bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher-order power harmonics of pulsed electrical stimulation modulates corticospinal contribution of peripheral nerve stimulation
Authors: Chen Chiun-Fan , Bikson Marom , Chou Li-Wei , Shan Chunlei , Khadka Niranjan , Chen Wen-Shiang , Fregni Felipe
Published: March 2017

It is well established that electrical-stimulation frequency is crucial to determining the scale of induced neuromodulation, particularly when attempting to modulate corticospinal excitability. However, the modulatory effects of stimulation frequency are not only determined by its absolute value but also by other parameters such as power at harmonics. The stimulus pulse shape further influences parameters such as excitation threshold and fiber selectivity. The explicit role of the power in these harmonics in determining the outcome of stimulation has not previously been analyzed. In this study, we adopted an animal model of peripheral electrical stimulation that includes an amplitude-adapted pulse train which induces force enhancements with a corticospinal contribution. We report that the electrical-stimulation-induced force enhancements were correlated with the amplitude of stimulation power harmonics during the amplitude-adapted pulse train. In an exploratory analysis, different levels of correlation were observed between force enhancement and power harmonics of 20–80 Hz (r = 0.4247, p = 0.0243), 100–180 Hz (r = 0.5894, p = 0.0001), 200–280 Hz (r = 0.7002, p < 0.0001), 300–380 Hz (r = 0.7449, p < 0.0001), 400–480 Hz (r = 0.7906, p < 0.0001), 500–600 Hz (r = 0.7717, p < 0.0001), indicating a trend of increasing correlation, specifically at higher order frequency power harmonics. This is a pilot, but important first demonstration that power at high order harmonics in the frequency spectrum of electrical stimulation pulses may contribute to neuromodulation, thus warrant explicit attention in therapy design and analysis.
PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load
Authors: Zhou Yajuan , Shi Dingbo , Miao Jingjing , Wu Haijun , Chen Jiewei , Zhou Xiaoyi , Hu Desheng , Zhao Chong , Deng Wuguo , Xie Conghua
Published: March 2017

Programmed death-1 (PD-1) is an immunosuppressive receptor functionally bound with programmed death-ligand 1 (PD-L1), which has been reported in various malignancies. However, only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). In this study, we aim to investigate alterations in PD-1/PD-L1 by using immunohistochemistry analysis in a cohort of consecutively enrolled NPC patients (n = 99). To further analyse the correlation between PD-1/PD-L1 and factors involved in clinico-pathology, haematologic biomarkers, EBV-DNA load and outcomes, we collected clinical data for statistical analysis. We observed that lower haemoglobin (HB) and Body Mass Index (BMI) levels were associated with high levels of PD-L1 staining in NPC patients. Importantly, our results suggested that PD-L1 might be a negative indicator for NPC patients. In contrast, a correlation between the PD-1/PD-L1 level and EBV load was not identified. Moreover, PD-1 positivity was suggested to not be significantly correlated with clinical outcomes. Taken together, our results revealed that PD-L1 might be a potential prognostic biomarker for NPC patients. However, further studies are needed to clarify the underlying mechanism of EBV status in the immunosuppression process induced by the PD-1/PD-L1 axis.
Predicting bone strength with ultrasonic guided waves
Authors: Bochud Nicolas , Vallet Quentin , Minonzio Jean-Gabriel , Laugier Pascal
Published: March 2017

Recent bone quantitative ultrasound approaches exploit the multimode waveguide response of long bones for assessing properties such as cortical thickness and stiffness. Clinical applications remain, however, challenging, as the impact of soft tissue on guided waves characteristics is not fully understood yet. In particular, it must be clarified whether soft tissue must be incorporated in waveguide models needed to infer reliable cortical bone properties. We hypothesize that an inverse procedure using a free plate model can be applied to retrieve the thickness and stiffness of cortical bone from experimental data. This approach is first validated on a series of laboratory-controlled measurements performed on assemblies of bone- and soft tissue mimicking phantoms and then onin vivomeasurements. The accuracy of the estimates is evaluated by comparison with reference values. To further support our hypothesis, these estimates are subsequently inserted into a bilayer model to test its accuracy. Our results show that the free plate model allows retrieving reliable waveguide properties, despite the presence of soft tissue. They also suggest that the more sophisticated bilayer model, although it is more precise to predict experimental data in the forward problem, could turn out to be hardly manageable for solving the inverse problem.
Altered intestinal microbiota in patients with chronic pancreatitis: implications in diabetes and metabolic abnormalities
Authors: Jandhyala Sai Manasa , Madhulika A. , Deepika G. , Rao G. Venkat , Reddy D. Nageshwar , Subramanyam Chivukula , Sasikala Mitnala , Talukdar Rupjyoti
Published: March 2017

Intestinal dysbiosis and its functional implications in chronic pancreatitis (CP) have not been elaborately studied. We evaluated the taxonomic and functional alterations in intestinal microbiota in 30 well-characterised patients with CP (16 without, 14 with diabetes) and 10 healthy controls. The patients with CP and diabetes had significantly longer disease duration and greater degree of malnutrition. There was increase in plasma endotoxin concentrations from controls to CP non-diabetics to CP diabetics. We observed significant differences in richness and alpha diversity between the groups. We also observed increase in the Firmicutes:Bacteroidetes ratio in CP patients without and with diabetes. There was reduction in abundance of Faecalibacterium prausnitzii and Ruminococcus bromii from controls to CP non-diabetics to CP diabetics. On the other hand, there was increase in LPS (endotoxin) synthetic pathways (KEGG orthology) in the groups. Faecalibacterium prausnitzii abundance correlated negatively with plasma endotoxin and glycemic status; while plasma endotoxin correlated positively with blood glucose and negatively with plasma insulin. Our results have important implications for future studies exploring mechanistic insights on secondary diabetes in CP.
Reaching back: the relative strength of the retroactive emotional attentional blink
Authors: Ní Choisdealbha Áine , Piech Richard M. , Fuller John K. , Zald David H.
Published: March 2017

Visual stimuli with emotional content appearing in close temporal proximity either before or after a target stimulus can hinder conscious perceptual processing of the target via an emotional attentional blink (EAB). This occurs for targets that appear after the emotional stimulus (forward EAB) and for those appearing before the emotional stimulus (retroactive EAB). Additionally, the traditional attentional blink (AB) occurs because detection of any target hinders detection of a subsequent target. The present study investigated the relations between these different attentional processes. Rapid sequences of landscape images were presented to thirty-one male participants with occasional landscape targets (rotated images). For the forward EAB, emotional or neutral distractor images of people were presented before the target; for the retroactive EAB, such images were also targets and presented after the landscape target. In the latter case, this design allowed investigation of the AB as well. Erotic and gory images caused more EABs than neutral images, but there were no differential effects on the AB. This pattern is striking because while using different target categories (rotated landscapes, people) appears to have eliminated the AB, the retroactive EAB still occurred, offering additional evidence for the power of emotional stimuli over conscious attention.
Differences in electroencephalographic non-rapid-eye movement sleep slow-wave characteristics between young and old mice
Authors: Panagiotou Maria , Vyazovskiy Vladyslav V. , Meijer Johanna H. , Deboer Tom
Published: March 2017

Changes in sleep pattern are typical for the normal aging process. However, aged mice show an increase in the amount of sleep, whereas humans show a decrease when aging. Mice are considered an important model in aging studies, and this divergence warrants further investigation. Recently, insights into the network dynamics of cortical activity during sleep were obtained by investigating characteristics of individual electroencephalogram (EEG) slow waves in young and elderly humans. In this study, we investigated, for the first time, the parameters of EEG slow waves, including their incidence, amplitude, duration and slopes, in young (6 months) and older (18–24 months) C57BL/6J mice during undisturbed 24 h, and after a 6-h sleep deprivation (SD). As expected, older mice slept more but, in contrast to humans, absolute NREM sleep EEG slow-wave activity (SWA, spectral power density between 0.5–4 Hz) was higher in the older mice, as compared to the young controls. Furthermore, slow waves in the older mice were characterized by increased amplitude, steeper slopes and fewer multipeak waves, indicating increased synchronization of cortical neurons in aging, opposite to what was found in humans. Our results suggest that older mice, in contrast to elderly humans, live under a high sleep pressure.
High intensity aerobic exercise training improves chronic intermittent hypoxia-induced insulin resistance without basal autophagy modulation
Authors: Pauly Marion , Assense Allan , Rondon Aurélie , Thomas Amandine , Dubouchaud Hervé , Freyssenet Damien , Benoit Henri , Castells Josiane , Flore Patrice
Published: March 2017

Chronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is a major risk factor for cardiovascular and metabolic diseases (insulin resistance: IR). Autophagy is involved in the pathophysiology of IR and high intensity training (HIT) has recently emerged as a potential therapy. We aimed to confirm IH-induced IR in a tissue-dependent way and to explore the preventive effect of HIT on IR-induced by IH. Thirty Swiss 129 male mice were randomly assigned to Normoxia (N), Intermittent Hypoxia (IH: 21–5% FiO2, 30 s cycle, 8 h/day) or IH associated with high intensity training (IH HIT). After 8 days of HIT (2*24 min, 50 to 90% of Maximal Aerobic Speed or MAS on a treadmill) mice underwent 14 days IH or N. We found that IH induced IR, characterized by a greater glycemia, an impaired insulin sensitivity and lower AKT phosphorylation in adipose tissue and liver. Nevertheless, MAS and AKT phosphorylation were greater in muscle after IH. IH associated with HIT induced better systemic insulin sensitivity and AKT phosphorylation in liver. Autophagy markers were not altered in both conditions. These findings suggest that HIT could represent a preventive strategy to limit IH-induced IR without change of basal autophagy.
Multiscale image analysis reveals structural heterogeneity of the cell microenvironment in homotypic spheroids
Authors: Schmitz Alexander , Fischer Sabine C. , Mattheyer Christian , Pampaloni Francesco , Stelzer Ernst H. K.
Published: March 2017

Three-dimensional multicellular aggregates such as spheroids provide reliable in vitro substitutes for tissues. Quantitative characterization of spheroids at the cellular level is fundamental. We present the first pipeline that provides three-dimensional, high-quality images of intact spheroids at cellular resolution and a comprehensive image analysis that completes traditional image segmentation by algorithms from other fields. The pipeline combines light sheet-based fluorescence microscopy of optically cleared spheroids with automated nuclei segmentation (F score: 0.88) and concepts from graph analysis and computational topology. Incorporating cell graphs and alpha shapes provided more than 30 features of individual nuclei, the cellular neighborhood and the spheroid morphology. The application of our pipeline to a set of breast carcinoma spheroids revealed two concentric layers of different cell density for more than 30,000 cells. The thickness of the outer cell layer depends on a spheroid’s size and varies between 50% and 75% of its radius. In differently-sized spheroids, we detected patches of different cell densities ranging from 5 × 105 to 1 × 106cells/mm3. Since cell density affects cell behavior in tissues, structural heterogeneities need to be incorporated into existing models. Our image analysis pipeline provides a multiscale approach to obtain the relevant data for a system-level understanding of tissue architecture.
Consequences of biodiversity loss diverge from expectation due to post-extinction compensatory responses
Authors: Thomsen Matthias S. , Garcia Clement , Bolam Stefan G. , Parker Ruth , Godbold Jasmin A. , Solan Martin
Published: March 2017

Consensus has been reached that global biodiversity loss impairs ecosystem functioning and the sustainability of services beneficial to humanity. However, the ecosystem consequences of extinction in natural communities are moderated by compensatory species dynamics, yet these processes are rarely accounted for in impact assessments and seldom considered in conservation programmes. Here, we use marine invertebrate communities to parameterise numerical models of sediment bioturbation – a key mediator of biogeochemical cycling – to determine whether post-extinction compensatory mechanisms alter biodiversity-ecosystem function relations following non-random extinctions. We find that compensatory dynamics lead to trajectories of sediment mixing that diverge from those without compensation, and that the form, magnitude and variance of each probabilistic distribution is highly influenced by the type of compensation and the functional composition of surviving species. Our findings indicate that the generalized biodiversity-function relation curve, as derived from multiple empirical investigations of random species loss, is unlikely to yield representative predictions for ecosystem properties in natural systems because the influence of post-extinction community dynamics are under-represented. Recognition of this problem is fundamental to management and conservation efforts, and will be necessary to ensure future plans and adaptation strategies minimize the adverse impacts of the biodiversity crisis.
Effective Removal of Tetracycline Antibiotics from Water using Hybrid Carbon Membranes
Authors: Liu Ming-kai , Liu Ying-ya , Bao Dan-dan , Zhu Gen , Yang Guo-hai , Geng Jun-feng , Li Hai-tao
Published: March 2017

Antibiotic residues in drinking water have become a global problem, especially in developing countries. However, effective purification of water contaminated by antibiotics remains a great challenge. Here, we investigated the removing of tetracycline by carbon nanomaterials with different structures and surface functionalities. The result shows that a membrane of thick graphene oxide (GO) and activated carbon (AC) with a thickness of 15 μm can effectively remove 98.9% of tetracycline hydrochloride (TCH) from water by vacuum filtration. Structural analysis indicated that the AC nanoparticles were uniformly inserted into the GO interstitial sites without any aggregations. Also, GO sheets were loosened by the encapsulated AC nanoparticles, leading to the formation of numerous tiny pores (3–10 nm) that acted as channels for fluid passage, whereas the carbons and chemical groups on the GO surface adsorbed TCH. GO/AC membrane exhibits the best adsorption efficiency among the investigated materials, including pure GO, AC, carbon nanotube (CNT), and CNT/AC and GO/CNT hybrids.
Consecutive record-breaking high temperatures marked the handover from hiatus to accelerated warming
Authors: Su Jingzhi , Zhang Renhe , Wang Huijun
Published: March 2017

Closely following the hiatus warming period, two astonishing high temperature records reached in 2014 and 2015 consecutively. To investigate the occurrence features of record-breaking high temperatures in recent years, a new index focusing the frequency of the top 10 high annual mean temperatures was defined in this study. Analyses based on this index shown that record-breaking high temperatures occurred over most regions of the globe with a salient increasing trend after 1960 s, even during the so-called hiatus period. Overlapped on the ongoing background warming trend and the interdecadal climate variabilities, the El Niño events, particularly the strong ones, can make a significant contribution to the occurrence of high temperatures on interannual timescale. High temperatures associated with El Niño events mainly occurred during the winter annual period. As the Pacific Decadal Oscillation (PDO) struggled back to its positive phase since 2014, the global warming returned back to a new accelerated warming period, marked by the record-breaking high temperatures in 2014. Intensified by the super strong El Niño, successive high records occurred in 2015 and 2016. Higher frequencies of record high temperatures would occur in the near future because the PDO tends to maintain a continuously positive phase.
Land-based salmon aquacultures change the quality and bacterial degradation of riverine dissolved organic matter
Authors: Kamjunke Norbert , Nimptsch Jorge , Harir Mourad , Herzsprung Peter , Schmitt-Kopplin Philippe , Neu Thomas R. , Graeber Daniel , Osorio Sebastian , Valenzuela Jose , Carlos Reyes Juan , Woelfl Stefan , Hertkorn Norbert
Published: March 2017

Aquacultures are of great economic importance worldwide but pollute pristine headwater streams, lakes, and estuaries. However, there are no in-depth studies of the consequences of aquacultures on dissolved organic matter (DOM) composition and structure. We performed a detailed molecular level characterization of aquaculture DOM quality and its bacterial degradation using four salmon aquacultures in Chile. Fluorescence measurements, ultrahigh-resolution mass spectrometry, and nuclear magnetic resonance spectroscopy of the DOM revealed specific and extensive molecular alterations caused by aquacultures. Aquacultures released large quantities of readily bioavailable metabolites (primarily carbohydrates and peptides/proteins, and lipids), causing the organic matter downstream of all the investigated aquacultures to deviate strongly from the highly processed, polydisperse and molecularly heterogeneous DOM found in pristine rivers. However, the upstream individual catchment DOM signatures remained distinguishable at the downstream sites. The benthic algal biovolume decreased and the bacterial biovolume and production increased downstream of the aquacultures, shifting stream ecosystems to a more heterotrophic state and thus impairing the ecosystem health. The bacterial DOM degradation rates explain the attenuation of aquaculture DOM within the subsequent stream reaches. This knowledge may aid the development of improved waste processing facilities and may help to define emission thresholds to protect sensitive stream ecosystems.
Characterization of the Dynamic Transcriptome of a Herpesvirus with Long-read Single Molecule Real-Time Sequencing
Authors: Tombácz Dóra , Balázs Zsolt , Csabai Zsolt , Moldován Norbert , Szűcs Attila , Sharon Donald , Snyder Michael , Boldogkői Zsolt
Published: March 2017

Herpesvirus gene expression is co-ordinately regulated and sequentially ordered during productive infection. The viral genes can be classified into three distinct kinetic groups: immediate-early, early, and late classes. In this study, a massively parallel sequencing technique that is based on PacBio Single Molecule Real-time sequencing platform, was used for quantifying the poly(A) fraction of the lytic transcriptome of pseudorabies virus (PRV) throughout a 12-hour interval of productive infection on PK-15 cells. Other approaches, including microarray, real-time RT-PCR and Illumina sequencing are capable of detecting only the aggregate transcriptional activity of particular genomic regions, but not individual herpesvirus transcripts. However, SMRT sequencing allows for a distinction between transcript isoforms, including length- and splice variants, as well as between overlapping polycistronic RNA molecules. The non-amplified Isoform Sequencing (Iso-Seq) method was used to analyse the kinetic properties of the lytic PRV transcripts and to then classify them accordingly. Additionally, the present study demonstrates the general utility of long-read sequencing for the time-course analysis of global gene expression in practically any organism.
Cholesterol depletion impairs contractile machinery in neonatal rat cardiomyocytes
Authors: Hissa Barbara , Oakes Patrick W. , Pontes Bruno , Ramírez-San Juan Guillermina , Gardel Margaret L.
Published: March 2017

Cholesterol regulates numerous cellular processes. Depleting its synthesis in skeletal myofibers induces vacuolization and contraction impairment. However, little is known about how cholesterol reduction affects cardiomyocyte behavior. Here, we deplete cholesterol by incubating neonatal cardiomyocytes with methyl-beta-cyclodextrin. Traction force microscopy shows that lowering cholesterol increases the rate of cell contraction and generates defects in cell relaxation. Cholesterol depletion also increases membrane tension, Ca2+ spikes frequency and intracellular Ca2+ concentration. These changes can be correlated with modifications in caveolin-3 and L-Type Ca2+ channel distributions across the sarcolemma. Channel regulation is also compromised since cAMP-dependent PKA activity is enhanced, increasing the probability of L-Type Ca2+ channel opening events. Immunofluorescence reveals that cholesterol depletion abrogates sarcomeric organization, changing spacing and alignment of α-actinin bands due to increase in proteolytic activity of calpain. We propose a mechanism in which cholesterol depletion triggers a signaling cascade, culminating with contraction impairment and myofibril disruption in cardiomyocytes.
Digital-analog quantum simulation of generalized Dicke models with superconducting circuits
Authors: Lamata Lucas
Published: March 2017

We propose a digital-analog quantum simulation of generalized Dicke models with superconducting circuits, including Fermi- Bose condensates, biased and pulsed Dicke models, for all regimes of light-matter coupling. We encode these classes of problems in a set of superconducting qubits coupled with a bosonic mode implemented by a transmission line resonator. Via digital-analog techniques, an efficient quantum simulation can be performed in state-of-the-art circuit quantum electrodynamics platforms, by suitable decomposition into analog qubit-bosonic blocks and collective single-qubit pulses through digital steps. Moreover, just a single global analog block would be needed during the whole protocol in most of the cases, superimposed with fast periodic pulses to rotate and detune the qubits. Therefore, a large number of digital steps may be attained with this approach, providing a reduced digital error. Additionally, the number of gates per digital step does not grow with the number of qubits, rendering the simulation efficient. This strategy paves the way for the scalable digital-analog quantum simulation of many-body dynamics involving bosonic modes and spin degrees of freedom with superconducting circuits.
Biophysical studies suggest a new structural arrangement of crotoxin and provide insights into its toxic mechanism
Authors: Fernandes Carlos A. H. , Pazin Wallance M. , Dreyer Thiago R. , Bicev Renata N. , Cavalcante Walter L. G. , Fortes-Dias Consuelo L. , Ito Amando S. , Oliveira Cristiano L. P. , Fernandez Roberto Morato , Fontes Marcos R. M.
Published: March 2017

Crotoxin (CTX) is the main neurotoxin found in Crotalus durissus rattlesnake venoms being composed by a nontoxic and non-enzymatic component (CA) and a toxic phospholipase A2 (CB). Previous crystallographic structures of CTX and CB provided relevant insights: (i) CTX structure showed a 1:1 molecular ratio between CA and CB, presenting three tryptophan residues in the CA/CB interface and one exposed to solvent; (ii) CB structure displayed a tetrameric conformation. This study aims to provide further information on the CTX mechanism of action by several biophysical methods. Our data show that isolated CB can in fact form tetramers in solution; however, these tetramers can be dissociated by CA titration. Furthermore, CTX exhibits a strong reduction in fluorescence intensity and lifetime compared with isolated CA and CB, suggesting that all tryptophan residues in CTX may be hidden by the CA/CB interface. By companying spectroscopy fluorescence and SAXS data, we obtained a new structural model for the CTX heterodimer in which all tryptophans are located in the interface, and the N-terminal region of CB is largely exposed to the solvent. Based on this model, we propose a toxic mechanism of action for CTX, involving the interaction of N-terminal region of CB with the target before CA dissociation.
A stochastic theoretical approach to study the size-dependent catalytic activity of a metal nanoparticle at the single molecule level
Authors: Singh Divya , Chaudhury Srabanti
Published: March 2017

We present a theoretical method based on the first passage time distribution formalism to study the size-dependent catalytic activity of metal nanoparticle at the single molecule level.
Water and hexane in an ionic liquid: computational evidence of association under high pressure
Authors: Mariani A. , Caminiti R. , Gontrani L.
Published: March 2017

Dissolving water and hexane in an ionic liquid, our simulations clearly show association between them at high pressures.
Correlation of single-cell ICP-MS intensity distributions for the study of heterogeneous cellular responses to environmental stresses
Authors: Lau Wai-Yin , Chun Ka-Him , Chan Wing-Tat
Published: March 2017

Correlation of the distributions of single-cell ICP-MS intensity and cell properties gives insights into heterogeneous cellular responses to external stresses.
A novel and rapid approach for the synthesis of biocompatible and highly stable Fe3O4/SiO2 and Fe3O4/C core/shell nanocubes and nanorods
Authors: Abbas Mohamed , RamuluTorati Sri , Iqbal Shawl Asif , Kim CheolGi
Published: March 2017

Core/shell nanostructures of MNPs/inorganic materials have attracted enormous research interest due to their promising applications in bio-medicine, energy, electronics, the environment, etc.
Highly monodisperse supported metal nanoparticles by basic ammonium functionalization of mesopore walls for industrially relevant catalysis
Authors: Cho Jangkeun , Xu Leilei , Jo Changbum , Ryoo Ryong
Published: March 2017

A strategy for achieving a high dispersion of metal and metal oxide nanoparticles in a mono-modal fashion is developed.
NMR signal enhancement of >50 000 times in fast dissolution dynamic nuclear polarization
Authors: Pinto L. F. , Marín-Montesinos I. , Lloveras V. , Muñoz-Gómez J. L. , Pons M. , Veciana J. , Vidal-Gancedo J.
Published: March 2017

A novel mixed biradical polarizing agent (BDPAesterTEMPO) showing one of the largest NMR signal enhancements to be observed so far in fast dissolution Dynamic Nuclear Polarization (dDNP).
Cu-catalyzed controllable C–H mono-/di-/triarylations of imidazolium salts for ionic functional materials
Authors: Li Shiqing , Tang Junbin , Zhao Yinsong , Jiang Ruyong , Wang Tianbao , Gao Ge , You Jingsong
Published: March 2017

The first Cu-catalyzed direct C–H mono-, di- and triarylations of imidazolium salts with aryl iodides/bromides are reported.
Symmetry assisted tuning of bending and brittle multi-component forms of probenecid
Authors: Rao Khandavilli U. B. , Bhogala Balakrishna R. , Maguire Anita R. , Lawrence Simon E.
Published: March 2017

Maintaining the flexibility of single component crystals when forming multi-component solids using symmetric ditopic co-formers.
Ring-opening of cyclic ethers by aluminum hydridotriphenylborate
Authors: Mukherjee Debabrata , Osseili Hassan , Truong Khai-Nghi , Spaniol Thomas P. , Okuda Jun
Published: March 2017

Ring-opening of THF or THP in the presence of pinacolborane can be catalyzed by a molecular aluminum hydride catalyst [(L)AlH2]2(L = Me3TACD)/BPh3and involves an isolable intermediate [(L)AlH][HBPh3].
Correction: Smart adsorbents with reversible photo-regulated molecular switches for selective adsorption and efficient regeneration
Authors: Zhu Jing , Tan Peng , Yang Piao-Ping , Liu Xiao-Qin , Jiang Yao , Sun Lin-Bing
Published: March 2017

Correction for ‘Smart adsorbents with reversible photo-regulated molecular switches for selective adsorption and efficient regeneration’ by Jing Zhu et al., Chem. Commun., 2016, 52, 11531–11534.
Can charged colloidal particles increase the thermoelectric energy conversion efficiency?
Authors: Salez Thomas J. , Huang Bo Tao , Rietjens Maud , Bonetti Marco , Wiertel-Gasquet Cécile , Roger Michel , Filomeno Cleber Lopes , Dubois Emmanuelle , Perzynski Régine , Nakamae Sawako
Published: March 2017

We show that charged colloidal particles can be used to increase the thermoelectric energy conversion of a thermocell.
Green chemistry and polymers made from sulfur
Authors: Worthington Max J. H. , Kucera Renata L. , Chalker Justin M.
Published: March 2017

Polysulfide polymers prepared from elemental sulfur have found increasing use in applications that benefit the environment.
Antimicrobial resistance in healthcare, agriculture and the environment: the biochemistry behind the headlines
Authors: Venter Henrietta , Henningsen Michael L. , Begg Stephanie L.
Published: March 2017

The crisis of antimicrobial resistance (AMR) is one of the most serious issues facing us today. The scale of the problem is illustrated by the recent commitment of Heads of State at the UN to coordinate efforts to curb the spread of AMR infections. In this review, we explore the biochemistry behind the headlines of a few stories that were recently published in the public media. We focus on examples from three different issues related to AMR: (i) hospital-acquired infections, (ii) the spread of resistance through animals and/or the environment and (iii) the role of antimicrobial soaps and other products containing disinfectants in the dissemination of AMR. Although these stories stem from three very different settings, the underlying message in all of them is the same: there is a direct relationship between the use of antimicrobials and the development of resistance. In addition, one type of antimicrobial could select for cross-resistance to another type and/or for multidrug resistance. Therefore, we argue the case for increased stewardship to not only cover clinical use of antibiotics, but also the use of antimicrobials in agriculture and stewardship of our crucially important biocides such as chlorhexidine.
Innovative approaches to treat Staphylococcus aureus biofilm-related infections
Authors: Richter Katharina , Van den Driessche Freija , Coenye Tom
Published: March 2017

Many bacterial infections in humans and animals are caused by bacteria residing in biofilms, complex communities of attached organisms embedded in an extracellular matrix. One of the key properties of microorganisms residing in a biofilm is decreased susceptibility towards antimicrobial agents. This decreased susceptibility, together with conventional mechanisms leading to antimicrobial resistance, makes biofilm-related infections increasingly difficult to treat and alternative antibiofilm strategies are urgently required. In this review, we present three such strategies to combat biofilm-related infections with the important human pathogen Staphylococcus aureus: (i) targeting the bacterial communication system with quorum sensing (QS) inhibitors, (ii) a ‘Trojan Horse’ strategy to disturb iron metabolism by using gallium-based therapeutics and (iii) the use of ‘non-antibiotics’ with antibiofilm activity identified through screening of repurposing libraries.
Fitness costs associated with the acquisition of antibiotic resistance
Authors: Hernando-Amado Sara , Sanz-García Fernando , Blanco Paula , Martínez José L.
Published: March 2017

Acquisition of antibiotic resistance is a relevant problem for human health. The selection and spread of antibiotic-resistant organisms not only compromise the treatment of infectious diseases, but also the implementation of different therapeutic procedures as organ transplantation, advanced surgery or chemotherapy, all of which require proficient methods for avoiding infections. It has been generally accepted that the acquisition of antibiotic resistance will produce a general metabolic burden: in the absence of selection, the resistant organisms would be outcompeted by the susceptible ones. If that was always true, discontinuation of antibiotic use would render the disappearance of resistant microorganisms. However, several studies have shown that, once resistance emerges, the recovery of a fully susceptible population even in the absence of antibiotics is not easy. In the present study, we review updated information on the effect of the acquisition of antibiotic resistance in bacterial physiology as well as on the mechanisms that allow the compensation of the fitness costs associated with the acquisition of resistance.
Antibiotic–non-antibiotic combinations for combating extremely drug-resistant Gram-negative ‘superbugs’
Authors: Schneider Elena K. , Reyes-Ortega Felisa , Velkov Tony , Li Jian
Published: March 2017

The emergence of antimicrobial resistance of Gram-negative pathogens has become a worldwide crisis. The status quo for combating resistance is to employ synergistic combinations of antibiotics. Faced with this fast-approaching post-antibiotic era, it is critical that we devise strategies to prolong and maximize the clinical efficacy of existing antibiotics. Unfortunately, reports of extremely drug-resistant (XDR) Gram-negative pathogens have become more common. Combining antibiotics such as polymyxin B or the broad-spectrum tetracycline and minocycline with various FDA-approved non-antibiotic drugs have emerged as a novel combination strategy against otherwise untreatable XDR pathogens. This review surveys the available literature on the potential benefits of employing antibiotic–non-antibiotic drug combination therapy. The apex of this review highlights the clinical utility of this novel therapeutic strategy for combating infections caused by ‘superbugs’.
The “pushmi-pullyu” of resistance to chloroquine in malaria
Authors: Skrzypek Ruth , Callaghan Richard
Published: March 2017

Malarial infection continues to impart devastating health problems in the developing world. Treatment of malaria has involved chemotherapy since 168 BC, with the most prevalent and successful forms using plant alkaloids. Perhaps the greatest treatment success against malaria was by chloroquine, a synthetic derivative of the quinines found in the Cinchona tree bark. Chloroquine is able to kill parasites by interfering with haem metabolism in the parasite’s digestive vacuole. The widespread use of chloroquine predictably resulted in the development of drug-resistant malaria and the most highly implicated resistance mediators are the transporter proteins P-glycoprotein (P-gp) homologue 1 (P-gh1) and Plasmodium falciparum chloroquine-resistance transporter (PfCRT), which reside on the parasite’s digestive vacuole. The presence of PfCRT and P-gh1 on the vacuole membrane is analogous to the two-headed fictional creature known as the “Pushmi-Pullyu”. P-gh1 (Pushmi) increases influx of chloroquine into the vacuole, while PfCRT (Pullmi) causes efflux of chloroquine from the vacuole. This review describes how drug-resistant malarial parasites co-ordinate chloroquine distribution through adaptive mutations to promote their survival in the presence of this cytotoxic drug.
Insights into drug resistance mechanisms in Clostridium difficile
Authors: Harnvoravongchai Phurt , Pipatthana Methinee , Chankhamhaengdecha Surang , Janvilisri Tavan
Published: March 2017

The incidence of Clostridium difficile infection has been elevated and becoming common in hospitals worldwide. Although antibiotics usually serve as the primary treatment for bacterial infection including C. difficile infection, limitations and failures have been evident due to drug resistance. Antibiotic resistance in C. difficile has been recognized as one of the most important factors to promote the infection and increase the level of severity and the recurrence rate. Several outbreaks in many countries have been linked to the emergence of hypervirulent drug-resistant strains. This pathogen harbours various mechanisms against the actions of antibiotics. The present study highlights three main drug-resistant strategies in C. difficile including drug inactivation, target modification and efflux pump. Other mechanisms that potentially contribute to drug-resistant traits in this organism are also discussed.
Intrinsic, adaptive and acquired antimicrobial resistance in Gram-negative bacteria
Authors: Arzanlou Mohsen , Chai Wern Chern , Venter Henrietta
Published: March 2017

Gram-negative bacteria are responsible for a large proportion of antimicrobial-resistant infections in humans and animals. Among this class of bacteria are also some of the most successful environmental organisms. Part of this success is their adaptability to a variety of different niches, their intrinsic resistance to antimicrobial drugs and their ability to rapidly acquire resistance mechanisms. These mechanisms of resistance are not exclusive and the interplay of several mechanisms causes high levels of resistance. In this review, we explore the molecular mechanisms underlying resistance in Gram-negative organisms and how these different mechanisms enable them to survive many different stress conditions.
Computational modelling of efflux pumps and their inhibitors
Authors: Ramaswamy Venkata Krishnan , Cacciotto Pierpaolo , Malloci Giuliano , Vargiu Attilio V. , Ruggerone Paolo
Published: March 2017

Antimicrobial resistance is based on the multifarious strategies that bacteria adopt to face antibiotic therapies, making it a key public health concern of our era. Among these strategies, efflux pumps (EPs) contribute significantly to increase the levels and profiles of resistance by expelling a broad range of unrelated compounds – buying time for the organisms to develop specific resistance. In Gram-negative bacteria, many of these chromosomally encoded transporters form multicomponent ‘pumps’ that span both inner and outer membranes and are driven energetically by a primary or secondary transporter component.

One of the strategies to reinvigorate the efficacy of antimicrobials is by joint administration with EP inhibitors (EPI), which either block the substrate binding and/or hinder any of the transport-dependent steps of the pump. In this review, we provide an overview of multidrug-resistance EPs, their inhibition strategies and the relevant findings from the various computational simulation studies reported to date with respect to deciphering the mechanism of action of inhibitors with the purpose of improving their rational design.
Service Delivery to Children With Mild Hearing Loss: Current Practice Patterns and Parent Perceptions
Authors: Walker Elizabeth A. , Spratford Meredith , Ambrose Sophie E. , Holte Lenore , Oleson Jacob
Published: March 2017

Purpose

This study investigates clinical practice patterns and parent perception of intervention for children with mild hearing loss (HL).

Method

Ages at and delays between service delivery steps (first diagnostic evaluation, confirmation of HL, hearing aid [HA] fitting, entry into early intervention) were investigated for 113 children with mild HL. Comparisons were made to children with moderate-to-severe HL. Parents of children with mild HL reported reasons for delays and their perceptions of intervention and amplification for their children.

Results

Seventy-four percent of children with mild HL were identified through the newborn hearing screen; 26% were identified later due to passing or not receiving a newborn hearing screen. Ninety-four percent of children with mild HL were fit with HAs, albeit at significantly later ages than children with moderate-to-severe HL. Most parents indicated that their children benefited from HA use, but some parents expressed ambivalence toward the amount of benefit.

Conclusions

Audiologists appear to be moving toward regularly providing amplification for children with mild HL. However, delays in HA fittings indicate that further educating professionals and parents about the benefits of early amplification and intervention is warranted to encourage timely fitting and consistent use of HAs.
Late Talkers: A Population-Based Study of Risk Factors and School Readiness Consequences
Authors: Hammer Carol Scheffner , Morgan Paul , Farkas George , Hillemeier Marianne , Bitetti Dana , Maczuga Steve
Published: March 2017

Purpose

This study was designed to (a) identify sociodemographic, pregnancy and birth, family health, and parenting and child care risk factors for being a late talker at 24 months of age; (b) determine whether late talkers continue to have low vocabulary at 48 months; and (c) investigate whether being a late talker plays a unique role in children's school readiness at 60 months.

Method

We analyzed data from the Early Childhood Longitudinal Study, a population-based sample of 9,600 children. Data were gathered when the children were 9, 24, 48, and 60 months old.

Results

The risk of being a late talker at 24 months was significantly associated with being a boy, lower socioeconomic status, being a nonsingleton, older maternal age at birth, moderately low birth weight, lower quality parenting, receipt of day care for less than 10 hr/week, and attention problems. Being a late talker increased children's risk of having low vocabulary at 48 months and low school readiness at 60 months. Family socioeconomic status had the largest and most profound effect on children's school readiness.

Conclusions

Limited vocabulary knowledge at 24 and 48 months is uniquely predictive of later school readiness. Young children with low vocabularies require additional supports prior to school entry.
Iridium-Catalyzed Site-Selective C–H Borylation of 2-Pyridones
Authors: Hirano Koji , Miura Masahiro , Miura Wataru
Published: March 2017

An iridium-catalyzed site-selective C–H borylation of 2-pyridones has been developed. The site selectivity is predominantly controlled by steric factors, and we can access C4, C5, and C6 C–H on the 2-pyridone ring by the judicious choice of ligand and solvent. Subsequent Suzuki–Miyaura cross-coupling of the borylated products also proceeds to form the corresponding arylated pyridones in good overall yields.
Limb Body Wall Complex Associated with Placenta Accreta: A Mere Coincidence or a Sign of an Etiopathogenic Link?
Authors: Berezowski Aderson Tadeu , Carvalho Sandra Regina Marques , Duarte Geraldo , Cavalli Ricardo de Carvalho , Marcolin Alessandra Cristina , Okido Marcos Masaru
Published: March 2017

A case was reported of a fetus with the anomaly of limb body wall complex associated with placenta accreta. To date, only one account of this condition has been published in the world literature. Due to the low frequency of both complications, the hypothesis has been raised that this association may have happened not by mere coincidence, but rather by a possible common etiopathogenic mechanism. For the first time, a study proposes the existence of a possible etiopathogenic connection between the anomaly of limb body wall complex and hypoxic disorders caused by inadequate placentation in previous uterine scarring.
Myocardial aging as a T-cell–mediated phenomenon
Authors: Ramos Gustavo Campos , van den Berg Anne , Nunes-Silva Vânia , Weirather Johannes , Peters Laura , Burkard Matthias , Friedrich Mike , Pinnecker Jürgen , Abeßer Marco , Heinze Katrin G. , Schuh Kai , Beyersdorf Niklas , Kerkau Thomas , Demengeot Jocelyne , Frantz Stefan , Hofmann Ulrich
Published: March 2017

Significance

Aging is a risk factor for heart diseases, and it is also known to impact on several immunological processes. Nevertheless, most studies addressing the cardio-immune cross-talk have focused on juvenile rather than senescent animal models. In the present study, we addressed this gap and found that immunological activity contributes to myocardial aging. By using different lymphocyte-deficient animal models and heterochronic adoptive cell-transfer protocols, our study revealed a pivotal role for CD4
+
T cells in mediating spontaneous local inflammation and mild organ dysfunction in aged hearts. These results might shed new light on the emerging field of “immunocardiology” because they reveal that spontaneous heart-directed immune responses arise even in the absence of previous myocardial tissue damage.
Herpes Zoster and Recurrent Herpes Zoster
Authors: Shiraki Kimiyasu , Toyama Nozomu , Daikoku Tohru , Yajima Misako ,   for the Miyazaki Dermatologist Society
Published: March 2017

Background

The incidence of recurrent herpes zoster (HZ) and the relationship between initial and recurrent HZ are not clear.

Methods

The Miyazaki Dermatologist Society has surveyed ~5000 patients with HZ annually since 1997. A questionnaire regarding HZ and its recurrence was completed by the dermatologists.

Results

A total of 34 877 patients with HZ were registered at 43 clinics between June 2009 and November 2015. Among 16 784 patients seen at 10 of the 43 clinics, 1076 patients (6.41%) experienced recurrence. Herpes zoster was more frequent in female than in male patients (5.27 vs 4.25 in 1000 person-years, P < .001), as was HZ recurrence (7.63% vs 4.73%, P < .001). Two and three recurrences were observed in 49 and 3 patients, respectively. Recurrence in the same dermatome was observed in 16.3% of patients, and more frequently this occurred in the left side (P = .027). The number of HZ-experienced persons increased with age, and one third of the population had experienced HZ by the age of 80.

Conclusions

Recurrent HZ was observed in 6.41% of patients, with a higher incidence in women. Moreover, HZ experience reduced the HZ incidence to 31.7% of the incidence in the HZ-naive population.