multivariate (five traits) model included the fixed effects of age at calving, stage of lactation, and herd-round-classifier for type traits; age at calving, stage of lactation, and herd–year–season of calving (HYS) for BCS; age at calving and HYS for MY, feed intake, and NOB. Animal and residual effects were fitted as random effects for all traits. Estimates of heritabilities for MY, dry matter intake (DMI), angularity, body depth, stature, dairy strength, final score, BCS, and NOB were 0.41, 0.13, 0.24, 0.30, 0.50, 0.30, 0.22, 0.20, and 0.02, respectively. Genetic correlations between type traits and DMI ranged from 0.16 to 0.60. Results indicate that type traits appear to have the potential to predict DMI as a combination/index of two or more traits.
Average Case Analysis of Brzozowski's Algorithm
Authors: Felice Sven De , Nicaud Cyril
Published: May 2016

We analyze the average complexity of Brzozowski's minimization algorithm for distributions of deterministic automata with a small number of final states. We show that, as in the case of the uniform distribution, the average complexity is super-polynomial even if we consider random deterministic automata with only one final state. Such results were only known for distributions where the expected number of final states was linear in the number of states.
New Results on the Minimum Amount of Useful Space
Authors: Bednárová Zuzana , Geffert Viliam , Reinhardt Klaus , Yakaryilmaz Abuzer
Published: May 2016

We present several new results on minimal space requirements to recognize a nonregular language: (i) realtime nondeterministic Turing machines can recognize a nonregular unary language within weak log log n space, (ii) log log n is a tight space lower bound for accepting general nonregular languages on weak realtime pushdown automata, (iii) there exist unary nonregular languages accepted by realtime alternating one-counter automata within weak log n space, (iv) there exist nonregular languages accepted by two-way deterministic pushdown automata within strong log log n space, and, (v) there exist unary nonregular languages accepted by two-way one-counter automata using quantum and classical states with middle log n space and bounded error.
Probing to Observe Neural Dynamics Investigated with Networked Kuramoto Oscillators
Authors: O’Sullivan-Greene Elma , Kuhlmann Levin , Nurse Ewan S. , Freestone Dean R. , Grayden David B. , Cook Mark , Burkitt Anthony , Mareels Iven
Published: May 2016

The expansion of frontiers in neural engineering is dependent on the ability to track, detect and predict dynamics in neural tissue. Recent innovations to elucidate information from electrical recordings of brain dynamics, such as epileptic seizure prediction, have involved switching to an active probing paradigm using electrically evoked recordings rather than traditional passive measurements. This paper positions the advantage of probing in terms of information extraction, by using a coupled oscillator Kuramoto model to represent brain dynamics. While active probing performs better at observing underlying system synchrony in Kuramoto networks, especially in non-Gaussian measurement environments, the benefits diminish with increasing relative size of electrode spatial resolution compared to synchrony area. This suggests probing will be useful for improved characterization of synchrony for suitably dense electrode recordings.
Particle Swarm Optimization Design of Low-Power Multistage Amplifier using gm/ID Methodology
Authors: Zhang Gengyu , Xiao Xia , Xu Jiangtao , Nie Kaiming , Gao Zhiyuan
Published: May 2016

A design flow using the [Formula: see text]/[Formula: see text] methodology with the adaptive particle swarm optimization (PSO) algorithm is proposed for the modern analog circuit in this paper. For the advanced CMOS process, [Formula: see text]/[Formula: see text] methodology is suitable to the long channel and short channel design in all transistor operation regions. Different from the classical PSO algorithm, the adaptive PSO algorithm features the better search efficiency and faster convergence speed over the global search. Two amplifiers were designed and implemented in a standard 0.11[Formula: see text][Formula: see text]m CMOS process using MATLAB and HSPICE. Using the thermal noise coefficient [Formula: see text] and the corner frequency [Formula: see text], this paper explored the noise design budget of low-power multistage amplifier in different saturation modes. Detailed optimization of the objective function and constraints are classified into the mono-objective case and the multi-objective case. The total running times of simulations are 5649 s and 6813 s while the errors are less than 9% and 10%, respectively. Compared with CODE, GA[Formula: see text]PF and DE[Formula: see text]PF algorithms, it can save more running time and improve the accuracy of the design. Moreover, it provides more design freedom for the trade-off among gain, the gain-bandwidth (GBW) product, noise and the phase margin under worst cases without extra tweaking. Not only can the methodology work in the 0.18[Formula: see text][Formula: see text]m CMOS process, but also be migrated to the 0.11[Formula: see text][Formula: see text]m CMOS process, even in the nanometer analog circuit.
A note on Schwarzschild–de Sitter black holes in mimetic F(R) gravity
Authors: Oikonomou V. K.
Published: May 2016

In this paper, we investigate the conditions under which a Schwarzschild–de Sitter black hole spacetime is a solution of the mimetic [Formula: see text] gravity with Lagrange multiplier and potential. As we demonstrate, the resulting mimetic [Formula: see text] gravity is a slight modification of the ordinary [Formula: see text] gravity case, however the resulting perturbation equations are not in all cases identical to the ordinary [Formula: see text] gravity case. In the latter case, the perturbation equations are identical to the ones corresponding to the Reissner–Nordström anti-de Sitter black hole.
Lebesgue points and restricted convergence of Fourier transforms and Fourier series
Authors: Weisz Ferenc
Published: May 2016

In this paper, a general summability method of multi-dimensional Fourier transforms, the so-called [Formula: see text]-summability, is investigated. It is shown that if [Formula: see text] is in a Herz space, then the summability means [Formula: see text] of a function [Formula: see text] converge to [Formula: see text] at each modified Lebesgue point, whenever [Formula: see text] and [Formula: see text] is in a cone. The same holds for Fourier series. Some special cases of the [Formula: see text]-summation are considered, such as the Weierstrass, Abel, Picard, Bessel, Fejér, Cesàro, de la Vallée-Poussin, Rogosinski and Riesz summations.
REDEFINING CREATIVITY AND INNOVATION IN ORGANISATIONS: SUGGESTIONS FOR REDIRECTING RESEARCH
Authors: CASTAÑER XAVIER
Published: May 2016

In this paper, I examine three questions: (1) how creativity and innovation in organisations are defined in the scientific literature, (2) which theories are applied and hence which explanatory factors have been discussed, and (3) what the empirical evidence is regarding these factors. I uncover an overlap between the definitions of creativity and innovation, which in my view are distinct but related concepts. Further, despite the significant overlap in their definitions, research has evolved in two almost separate streams. Moreover, I observe that the multiple theories used (even regarding the same factor) to explain organisational creativity are not always integrated and that the empirical evidence about factors concerning individuals seems to converge but is much more mixed in relation to factors at the organisational level. Finally, I propose a new definition of organisational creativity and organisational innovation to distinguish them and suggest some avenues for future research.
Atomic-scale analysis of nanoindentation behavior of high-entropy alloy
Authors: Li Jia , Fang QiHong , Liu Bin , Liu YouWen , Liu Yong
Published: May 2016

Using molecular dynamics simulations, we study the elastic and plastic deformations of indentation in FeCrCuAlNi high-entropy alloy (HEA). The indentation tests are carried out using spherical rigid indenter to investigate the effects of high-entropy and severe lattice distortion in terms of shear strain, indentation force, surface morphology, defect structure, dislocation evolution and radial distribution function on the deformation processes. It can be found that when the indentation depth increases, the shear stress requires for the occurrence of the contact area between the indenter and the substrate increased, which is attributable to a higher probability to observe the dislocation evolution under a large indentation depth. The indentation test also shows that the equal element addition can significantly improve the mechanical properties of HEA compared with the conventional alloy. Based on the Hertzian fitting, the FeCrCuAlNi HEA has the Young’s modulus of 161[Formula: see text]GPa and hardness of 15.4[Formula: see text]GPa, respectively. These values are higher than that of traditional metal materials, due to the low stacking fault energy and the dense atomic arrangement in the slip plane of HEA. In the plastic region, the Fe element causes the more stable crystal structure, much stronger than the Cu element, presumably resulted from a variety of crystal structures for Fe in the multicomponent FeCrCuAlNi alloy. Further, this effective strategy is used to accelerate the discovery of excellent mechanical properties of HEAs.
Pregnancy-associated adaptations in [Ca2+]i-dependent and Ca2+sensitization mechanisms of venous contraction: implications in pregnancy-related venous disorders
Authors: Xia Yin , Khalil Raouf A.
Published: May 2016

Pregnancy is associated with significant adaptations in the maternal hemodynamics and arterial circulation, but the changes in the venous mechanisms during pregnancy are less clear. We hypothesized that pregnancy is associated with alterations in venous function, intracellular free Ca2+concentration ([Ca2+]i), and Ca2+-dependent mechanisms of venous contraction. Circular segments of inferior vena cava (IVC) from virgin and late pregnant (Preg, day 19) Sprague-Dawley rats were suspended between two hooks, labeled with fura-2, and placed in a cuvet inside a spectrofluorometer for simultaneous measurement of contraction and [Ca2+]i(fura-2 340/380 ratio). KCl (96 mM), which stimulates Ca2+influx, caused less contraction (35.6 ± 6.3 vs. 92.6 ± 19.9 mg/mg tissue) and smaller increases in [Ca2+]i(1.67 ± 0.12 vs. 2.19 ± 0.11) in Preg vs. virgin rat IVC. The α-adrenergic receptor agonist phenylephrine (Phe; 10−5M) caused less contraction (23.8 ± 3.4 vs. 70.9 ± 12.9 mg/mg tissue) and comparable increases in [Ca2+]i(1.76 ± 0.10 vs. 1.89 ± 0.08) in Preg vs. virgin rat IVC. At increasing extracellular Ca2+concentrations ([Ca2+]e) (0.1, 0.3, 0.6, 1, and 2.5 mM), KCl and Phe induced [Ca2+]e-contraction and [Ca2+]e-[Ca2+]icurves that were reduced in Preg vs. virgin IVC, supporting reduced Ca2+entry mechanisms. The [Ca2+]e-contraction and [Ca2+]e-[Ca2+]icurves were used to construct the [Ca2+]i-contraction relationship. Despite reduced contraction and [Ca2+]iin Preg IVC, the Phe-induced [Ca2+]i-contraction relationship was greater than that of KCl and was enhanced in Preg vs. virgin IVC, suggesting parallel activation of Ca2+-sensitization pathways. The Ca2+channel blocker diltiazem, protein kinase C (PKC) inhibitor GF-109203X, and Rho-kinase (ROCK) inhibitor Y27632 inhibited KCl- and Phe-induced contraction and abolished the shift in the Phe [Ca2+]i-contraction relationship in Preg IVC, suggesting an interplay between the decrease in Ca2+influx and possible compensatory activation of PKC- and ROCK-mediated Ca2+-sensitization pathways. The reduced [Ca2+]iand [Ca2+]i-dependent contraction in Preg rat IVC, despite the parallel rescue activation of Ca2+-sensitization pathways, suggests that the observed reduction in [Ca2+]i-dependent contraction mechanisms is likely underestimated, and that the veins without the rescue Ca2+-sensitization pathways could be even more prone to dilation during pregnancy. These pregnancy-associated reductions in Ca2+entry-dependent mechanisms of venous contraction, if occurring in human lower extremity veins and if not adequately compensated by Ca2+-sensitization pathways, may play a role in pregnancy-related venous disorders.
Recent advances in renal hypoxia: insights from bench experiments and computer simulations
Authors: Layton Anita T.
Published: May 2016

The availability of oxygen in renal tissue is determined by the complex interactions among a host of processes, including renal blood flow, glomerular filtration, arterial-to-venous oxygen shunting, medullary architecture, Na+ transport, and oxygen consumption. When this delicate balance is disrupted, the kidney may become susceptible to hypoxic injury. Indeed, renal hypoxia has been implicated as one of the major causes of acute kidney injury and chronic kidney diseases. This review highlights recent advances in our understanding of renal hypoxia; some of these studies were published in response to a recent Call for Papers of this journal: Renal Hypoxia.
Control of Sexually Transmitted Disease: The Canadian Perspective
Authors: Gully Paul R
Published: May 2016

The ability to control a disease depends on knowledge of
its epidemiology. Such information on sexually transmitted diseases (STDs) can be ascertained
by surveillance data involving the analysis of notification reports, as well as laboratory reports,
hospital discharge data, and data from sentinel clinics and health units. In the case of sexually
transmitted hepatitis B, notification data will probably have to be corroborated by data from
sentinel clinics, health units or physicians. A vigorous attempt must be made to elucidate the
mode of transmission in acute cases and newly discovered carriers. Appropriate treatment,
contact tracing and primary prevention strategies appear to have had some success in
controlling gonorrhea and syphilis. Rates of genital chlamydial infection may also be reduced
by the same methods. These diseases will, however, persist in certain ′core groups′. Control of
sexually transmitted hepatitis B will require a primary prevention strategy of risk reduction,
sexual health promotion and immunization. Targeted immunization programs on their own
are not Likely to work. Thus, universal immunization will probably be required along with public
acceptance of immunization against STDs and appropriate human and financial resources.
Reliable surveillance data will be required for program evaluation.
Cannabinoids for the Treatment of Pain: An Update on Recent Clinical Trials
Authors: Ware Mark , Beaulieu Pierre
Published: May 2016

Over the past five years, there has been a considerable increase in clinical research on cannabinoid use for a range of pain syndromes. Cannabinoid products are becoming available for research and clinical use, and pharmaceutical industry interest in the potential for cannabinoids in therapeutics is also gaining momentum. The present article summarizes recent clinical trial data in the field of pain management and suggests that the potential for cannabinoid therapy for chronic pain states is encouraging. Clinicians working in pain management should be aware of the options becoming available from the cannabinoid class of medications.
Guidelines for the Use of Cannabinoid Compounds in Chronic Pain
Authors: Clark AJ , Lynch ME , Ware M , Beaulieu P , McGilveray IJ , Gourlay D
Published: May 2016

OBJECTIVE: To provide clinicians with guidelines for the use of cannabinoid compounds in the treatment of chronic pain.

METHODS: Publications indexed from 1990 to 2005 in the National Library of Medicine Index Medicus were searched through PubMed. A consensus concerning these guidelines was achieved by the authors through review and discussion.

RESULTS: There are few clinical trials, case reports or case series concerning the use of cannabinoid compounds in the treatment of chronic pain. There are no randomized clinical trials examining the use of herbal cannabis in the treatment of chronic pain.

CONCLUSIONS: A practical approach to the treatment of chronic pain with cannabinoid compounds is presented. Specific suggestions about the off‐label dosing of nabilone (Cesamet, Valeant Canada limitée/Limited) and dronabinol (Marinol, Solvay Pharma Inc, Canada) in the treatment of chronic pain are provided.
Astrocyte Hypertrophy Contributes to Aberrant Neurogenesis after Traumatic Brain Injury
Authors: Robinson Clark , Apgar Christopher , Shapiro Lee A.
Published: May 2016

Traumatic brain injury (TBI) is a widespread epidemic with severe cognitive, affective, and behavioral consequences. TBIs typically result in a relatively rapid inflammatory and neuroinflammatory response. A major component of the neuroinflammatory response is astrocytes, a type of glial cell in the brain. Astrocytes are important in maintaining the integrity of neuronal functioning, and it is possible that astrocyte hypertrophy after TBIs might contribute to pathogenesis. The hippocampus is a unique brain region, because neurogenesis persists in adults. Accumulating evidence supports the functional importance of these newborn neurons and their associated astrocytes. Alterations to either of these cell types can influence neuronal functioning. To determine if hypertrophied astrocytes might negatively influence immature neurons in the dentate gyrus, astrocyte and newborn neurons were analyzed at 30 days following a TBI in mice. The results demonstrate a loss of radial glial-like processes extending through the granule cell layer after TBI, as well as ectopic growth and migration of immature dentate neurons. The results further show newborn neurons in close association with hypertrophied astrocytes, suggesting a role for the astrocytes in aberrant neurogenesis. Future studies are needed to determine the functional significance of these alterations to the astrocyte/immature neurons after TBI.
Contrast Enhancement Method Based on Gray and Its Distance Double-Weighting Histogram Equalization for 3D CT Images of PCBs
Authors: Zeng Lei , Yan Bin , Wang Weidong
Published: May 2016

Cone beam computed tomography (CBCT) is a new detection method for 3D nondestructive testing of printed circuit boards (PCBs). However, the obtained 3D image of PCBs exhibits low contrast because of several factors, such as the occurrence of metal artifacts and beam hardening, during the process of CBCT imaging. Histogram equalization (HE) algorithms cannot effectively extend the gray difference between a substrate and a metal in 3D CT images of PCBs, and the reinforcing effects are insignificant. To address this shortcoming, this study proposes an image enhancement algorithm based on gray and its distance double-weighting HE. Considering the characteristics of 3D CT images of PCBs, the proposed algorithm uses gray and its distance double-weighting strategy to change the form of the original image histogram distribution, suppresses the grayscale of a nonmetallic substrate, and expands the grayscale of wires and other metals. The proposed algorithm also enhances the gray difference between a substrate and a metal and highlights metallic materials. The proposed algorithm can enhance the gray value of wires and other metals in 3D CT images of PCBs. It applies enhancement strategies of changing gray and its distance double-weighting mechanism to adapt to this particular purpose. The flexibility and advantages of the proposed algorithm are confirmed by analyses and experimental results.
Sound Attenuation of Membranes Loaded with Square Frame-Shaped Masses
Authors: Chen J. S. , Kao D. W.
Published: May 2016

This study examines sound transmission of thin membranes with square frame-shaped masses. Numerical results indicate that multiple transmission loss peaks can be generated by adding more frame mass inclusions. The number and the location of the peaks are controlled by the number of frames, the frame distribution, and the frame width. Near the transmission loss peak frequencies, the dynamic effective mass density turns from positive to negative. The validity of the present model has been verified by comparing the analytical results with FE results. Two types of cell arrangements are also considered in this study, namely, cells in series and cells in array. It is seen that either the stacked or array configurations can produce better sound attenuation than single-celled structures. Moreover, the frequency band where sound wave is blocked can be broadened by stacking more layers with different mass magnitudes. Furthermore, additional frequency bands due to the periodicity of the structure are found in the stacked configurations.
Prevention and Therapeutic Effects and Mechanisms of Tanshinone IIA Sodium Sulfonate on Acute Liver Injury Mice Model
Authors: Lu Lunjie , Zhou Jun , Zhang Jingying , Che Jun , Jiao Yang , Zhang Yusong
Published: May 2016

Tanshinone IIA sodium sulfonate (TSS) is a water‐soluble derivative of tanshinone IIA, which is the main pharmacologically active component of Salvia miltiorrhiza. This study aimed to verify the preventive and therapeutic effects of TSS and its combined therapeutic effects with magnesium isoglycyrrhizinate (MI) in D‐galactosamine‐ (D‐Gal‐) induced acute liver injury (ALI) in mice. The potential regulatory mechanisms of TSS on ALI were also examined. Our results may provide a basis for the development of novel therapeutics for ALI.
Functional Properties of Human Stem Cell‐Derived Neurons in Health and Disease
Authors: Weick Jason P.
Published: May 2016

Stem cell‐derived neurons from various source materials present unique model systems to examine the fundamental properties of central nervous system (CNS) development as well as the molecular underpinnings of disease phenotypes. In order to more accurately assess potential therapies for neurological disorders, multiple strategies have been employed in recent years to produce neuronal populations that accurately represent in vivo regional and transmitter phenotypes. These include new technologies such as direct conversion of somatic cell types into neurons and glia which may accelerate maturation and retain genetic hallmarks of aging. In addition, novel forms of genetic manipulations have brought human stem cells nearly on par with those of rodent with respect to gene targeting. For neurons of the CNS, the ultimate phenotypic characterization lies with their ability to recapitulate functional properties such as passive and active membrane characteristics, synaptic activity, and plasticity. These features critically depend on the coordinated expression and localization of hundreds of ion channels and receptors, as well as scaffolding and signaling molecules. In this review I will highlight the current state of knowledge regarding functional properties of human stem cell‐derived neurons, with a primary focus on pluripotent stem cells. While significant advances have been made, critical hurdles must be overcome in order for this technology to support progression toward clinical applications.
Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells
Authors: Vondráček Jan , Machala Miroslav
Published: May 2016

The toxicity of environmental and dietary ligands of the aryl hydrocarbon receptor (AhR) in mature liver parenchymal cells is well appreciated, while considerably less attention has been paid to their impact on cell populations exhibiting phenotypic features of liver progenitor cells. Here, we discuss the results suggesting that the consequences of the AhR activation in the cellular models derived from bipotent liver progenitors could markedly differ from those in hepatocytes. In contact‐inhibited liver progenitor cells, the AhR agonists induce a range of effects potentially linked with tumor promotion. They can stimulate cell cycle progression/proliferation and deregulate cell‐to‐cell communication, which is associated with downregulation of proteins forming gap junctions, adherens junctions, and desmosomes (such as connexin 43, E‐cadherin, β‐catenin, and plakoglobin), as well as with reduced cell adhesion and inhibition of intercellular communication. At the same time, toxic AhR ligands may affect the activity of the signaling pathways contributing to regulation of liver progenitor cell activation and/or differentiation, such as downregulation of Wnt/β‐catenin and TGF‐β signaling, or upregulation of transcriptional targets of YAP/TAZ, the effectors of Hippo signaling pathway. These data illustrate the need to better understand the potential role of liver progenitors in the AhR‐mediated liver carcinogenesis and tumor promotion.
A Case Study of MasterMind Chess: Comparing Mouse/Keyboard Interaction with Kinect-Based Gestural Interface
Authors: Vasiljevic Gabriel Alves Mendes , de Miranda Leonardo Cunha , de Miranda Erica Esteves Cunha
Published: May 2016

As gestural interfaces emerged as a new type of user interface, their use has been vastly explored by the entertainment industry to better immerse the player in games. Despite being mainly used in dance and sports games, little use was made of gestural interaction in more slow-paced genres, such as board games. In this work, we present a Kinect-based gestural interface for an online and multiplayer chess game and describe a case study with users with different playing skill levels. Comparing the mouse/keyboard interaction with the gesture-based interaction, the results of the activity were synthesized into lessons learned regarding general usability and design of game control mechanisms. These results could be applied to slow-paced board games like chess. Our findings indicate that gestural interfaces may not be suitable for competitive chess matches, yet it can be fun to play while using them in casual matches.
Statistics and Analysis of the Relations between Rainstorm Floods and Earthquakes
Authors: Hou Baodeng , Wu Yongxiang , Wang Jianhua , Wu Kai , Xiao Weihua
Published: May 2016

The frequent occurrence of geophysical disasters under climate change has drawn Chinese scholars to pay their attention to disaster relations. If the occurrence sequence of disasters could be identified, long-term disaster forecast could be realized. Based on the Earth Degassing Effect (EDE) which is valid, this paper took the magnitude, epicenter, and occurrence time of the earthquake, as well as the epicenter and occurrence time of the rainstorm floods as basic factors to establish an integrated model to study the correlation between rainstorm floods and earthquakes. 2461 severe earthquakes occurred in China or within 3000 km from China and the 169 heavy rainstorm floods occurred in China over the past 200+ years as the input data of the model. The computational results showed that although most of the rainstorm floods have nothing to do with the severe earthquakes from a statistical perspective, some floods might relate to earthquakes. This is especially true when the earthquakes happen in the vapor transmission zone where rainstorms lead to abundant water vapors. In this regard, earthquakes are more likely to cause big rainstorm floods. However, many cases of rainstorm floods could be found after severe earthquakes with a large extent of uncertainty.
Incorporation of Amphipathic Diblock Copolymer in Lipid Bilayer for Improving pH Responsiveness
Authors: Xia Tian , Hao Weiju , Shang Yazhuo , Xu Shouhong , Liu Honglai
Published: May 2016

Diblock copolymers (mPEG-b-PDPA), which were designed to possess pH-sensitivity as well as amphipathy, were used as an intelligent lock in the liposomal membrane. The so-called pH-sensitive liposomes were prepared by simple mixing of the synthesized mPEG-b-PDPA with phospholipids and cholesterol. Fluorescence polarization at pH 7.4 showed that the membrane stability of the hybrid liposome was significantly increased compared with the pure liposome. Therefore, in the neutral environment, the leakage of doxorubicin (DOX) was inhibited. However, when pH decreased to 6.0, DOX release rate increased by 60% due to the escape of copolymer. The effects of the membrane composition and the PDPA segment length on bilayer membrane functions were investigated. These results revealed that the synthesized copolymers increased the difference in DOX cumulative release between pH 7.4 and 6.0, that is, improved the pH-controllability of the drug release from hybrid liposomes.
Diagnostic Value of White Blood Cell and C-Reactive Protein in Pediatric Appendicitis
Authors: Buyukbese Sarsu Sevgi , Sarac Fatma
Published: May 2016

Background.Acute appendicitis (AA) associated with acute phase reaction is the most prevalent disease which requires emergency surgery. Its delayed diagnosis and unnecessarily performed appendectomies lead to numerous complications. In our study, we aimed to detect the role of WBC and CRP in the exclusion of acute and complicated appendicitis and diagnostic accuracy in pediatric age group.Methods.Appendectomized patient groups were constructed based on the results of histological evaluation. The area under a receiver operating characteristic (ROC) curve (AUC) was performed to examine diagnostic accuracy.Results.When WBC and CRP were used in combination, based on cut-off values of ≥13.1 × 103/μL for WBC counts and ≥1.17 mg/dL for CRP level, diagnostic parameters were as follows: sensitivity, 98.7%; specificity, 71.3%; PPV, 50.6%; NPV, 99.5%; diagnostic accuracy, 77.6%; LR(+), 3.44; LR(−), 0.017. AUC values were 0.845 (95% CI 0.800–0.891) for WBC and 0.887 (95% CI 0.841–0.932) for CRP.Conclusions.For complicated appendicitis, CRP has the highest degree of diagnostic accuracy. The diagnosis of appendicitis should be made primarily based on clinical examination, and obviously more specific and systemic inflammatory markers are needed. Combined use of cut-off values of WBC (≥13100/μL) and CRP (≥1.17 mg/L) yields a higher sensitivity and NPV for the diagnosis of complicated appendicitis.
Synthesis and Magnetic Characterization of Graphite-Coated Iron Nanoparticles
Authors: Espinoza-Rivas A. M. , Pérez-Guzmán M. A. , Ortega-Amaya R. , Santoyo-Salazar J. , Gutiérrez-Lazos C. D. , Ortega-López M.
Published: May 2016

Graphite-coated iron nanoparticles were prepared from magnetite nanoparticles by chemical vapour deposition (CVD) under methane and hydrogen atmosphere. After being purified from carbon excess, graphite-coated iron nanoparticles were tested for morphological and magnetic properties. It was found that, during the thermal process, magnetite nanoparticles 6 nm in size coalesce and transform into graphite-coated iron 200 nm in size, as revealed by scanning electron microscopy (SEM). Raman characterization assessed that high-quality graphite coats the iron core. Magnetic measurements revealed the phase change (magnetite to iron) as an increase in the saturation magnetization from 50 to 165 emu/g after the CVD process.
Effect of Electroacupuncture on the Expression of Glycyl‐tRNA Synthetase and Ultrastructure Changes in Atrophied Rat Peroneus Longus Muscle Induced by Sciatic Nerve Injection Injury
Authors: Wang Meng , Zhang Xiao Ming , Yang Sheng Bo
Published: May 2016

Glycyl‐tRNA synthetase (GlyRS) is one of the key enzymes involved in protein synthesis. Its mutations have been reported to cause Charcot‐Marie‐Tooth disease which demonstrates muscular atrophy in distal extremities, particularly manifested in peroneus muscles. In this situation, the dysfunctions of mitochondria and sarcoplasmic reticulum (SR) affect energy supply and excitation‐contraction coupling of muscle fibers, therefore resulting in muscular atrophy. Although the treatment of muscular atrophy is a global urgent problem, it can be improved by electroacupuncture (EA) treatment. To investigate the mechanism underlying EA treatment improving muscular atrophy, we focused on the perspective of protein synthesis by establishing a penicillin injection‐induced sciatic nerve injury model. In our model, injured rats without treatment showed decreased sciatic functional index (SFI), decreased peroneus longus muscle weight and muscle fiber cross‐sectional area, aggregated mitochondria with vacuoles appearing, swollen SR, and downregulated mRNA and protein expression levels of GlyRS and myosin heavy chain IIb (MHC‐IIb). The injured rats with EA treatment showed significant recovery. These results indicated that EA stimulation can alleviate peroneus longus muscular atrophy induced by iatrogenic sciatic nerve injury through promoting the recovery of GlyRS and muscle ultrastructure and increasing muscle protein synthesis.
Tanshinone IIA Alleviates the AD Phenotypes in APP and PS1 Transgenic Mice
Authors: Li Fengling , Han Guosheng , Wu Kexiang
Published: May 2016

Therapeutic approach for Alzheimer’s disease (AD) is still deficient. To find active compounds from herbal medicine is of interest in the alleviation of AD symptoms. This study aimed to investigate the protective effects of Tanshinone IIA (TIIA) on memory performance and synaptic plasticity in a transgenic AD model at the early phase. 25–100 mg/kg TIIA (intraperitoneal injection,i.p.) was administered to the six-month-old APP and PS1 transgenic mice for 30 consecutive days. After treatment, spatial memory, synaptic plasticity, and related mechanisms were investigated. Our result showed that memory impairment in AD mice was mitigated by 50 and 100 mg/kg TIIA treatments. Hippocampal long-term potentiation was impaired in AD model but rescued by 100 mg/kg TIIA treatment. Mechanically, TIIA treatment reduced the accumulations of beta-amyloid 1–42, C-terminal fragments (CTFs), and p-Tau in the AD model. TIIA did not affect basal BDNF but promoted depolarization-induced BDNF synthesis in the AD mice. Taken together, TIIA repairs hippocampal LTP and memory, likely, through facilitating the clearance of AD-related proteins and activating synaptic BDNF synthesis. TIIA might be a candidate drug for AD treatment.