bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a Multipeptide Lantibiotic Locus in Streptococcus pneumoniae
Authors: Maricic Natalie , Anderson Erica S. , Opipari AnneMarie E. , Yu Emily A. , Dawid Suzanne
Published: January 2016

Bacterial communities are established through a combination of cooperative and antagonistic interactions between the inhabitants. Competitive interactions often involve the production of antimicrobial substances, including bacteriocins, which are small antimicrobial peptides that target other community members. Despite the nearly ubiquitous presence of bacteriocin-encoding loci, inhibitory activity has been attributed to only a small fraction of gene clusters. In this study, we characterized a novel locus (the
pld
locus) in the pathogen
Streptococcus pneumoniae
that drives the production of a bacteriocin called pneumolancidin, which has broad antimicrobial activity. The locus encodes an unusual tandem array of four inhibitory peptides, three of which are absolutely required for antibacterial activity. The three peptide sequences are similar but appear to play distinct roles in regulation and inhibition. A modification enzyme typically found in loci encoding a class of highly modified bacteriocins called lantibiotics was required for inhibitory activity. The production of pneumolancidin is controlled by a two-component regulatory system that is activated by the accumulation of modified peptides. The locus is located on a mobile element that has been found in many pneumococcal lineages, although not all elements carry the
pld
genes. Intriguingly, a minimal region containing only the genes required for pneumolancidin immunity was found in several
Streptococcus mitis
strains. The pneumolancidin-producing strain can inhibit nearly all pneumococci tested to date and provided a competitive advantage
in vivo
. These peptides not only represent a unique strategy for bacterial competition but also are an important resource to guide the development of new antimicrobials.

IMPORTANCE
Successful colonization of a polymicrobial host surface is a prerequisite for the subsequent development of disease for many bacterial pathogens. Bacterial factors that directly inhibit the growth of neighbors may provide an advantage during colonization if the inhibition of competitors outweighs the energy for production. In this work, we found that production of a potent antimicrobial called pneumolancidin conferred a competitive advantage to the pathogen
Streptococcus pneumoniae
.
S. pneumoniae
secreting pneumolancidin inhibits a wide array of Gram-positive organisms, including all but one tested pneumococcal strain. The pneumolancidin genetic locus is of particular interest because it encodes three similar modified peptides (lantibiotics), each of which has a distinct role in the function of the locus. Lantibiotics represent a relatively untapped resource for the development of clinically useful antibiotics which are desperately needed. The broad inhibitory activity of pneumolancidin makes it an ideal candidate for further characterization and development.
The Atomic Structure of the Phage Tuc2009 Baseplate Tripod Suggests that Host Recognition Involves Two Different Carbohydrate Binding Modules
Authors: Legrand Pierre , Collins Barry , Blangy Stéphanie , Murphy James , Spinelli Silvia , Gutierrez Carlos , Richet Nicolas , Kellenberger Christine , Desmyter Aline , Mahony Jennifer , van Sinderen Douwe , Cambillau Christian
Published: January 2016

The Gram-positive bacterium
Lactococcus lactis
, used for the production of cheeses and other fermented dairy products, falls victim frequently to fortuitous infection by tailed phages. The accompanying risk of dairy fermentation failures in industrial facilities has prompted in-depth investigations of these phages. Lactococcal phage Tuc2009 possesses extensive genomic homology to phage TP901-1. However, striking differences in the baseplate-encoding genes stimulated our interest in solving the structure of this host’s adhesion device. We report here the X-ray structures of phage Tuc2009 receptor binding protein (RBP) and of a “tripod” assembly of three baseplate components, BppU, BppA, and BppL (the RBP). These structures made it possible to generate a realistic atomic model of the complete Tuc2009 baseplate that consists of an 84-protein complex: 18 BppU, 12 BppA, and 54 BppL proteins. The RBP head domain possesses a different fold than those of phages p2, TP901-1, and 1358, while the so-called “stem” and “neck” domains share structural features with their equivalents in phage TP901-1. The BppA module interacts strongly with the BppU N-terminal domain. Unlike other characterized lactococcal phages, Tuc2009 baseplate harbors two different carbohydrate recognition sites: one in the bona fide RBP head domain and the other in BppA. These findings represent a major step forward in deciphering the molecular mechanism by which Tuc2009 recognizes its saccharidic receptor(s) on its host.

IMPORTANCE
Understanding how siphophages infect
Lactococcus lactis
is of commercial importance as they cause milk fermentation failures in the dairy industry. In addition, such knowledge is crucial in a general sense in order to understand how viruses recognize their host through protein-glycan interactions. We report here the lactococcal phage Tuc2009 receptor binding protein (RBP) structure as well as that of its baseplate. The RBP head domain has a different fold than those of phages p2, TP901-1, and 1358, while the so-called “stem” and “neck” share the fold characteristics also found in the equivalent baseplate proteins of phage TP901-1. The baseplate structure contains, in contrast to other characterized lactococcal phages, two different carbohydrate binding modules that may bind different motifs of the host’s surface polysaccharide.
Kisameet Clay Exhibits Potent Antibacterial Activity against the ESKAPE Pathogens
Authors: Behroozian Shekooh , Svensson Sarah L. , Davies Julian
Published: January 2016

The ESKAPE (
Enterococcus faecium
,
Staphylococcus aureus
,
Klebsiella pneumoniae
,
Acinetobacter baumannii
,
Pseudomonas aeruginosa
, and
Enterobacter
species) pathogens cause an increasing number of nosocomial infections worldwide since they escape the inhibitory effect of the available antibiotics and the immune response. Here, we report the broad-spectrum and potent antibacterial activity of Kisameet clay, a natural clay mineral from British Columbia, Canada, against a group of multidrug-resistant ESKAPE strains. The results suggest that this natural clay might be developed as a therapeutic option for the treatment of serious infections caused by these important pathogens.

IMPORTANCE
More than 50 years of misuse and overuse of antibiotics has led to a plague of antibiotic resistance that threatens to reduce the efficacy of antimicrobial agents available for the treatment of infections due to resistant organisms. The main threat is nosocomial infections in which certain pathogens, notably the ESKAPE organisms, are essentially untreatable and contribute to increasing mortality and morbidity in surgical wards. The pipeline of novel antimicrobials in the pharmaceutical industry is essentially empty. Thus, there is a great need to seek for new sources for the treatment of recalcitrant infectious diseases. We describe experiments that demonstrate the efficacy of a “natural” medicine, Kisameet clay, against all of the ESKAPE strains. We suggest that this material is worthy of clinical investigation for the treatment of infections due to multidrug-resistant organisms.
Identification and Characterization of the Novel Subunit CcoM in the
cbb
3
-Cytochrome
c
Oxidase from Pseudomonas stutzeri ZoBell
Authors: Kohlstaedt Martin , Buschmann Sabine , Xie Hao , Resemann Anja , Warkentin Eberhard , Langer Julian D. , Michel Hartmut
Published: January 2016

Cytochrome
c
oxidases (C
c
Os), members of the heme-copper containing oxidase (HCO) superfamily, are the terminal enzymes of aerobic respiratory chains. The
cbb
3
-type cytochrome
c
oxidases (
cbb
3
-C
c
O) form the C-family and have only the central catalytic subunit in common with the A- and B-family HCOs. In
Pseudomonas stutzeri
, two
cbb
3
operons are organized in a tandem repeat. The atomic structure of the first
cbb
3
isoform (Cbb
3
-1) was determined at 3.2 Å resolution in 2010 (S. Buschmann, E. Warkentin, H. Xie, J. D. Langer, U. Ermler, and H. Michel, Science 329:327–330, 2010,
http://dx.doi.org/10.1126/science.1187303
). Unexpectedly, the electron density map of Cbb
3
-1 revealed the presence of an additional transmembrane helix (TMH) which could not be assigned to any known protein. We now identified this TMH as the previously uncharacterized protein PstZoBell_05036, using a customized matrix-assisted laser desorption ionization (MALDI)–tandem mass spectrometry setup. The amino acid sequence matches the electron density of the unassigned TMH. Consequently, the protein was renamed CcoM. In order to identify the function of this new subunit in the
cbb
3
complex, we generated and analyzed a CcoM knockout strain. The results of the biochemical and biophysical characterization indicate that CcoM may be involved in C
c
O complex assembly or stabilization. In addition, we found that CcoM plays a role in anaerobic respiration, as the ΔCcoM strain displayed altered growth rates under anaerobic denitrifying conditions.

IMPORTANCE
The respiratory chain has recently moved into the focus for drug development against prokaryotic human pathogens, in particular, for multiresistant strains (P. Murima, J. D. McKinney, and K. Pethe, Chem Biol 21:1423–1432, 2014,
http://dx.doi.org/10.1016/j.chembiol.2014.08.020
).
cbb
3
-C
c
O is an essential enzyme for many different pathogenic bacterial species, e.g.,
Helicobacter pylori
,
Vibrio cholerae
, and
Pseudomonas aeruginosa
, and represents a promising drug target. In order to develop compounds targeting these proteins, a detailed understanding of the molecular architecture and function is required. Here we identified and characterized a novel subunit, CcoM, in the
cbb
3
-C
c
O complex and thereby completed the crystal structure of the Cbb
3
oxidase from
Pseudomonas stutzeri
, a bacterium closely related to the human pathogen
Pseudomonas aeruginosa
.
Unusual presentation of bladder cancer resurgence and efficacy of radiotherapy
Authors: Galot Rachel , Christian Nicolas , Bitar Marie , Seront Emmanuel
Published: January 2016

A 68-year-old man with a history of bladder cancer presented with perineal pain and penile priapism. The work up showed multiple lesions strictly located in the penis; biopsy confirmed metastases of bladder cancer. Surgery was judged unfeasible and chemotherapy failed to improve symptoms. Radiotherapy was therefore delivered on the whole penis and resulted in a rapid clinical benefit and persistent control of the disease. Penile metastases are very rare and no consensus exists concerning their management; radiotherapy appears as a promising therapeutic option not only to palliate pain but also to control the disease.
Necrotic lipoma at the posterior thigh mimicking liposarcoma
Authors: Ohki Takahiro , Ushiku Tetsuo , Shinoda Yusuke , Kobayashi Hiroshi
Published: January 2016

A lipoma is one of the most common benign tumours and can develop at any location in the body. Lipomas present characteristic imaging features; hence, they are easy to identify on CT and MRI. However, cases of necrotic lipoma are rarely encountered; therefore, information on the imaging findings of necrotic lipomas is scarce. In the present report, we describe the case of a 63-year-old man with necrotic lipoma in the deep layer of the posterior thigh, which resembled a liposarcoma on imaging. To the best of our knowledge, only a few reports on necrotic lipoma on the extremities have been published.
Thoracic spondylodiscitis presenting as abdominal pain
Authors: Luney Matthew , Adiamah Alfred , Pearson Lydia
Published: January 2016

A 42-year-old woman presented to our hospital with weeks of worsening pain around her lower ribs. Preceding this, she was managed in primary care with anti-inflammatory drugs and physiotherapy for presumed costochondritis. Assessment in accident and emergency suggested a tender right upper quadrant with fever and neutrophilia. A surgical review of the patient was requested to assess for cholecystitis or delayed pancreatitis. On direct questioning, the patient's back pain was the predominating symptom with no neurological deficit. To assess for delayed pancreatitis, CT imaging was obtained, demonstrating unremarkable intra-abdominal organs. There was also the incidental finding of thickened prevertebral soft tissues anterior to T9 and T10 vertebrae, with vertebral endplate irregularity locally. Subsequent MRI demonstrated typical appearances of infective spondylodiscitis at this level. The patient made a good recovery with intravenous antimicrobials. This case highlights how vertebrodiscitis can present insidiously and unexpectedly, manifesting as abdominal pain.
Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity
Authors: Patterson Rainey E. , Kalavalapalli Srilaxmi , Williams Caroline M. , Nautiyal Manisha , Mathew Justin T. , Martinez Janie , Reinhard Mary K. , McDougall Danielle J. , Rocca James R. , Yost Richard A. , Cusi Kenneth , Garrett Timothy J. , Sunny Nishanth E.
Published: January 2016

The hepatic tricarboxylic acid (TCA) cycle is central to integrating macronutrient metabolism and is closely coupled to cellular respiration, free radical generation, and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through the hepatic TCA cycle. Mice (C57/BL6) were fed a high- trans-fat high-fructose diet (TFD) for 8 wk to induce simple steatosis and NASH by 24 wk. In vivo fasting hepatic mitochondrial fluxes were determined by13C-nuclear magnetic resonance (NMR)-based isotopomer analysis. Hepatic metabolic intermediates were quantified using mass spectrometry-based targeted metabolomics. Hepatic triglyceride accumulation and insulin resistance preceded alterations in mitochondrial metabolism, since TCA cycle fluxes remained normal during simple steatosis. However, mice with NASH had a twofold induction ( P < 0.05) of mitochondrial fluxes (μmol/min) through the TCA cycle (2.6 ± 0.5 vs. 5.4 ± 0.6), anaplerosis (9.1 ± 1.2 vs. 16.9 ± 2.2), and pyruvate cycling (4.9 ± 1.0 vs. 11.1 ± 1.9) compared with their age-matched controls. Induction of the TCA cycle activity during NASH was concurrent with blunted ketogenesis and accumulation of hepatic diacylglycerols (DAGs), ceramides (Cer), and long-chain acylcarnitines, suggesting inefficient oxidation and disposal of excess free fatty acids (FFA). Sustained induction of mitochondrial TCA cycle failed to prevent accretion of “lipotoxic” metabolites in the liver and could hasten inflammation and the metabolic transition to NASH.
Corticosterone administration in drinking water decreases high-fat diet intake but not preference in male rats
Authors: Boersma Gretha J. , Tamashiro Kellie L. , Moran Timothy H. , Liang Nu-Chu
Published: January 2016

One of the mechanisms through which regular exercise contributes to weight maintenance could be by reducing intake and preference for high-fat (HF) diets. Indeed, we previously demonstrated that wheel-running rats robustly reduced HF diet intake and preference. The reduced HF diet preference by wheel running can be so profound that the rats consumed only the chow diet and completely avoided the HF diet. Because previous research indicates that exercise activates the hypothalamic-pituitary-adrenal axis and increases circulating levels of corticosterone, this study tested the hypothesis that elevation of circulating corticosterone is involved in wheel running-induced reduction in HF diet preference in rats. Experiment 1 measured plasma corticosterone levels under sedentary and wheel-running conditions in the two-diet-choice (high-carbohydrate chow vs. HF) feeding regimen. The results revealed that plasma corticosterone is significantly increased and positively correlated with the levels of running in wheel-running rats with two-diet choice. Experiments 2 and 3 determined whether elevated corticosterone without wheel running is sufficient to reduce HF diet intake and preference. Corticosterone was elevated by adding it to the drinking water. Compared with controls, corticosterone-drinking rats had reduced HF diet intake and body weight, but the HF diet preference between groups did not differ. The results of this study support a role for elevated corticosterone on the reduced HF diet intake during wheel running. The elevation of corticosterone alone, however, is not sufficient to produce a robust reduction in HF diet preference.
Behavior of the Solutions for Predator-Prey Dynamic Systems with Beddington-DeAngelis Type Functional Response on Periodic Time Scales in Shifts
Authors: Pelen Neslihan Nesliye , Güvenilir Ayşe Feza , Kaymakçalan Billur
Published: January 2016

We consider two-dimensional predator-prey system with Beddington-DeAngelis type functional response on periodic time scales in shifts. For this special case we try to find under which conditions the system hasδ±-periodic solution.
Effect of the Longitudinal Contact Location on Vehicle Dynamics Simulation
Authors: Burgelman N. , Li Z. , Dollevoet R.
Published: January 2016

This paper investigates the effect of the calculation of the longitudinal location of a wheel rail contact point on the wheelset’s motion in a vehicle dynamic simulation. All current vehicle dynamic software programs assume that the contact between wheel and rail takes place in the vertical plane through the wheelset’s rolling axis. However, when the yaw angle of the wheelset is nonzero, the contact point is situated up to 10 mm from that plane. This difference causes a difference in the yaw moment on the wheelset which is used in the vehicle dynamic simulation. To such an end, an existing analytical method to determine the longitudinal method was validated using a numerical approach. Then vehicle dynamic simulations with both the classic and the new contact location were performed, concluding that using a more accurate contact point location results in a smaller wheelset yaw angle in a vehicle dynamic simulation, although the effect is small.
Quantification of Climate Changes and Human Activities That Impact Runoff in the Taihu Lake Basin, China
Authors: Peng Dingzhi , Qiu Linghua , Fang Jing , Zhang Zhongyuan
Published: January 2016

Although a fragile climate region, the Taihu Lake Basin is among the most developed regions in China and is subjected to intense anthropogenic interference. In this basin, water resources encounter major challenges (e.g., floods, typhoons, and water pollution). In this study, the impacts of climate changes and human activities on hydrological processes were estimated to aid water resource management in developed regions in China. The Mann-Kendall test and cumulative anomaly curve were applied to detect the turning points in the runoff series. The year of 1982 divides the study period (1956~2008) into a baseline period (1956~1981) and a modified period (1982~2008). The double mass curve method and the hydrological sensitivity method based on the Budyko framework were applied to quantitatively attribute the runoff variation to climate changes and human activities. The results demonstrated that human activities are the dominant driving force of runoff variations in the basin, with a contribution of 83~89%; climate changes contributed to 11~17% of the variations. Moreover, the subregions of the basin indicated that humans severely disturbed the runoff variation, with contributions as high as 95~97%.
Overtaking Safety Evaluation and Setting of Auxiliary Lane on Two-Lane Highway in China
Authors: Cheng Guozhu , Wu Lixin , Xu Liang , Qin Lihui , Wang Yuxia
Published: January 2016

Overtaking experiments on four two-lane highways were conducted. The data of overtaking conflict time (the time difference between the time of driving back to the original lane and the time of meeting with the first opposing vehicle) and experimental drivers’ risk feeling were observed. Membership was adopted to denote the experimental drivers’ risk feelings which also denote the severity of traffic conflict. Membership ranges from 0 to 1 and corresponding risk becomes higher; that is, traffic conflict becomes more serious. According to the observed relationship between overtaking conflict time, and drivers’ risk feeling membership, Cauchy distribution function was adopted as membership function. The thresholds of the severity of traffic conflict were determined through Delphi method. The relationship model among traffic volume, overtaking conflict time and design speed was established according to experimental data. Then the idea of setting auxiliary lane on two-lane highway in China was presented. And the traffic volume values that need setting auxiliary lane corresponding to different design speed and traffic conflict degree were given according to the established model. It is expected to improve the traffic safety level of two-lane highway in China through setting auxiliary lane.
Time and Frequency Localized Pulse Shape for Resolution Enhancement in STFT-BOTDR
Authors: Luo Linqing , Li Bo , Yu Yifei , Xu Xiaomin , Soga Kenichi , Yan Jize
Published: January 2016

Short-Time Fourier Transform-Brillouin Optical Time-Domain Reflectometry (STFT-BOTDR) implements STFT over the full frequency spectrum to measure the distributed temperature and strain along the optic fiber, providing new research advances in dynamic distributed sensing. The spatial and frequency resolution of the dynamic sensing are limited by the Signal to Noise Ratio (SNR) and the Time-Frequency (T-F) localization of the input pulse shape.T-Flocalization is fundamentally important for the communication system, which suppresses interchannel interference (ICI) and intersymbol interference (ISI) to improve the transmission quality in multicarrier modulation (MCM). This paper demonstrates that theT-Flocalized input pulse shape can enhance the SNR and the spatial and frequency resolution in STFT-BOTDR. Simulation and experiments ofT-Flocalized different pulses shapes are conducted to compare the limitation of the system resolution. The result indicates that rectangular pulse should be selected to optimize the spatial resolution and Lorentzian pulse could be chosen to optimize the frequency resolution, while Gaussian shape pulse can be used in general applications for its balanced performance in both spatial and frequency resolution. Meanwhile,T-Flocalization is proved to be useful in the pulse shape selection for system resolution optimization.
Wide Range Fiber Displacement Sensor Based on Bending Loss
Authors: Zhao Jinlei , Bao Tengfei , Kundu Tribikram
Published: January 2016

A wide range fiber optic sensor system for displacement and crack monitoring is developed. In the proposed fiber optic sensor system, a number of fiber loops are formed from a single fiber and each fiber loop is used as a crack or displacement sensor. The feasibility and the dynamic range of the fiber sensor developed in this manner are investigated experimentally. Both glass fibers and plastic fibers are used in the experiments. Experimental results show that the new fiber optic sensor has a wide range (maximum range is 88 mm) and this sensor also has a high sensitivity for displacement and crack monitoring when an appropriate diameter of the fiber loop is selected as the sensor. Moreover, the proposed method is very simple and has low cost, so in situ application potential of the proposed sensor is high.
Fractal Dimension Based on Morphological Covering for Ground Target Classification
Authors: Du Kai , Fang Xiang , Zhang Wei-ping , Ding Kai
Published: January 2016

Seismic waves are widely used in ground target classification due to its inherent characteristics. However, they are often affected by extraneous factors and have been found to demonstrate a complicated nonlinear characteristic. The traditional signal analysis methods cannot effectively extract the nonlinear features. Motivated by this fact, this paper applies the fractal dimension (FD) based on morphological covering (MC) method to extract features of the seismic signals for ground targets classification. With the data measured from test field, three different schemes based on MC method are employed to classify tracked vehicle and wheeled vehicle in different operation conditions. Experiment results demonstrate that the three proposed methods achieve more than 90% accuracy for vehicle classification.
Nonuniform Illumination Correction Algorithm for Underwater Images Using Maximum Likelihood Estimation Method
Authors: Sankpal Sonali Sachin , Deshpande Shraddha Sunil
Published: January 2016

Scattering and absorption of light is main reason for limited visibility in water. The suspended particles and dissolved chemical compounds in water are also responsible for scattering and absorption of light in water. The limited visibility in water results in degradation of underwater images. The visibility can be increased by using artificial light source in underwater imaging system. But the artificial light illuminates the scene in a nonuniform fashion. It produces bright spot at the center with the dark region at surroundings. In some cases imaging system itself creates dark region in the image by producing shadow on the objects. The problem of nonuniform illumination is neglected by the researchers in most of the image enhancement techniques of underwater images. Also very few methods are discussed showing the results on color images. This paper suggests a method for nonuniform illumination correction for underwater images. The method assumes that natural underwater images are Rayleigh distributed. This paper used maximum likelihood estimation of scale parameter to map distribution of image to Rayleigh distribution. The method is compared with traditional methods for nonuniform illumination correction using no-reference image quality metrics like average luminance, average information entropy, normalized neighborhood function, average contrast, and comprehensive assessment function.
Equalization Technique for Balancing the Modulation Ratio Characteristics of the Single-Phase-to-Three-Phase Matrix Converter
Authors: Velu Vengadeshwaran , Mariun Norman , Mohd Radzi Mohd Amran , Mailah Nashiren Farzilah
Published: January 2016

Three-phase system has numerous advantages over the single-phase system in terms of instantaneous power, stability, and cost. Three-phase systems are not available in every location particularly in remote rural areas, hill stations, low voltage distribution homes, and so forth. Having a system that is capable of converting directly the readily available single-phase system to three phases will have greater usability in various applications. The routine techniques adopted in the direct ac-ac single-phase-to-three-phase converters do not yield the best desired outputs because of their complexity in the segregation process and bidirectional nature of the input signal. Other initiatives use ac-dc-ac converters which are huge and costly due to dc link energy storage devices. Further, none of these systems provide a convincing result in producing the standard three-phase output voltages that are 120° away from each other. This paper proposes an effective direct ac-ac single-phase-to-three-phase conversion technique based on space vector pulse width modulation based matrix converter system that produces a convincing three-phase output signals from a single-phase source with balanced modulation index characteristics. The details of the scientific programming adopted on the proposed technique were presented.
Treatment of Class III with Facemask Therapy
Authors: Pattanaik Snigdha , Mishra Sumita
Published: January 2016

Class III malocclusion is one of the most difficult problems to treat in the mixed dentition. It has a multifactorial etiology involving both genetic and environmental causes. The dental and skeletal effects of maxillary protraction with a facemask are well documented in several studies. Although treatment in the late mixed or early permanent dentition can be successful, results are generally better in the deciduous or early mixed dentition. The following case shows early treatment of a young patient with severe sagittal and transverse discrepancy of the maxilla and mandible, using a facemask.
Oxidative DNA Damage Mediated by Intranuclear MMP Activity Is Associated with Neuronal Apoptosis in Ischemic Stroke
Authors: Kimura-Ohba Shihoko , Yang Yi
Published: January 2016

Evidence of the pathological roles of matrix metalloproteinases (MMPs) in various neurological disorders has made them attractive therapeutic targets. MMPs disrupt the blood‐brain barrier and cause neuronal death and neuroinflammation in acute cerebral ischemia and are critical for angiogenesis during recovery. However, some challenges have to be overcome before MMPs can be further validated as drug targets in stroke injury. Identifying in vivo substrates of MMPs should greatly improve our understanding of the mechanisms of ischemic injury and is critical for providing more precise drug targets. Recent works have uncovered nontraditional roles for MMPs in the cytosol and nucleus. These have shed light on intracellular targets and biological actions of MMPs, adding additional layers of complexity for therapeutic MMP inhibition. In this review, we discussed the recent advances made in understanding nuclear location of MMPs, their regulation of intranuclear sorting, and their intranuclear proteolytic activity and substrates. In particular, we highlighted the roles of intranuclear MMPs in oxidative DNA damage, neuronal apoptosis, and neuroinflammation at an early stage of stroke insult. These novel data point to new putative MMP‐mediated intranuclear actions in stroke‐induced pathological processes and may lead to novel approaches to treatment of stroke and other neurological diseases.
Body Mass Index Trajectories among Middle-Aged and Elderly Canadians and Associated Health Outcomes
Authors: Wang Meng , Yi Yanqing , Roebothan Barbara , Colbourne Jennifer , Maddalena Victor , Wang Peizhong Peter , Sun Guang
Published: January 2016

Background. Whether there is heterogeneity in the development of BMI from middle-age onward is still unknown. The primary aim of this study is to analyze long-term obesity and how BMI trajectories are associated with health outcomes in midlife.Methods. Latent Class Growth Modelling was used to capture the changes in BMI over time. In this study, 3070 individuals from the National Population Health Survey (NPHS), aged 40–55 years at baseline, were included.Results. Four BMI trajectory groups, “Normal-Stable” (N-S), “Overweight-Stable” (OV-S), “Obese I-Stable” (OB I-S), and “Obese II-Stable” (OB II-S), were identified. Men, persons of White ancestry, and individuals who had no postsecondary education had higher odds of being in the latter three groups. Moreover, members of the OV-S, OB I-S, and OB II-S groups experienced more asthma, arthritis, hypertension, diabetes, heart disease, cognitive impairment, and reduced self-rated overall health. Individuals in the OB II-S group were at greater risk for back problems, chronic bronchitis or emphysema, and emotional issues when compared to the N-S group.Conclusion. Understanding different BMI trajectories is important in order to identify people who are at the highest risk of developing comorbidities due to obesity and to establish programs to intervene appropriately.
Determination of Saponin Content in Hang Maidong and Chuan Maidong via HPLC-ELSD Analysis
Authors: Li Xian-En , Wang Yu-Xia , Sun Peng , Liao Deng-Qun
Published: January 2016

Zhejiang and Sichuan are regarded as two genuine producing areas of Ophiopogonis radix in China. To study the difference in the quality of Ophiopogonis radix from these two places, the contents of three reported bioactive saponins, that is, ophiopogonins B, D, and D′, in tubers and fibrous roots ofOphiopogon japonicusfrom Cixi city of Zhejiang and Santai county of Sichuan were quantified using HPLC-ELSD method and compared. Ophiopogonin B and ophiopogonin D′ content in tubers of HMD were higher than those in radix of CMD, whereas ophiopogonin D in HMD was about twice lower than that of CMD. Three ophiopogonins were all detected in fibrous roots of both HMD and CMD. Their averaged content in fibrous roots of CMD was about twice higher than that in tubers of CMD. Ophiopogonin D in fibrous roots of CMD was about five times higher than that of HMD. Our biochemical assay revealed that fibrous roots and tubers of CMD can be of an important saponin source, especially for ophiopogonin D.
A New Classification Analysis of Customer Requirement Information Based on Quantitative Standardization for Product Configuration
Authors: Xiao Zheng , Zhou Zude , Sheng Buyun
Published: January 2016

Traditional methods used for the classification of customer requirement information are typically based on specific indicators, hierarchical structures, and data formats and involve a qualitative analysis in terms of stationary patterns. Because these methods neither consider the scalability of classification results nor do they regard subsequent application to product configuration, their classification becomes an isolated operation. However, the transformation of customer requirement information into quantifiable values would lead to a dynamic classification according to specific conditions and would enable an association with product configuration in an enterprise. This paper introduces a classification analysis based on quantitative standardization, which focuses on (i) expressing customer requirement information mathematically and (ii) classifying customer requirement information for product configuration purposes. Our classification analysis treated customer requirement information as follows: first, it was transformed into standardized values using mathematics, subsequent to which it was classified through calculating the dissimilarity with general customer requirement information related to the product family. Finally, a case study was used to demonstrate and validate the feasibility and effectiveness of the classification analysis.
Assessment of the Protective Role of Prenatal Zinc versus Insulin Supplementation on Fetal Cardiac Damage Induced by Maternal Diabetes in Rat Using Caspase-3 and KI67 Immunohistochemical Stains
Authors: Shams Ahmed S. , Mohammed Mona H. , Loka Mona M. , Abdel Rahman Gamal M.
Published: January 2016

Maternal diabetes mellitus (DM) affects early organogenesis. Metabolic disorders of DM are associated with a depleted zinc status. This study evaluated the effect of maternal DM on cardiac development of rat fetuses and protective roles of prenatal zinc versus insulin supplementation. Pregnant rats were divided into 4 groups ((I) control, (II) STZ-induced DM, (III) STZ-induced DM treated with Zn, and (IV) STZ induced DM treated with insulin), all sacrificed on GD 20. Fetal heart weight of diabetic rats showed significant decrease compared to controls (P<0.05). H&E stained section of controls had normal appearance of the myocardium, compared to diabetics that showed myocardial disarray with characteristic degenerative changes. Sections of zinc treated group showed restored architecture of normal myofibrils with minimal degenerative changes, while those of insulin treated group show partial restoration of the normal architecture of cardiomyocytes with focal improvement of cardiac tissue. Caspase-3 immunostained slides showed positive cytoplasmic immunoreactivity in diabetic group. But KI67 immunostained slides revealed negative nuclear immunoreaction in diabetics. We observed that gestational diabetes was associated with increased risk of fetal myocardial damage that might be caused by increased apoptotic level. Treating diabetic pregnant subjects with zinc and insulin was associated with improvement in myocardial integrity.
Plasma Levels of Monocyte Chemotactic Protein-1 Are Associated with Clinical Features and Angiogenesis in Patients with Multiple Myeloma
Authors: Valković Toni , Babarović Emina , Lučin Ksenija , Štifter Sanja , Aralica Merica , Seili-Bekafigo Irena , Duletić-Načinović Antica , Jonjić Nives
Published: January 2016

The aim of this pilot study was to determine the plasma levels of monocyte chemotactic protein-1 (MCP-1) and possible associations with angiogenesis and the main clinical features of untreated patients with multiple myeloma (MM). ELISA was used to determine plasma MCP-1 levels in 45 newly diagnosed MM patients and 24 healthy controls. The blood vessels were highlighted by immunohistochemical staining, and computer-assisted image analysis was used for more objective and accurate determination of two parameters of angiogenesis: microvessel density (MVD) and total vascular area (TVA). The plasma levels of MCP-1 were compared to these parameters and the presence of anemia, renal dysfunction, and bone lesions. A significant positive correlation was found between plasma MCP-1 concentrations and TVA (p=0.02). The MCP-1 levels were significantly higher in MM patients with evident bone lesions (p=0.01), renal dysfunction (p=0.02), or anemia (p=0.04). Therefore, our preliminary results found a positive association between plasma MCP-1 levels, angiogenesis (expressed as TVA), and clinical features in patients with MM. However, additional prospective studies with a respectable number of patients should be performed to authenticate these results and establish MCP-1 as a possible target of active treatment.
Assessing ABO/Rh Blood Group Frequency and Association with Asymptomatic Malaria among Blood Donors Attending Arba Minch Blood Bank, South Ethiopia
Authors: Alemu Getaneh , Mama Mohammedaman
Published: January 2016

Background. Determination of the various ABO/Rh blood group distributions and their association with malaria infection has paramount importance in the context of transfusion medicine and malaria control.Methods. Facility based cross-sectional study was conducted from February to June, 2015, to assess ABO/Rh blood groups distribution and their association with asymptomatic malaria. A structured questionnaire was used to collect data. Blood grouping was done using monoclonal antibodies. Thin and thick blood films were examined forPlasmodiumparasites. Data were analyzed using SPSS version 20.0.Results. A total of 416 blood donors participated with median age of22±0.29(median ± standard error of the mean). Distribution of ABO phenotypes, in decreasing order, was O (175, 42.1%), A (136, 32.7%), B (87, 20.9%), and AB (18, 4.3%). Most of them were Rh+ (386, 92.8%). The overall malaria prevalence was 4.1% (17/416). ABO blood group is significantly associated with malaria infection (P=0.022). High rate of parasitemia was seen in blood group O donors (6.899,P=0.003) compared to those with other ABO blood groups.Conclusion. Blood groups O and AB phenotypes are the most and the least ABO blood groups, respectively. There is significant association between ABO blood group and asymptomatic malaria parasitemia.
Historical Prospective: Boltzmann’s versus Planck’s State Counting—Why Boltzmann Did Not Arrive at Planck’s Distribution Law
Authors: Enders Peter
Published: January 2016

Why does Planck (1900), referring to Boltzmann’s 1877 probabilistic treatment, obtain his quantum distribution function while Boltzmann did not? To answer this question, both treatments are compared on the basis of Boltzmann’s 1868 three-level scheme (configuration—occupation—occupancy). Some calculations by Planck (1900, 1901, and 1913) and Einstein (1907) are also sketched. For obtaining a quantum distribution, it is crucial to stick with a discrete energy spectrum and to make the limit transitions to infinity at the right place. For correct state counting, the concept of interchangeability of particles is superior to that of indistinguishability.
A Modified Method for Hardness Determination from Nanoindentation Experiments with Imperfect Indenters
Authors: Guo Wei Chao , Xu Heng , Gao Xin Qin , Hou Xiao Li , Li Yan
Published: January 2016

Nanoindentation is an effective nondestructive method for small scale determination of mechanical properties of materials. However, indentation response of metallic materials is very sensitive to indenter tip roundness, size effects, loading rate, and so forth. This study will analyze the effect of indenter shape imperfections on hardness determination. For this purpose, experimental investigations and finite element simulations are carried out. At first, it is found that hardness values determined with Oliver and Pharr’s method are affected by errors caused by imperfect indenter tip: errors increase for imperfect indenters with larger tip radii. Afterwards, several commonly used methods accounting at different extents for tip radius variations are compared. However, most of those methods are found not to be accurate for shallow indentation. For this reason, a novel hardness determination method based on geometrical relations of the imperfect indenter tip is developed. Results show that the new approach is very effective even in the case of shallow indentation.
Dynamics Analysis of a Nutrient-Plankton Model with a Time Delay
Authors: Wang Beibei , Zhao Min , Dai Chuanjun , Yu Hengguo , Wang Nan , Wang Pengfei
Published: January 2016

We analyze a nutrient-plankton system with a time delay. We choose the time delay as a bifurcation parameter and investigate the stability of a positive equilibrium and the existence of Hopf bifurcations. By using the center manifold theorem and the normal form theory, the direction of the Hopf bifurcation and the stability of the bifurcating periodic solutions are researched. The theoretical results indicate that the time delay can induce a positive equilibrium to switch from a stable to an unstable to a stable state and so on. Numerical simulations show that the theoretical results are correct and feasible, and the system exhibits rich complex dynamics.
The Combination of DNA Ploidy Status and PTEN/6q15 Deletions Provides Strong and Independent Prognostic Information in Prostate Cancer
Authors: Lennartz Maximilian , Minner Sarah , Brasch Sophie , Wittmann Hilko , Paterna Leonard , Angermeier Katja , Öztürk Eray , Shihada Rami , Ruge Mingu , Kluth Martina , Koop Christina , Wilczak Waldemar , Krech Till , Lebok Patrick , Wittmer Corinna , Heinzer Hans , Steuber Thomas , Adam Meike , Huland Hartwig , Graefen Markus , Haese Alexander , Simon Ronald , Sauter Guido , Schlomm Thorsten
Published: January 2016

Purpose: Aberrant DNA content has been discussed as a potential prognostic feature in prostate cancer.

Experimental Design: We analyzed the clinical significance of DNA ploidy in combination with prognostic relevant deletions of PTEN and 6q15 in 3,845 prostate cancers.

Result: The DNA status was diploid in 67.8%, tetraploid in 25.6%, and aneuploid in 6.8% of tumors, and deletions of PTEN and 6q15 occurred in 17.8% and 20.3% of tumors. Abnormal DNA content and deletions were linked to high Gleason score, advanced tumor stage, and positive nodal stage (P < 0.0001 each). The risk of PSA recurrence increased from diploid to tetraploid and from tetraploid to aneuploid DNA status (P < 0.0001 each). However, 40% of patients with Gleason score ≥4+4 and 55% of patients with PSA recurrence had diploid cancers. This fraction decreased to 21% (Gleason ≥4+4) and 29% (PSA recurrence) if PTEN and/or 6q deletion data were added to ploidy data to identify cancers with an aberrant DNA status. The significance of combining both deletions and ploidy was further demonstrated in a combined recurrence analysis. Presence of deletions increased the risk of PSA recurrence in diploid (P < 0.0001), tetraploid (P < 0.0001), and aneuploid cancers (P = 0.0049), and the combination of ploidy data and deletions provided clinically relevant information beyond the CAPRA-S nomogram. Multivariate modeling including preoperatively and postoperatively available parameters identified the “combined DNA status” as a strong independent predictor of poor patient outcome.

Conclusions: The combinatorial DNA content analysis involving general (ploidy) and specific events (deletions) has the potential for clinical utility in prostate cancer. Clin Cancer Res; 22(11); 2802–11. ©2016 AACR.
Serum Glycans as Risk Markers for Non–Small Cell Lung Cancer
Authors: Ruhaak L. Renee , Stroble Carol , Dai Jianliang , Barnett Matt , Taguchi Ayumu , Goodman Gary E. , Miyamoto Suzanne , Gandara David , Feng Ziding , Lebrilla Carlito B. , Hanash Samir
Published: January 2016

Previous studies have suggested occurrence of altered serum glycan profiles in patients with lung cancer. Here, we aimed to determine the predictive value of serum glycans to distinguish non–small cell lung cancer (NSCLC) cases from controls in prediagnostic samples using a previously validated predictive protein marker pro-SFTPB, as anchor. Blinded prediagnostic serum samples were obtained from the Carotene and Retinol Efficacy Trial (CARET), and included a discovery set of 100 NSCLC cases and 199 healthy controls. A second test set consisted of 108 cases and 216 controls. Cases and controls were matched for age at baseline (5-year groups), sex, smoking status (current vs. former), study enrollment cohort, and date of blood draw. Serum glycan profiles were determined by mass spectrometry. Twelve glycan variables were identified to have significant discriminatory power between cases and controls in the discovery set (AUC > 0.6). Of these, four were confirmed in the independent validation set. A combination marker yielded AUCs of 0.74 and 0.64 in the discovery and test set, respectively. Four glycan variables exhibited significant incremental value when combined with pro-SFTPB compared with pro-SFTPB alone with AUCs of 0.73, 0.72, 0.72, and 0.72 in the test set, indicating that serum glycan signatures have relevance to risk assessment for NSCLC. Cancer Prev Res; 9(4); 317–23. ©2016 AACR.
Premalignancy in Prostate Cancer: Rethinking What We Know
Authors: De Marzo Angelo M. , Haffner Michael C. , Lotan Tamara L. , Yegnasubramanian Srinivasan , Nelson William G.
Published: January 2016

High-grade prostatic intraepithelial neoplasia (PIN) has been accepted as the main precursor lesion to invasive adenocarcinoma of the prostate, and this is likely to be the case. However, in an unknown number of cases, lesions fulfilling the diagnostic criteria for high-grade PIN may actually represent intra-acinar or intraductal spread of invasive carcinoma. Intriguingly, this possibility would not contradict many of the findings of previous epidemiologic studies linking high-grade PIN to carcinoma or molecular pathologic studies showing similar genomic (e.g., TMPRSS2-ERG gene fusion) as well as epigenomic and molecular phenotypic alterations between high-grade PIN and carcinoma. Also, this possibility would be consistent with previous anatomic studies in prostate specimens linking high-grade PIN and carcinoma in autopsy and other whole prostate specimens. In addition, if some cases meeting morphologic criteria for PIN actually represent intra-acinar spread of invasive carcinoma, this could be an important potential confounder of the interpretation of past clinical trials enrolling patients presumed to be without carcinoma, who are at high risk of invasive carcinoma. Thus, in order to reduce possible bias in future study/trial designs, novel molecular pathology approaches are needed to decipher when an apparent PIN lesion may be intra-acinar/intra-ductal spread of an invasive cancer and when it truly represents a precursor state. Similar approaches are needed for lesions known as intraductal carcinoma to facilitate better classification of them as true intra-ductal/acinar spread on one hand or as precursor high-grade PIN (cribriform type) on the other hand; a number of such molecular approaches (e.g., coevaluating TMPRSS-ERG fusion and PTEN loss) are already showing excellent promise. Cancer Prev Res; 9(8); 648–56. ©2016 AACR.