bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing capacity to consent to treatment with cholinesterase inhibitors in dementia using a specific and standardized version of the MacArthur Competence Assessment Tool (MacCAT-T)
Authors: Mueller Tanja , Haberstroh Julia , Knebel Maren , Oswald Frank , Kaspar Roman , Kemper Christoph J. , Halder-Sinn Petra , Schroeder Johannes , Pantel Johannes
Published: November 2016

Background:

The use of assessment tools has been shown to improve the inter-rater reliability of capacity assessments. However, instrument-based capacity assessments of people with dementia face challenges. In dementia research, measuring capacity with instruments like the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) mostly employ hypothetical treatment vignettes that can overwhelm the abstraction capabilities of people with dementia and are thus not always suitable for this target group. The primary aim of this study was to provide a standardized real informed consent paradigm that enables the dementia-specific properties of capacity to consent to treatment in people with dementia to be identified in a real informed consent process that is both externally valid and ethically justifiable.

Methods:

The sample consisted of 53 people with mild to moderate dementia and a group of 133 people without cognitive impairment. Rather than using a hypothetical treatment vignette, we used a standardized version of the MacCAT-T to assess capacity to consent to treatment with cholinesterase inhibitors in people with dementia. Inter-rater reliability, item statistics, and psychometric properties were also investigated.

Results:

Intraclass correlations (ICCs) (0.951–0.990) indicated high inter-rater reliability of the standardized real informed consent paradigm. In the dementia group, performance on different items of the MacCAT-T varied. Most people with dementia were able to express a treatment choice, and were aware of the need to take a tablet. Further information on the course of the disorder and the benefits and risks of the treatment were less understood, as was comparative reasoning regarding treatment alternatives.

Conclusion:

The standardized real informed consent paradigm enabled us to detect dementia-specific characteristics of patients’ capacity to consent to treatment with cholinesterase inhibitors. In order to determine suitable enhanced consent procedures for this treatment, we recommend the consideration of MacCAT-T results on an item level. People with dementia seem to understand only basic information. Our data indicate that one useful strategy to enhance capacity to consent is to reduce attention and memory demands as far as possible.
The functional approach in comparative socio-legal research: reflections based on a study of plural work regulation in Australia and Indonesia
Authors: Mahy Petra
Published: November 2016

This paper examines the potential use and limits of Zweigert and Kötz's classical functional approach in comparative law for an empirical socio-legal research project. The project involves a comparison of the formal labour laws and informal norms and institutions which regulate restaurant work in the cities of Melbourne, Australia, and Yogyakarta, Indonesia. The paper argues that the functional approach is a necessary but incomplete method for overcoming the many issues of comparability between the two research sites; the method requires both extension of its analytical steps and explicit explanation of its limitations.
Nested comparisons: nation-building through comparative thinking about Albanian law
Authors: Pritchard Eleanor
Published: November 2016

Since the late nineteenth century, ideas about law, both Albanian and ‘other’, have played significant parts in the development of a sense of ‘Albanian-ness’ and remain central to the ongoing construction of the nation. In this paper, I examine how comparative thinking about ‘Albanian law’ in northern Albania and predominantly Albanian Kosovo has contributed to nation-building aims, with particular reference to comparative thinking around theKanunof Lekë Dukagjin, an early-twentieth-century legal code rooted in northern-Albanian customary practices. I look at this from two perspectives: comparative thinking by the law-writer in theKanunand comparative thinking by a contemporaneous writer about theKanun. Through these perspectives, we gain a more nuanced understanding of the intellectual context of theKanun’s production than is reflected in the existing literature, and a glimpse of its continued relevance today to ideas of nation.
Gain and bandwidth enhancement of New Planar microstrip array antennas geometry for C band weather radar applications
Authors: Slimani Abdellatif , Bennani Saad Dosse , El Alami Ali , Amellal Mohamed
Published: November 2016

A 4–8 GHz ultra wide band microstrip array antennas with improved gain for weather Radar applications was designed and fabricated. The microstrip radiating elements of the proposed array antennas are powered using a T-junction power divider with quarter wave-transformer impedance for a best matching. The design of this array antennas is based on the geometry of a linear array antennas well studied [ref (8)], which is based on minimizing of the electromagnetic (EM) coupling between the radiating elements and as decreasing the number of side lobes. The array antennas with dimension of (110 × 214 × 1.58 mm3) is fabricated on FR-4 epoxy dielectric with relative permittivity of 4.4 and thicknessh= 1.58 mm, it is performed in the full-wave EM solver High Frequency Structure Simulator, CST and verified by measurement. The proposed broadband array antennas show a better performance than the references antennas in deferent parameter which cited after.
New Insight into Silica Explains Planetary Smashup
Authors: Hall Shannon
Published: November 2016

A better equation of state for silica will help planetary scientists accurately constrain the giant impacts that have shaped our solar system.
Phagocytosis of live versus killed or fluorescently labeled bacteria by macrophages differ in both magnitude and receptor specificity
Authors: Peruń Angelika , Biedroń Rafał , Konopiński Maciej K , Białecka Anna , Marcinkiewicz Janusz , Józefowski Szczepan
Published: November 2016

Scavenger receptor (SR)‐mediated opsonin‐independent phagocytosis of bacteria by macrophages has been suggested to represent an important, early mechanism of anti‐bacterial host defense. However, although the ability to bind bacteria has been demonstrated to be a shared feature of all types of SRs, in many cases the evidence is limited to the demonstration of increased binding of killed, fluorescently labeled bacteria to non‐phagocytic cells transfected with these receptors. We sought to verify the ability of SRs to mediate non‐opsonic phagocytosis of live Escherichia coli (Ec) and Staphylococcus aureus (Sa), model species of Gram‐negative and ‐positive bacteria, respectively, and to assess the relative contributions of different SRs expressed on murine macrophages in this process. We found that the class A SR SR‐A/CD204 was the major receptor mediating phagocytosis of fluorescently labeled Sa, whereas different SRs had highly redundant roles in the phagocytosis of live Sa. Conversely, different SRs contributed to the phagocytosis of fluorescently labeled Ec. In comparison, phagocytosis of live Ec was of much lower magnitude and was selectively mediated by SR‐A. These results question the use of fluorescently labeled bacteria as valid replacements for live bacteria. The low magnitude of opsonin‐independent phagocytosis of Ec and unimpaired phagocytosis of Sa in SR‐A‐ or CD36‐deficient macrophages indicate that the defect in this process might not be responsible for the reported impaired bacteria clearance in mice deficient in these receptors. We postulate that this impairment might result to a larger extent from inhibition of intracellular bacteria killing caused by pro‐inflammatory cytokines, produced in excessive amounts by SR‐deficient cells in response to bacterial products.
MHC class II complexes sample intermediate states along the peptide exchange pathway
Authors: Wieczorek Marek , Sticht Jana , Stolzenberg Sebastian , Günther Sebastian , Wehmeyer Christoph , El Habre Zeina , Álvaro-Benito Miguel , Noé Frank , Freund Christian
Published: November 2016

The presentation of peptide-MHCII complexes (pMHCIIs) for surveillance by T cells is a well-known immunological concept in vertebrates, yet the conformational dynamics of antigen exchange remain elusive. By combining NMR-detected H/D exchange with Markov modelling analysis of an aggregate of 275 microseconds molecular dynamics simulations, we reveal that a stable pMHCII spontaneously samples intermediate conformations relevant for peptide exchange. More specifically, we observe two major peptide exchange pathways: the kinetic stability of a pMHCII’s ground state defines its propensity for intrinsic peptide exchange, while the population of a rare, intermediate conformation correlates with the propensity of the HLA-DM-catalysed pathway. Helix-destabilizing mutants designed based on our model shift the exchange behaviour towards the HLA-DM-catalysed pathway and further allow us to conceptualize how allelic variation can shape an individual’s MHC restricted immune response.
Control of diabetic hyperglycaemia and insulin resistance through TSC22D4
Authors: Ekim Üstünel Bilgen , Friedrich Kilian , Maida Adriano , Wang Xiaoyue , Krones-Herzig Anja , Seibert Oksana , Sommerfeld Anke , Jones Allan , Sijmonsma Tjeerd P. , Sticht Carsten , Gretz Norbert , Fleming Thomas , Nawroth Peter P. , Stremmel Wolfgang , Rose Adam J. , Berriel-Diaz Mauricio , Blüher Matthias , Herzig Stephan
Published: November 2016

Obesity-related insulin resistance represents the core component of the metabolic syndrome, promoting glucose intolerance, pancreatic beta cell failure and type 2 diabetes. Efficient and safe insulin sensitization and glucose control remain critical therapeutic aims to prevent diabetic late complications Here, we identify transforming growth factor beta-like stimulated clone (TSC) 22 D4 as a molecular determinant of insulin signalling and glucose handling. Hepatic TSC22D4 inhibition both prevents and reverses hyperglycaemia, glucose intolerance and insulin resistance in diabetes mouse models. TSC22D4 exerts its effects on systemic glucose homeostasis—at least in part—through the direct transcriptional regulation of the small secretory protein lipocalin 13 (LCN13). Human diabetic patients display elevated hepatic TSC22D4 expression, which correlates with decreased insulin sensitivity, hyperglycaemia and LCN13 serum levels. Our results establish TSC22D4 as a checkpoint in systemic glucose metabolism in both mice and humans, and propose TSC22D4 inhibition as an insulin sensitizing option in diabetes therapy.
Functional competence of a partially engaged GPCR–β-arrestin complex
Authors: Kumari Punita , Srivastava Ashish , Banerjee Ramanuj , Ghosh Eshan , Gupta Pragya , Ranjan Ravi , Chen Xin , Gupta Bhagyashri , Gupta Charu , Jaiman Deepika , Shukla Arun K.
Published: November 2016

G Protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors and drug targets. GPCR signalling and desensitization is critically regulated by β-arrestins (βarr). GPCR–βarr interaction is biphasic where the phosphorylated carboxyl terminus of GPCRs docks to the N-domain of βarr first and then seven transmembrane core of the receptor engages with βarr. It is currently unknown whether fully engaged GPCR–βarr complex is essential for functional outcomes or partially engaged complex can also be functionally competent. Here we assemble partially and fully engaged complexes of a chimeric β2V2R with βarr1, and discover that the core interaction is dispensable for receptor endocytosis, ERK MAP kinase binding and activation. Furthermore, we observe that carvedilol, a βarr biased ligand, does not promote detectable engagement between βarr1 and the receptor core. These findings uncover a previously unknown aspect of GPCR-βarr interaction and provide novel insights into GPCR signalling and regulatory paradigms.
Neural correlates of working memory development in adolescent primates
Authors: Zhou Xin , Zhu Dantong , Qi Xue-Lian , Li Sihai , King Samson G. , Salinas Emilio , Stanford Terrence R. , Constantinidis Christos
Published: November 2016

Working memory ability matures after puberty, in parallel with structural changes in the prefrontal cortex, but little is known about how changes in prefrontal neuronal activity mediate this cognitive improvement in primates. To address this issue, we compare behavioural performance and neurophysiological activity in monkeys as they transitioned from puberty into adulthood. Here we report that monkeys perform working memory tasks reliably during puberty and show modest improvement in adulthood. The adult prefrontal cortex is characterized by increased activity during the delay period of the task but no change in the representation of stimuli. Activity evoked by distracting stimuli also decreases in the adult prefrontal cortex. The increase in delay period activity relative to the baseline activity of prefrontal neurons is the best correlate of maturation and is not merely a consequence of improved performance. Our results reveal neural correlates of the working memory improvement typical of primate adolescence.
MicroRNA-126 overexpression rescues diabetes-induced impairment in efferocytosis of apoptotic cardiomyocytes
Authors: Suresh Babu Sahana , Thandavarayan Rajarajan A. , Joladarashi Darukeshwara , Jeyabal Prince , Krishnamurthy Shashirekha , Bhimaraj Arvind , Youker Keith A. , Krishnamurthy Prasanna
Published: November 2016

Efferocytosis, a process of clearance of apoptotic cells by phagocytes, is essential for successful resolution of inflammation and maintenance of tissue homeostasis. Diabetes compromises the function of macrophages leading to adverse inflammatory response during wound healing, myocardial injury, atherosclerosis and autoimmune disorders. However, the effect of diabetes on macrophage-mediated efferocytosis of apoptotic cardiomyocytes (ACM) and the molecular mechanisms involved are not understood so far. In the present study we found that invitro efferocytosis of ACM was impaired in macrophages from db/db (diabetic) mice. Macrophages exposed to high glucose (HG) decreases microRNA-126 (miR-126) expression with a corresponding increase in ADAM9 expression. Dual-luciferase reporter assay confirms that ADAM9 3′UTR contains miR-126 target site. ADAM9 inhibition reduces HG-induced proteolytic cleavage of Mer tyrosine receptor kinase (MerTK, a proto-oncogene that plays a critical role in phagocytosis), resulting in shedding of soluble-Mer (sMER) and loss of MERTK function. Over-expression of miR-126 attenuates HG-induced impairment of efferocytosis. Furthermore, human diabetic hearts show lower miR-126 expression with a corresponding increase in ADAM9 expression vs. normal counterparts. These data suggests that diabetes impairs efferocytosis of ACM and that strategies to enhance efferocytosis might attenuate diabetes-induced impairment in inflammation resolution and cardiac repair after injury.
Evolutionary origins of non-adjacent sequence processing in primate brain potentials
Authors: Milne Alice E. , Mueller Jutta L. , Männel Claudia , Attaheri Adam , Friederici Angela D. , Petkov Christopher I.
Published: November 2016

There is considerable interest in understanding the ontogeny and phylogeny of the human language system, yet, neurobiological work at the interface of both fields is absent. Syntactic processes in language build on sensory processing and sequencing capabilities on the side of the receiver. While we better understand language-related ontogenetic changes in the human brain, it remains a mystery how neurobiological processes at specific human development stages compare with those in phylogenetically closely related species. To address this knowledge gap, we measured EEG event-related potentials (ERPs) in two macaque monkeys using a paradigm developed to evaluate human infant and adult brain potentials associated with the processing of non-adjacent ordering relationships in sequences of syllable triplets. Frequent standard triplet sequences were interspersed with infrequent voice pitch or non-adjacent rule deviants. Monkey ERPs show early pitch and rule deviant mismatch responses that are strikingly similar to those previously reported in human infants. This stands in contrast to adults’ later ERP responses for rule deviants. The results reveal how non-adjacent sequence ordering relationships are processed in the primate brain and provide evidence for evolutionarily conserved neurophysiological effects, some of which are remarkably like those seen at an early human developmental stage.
Emergence of Ebola virus disease in a french acute care setting: a simulation study based on documented inter-individual contacts
Authors: Vanhems Philippe , Von Raesfeldt Rosette , Ecochard René , Voirin Nicolas
Published: November 2016

The potential spread of nosocomial Ebola virus disease (EVD) in non-outbreak areas is not known. The objective was to use detailed contact data on patients and healthcare workers (HCW) to estimate emergence probability and secondary incident cases (SIC) of EVD after hospitalization of an index case with undetected EVD. Contact data were collected through RFID devices used by patients and HCW during hospital care. A “susceptible-exposed-infected” model was used. Emergence probability, ranged from 7% to 84%. A plateau around 84% was observed. Emergence probability was proportional to time exposed to the dry phase of patients with nonspecific symptoms. Nurses were at higher risk of nosocomial EVD than physicians with around 60% emergence probability in this subgroup. The risk of nosocomial EVD in non-outbreak areas might be substantial if no preventive measures are implemented when asymptomatic patients or those with mild symptoms are hospitalized.
Evidence of Olfactory Imprinting at an Early Life Stage in Pink Salmon (Oncorhynchus gorbuscha)
Authors: Bett Nolan N. , Hinch Scott G. , Dittman Andrew H. , Yun Sang-Seon
Published: November 2016

Pacific salmon (Oncorhynchus spp.) navigate towards spawning grounds using olfactory cues they imprinted on as juveniles. The timing at which imprinting occurs has been studied extensively, and there is strong evidence that salmon imprint on their natal water during the parr-smolt transformation (PST). Researchers have noted, however, that the life histories of some species of Pacific salmon could necessitate imprinting prior to the PST. Juvenile pink salmon (O. gorbuscha) spend less time in fresh water than any other species of Pacific salmon, and presumably must imprint on their natal water at a very young age. The time at which imprinting occurs in this species, however, has not been experimentally tested. We exposed juvenile pink salmon as alevins to phenethyl alcohol (PEA) or control water, reared these fish to adulthood, and then tested their behavioural responses to PEA to determine whether the fish successfully imprinted. We found that pink salmon exposed to PEA as alevins were attracted to the chemical as adults, suggesting that imprinting can occur during this stage. Our finding provides some of the first evidence to support the long-standing belief that imprinting can occur in pink salmon prior to the PST.
Himalayan uplift shaped biomes in Miocene temperate Asia: evidence from leguminous Caragana
Authors: Zhang Ming-Li , Xiang Xiao-Guo , Xue Juan-Juan , Sanderson Stewart C. , Fritsch Peter W.
Published: November 2016

Caragana, with distinctive variation in leaf and rachis characters, exhibits three centers of geographic distribution, i.e., Central Asia, the Qinghai-Tibetan Plateau (QTP), and East Asia, corresponding to distinct biomes. Because Caragana species are often ecologically dominant components of the vegetation in these regions, it is regarded as a key taxon for the study of floristic evolution in the dry regions of temperate Asia. Based on an expanded data set of taxa and gene regions from those previously generated, we employed molecular clock and biogeographical analyses to infer the evolutionary history of Caragana and link it to floristic patterns, paleovegetation, and paleoclimate. Results indicate that Caragana is of arid origin from the Junggar steppe. Diversification of crown group Caragana, dated to the early Miocene ca. 18 Ma and onwards, can be linked to the Himalayan Motion stage of QTP uplift. Diversification of the major clades in the genus corresponding to taxonomic sections and morphological variation is inferred to have been driven by the uplift, as well as Asian interior aridification and East Asian monsoon formation, in the middle to late Miocene ca. 12~6 Ma. These findings demonstrate a synchronous evolution among floristics, vegetation and climate change in arid Central Asia, cold arid alpine QTP, and mesophytic East Asia.
miR-107 regulates tumor progression by targeting NF1 in gastric cancer
Authors: Wang Shizhi , Ma Gaoxiang , Zhu Haixia , Lv Chunye , Chu Haiyan , Tong Na , Wu Dongmei , Qiang Fulin , Gong Weida , Zhao Qinghong , Tao Guoquan , Zhou Jianwei , Zhang Zhengdong , Wang Meilin
Published: November 2016

Our previous genome-wide miRNA microarray study revealed that miR-107 was upregulated in gastric cancer (GC). In this study we aimed to explore its biological role in the pathogenesis of GC. Integrating in silico prediction algorithms with western blotting assays revealed that miR-107 inhibition enhanced NF1 (neurofibromin 1) mRNA and protein levels, suggesting that NF1 is one of miR-107 targets in GC. Luciferase reporter assay revealed that miR-107 suppressed NF1 expression by binding to the first potential binding site within the 3′-UTR of NF1 mRNA. mRNA stable assay indicated this binding could result in NF1 mRNA instability, which might contribute to its abnormal protein expression. Functional analyses such as cell growth, transwell migration and invasion assays were used to investigate the role of interaction between miR-107 and its target on GC development and progression. Moreover, We investigated the association between the clinical phenotype and the status of miR-107 expression in 55 GC tissues, and found the high expression contributed to the tumor size and depth of invasion. The results exhibited that down regulation of miR-107 opposed cell growth, migration, and invasion, whereas NF1 repression promoted these phenotypes. Our findings provide a mechanism by which miR-107 regulates NF1 in GC, as well as highlight the importance of interaction between miR-107 and NF1 in GC development and progression.
FANCD2 functions as a critical factor downstream of MiTF to maintain the proliferation and survival of melanoma cells
Authors: Bourseguin Julie , Bonet Caroline , Renaud Emilie , Pandiani Charlotte , Boncompagni Marina , Giuliano Sandy , Pawlikowska Patrycja , Karmous-Benailly Houda , Ballotti Robert , Rosselli Filippo , Bertolotto Corine
Published: November 2016

Proteins involved in genetic stability maintenance and safeguarding DNA replication act not only against cancer initiation but could also play a major role in sustaining cancer progression. Here, we report that the FANC pathway is highly expressed in metastatic melanoma harboring the oncogenic microphthalmia-associated transcription factor (MiTF). We show that MiTF downregulation in melanoma cells lowers the expression of several FANC genes and proteins. Moreover, we observe that, similarly to the consequence of MiTF downregulation, FANC pathway silencing alters proliferation, migration and senescence of human melanoma cells. We demonstrate that the FANC pathway acts downstream MiTF and establish the existence of an epistatic relationship between MiTF and the FANC pathway. Our findings point to a central role of the FANC pathway in cellular and chromosomal resistance to both DNA damage and targeted therapies in melanoma cells. Thus, the FANC pathway is a promising new therapeutic target in melanoma treatment.
Mitochondrial Ca2+ uptake controls actin cytoskeleton dynamics during cell migration
Authors: Prudent Julien , Popgeorgiev Nikolay , Gadet Rudy , Deygas Mathieu , Rimokh Ruth , Gillet Germain
Published: November 2016

Intracellular Ca2+ signaling regulates cell migration by acting on cytoskeleton architecture, cell directionality and focal adhesions dynamics. In migrating cells, cytosolic Ca2+ pool and Ca2+ pulses are described as key components of these effects. Whereas the role of the mitochondrial calcium homeostasis and the Mitochondria Cacium Uniporter (MCU) in cell migration were recently highlighted in vivo using the zebrafish model, their implication in actin cystokeleton dynamics and cell migration in mammals is not totally characterized. Here, we show that mcu silencing in two human cell lines compromises their migration capacities. This phenotype is characterized by actin cytoskeleton stiffness, a cell polarization loss and an impairment of the focal adhesion proteins dynamics. At the molecular level, these effects appear to be mediated by the reduction of the ER and cytosolic Ca2+ pools, which leads to a decrease in Rho-GTPases, RhoA and Rac1, and Ca2+-dependent Calpain activites, but seem to be independent of intracellular ATP levels. Together, this study highlights the fundamental and evolutionary conserved role of the mitochondrial Ca2+ homeostasis in cytoskeleton dynamics and cell migration.
SGTA interacts with the proteasomal ubiquitin receptor Rpn13 via a carboxylate clamp mechanism
Authors: Thapaliya Arjun , Nyathi Yvonne , Martínez-Lumbreras Santiago , Krysztofinska Ewelina M. , Evans Nicola J. , Terry Isabelle L. , High Stephen , Isaacson Rivka L.
Published: November 2016

The fate of secretory and membrane proteins that mislocalize to the cytosol is decided by a collaboration between cochaperone SGTA (small, glutamine-rich, tetratricopeptide repeat protein alpha) and the BAG6 complex, whose operation relies on multiple transient and subtly discriminated interactions with diverse binding partners. These include chaperones, membrane-targeting proteins and ubiquitination enzymes. Recently a direct interaction was discovered between SGTA and the proteasome, mediated by the intrinsic proteasomal ubiquitin receptor Rpn13. Here, we structurally and biophysically characterize this binding and identify a region of the Rpn13 C-terminal domain that is necessary and sufficient to facilitate it. We show that the contact occurs through a carboxylate clamp-mediated molecular recognition event with the TPR domain of SGTA, and provide evidence that the interaction can mediate the association of Rpn13 and SGTA in a cellular context.
Composition of gut microbiota in infants in China and global comparison
Authors: Kuang Ya-Shu , Li Sheng-Hui , Guo Yong , Lu Jin-Hua , He Jian-Rong , Luo Bei-Jun , Jiang Feng-Ju , Shen Hui , Papasian Christopher J. , Pang Herbert , Xia Hui-Min , Deng Hong-Wen , Qiu Xiu
Published: November 2016

Symbiotic gut microbiota is essential for human health, and its compositional changes have been associated with various complex disorders. However, systematic investigation of the acquisition and development of gut microbial communities during early infancy are relatively rare, particularly for infants from non-Western countries. In this study, we characterize the colonization and development of infant microbiota in healthy Chinese infants and compare the pattern with those from other countries. The fecal microbiota of 2-month-old infants was considerably more diverse than that of neonates, as indicated by higher relative abundances of Veillonella, Clostridium, Bacteroides, Lactobacillus, Collinsella and Prevotella, and reduction of Escherichia and Enterococcus. The fecal microbiota of vaginally delivered infants (both neonates and 2-month-old) had significant enrichment of Bacteroides, Parabacteroides and Megamonas, whereas cesarean delivered infants had enrichment of Prevotella, Streptococcus and Trabulsiella. By global comparison, we identify three different enterotypes, referred as “P-type”, “A-type ”and “F-type” which were highly abundant in Proteobacteria, Actinobacteria and Firmicutes, respectively. The three enterotypes’ compositons vary geographically. All Chinese infants in our study belong to the P-type. These findings may provide novel insights into our understanding of the establishment of infant fecal bacterial communities.
Potent Inducers of Endogenous Antimicrobial Peptides for Host Directed Therapy of Infections
Authors: Ottosson H. , Nylén F. , Sarker P. , Miraglia E. , Bergman P. , Gudmundsson G. H. , Raqib R. , Agerberth B. , Strömberg R.
Published: November 2016

A new concept for treatment of infections is induction of our own antimicrobial peptides and the presented novel class of inducer, aroylated phenylenediamines (APDs), gives up to 20 to 30-fold induction of the human antimicrobial peptide LL-37, in vitro. In addition, oral administration of an APD in a rabbit model of Shigellosis resulted in recovery from the infection in a few days implying that APD’s are promising candidates for treatment of infections.
Nonlinear network model analysis of vibrational energy transfer and localisation in the Fenna-Matthews-Olson complex
Authors: Morgan Sarah E. , Cole Daniel J. , Chin Alex W.
Published: November 2016

Collective protein modes are expected to be important for facilitating energy transfer in the Fenna-Matthews-Olson (FMO) complex of photosynthetic green sulphur bacteria, however to date little work has focussed on the microscopic details of these vibrations. The nonlinear network model (NNM) provides a computationally inexpensive approach to studying vibrational modes at the microscopic level in large protein structures, whilst incorporating anharmonicity in the inter-residue interactions which can influence protein dynamics. We apply the NNM to the entire trimeric FMO complex and find evidence for the existence of nonlinear discrete breather modes. These modes tend to transfer energy to the highly connected core pigments, potentially opening up alternative excitation energy transfer routes through their influence on pigment properties. Incorporating localised modes based on these discrete breathers in the optical spectra calculations for FMO using ab initio site energies and excitonic couplings can substantially improve their agreement with experimental results.
First-Principles Studies on the Structural Stability of Spinel ZnCo2O4 as an Electrode Material for Lithium-ion Batteries
Authors: Liu Wei-Wei , Jin M. T. , Shi W. M. , Deng J. G. , Lau Woon-Ming , Zhang Y. N.
Published: November 2016

Systematic first principles calculations were performed for ZnCo2O4 to clarify its structural and electronic properties, and particularly the structural stability as an electrode material for lithium-ion batteries. For samples with low Li concentration, e.g., LinZnCo2O4 with n < 1, Li atoms take the center of oxygen octahedra and may diffuse rapidly. Structure distortions and volume expansions can be observed in LinZnCo2O4 with n > 1 and amorphous structures eventually prevail. The AIMD simulations for Li9ZnCo2O4 suggest the formation of Li2O, Co3O4 and LiZn local compounds or alloys. In particular, the formation of Zn-Co aggregations and the losing of ZnO pairs are identified as the possible reasons that are responsible to the Li capacity fading in ZnCo2O4 anodes.
Degradable emulsion as vaccine adjuvant reshapes antigen-specific immunity and thereby ameliorates vaccine efficacy
Authors: Huang Chung-Hsiung , Huang Chiung-Yi , Cheng Chih-Ping , Dai Shih-Hsiung , Chen Hsin-Wei , Leng Chih-Hsiang , Chong Pele , Liu Shih-Jen , Huang Ming-Hsi
Published: November 2016

This study describes the feasibility and adjuvant mechanism of a degradable emulsion for tuning adaptive immune responses to a vaccine antigen. We featured a mouse model with ovalbumin (OVA) as the antigen to deepen our understanding of the properties of a degradable emulsion-based adjuvant, dubbed PELC, interacting with immune cells and to elucidate their roles in vaccine immunogenicity in vivo. First, we demonstrated that the emulsion, which is stabilized by an amphiphilic bioresorbable polymer, shows degradation in mimic human body conditions and considerable tolerance in vivo. Then, we confirmed the model protein could be loaded into the emulsion and released from the matrix in a sustained manner, subsequently driving the production of antigen-specific antibodies. We also comprehended that PELC not only recruits antigen-presenting cells (APCs) to the injection site but also induces the activation of the recruited APCs and migration to the draining lymph nodes. As an adjuvant for cancer immunotherapy, PELC-formulated OVA could strongly enhance antigen-specific T-cell responses as well as anti-tumor ability with respected to non-formulated OVA, using OVA protein/EG7 cells as a tumor antigen/tumor cell model. Accordingly, our data paved the way for the clinical application of degradable emulsions based on amphiphilic bioresorbable polymers as vaccine adjuvants.
Fast generation of W states of superconducting qubits with multiple Schrödinger dynamics
Authors: Kang Yi-Hao , Chen Ye-Hong , Wu Qi-Cheng , Huang Bi-Hua , Song Jie , Xia Yan
Published: November 2016

In this paper, we present a protocol to generate a W state of three superconducting qubits (SQs) by using multiple Schrödinger dynamics. The three SQs are respective embedded in three different coplanar waveguide resonators (CPWRs), which are coupled to a superconducting coupler (SCC) qubit at the center of the setups. With the multiple Schrödinger dynamics, we build a shortcuts to adiabaticity (STA), which greatly accelerates the evolution of the system. The Rabi frequencies of the laser pulses being designed can be expressed by the superpositions of Gaussian functions via the curves fitting, so that they can be realized easily in experiments. What is more, numerical simulation result shows that the protocol is robust against control parameters variations and decoherence mechanisms, such as the dissipations from the CPWRs and the energy relaxation. In addition, the influences of the dephasing are also resisted on account of the accelerating for the dynamics. Thus, the performance of the protocol is much better than that with the conventional adiabatic passage techniques when the dephasing is taken into account. We hope the protocol could be implemented easily in experiments with current technology.
Lactate is a potent inhibitor of the capsaicin receptor TRPV1
Authors: de la Roche Jeanne , Walther Isabella , Leonow Waleria , Hage Axel , Eberhardt Mirjam , Fischer Martin , Reeh Peter W. , Sauer Susanne , Leffler Andreas
Published: November 2016

Tissue ischemia results in an accumulation of lactate and local or systemic lactic acidosis. In nociceptive sensory neurons, lactate was reported to sensitize or activate the transient receptor potential ion channel TRPA1 and acid-sensing ion channels (ASICs). However, it is unclear how lactate modulates the TRPV1 regarded as the main sensor for acidosis in sensory neurons. In this study we investigated the effects of lactate (LA) on recombinant and native TRPV1 channels and on TRPV1-mediated release of neuropeptides from mouse nerves. TRPV1-mediated membrane currents evoked by protons, capsaicin or heat are inhibited by LA at concentrations ranging from 3 μM to 100 mM. LA inhibits TRPV1-mediated proton-induced Ca2+-influx in dorsal root ganglion neurons as well as proton-evoked neuropeptide release from mouse nerves. Inhibition of TRPV1 by LA is significantly stronger on inward currents as compared to outward currents since LA affects channel gating, shifting the activation curve towards more positive potentials. The mutation I680A in the pore lower gate displays no LA inhibition. Cell-attached as well as excised inside- and outside-out patches suggest an interaction through an extracellular binding site. In conclusion, our data demonstrate that lactate at physiologically relevant concentrations is a potent endogenous inhibitor of TRPV1.
Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease
Authors: Giacomin Paul , Zakrzewski Martha , Jenkins Timothy P. , Su Xiaopei , Al-Hallaf Rafid , Croese John , de Vries Stefan , Grant Andrew , Mitreva Makedonka , Loukas Alex , Krause Lutz , Cantacessi Cinzia
Published: November 2016

A reduced diversity of the gastrointestinal commensal microbiota is associated with the development of several inflammatory diseases. Recent reports in humans and animal models have demonstrated the beneficial therapeutic effects of infections by parasitic worms (helminths) in some inflammatory disorders, such as inflammatory bowel disease (IBD) and coeliac disease (CeD). Interestingly, these studies have described how helminths may alter the intestinal microbiota, potentially representing a mechanism by which they regulate inflammation. However, for practical reasons, these reports have primarily analysed the faecal microbiota. In the present investigation, we have assessed, for the first time, the changes in the microbiota at the site of infection by a parasitic helminth (hookworm) and gluten-dependent inflammation in humans with CeD using biopsy tissue from the duodenum. Hookworm infection and gluten exposure were associated with an increased abundance of species
within the Bacteroides phylum, as well as increases in the richness and diversity of the tissue-resident microbiota within the intestine, results that are consistent with previous reports using other helminth species in humans and animal models. Hence, this may represent a mechanism by which parasitic helminths may restore intestinal immune homeostasis and exert a therapeutic benefit in CeD, and potentially other inflammatory disorders.
Ecological dynamics of influenza A viruses: cross-species transmission and global migration
Authors: Ren Hongguang , Jin Yuan , Hu Mingda , Zhou Jing , Song Ting , Huang Zhisong , Li Beiping , Li Kaiwu , Zhou Wei , Dai Hongmei , Shi Weifeng , Yue Junjie , Liang Long
Published: November 2016

A comprehensive study of cross-species transmission and inter-regional migration would provide insights into the global ecology of influenza A viruses (IAVs). To this end, we assembled 17,241 non-redundant IAV whole-genome sequences with complete epidemiological information. We hierarchically divided the movements of IAVs into the cross-species transmission in each region and the inter-regional migration driven by each host species. We then systematically identified the potential cross-species transmission and inter-regional migration events. Cross-species transmission networks were obtained for each gene segment of the IAVs. Waterfowl, domestic birds and swine showed higher degrees of connection than did other species in all of the transmission networks. East Asia and Southeast Asia were hot regions for avian-mammal transmissions. Swine and migratory birds were the dominant species for global virus delivery. The importance of swine was reemphasized because it has not only provided an environment for adaptive evolution during the avian-human transmission of IAVs (as incubators) but also served as a key species for the global dissemination of the viruses (as carriers). Therefore, monitoring the global live trade of swine and survey of migratory birds along flyways would be beneficial for the prevention and control of IAVs.
The Magic Angle Effect in NMR and MRI of Cartilage
Authors: Fullerton Gary D.
Published: November 2016

This chapter reviews the molecular basis of “magic angle” effect in cartilage beginning from fundamental concepts of physics and physical chemistry. The magic angle effect is due to the unique oriented structure of collagen fibrils that occur in cartilage, tendon, ligaments and other connective tissues. One-dimensional ice-like water bridges bound in a repetitive manner to the backbone of the collagen molecule form a constant time-average proton–proton (P–P) vector coaxial with fibril orientation. Constant P–P induces frequency shifts (Δωmax ∼ 1000 Hz) due to the fixed orientation of an exchangeable proton relative to the fixed magnetic dipole field (ΔBmax ∼ ±10 Gauss) of the neighboring immobilized bridge proton on the same water molecule. The T2* relaxation time caused by rapid dephasing of net magnetization in the x–y plane results from stochastic sampling of solid-like dipole coupling ΔB(θ) by mobile protons. T2*(θ) becomes a function of orientation as the effective local field in the collagen fibril is Be = Bo + ΔB(θ) and ΔB(θ) varies as a function of the angle between the vectors B0 and P–P. The stoichiometric hydration model provides modeling tools to relate changes in T1, T2* and T1ρ with orientation to specific changes in collagen structure. It is anticipated that advanced studies will in future relate measurable molecular shifts to disease progression in osteoarthritis and other injuries to cartilage.
Loading-Induced Changes in Cartilage Studied by NMR and MRI
Authors: Wang Nian , Xia Yang
Published: November 2016

Articular cartilage is a load-bearing tissue in joints that is compressed constantly in our daily activities. Compression (loading) causes complex changes in cartilage, due to its unique molecular composition and structural organization. Since cartilage is a thin layer of tissue (becoming thinner after loading), high resolution in imaging is critically important to gaining an understanding of the depth-dependent, orientation-dependent, and strain-dependent load-induced changes in articular cartilage. This chapter discusses the consequences of loading on nuclear magnetic resonance and magnetic resonance imaging (MRI) measurements of cartilage, based on a number of MRI studies of compressed cartilage at microscopic resolutions. Specifically, the influences of tissue loading on the relaxation times (T1, T2, and T1ρ) in cartilage are discussed. The roles of MRI contrast agents (e.g. gadolinium) in the MRI of cartilage loading are illustrated with examples. A thorough understanding of the complex consequences of tissue loading, which often involve several competing factors in its mechanisms, will facilitate the development and validation of useful protocols for clinical diagnosis of early cartilage degradation in osteoarthritis and related joint diseases.
The Critical Role of High Imaging Resolution in MRI of Cartilage—The MRI Microscope
Authors: Xia Yang
Published: November 2016

A talk by Richard Feynman on December 29, 1959 at an American Physical Society meeting has been considered by many to be a seminal event in the history of nano-science. In his talk, titled There's Plenty of Room at the Bottom, Dr Feynman said “It is very easy to answer many of these fundamental biological questions; you just look at the thing! … Unfortunately, the present microscope sees at a scale which is just a bit too crude. Make the microscope one hundred times more powerful, and many problems of biology would be made very much easier. I exaggerate, of course, but the biologists would surely be very thankful to you …” (The editing inside the quotation marks is mine.) If we replaced the words “biological” and “microscope” with “osteoarthritic” and “magnetic resonance imaging (MRI)”, respectively, the same statements could become equally inspirational for the readers of this chapter, which justifies the need to have high spatial resolutions in MRI of articular cartilage. This chapter also suggests a sweet spot—microscopic MRI of animal models of osteoarthritis—that bypasses the major limitations in clinical MRI of arthritic diseases.
Synthesis of stilbene derivatives via visible-light-induced cross-coupling of aryl diazonium salts with nitroalkenes using –NO2 as a leaving group
Authors: Zhang Na , Quan Zheng-Jun , Zhang Zhang , Da Yu-Xia , Wang Xi-Cun
Published: November 2016

Photocatalytic coupling of nitroalkenes with diazonium salts.
One-pot four-enzyme synthesis of thymidinediphosphate-l-rhamnose
Authors: Li Siqiang , Wang Hong , Ma Juncai , Gu Guofeng , Chen Zonggang , Guo Zhongwu
Published: November 2016

A concise and effective one-pot four-enzyme synthesis of dTDP-Rha, the substrate of rhamnosyltransferases, is described.
Correction: Dielectric constant enhancement of non-fullerene acceptors via side-chain modification
Authors: Donaghey Jenny E. , Armin Ardalan , Stoltzfus Dani M. , Burn Paul L. , Meredith Paul
Published: November 2016

Correction for ‘Dielectric constant enhancement of non-fullerene acceptors via side-chain modification’ by Jenny E. Donaghey et al., Chem. Commun., 2015, 51, 14115–14118.
Electrochemical DNA sensing strategy based on strengthening electronic conduction and a signal amplifier carrier of nanoAu/MCN composited nanomaterials for sensitive lead detection
Authors: Zeng Guangming , Zhu Yuan , Zhang Yi , Zhang Chang , Tang Lin , Guo Pucan , Zhang Lihua , Yuan Yujie , Cheng Min , Yang Chunping
Published: November 2016

A DNA electrochemical sensor was fabricated for Pb2+ detection.
Microfluidic PDMS on paper (POP) devices
Authors: Shangguan Jin-Wen , Liu Yu , Pan Jian-Bin , Xu Bi-Yi , Xu Jing-Juan , Chen Hong-Yuan
Published: November 2016

Microfluidic PDMS on paper devices (POP devices) make in situ analysis fast, reliable and easy to carry out.
High porosity microspheres with functional groups synthesized by thiol–yne click suspension polymerization
Authors: Cai Shengying , Weng Zhulin , Zheng Yaochen , Zhao Bo , Gao Zhengguo , Gao Chao
Published: November 2016

We employed a combination of thiol–yne click polymerization and suspension polymerization for the synthesis of porous epoxy-functionalized polymeric microspheres.
Single step synthesis of a magnesium doped lithium manganese oxide ion sieve nanomaterial and a SPES/ion sieve composite membrane for the separation of lithium
Authors: Saravaia Hitesh , Gupta Hariom , Kulshrestha Vaibhav
Published: November 2016

Magnesium doped lithium manganese oxide nanostructured ion sieve materials are prepared through a single step solid state reaction and characterized with appropriate analytical techniques.
Fabrication and characterization of electrospinning/3D printing bone tissue engineering scaffold
Authors: Yu Yinxian , Hua Sha , Yang Mengkai , Fu Zeze , Teng Songsong , Niu Kerun , Zhao Qinghua , Yi Chengqing
Published: November 2016

A composite scaffold was fabricated with a method involving both electrospinning and 3D printing to give microscale pores and good mechanical properties. Biocompatibility and cell infiltration on the scaffold was evaluated by anin vitrostudy.
Green synthesis of primary, secondary, and tertiary amides through oxidative amidation of methyl groups with amine hydrochlorides over recyclable CoFe2O4 NPs
Authors: Eidi Esmaiel , Kassaee Mohammad Zaman
Published: November 2016

This protocol provides high yield, short reaction time, and operational simplicity, green and low cast procedure for the synthesis of all types of amides.
Dual applications of silver nanoparticles incorporated functionalized MWCNTs grafted surface modified PAN nanofibrous membrane for water purification
Authors: Raj Kumar S. , Gopinath P.
Published: November 2016

Herein, we have developed silver nanoparticles (Ag NPs) incorporated carboxylated multiwalled carbon nanotubes (MWCNTs) grafted aminated polyacrylonitrile (APAN) nanofibrous membrane pertinent for the removal of toxic heavy metals and bacteria.
Sensitive and accurate determination of neurotransmitters from in vivo rat brain microdialysate of Parkinson's disease using in situ ultrasound-assisted derivatization dispersive liquid–liquid microextraction by UHPLC-MS/MS
Authors: Zhao Xian-En , He Yongrui , Yan Ping , Wei Na , Wang Renjun , Sun Jing , Zheng Longfang , Zhu Shuyun , You Jinmao
Published: November 2016

In situ UA-DDLLME coupled with UHPLC-MS/MS has been developed for simultaneous determination of neurotransmitters and baicalein from Parkinson's disease rats.
Integrated super-hydrophobic and antireflective PDMS bio-templated from nano-conical structures of cicada wings
Authors: Liu Yan , Song Yunyun , Niu Shichao , Zhang Yonglai , Han Zhiwu , Ren Luquan
Published: November 2016

A PDMS positive replica bio-templated from cicada wings demonstrates excellent antireflective properties and super-hydrophobic capacity.