bluuebunny/crossref_metadata_2025 huggingface dataset:
Archaeology, symmetry and the ontology of things. A response to critics
Authors: Olsen Bjørnar , Witmore Christopher
Published: November 2015

This article responds to recent critiques of ‘symmetrical archaeology’. It addresses three common claims: (1) that symmetrical archaeology fails to see a difference between living and non-living entities, (2) that symmetrical archaeology makes no room for humans and other living things, (3) that symmetrical archaeology lacks any sincere ethical concern for things. This article demonstrates how these claims are based on common misunderstandings or misreadings, and offers further clarifications as to its perspective on ontology, ethics and things.
Agency ‘in itself’. A discussion of inanimate, animal and human agency
Authors: Lindstrøm Torill Christine
Published: November 2015

‘Agency’, the concept, its connections to ontology and its uses within archaeological theory, are discussed and criticized. In recent archaeological theory, the term ‘agency’ has been attributed to things, plants, animals and humans. In this paper it is argued that the term ‘agency’ is logically meaningless if applied to everything that moves or has effects on its surroundings, and that we need a new, more precise terminology that discriminates between ‘agency’, ‘effect’, ‘actant’ and ‘effectant’. That people, of all cultures, perceive and experience things/objects as having agency is explained as being due to projections of human characteristics, human psycho-neurological functioning, and the fact that all individuals and cultures are deeply involved with and dependent on things/objects. Connected to this, questions regarding different ontologies, animism, ethics and sciences are discussed. The paper presents a critique of symmetrical archaeology and materiality studies. Broader paradigmatic perspectives, more theoretical and methodological inclusiveness, and more inter- and trans-disciplinary endeavours are suggested to increase archaeology's ‘agency’.
Evaluating the Use of Synthetic Replicas for SEM Identification of Bloodstains (with Emphasis on Archaeological and Ethnographic Artifacts)
Authors: Hortolà Policarp
Published: November 2015

Some archaeological or ethnographic specimens are unavailable for direct examination using a scanning electron microscope (SEM) due to methodological obstacles or legal issues. In order to assess the feasibility of using SEM synthetic replicas for the identification of bloodstains (BSs) via morphology of red blood cells (RBCs), three fragments of different natural raw material (inorganic, stone; plant, wood; animal, shell) were smeared with peripheral human blood. Afterwards, molds and casts of the bloodstained areas were made using vinyl polysiloxane (VPS) silicone impression and polyurethane (PU) resin casting material, respectively. Then, the original samples and the resulting casts were coated with gold and examined in secondary-electron mode using a high-vacuum SEM. Results suggest that PU resin casts obtained from VPS silicone molds can preserve RBC morphology in BSs, and consequently that synthetic replicas are feasible for SEM identification of BSs on cultural heritage specimens made of natural raw materials. Although the focus of this study was on BSs, the method reported in this paper may be applicable to organic residues other than blood, as well as to the surface of other specimens when, for any reason, the original is unavailable for an SEM.
Astroblastoma: a rare case report
Authors: Palled Siddanna R. , Thimmaya Naveen , Jagadheesan Sugashwaran , Khaleel Ibrahim
Published: November 2015

Background

An astroblastoma is a rare primary glial tumour occurring preferentially in young adults. It is characterised by a perivascular arrangement of tumour cells forming perivascular pseudorosettes mimicking ependymomas. The histogenesis of astroblastoma is unclear.

Case description

We present the history of a 13-year-old girl with chief complaints of headache associated with vomiting, blurring of vision on the left eye and a history of diplopia on the right eye. She underwent left parietal parasagittal craniotomy and near-total excision of tumour. She was planned for postoperative radiotherapy 5,940 cGy in 28 fractions along with concurrent temozolamide100 mg. She had no neurological deficit or complaints during her last visit.

Conclusion

Astroblastomas are a distinct clinic pathologic entity, with well-described radiologic, pathologic and cytogenetic features. Its recurrence is high, and efforts must be made to elucidate the role and usefulness of radiotherapy and chemotherapy in these tumours.
Implementation of NHS Health Checks in general practice: variation in delivery between practices and practitioners
Authors: Krska Janet , du Plessis Ruth , Chellaswamy Hannah
Published: November 2015

Aim

To evaluate NHS Health Check implementation in terms of frequency of data recording, advice provided, referrals to community-based lifestyle support services, statin prescribing and new diagnoses, and to assess variation in these aspects between practices and health professionals involved in delivery.

Background

Most NHS Health Checks are delivered by general practices, but little detail is known about the extent of variation in how they are delivered in different practices and by different health professionals.

Methods

This was an observational study conducted in a purposively selected sample of 13 practices in Sefton, North West England. Practices used previously recorded information from their clinical management systems to identify patients with cardiovascular disease (CVD) risk ⩾20%, a potentially cost-effective approach. The evaluation was conducted during the first year of delivery in Sefton. Data were extracted from medical records of all patients identified, regardless of Health Check attendance.

Findings

Of the 2892 patients identified by the 13 practices, 1070 had received an NHS Health Check at the time of the study. Of these, only 936 (87.5%) had a recorded CVD risk score, with risk ⩾20% confirmed in 92.0%. Estimated risk category was correct in 456/677 (67.4%) of patients with estimated and actual risk scores.

Significant variation was found between practices and health professionals in parameters recorded, tests requested, advice given and referrals for lifestyle support. Only 45.3% of patients had body mass index, smoking, alcohol, exercise, blood pressure and cholesterol all recorded.

Lifestyle advice and referral into lifestyle services were documented in 80.6% and 6.4% of attenders, respectively, again with significant variation between practices and professionals. Statin prescribing rose in attenders from 19.6% to 34.6%. A similar proportion of attenders and non-attenders received new diagnoses.

Conclusion

Effort is required to reduce variation in how practices deliver and follow-up NHS Health Checks, to ensure the consistency of the programme.
LeFiS-Lernförderung in Schulen – Evaluation eines Modellprojekts zur schulinternen Lerntherapie für Kinder mit Lese- & Rechtschreibschwierigkeiten
Authors: Balke-Melcher Christina , Schuchardt Kirsten , Wolpers Josef-Godehard , Mähler Claudia
Published: November 2015

Zusammenfassung. Kinder mit Schwierigkeiten im Lesen und Rechtschreiben haben es im schulischen Alltag besonders schwer. Sie in diesen Bereichen zu unterstützen und zu fördern, blieb bisher meist den Eltern überlassen, d. h. war auf den außerschulischen Bereich beschränkt. Dies ändert sich jedoch zunehmend und die Verantwortung zur Förderung wird mehr und mehr den Schulen übertragen. Im vorliegenden Artikel wird ein Pilotprojekt vorgestellt, in welchem Lernförderung für Kinder mit Lese-Rechtschreibschwächen innerschulisch durch Lerntherapeuten durchgeführt wurde. Das Projekt und seine Wirksamkeit werden im Kontext des „Response to Intervention“ – Ansatzes diskutiert.
Rethinking Approach and Avoidance in Achievement Contexts: The Perspective of Dynamical Systems
Authors: Gernigon Christophe , Vallacher Robin R. , Nowak Andrzej , Conroy David E.
Published: November 2015

An integrative model of approach and avoidance goals in achievement contexts is proposed based on the concepts and principles of nonlinear dynamical systems. These goals are conceptualized as self-organizing systems in which information relevant to competence expectancies and perceptions of benefit and threat for the self is integrated with respect to either a single coherent state ( static integration) or 2 conflicting coherent states ( dynamic integration). Mathematical equations depict the emergence of approach and avoidance attractor dynamics from the proposed integration process. The model specifies the conditions under which states of goal involvement will display patterns of resistance (stability), oscillation between approach and avoidance (instability), or reversal (nonlinear change). As a result, this model of approach and avoidance goals equips previous dynamical models of self-regulation with greater social–cognitive substance. It also provides a parsimonious account of achievement motivation and resolves lingering inconsistencies and uncertainties in the achievement goal literature. Moreover, the dynamical systems approach, on which the model is based, provides a heuristic framework for generating new predictions regarding the ebb and flow of approach and avoidance in achievement contexts.
DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age
Authors: Marangos Petros , Stevense Michelle , Niaka Konstantina , Lagoudaki Michaela , Nabti Ibtissem , Jessberger Rolf , Carroll John
Published: November 2015

In mammalian oocytes DNA damage can cause chromosomal abnormalities that potentially lead to infertility and developmental disorders. However, there is little known about the response of oocytes to DNA damage. Here we find that oocytes with DNA damage arrest at metaphase of the first meiosis (MI). The MI arrest is induced by the spindle assembly checkpoint (SAC) because inhibiting the SAC overrides the DNA damage-induced MI arrest. Furthermore, this MI checkpoint is compromised in oocytes from aged mice. These data lead us to propose that the SAC is a major gatekeeper preventing the progression of oocytes harbouring DNA damage. The SAC therefore acts to integrate protection against both aneuploidy and DNA damage by preventing production of abnormal mature oocytes and subsequent embryos. Finally, we suggest escaping this DNA damage checkpoint in maternal ageing may be one of the causes of increased chromosome anomalies in oocytes and embryos from older mothers.
Engineering intracellular biomineralization and biosensing by a magnetic protein
Authors: Matsumoto Yuri , Chen Ritchie , Anikeeva Polina , Jasanoff Alan
Published: November 2015

Remote measurement and manipulation of biological systems can be achieved using magnetic techniques, but a missing link is the availability of highly magnetic handles on cellular or molecular function. Here we address this need by using high-throughput genetic screening in yeast to select variants of the iron storage ferritin (Ft) that display enhanced iron accumulation under physiological conditions. Expression of Ft mutants selected from a library of 107 variants induces threefold greater cellular iron loading than mammalian heavy chain Ft, over fivefold higher contrast in magnetic resonance imaging, and robust retention on magnetic separation columns. Mechanistic studies of mutant Ft proteins indicate that improved magnetism arises in part from increased iron oxide nucleation efficiency. Molecular-level iron loading in engineered Ft enables detection of individual particles inside cells and facilitates creation of Ft-based intracellular magnetic devices. We demonstrate construction of a magnetic sensor actuated by gene expression in yeast.
The evolutionary landscape of intergenic trans-splicing events in insects
Authors: Kong Yimeng , Zhou Hongxia , Yu Yao , Chen Longxian , Hao Pei , Li Xuan
Published: November 2015

To explore the landscape of intergenic trans-splicing events and characterize their functions and evolutionary dynamics, we conduct a mega-data study of a phylogeny containing eight species across five orders of class Insecta, a model system spanning 400 million years of evolution. A total of 1,627 trans-splicing events involving 2,199 genes are identified, accounting for 1.58% of the total genes. Homology analysis reveals that mod(mdg4)-like trans-splicing is the only conserved event that is consistently observed in multiple species across two orders, which represents a unique case of functional diversification involving trans-splicing. Thus, evolutionarily its potential for generating proteins with novel function is not broadly utilized by insects. Furthermore, 146 non-mod trans-spliced transcripts are found to resemble canonical genes from different species. Trans-splicing preserving the function of ‘breakup’ genes may serve as a general mechanism for relaxing the constraints on gene structure, with profound implications for the evolution of genes and genomes.
Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization
Authors: Haq Tamanna , Richards Mark W. , Burgess Selena G. , Gallego Pablo , Yeoh Sharon , O’Regan Laura , Reverter David , Roig Joan , Fry Andrew M. , Bayliss Richard
Published: November 2015

Mitotic spindle assembly requires the regulated activities of protein kinases such as Nek7 and Nek9. Nek7 is autoinhibited by the protrusion of Tyr97 into the active site and activated by the Nek9 non-catalytic C-terminal domain (CTD). CTD binding apparently releases autoinhibition because mutation of Tyr97 to phenylalanine increases Nek7 activity independently of Nek9. Here we find that self-association of the Nek9-CTD is needed for Nek7 activation. We map the minimal Nek7 binding region of Nek9 to residues 810–828. A crystal structure of Nek7Y97F bound to Nek9810–828 reveals a binding site on the C-lobe of the Nek7 kinase domain. Nek7Y97F crystallizes as a back-to-back dimer between kinase domain N-lobes, in which the specific contacts within the interface are coupled to the conformation of residue 97. Hence, we propose that the Nek9-CTD activates Nek7 through promoting back-to-back dimerization that releases the autoinhibitory tyrosine residue, a mechanism conserved in unrelated kinase families.
High-throughput 3D tracking of bacteria on a standard phase contrast microscope
Authors: Taute K.M. , Gude S. , Tans S.J. , Shimizu T.S.
Published: November 2015

Bacteria employ diverse motility patterns in traversing complex three-dimensional (3D) natural habitats. 2D microscopy misses crucial features of 3D behaviour, but the applicability of existing 3D tracking techniques is constrained by their performance or ease of use. Here we present a simple, broadly applicable, high-throughput 3D bacterial tracking method for use in standard phase contrast microscopy. Bacteria are localized at micron-scale resolution over a range of 350 × 300 × 200 μm by maximizing image cross-correlations between their observed diffraction patterns and a reference library. We demonstrate the applicability of our technique to a range of bacterial species and exploit its high throughput to expose hidden contributions of bacterial individuality to population-level variability in motile behaviour. The simplicity of this powerful new tool for bacterial motility research renders 3D tracking accessible to a wider community and paves the way for investigations of bacterial motility in complex 3D environments.
Omentin-1 plasma levels and cholesterol metabolism in obese patients with diabetes mellitus type 1: impact of weight reduction
Authors: Lesná J , Tichá A , Hyšpler R , Musil F , Bláha V , Sobotka L , Zadák Z , Šmahelová A
Published: November 2015

Background:

Omentin-1 is an anti-inflammatory adipokine produced preferentially by visceral adipose tissue. Plasma levels of omentin-1 are decreased in obesity and other insulin-resistant states. Insulin resistance contributes to the changes of cholesterol synthesis and absorption as well. The aim of this study was to characterise omentin-1 plasma levels in obese patients with diabetes mellitus type 1 during weight reduction, and to elucidate the relationship between cholesterol metabolism and omentin-1.

Methods:

Plasma levels of omentin-1 were measured in obese type 1 diabetics (n=14, body mass index >30 kg m−2, age 29–62 years) by enzyme-linked immunosorbent assay (BioVendor). Gas chromatography with flame ionisation detector (Fisons Plc.,) was used to measure squalene and non-cholesterol sterols—markers of cholesterol synthesis and absorption (phase I). Measurements were repeated after 1 month (phase II; 1 week of fasting in the hospital setting and 3 weeks on a diet containing 150 g saccharides per day) and after 1 year (phase III) on a diet with 225 g saccharides per day.

Results:

Omentin-1 plasma levels were stable during phases I and II, but significantly increased (P<0.001) during phase III. Omentin-1 plasma dynamics were significantly associated with plasma levels of high-density lipoprotein (P=0.005) and triacylglycerols (P=0.01), as well as with lathosterol (P=0.03).

Conclusion:

Omentin-1 plasma levels significantly increased during the weight reduction programme. Omentin-1 plasma dynamics suggest a close relationship with cholesterol metabolism.
Erratum: Comparative transcriptomics reveals key differences in the response to milk oligosaccharides of infant gut-associated bifidobacteria
Authors: Garrido Daniel , Ruiz-Moyano Santiago , Lemay Danielle G. , Sela David A. , German J. Bruce , Mills David A.
Published: November 2015

Breast milk enhances the predominance of Bifidobacterium species in the infant gut, probably due to its large concentration of human milk oligosaccharides (HMO). Here we screened infant-gut isolates of Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum using individual HMO, and compared the global transcriptomes of representative isolates on major HMO by RNA-seq. While B. infantis displayed homogeneous HMO-utilization patterns, B. bifidum were more diverse and some strains did not use fucosyllactose (FL) or sialyllactose (SL). Transcriptomes of B. bifidum SC555 and B. infantis ATCC 15697 showed that utilization of pooled HMO is similar to neutral HMO, while transcriptomes for growth on FL were more similar to lactose than HMO in B. bifidum. Genes linked to HMO-utilization were upregulated by neutral HMO and SL, but not by FL in both species. In contrast, FL induced the expression of alternative gene clusters in B. infantis. Results also suggest that B. bifidum SC555 does not utilize fucose or sialic acid from HMO. Surprisingly, expression of orthologous genes differed between both bifidobacteria even when grown on identical substrates. This study highlights two major strategies found in Bifidobacterium species to process HMO, and presents detailed information on the close relationship between HMO and infant-gut bifidobacteria.
NEFI: Network Extraction From Images
Authors: Dirnberger M. , Kehl T. , Neumann A.
Published: November 2015

Networks are amongst the central building blocks of many systems. Given a graph of a network, methods from graph theory enable a precise investigation of its properties. Software for the analysis of graphs is widely available and has been applied to study various types of networks. In some applications, graph acquisition is relatively simple. However, for many networks data collection relies on images where graph extraction requires domain-specific solutions. Here we introduce NEFI, a tool that extracts graphs from images of networks originating in various domains. Regarding previous work on graph extraction, theoretical results are fully accessible only to an expert audience and ready-to-use implementations for non-experts are rarely available or insufficiently documented. NEFI provides a novel platform allowing practitioners to easily extract graphs from images by combining basic tools from image processing, computer vision and graph theory. Thus, NEFI constitutes an alternative to tedious manual graph extraction and special purpose tools. We anticipate NEFI to enable time-efficient collection of large datasets. The analysis of these novel datasets may open up the possibility to gain new insights into the structure and function of various networks. NEFI is open source and available at http://nefi.mpi-inf.mpg.de.
Doxorubicin-induced necrosis is mediated by poly-(ADP-ribose) polymerase 1 (PARP1) but is independent of p53
Authors: Shin Hyeon-Jun , Kwon Hyuk-Kwon , Lee Jae-Hyeok , Gui Xiangai , Achek Asma , Kim Jae-Ho , Choi Sangdun
Published: November 2015

Necrosis, unregulated cell death, is characterized by plasma membrane rupture as well as nuclear and cellular swelling. However, it has recently been reported that necrosis is a regulated form of cell death mediated by poly-(ADP-ribose) polymerase 1 (PARP1). PARP1 is thought to mediate necrosis by inducing DNA damage, although this remains unconfirmed. In this study, we examined the mechanisms of PARP1-mediated necrosis following doxorubicin (DOX)-induced DNA damage in human kidney proximal tubular (HK-2) cells. DOX initiated DNA damage response (DDR) and upregulated PARP1 and p53 expression, resulting in morphological changes similar to those observed during necrosis. Additionally, DOX induced mitochondrial hyper-activation, as evidenced by increased mitochondrial respiration and cytosolic ATP (cATP) production. However, DOX affected mitochondrial mass. DOX-induced DNA damage, cytosolic reactive oxygen species (cROS) generation and mitochondrial hyper-activation decreased in cells with inhibited PARP1 expression, while generation of nitric oxide (NO) and mitochondrial ROS (mROS) remained unaffected. Moreover, DOX-induced DNA damage, cell cycle changes and oxidative stress were not affected by p53 inhibition. These findings suggest that DNA damage induced necrosis through a PARP1-dependent and p53-independent pathway.
A novel electroporation system for efficient molecular delivery into Chlamydomonas reinhardtii with a 3-dimensional microelectrode
Authors: Kang Seongsu , Kim Kwon-Ho , Kim Yeu-Chun
Published: November 2015

Electroporation is one of the most widely used transfection methods because of its high efficiency and convenience among the various transfection methods. Previous micro-electroporation systems have some drawbacks such as limitations in height and design, time-consuming and an expensive fabrication process due to technical constraints. This study fabricates a three dimensional microelectrode using the 3D printing technique. The interdigitated microstructure consisting of poly lactic acid was injected by a 3D printer and coated with silver and aluminum with a series of dip-coatings. With the same strength of electric field (V cm−1), a higher efficiency for molecular delivery and a higher cellular viability are achieved with the microelectrode than with a standard cuvette. In addition, this study investigates chemicophysical changes such as Joule heating and dissolved metal during electroporation and showed the micro-electroporation system had less chemicophysical changes. It was concluded that the proposed micro-electroporation system will contribute to genetic engineering as a promising delivery tool and this combination of 3D printing and electroporation has many potential applications for diverse designs or systems.
Evolving pneumococcal serotypes and sequence types in relation to high antibiotic stress and conditional pneumococcal immunization
Authors: Su Lin-Hui , Kuo An-Jing , Chia Ju-Hsin , Li Hsin-Chieh , Wu Tsu-Lan , Feng Ye , Chiu Cheng-Hsun
Published: November 2015

In Taiwan, beginning in 2013, the 13-valent pneumococcal conjugate vaccine (PCV13) was provided free of charge to children 2–5 years of age. In 2014, this was extended to children 1–5 years old. During 2012–2014, 953 cases of culture-confirmed pneumococcal disease (CCPD), including 104 invasive pneumococcal disease (IPD), were prospectively identified and analyzed at a 3,700-bed hospital in Taiwan. From 2012 to 2014, the incidence per 10,000 admissions decreased from 26.7 to 20.4 for CCPD (P < 0.001) and from 3.2 to 1.9 for IPD (P < 0.05). Significant reduction of PCV13 serotypes was firstly noted in children in 2013 and extended to both paediatric and adult populations in 2014. Simultaneously, the incidence per 10,000 admissions of non-PCV13 serotypes increased from 6.1 in 2012 to 9.3 in 2014 (P < 0.005). The most prevalent non-PCV13 serotypes were 15A, 15B and 23A, each containing a predominant clone, ST6315A, ST8315B and ST33823A. From 2012 to 2014, isolates with penicillin minimum inhibitory concentrations >2 mg/L decreased from 27.8% to 8.1% (P < 0.001) among all isolates. PCV13 immunization in young children demonstrated an early protective effect in all ages. However, in the elderly, the effect was compromised by an emergence of non-PCV13 serotypes.
Notching early repolarization pattern in inferior leads increases risk of ventricular tachyarrhythmias in patients with acute myocardial infarction: a meta-analysis
Authors: Zhang Zhiwei , Letsas Konstantinos P. , Yang Yajuan , Korantzopoulos Panagiotis , Li Guangping , Yan Gan-Xin , Liu Tong
Published: November 2015

The aim of this of this meta-analysis was to examine the potential association between certain early repolarization (ER) characteristics and ventricular tachyarrhythmias (VTAs) in patients with acute myocardial infarction (AMI). We searched PubMed, Embase and Web of Science databases for records published until December 2014. Of the 658 initially identified records, 7 studies with a total of 1,565 patients (299 with ER and 1,266 without ER) were finally analyzed. Overall, patients with ER displayed a higher risk of VTAs following AMI compared to patients without ER [odds ratio (OR): 3.75, 95% CI: 2.62–5.37, p < 0.00001]. Subgroup analyses showed that the diagnosis of ER prior to AMI onset is a better predictor of VTAs (OR: 5.70, p < 0.00001) compared to those diagnosed after AMI onset (OR: 2.60, p = 0.00001). Remarkably, a notching morphology was a significant predictor of VTAs compared to slurring morphology (OR: 3.85, p = 0.002). Finally, an inferior ER location (OR: 8.85, p < 0.00001) was significantly associated with increased risk of VTAs in AMI patients. In conclusion, our meta-analysis suggests that ER pattern is associated with greater risk of VTAs in patients with AMI. A notched ER pattern located in inferior leads confers the highest risk for VTAs in AMI.
Monocyte-derived extracellular Nampt-dependent biosynthesis of NAD+ protects the heart against pressure overload
Authors: Yano Masamichi , Akazawa Hiroshi , Oka Toru , Yabumoto Chizuru , Kudo-Sakamoto Yoko , Kamo Takehiro , Shimizu Yu , Yagi Hiroki , Naito Atsuhiko T. , Lee Jong-Kook , Suzuki Jun-ichi , Sakata Yasushi , Komuro Issei
Published: November 2015

Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step in the salvage pathway for nicotinamide adenine dinucleotide (NAD+) biosynthesis and thereby regulates the deacetylase activity of sirtuins. Here we show accommodative regulation of myocardial NAD+ by monocyte-derived extracellular Nampt (eNampt), which is essential for hemodynamic compensation to pressure overload. Although intracellular Nampt (iNampt) expression was decreased in pressure-overloaded hearts, myocardial NAD+ concentration and Sirt1 activity were preserved. In contrast, iNampt was up-regulated in spleen and monocytes and circulating eNampt protein and nicotinamide mononucleotide (NMN), a key precursor of NAD+, were significantly increased. Pharmacological inhibition of Nampt by FK866 or depletion of monocytes/macrophages by clodronate liposomes disrupted the homeostatic mechanism of myocardial NAD+ levels and NAD+-dependent Sirt1 activity, leading to susceptibility to cardiomyocyte apoptosis and cardiac decompensation in pressure-overloaded mice. These biochemical and hemodynamic defects were prevented by systemic administration of NMN. Our studies uncover a crucial role of monocyte-derived eNampt in myocardial adaptation to pressure overload and highlight a potential intervention controlling myocardial NAD+ against heart failure.
Knockout crickets for the study of learning and memory: Dopamine receptor Dop1 mediates aversive but not appetitive reinforcement in crickets
Authors: Awata Hiroko , Watanabe Takahito , Hamanaka Yoshitaka , Mito Taro , Noji Sumihare , Mizunami Makoto
Published: November 2015

Elucidation of reinforcement mechanisms in associative learning is an important subject in neuroscience. In mammals, dopamine neurons are thought to play critical roles in mediating both appetitive and aversive reinforcement. Our pharmacological studies suggested that octopamine and dopamine neurons mediate reward and punishment, respectively, in crickets, but recent studies in fruit-flies concluded that dopamine neurons mediates both reward and punishment, via the type 1 dopamine receptor Dop1. To resolve the discrepancy between studies in different insect species, we produced Dop1 knockout crickets using the CRISPR/Cas9 system and found that they are defective in aversive learning with sodium chloride punishment but not appetitive learning with water or sucrose reward. The results suggest that dopamine and octopamine neurons mediate aversive and appetitive reinforcement, respectively, in crickets. We suggest unexpected diversity in neurotransmitters mediating appetitive reinforcement between crickets and fruit-flies, although the neurotransmitter mediating aversive reinforcement is conserved. This study demonstrates usefulness of the CRISPR/Cas9 system for producing knockout animals for the study of learning and memory.
Sampling frequency affects estimates of annual nitrous oxide fluxes
Authors: Barton L. , Wolf B. , Rowlings D. , Scheer C. , Kiese R. , Grace P. , Stefanova K. , Butterbach-Bahl K.
Published: November 2015

Quantifying nitrous oxide (N2O) fluxes, a potent greenhouse gas, from soils is necessary to improve our knowledge of terrestrial N2O losses. Developing universal sampling frequencies for calculating annual N2O fluxes is difficult, as fluxes are renowned for their high temporal variability. We demonstrate daily sampling was largely required to achieve annual N2O fluxes within 10% of the ‘best’ estimate for 28 annual datasets collected from three continents—Australia, Europe and Asia. Decreasing the regularity of measurements either under- or overestimated annual N2O fluxes, with a maximum overestimation of 935%. Measurement frequency was lowered using a sampling strategy based on environmental factors known to affect temporal variability, but still required sampling more than once a week. Consequently, uncertainty in current global terrestrial N2O budgets associated with the upscaling of field-based datasets can be decreased significantly using adequate sampling frequencies.
Farnesylated and methylated KRAS4b: high yield production of protein suitable for biophysical studies of prenylated protein-lipid interactions
Authors: Gillette William K. , Esposito Dominic , Abreu Blanco Maria , Alexander Patrick , Bindu Lakshman , Bittner Cammi , Chertov Oleg , Frank Peter H. , Grose Carissa , Jones Jane E. , Meng Zhaojing , Perkins Shelley , Van Que , Ghirlando Rodolfo , Fivash Matthew , Nissley Dwight V. , McCormick Frank , Holderfield Matthew , Stephen Andrew G.
Published: November 2015

Prenylated proteins play key roles in several human diseases including cancer, atherosclerosis and Alzheimer’s disease. KRAS4b, which is frequently mutated in pancreatic, colon and lung cancers, is processed by farnesylation, proteolytic cleavage and carboxymethylation at the C-terminus. Plasma membrane localization of KRAS4b requires this processing as does KRAS4b-dependent RAF kinase activation. Previous attempts to produce modified KRAS have relied on protein engineering approaches or in vitro farnesylation of bacterially expressed KRAS protein. The proteins produced by these methods do not accurately replicate the mature KRAS protein found in mammalian cells and the protein yield is typically low. We describe a protocol that yields 5–10 mg/L highly purified, farnesylated and methylated KRAS4b from insect cells. Farnesylated and methylated KRAS4b is fully active in hydrolyzing GTP, binds RAF-RBD on lipid Nanodiscs and interacts with the known farnesyl-binding protein PDEδ.
IL-10-producing CD4+ T cells negatively regulate fucosylation of epithelial cells in the gut
Authors: Goto Yoshiyuki , Lamichhane Aayam , Kamioka Mariko , Sato Shintaro , Honda Kenya , Kunisawa Jun , Kiyono Hiroshi
Published: November 2015

Fucosylated glycans on the surface of epithelial cells (ECs) regulate intestinal homeostasis by serving as attachment receptors and a nutrient source for some species of bacteria. We show here that epithelial fucosylation in the ileum is negatively regulated by IL-10-producing CD4+ T cells. The number of fucosylated ECs was increased in the ileum of mice lacking T cells, especially those expressing αβ T cell receptor (TCR), CD4 and IL-10. No such effect was observed in mice lacking B cells. Adoptive transfer of αβTCR+ CD4+ T cells from normal mice, but not IL-10-deficient mice, normalized fucosylation of ECs. These findings suggest that IL-10-producing CD4+ T cells contribute to the maintenance of the function of ECs by regulating their fucosylation.
Bridging the Gap between RF and Optical Patch Antenna Analysis via the Cavity Model
Authors: Unal G. S. , Aksun M. I.
Published: November 2015

Although optical antennas with a variety of shapes and for a variety of applications have been proposed and studied, they are still in their infancy compared to their radio frequency (rf) counterparts. Optical antennas have mainly utilized the geometrical attributes of rf antennas rather than the analysis tools that have been the source of intuition for antenna engineers in rf. This study intends to narrow the gap of experience and intuition in the design of optical patch antennas by introducing an easy-to-understand and easy-to-implement analysis tool in rf, namely, the cavity model, into the optical regime. The importance of this approach is not only its simplicity in understanding and implementation but also its applicability to a broad class of patch antennas and, more importantly, its ability to provide the intuition needed to predict the outcome without going through the trial-and-error simulations with no or little intuitive guidance by the user.
Species, Abundance and Function of Ammonia-oxidizing Archaea in Inland Waters across China
Authors: Zhou Leiliu , Wang Shanyun , Zou Yuxuan , Xia Chao , Zhu Guibing
Published: November 2015

Ammonia oxidation is the first step in nitrification and was thought to be performed solely by specialized bacteria. The discovery of ammonia-oxidizing archaea (AOA) changed this view. We examined the large scale and spatio-temporal occurrence, abundance and role of AOA throughout Chinese inland waters (n = 28). Molecular survey showed that AOA was ubiquitous in inland waters. The existence of AOA in extreme acidic, alkaline, hot, cold, eutrophic and oligotrophic environments expanded the tolerance limits of AOA, especially their known temperature tolerance to −25 °C and substrate load to 42.04 mM. There were spatio-temporal divergences of AOA community structure in inland waters and the diversity of AOA in inland water ecosystems was high with 34 observed species-level operational taxonomic units (OTUs; based on a 15% cutoff) distributed widely in group I.1b, I.1a and I.1a-associated. The abundance of AOA was quite high (8.5 × 104 to 8.5 × 109 copies g−1) and AOA outnumbered ammonia-oxidizing bacteria (AOB) in the inland waters where little human activities were involved. On the whole AOB predominate the ammonia oxidation rate over AOA in inland water ecosystems and AOA play an indispensable role in global nitrogen cycle considering that AOA occupy a broader habitat range than AOB, especially in extreme environments.
Cholesterol induces lipoprotein lipase expression in a tree shrew (Tupaia belangeri chinensis) model of non-alcoholic fatty liver disease
Authors: Zhang Linqiang , Zhang Zhiguo , Li Yunhai , Liao Shasha , Wu Xiaoyun , Chang Qing , Liang Bin
Published: November 2015

Animal models are indispensible to investigate the pathogenesis and treatments of non-alcoholic fatty liver diseases (NAFLD). Altered cholesterol metabolism has been implicated into the pathogenesis of NAFLD. Here, using high fat, cholesterol and cholate diet (HFHC), we generated a novel tree shrew (Tupaia belangeri chinensis) model of NAFLD, which displayed dyslipidemia with increased levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c) and high density lipoprotein-cholesterol (HDL-c), but decreased level of triglycerides (TG). Liver histopathology and genes expression indicated that HFHC diet successfully induced liver steatosis to inflammation and fibrosis progressively within 10 weeks. Moreover, HFHC induced the transcriptional expression of lipoprotein lipase (lpl) in the liver, but repressed the expression of LDL receptor and the endogenous synthesis pathway and excretion of cholesterol. Notably, Poloxamer 407 (P-407) inhibition of LPL improved the severity of steatosis and reduced inflammation. These results illustrated that LPL plays an important role in cholesterol metabolism in NAFLD and the tree shrew may be a valuable animal model for further research into NAFLD.
Deacetylation-mediated interaction of SIRT1-HMGB1 improves survival in a mouse model of endotoxemia
Authors: Hwang Jung Seok , Choi Hyuk Soo , Ham Sun Ah , Yoo Taesik , Lee Won Jin , Paek Kyung Shin , Seo Han Geuk
Published: November 2015

Inflammatory signal-mediated release of high-mobility group box 1 (HMGB1) is a damage-associated molecular pattern or alarmin. The inflammatory functions of HMGB1 have been extensively investigated; however, less is known about the mechanisms controlling HMGB1 release. We show that SIRT1, the human homolog of theSaccharomyces cerevisiaeprotein silent information regulator 2, which is involved in cellular senescence and possibly the response to inflammation, forms a stable complex with HMGB1 in murine macrophage RAW264.7 cells. SIRT1 directly interacted with HMGB1 via its N-terminal lysine residues (28–30) and thereby inhibited HMGB1 release to improve survival in an experimental model of sepsis. By contrast, inflammatory stimuli such as lipopolysaccharide (LPS) and tumor necrosis factor-α promoted HMGB1 release by provoking its dissociation from SIRT1 dependent on acetylation, thereby increasing the association between HMGB1 and chromosome region maintenance 1, leading to HMGB1 translocation.In vivoinfection with wild-type SIRT1 and HMGB1K282930R, a hypo-acetylation mutant, improved survival (85.7%) during endotoxemia more than infection with wild-type SIRT1 and HMGB1-expressing adenovirus, indicating that the acetylation-dependent interaction between HMGB1 and SIRT1 is critical for LPS-induced lethality. Taken together, we propose that SIRT1 forms an anti-inflammatory complex with HMGB1, allowing cells to bypass the response to inflammation.
Chemical-Free Technique to Study the Ultrastructure of Primary Cilium
Authors: Mohieldin Ashraf M. , AbouAlaiwi Wissam A. , Gao Min , Nauli Surya M.
Published: November 2015

A primary cilium is a hair-like structure with a width of approximately 200 nm. Over the past few decades, the main challenge in the study of the ultrastructure of cilia has been the high sensitivity of cilia to chemical fixation, which is required for many imaging techniques. In this report, we demonstrate a combined high-pressure freezing (HPF) and freeze-fracture transmission electron microscopy (FFTEM) technique to examine the ultrastructure of a cilium. Our objective is to develop an optimal high-resolution imaging approach that preserves cilia structures in their best natural form without alteration of cilia morphology by chemical fixation interference. Our results showed that a cilium has a swelling-like structure (termed bulb), which was previously considered a fixation artifact. The intramembrane particles observed via HPF/FFTEM indicated the presence of integral membrane proteins and soluble matrix proteins along the ciliary bulb, which is part of an integral structure within the ciliary membrane. We propose that HPF/FFTEM is an important and more suitable chemical-free method to study the ultrastructure of primary cilia.
Bub1 is required for maintaining cancer stem cells in breast cancer cell lines
Authors: Han Jeong Yoon , Han Yu Kyeong , Park Ga-Young , Kim Sung Dae , Geun Lee Chang
Published: November 2015

Breast cancer is a leading cause of death among women worldwide due to therapeutic resistance and cancer recurrence. Cancer stem cells are believed to be responsible for resistance and recurrence. Many efforts to overcome resistance and recurrence by regulating cancer stem cells are ongoing. Bub1 (Budding uninhibited by benzimidazoles 1) is a mitotic checkpoint serine/threonine kinase that plays an important role in chromosome segregation. Bub1 expression is correlated with a poor clinical prognosis in patients with breast cancer. We identified that depleting Bub1 using shRNAs reduces cancer stem cell potential of the MDA-MB-231 breast cancer cell line, resulting in inhibited formation of xenografts in immunocompromised mice. These results suggest that Bub1 may be associated with cancer stem cell potential and could be a target for developing anti-breast cancer stem cell therapies.
Mid-infrared ultrafast laser pulses induced third harmonic generation in nitrogen molecules on an excited state
Authors: Xie Hongqiang , Li Guihua , Yao Jinping , Chu Wei , Li Ziting , Zeng Bin , Wang Zhanshan , Cheng Ya
Published: November 2015

We report on generation of third harmonic from nitrogen molecules on the excited state with a weak driver laser pulse at a mid-infrared wavelength. The excited nitrogen molecules are generated using a circularly polarized intense femtosecond pulse which produces energetic electrons by photoionization to realize collisional excitation of nitrogen molecules. Furthermore, since the third harmonic is generated using a pump-probe scheme, it enables investigation of the excited-state dynamics of nitrogen molecules produced under different conditions. We also perform a comparative investigation in excited argon atoms, revealing different decay dynamics of the molecules and atoms from the excited states in femtosecond laser induced filaments.
Neither Single nor a Combination of Routine Laboratory Parameters can Discriminate between Gram-positive and Gram-negative Bacteremia
Authors: Ratzinger Franz , Dedeyan Michel , Rammerstorfer Matthias , Perkmann Thomas , Burgmann Heinz , Makristathis Athanasios , Dorffner Georg , Loetsch Felix , Blacky Alexander , Ramharter Michael
Published: November 2015

Adequate early empiric antibiotic therapy is pivotal for the outcome of patients with bloodstream infections. In clinical practice the use of surrogate laboratory parameters is frequently proposed to predict underlying bacterial pathogens; however there is no clear evidence for this assumption. In this study, we investigated the discriminatory capacity of predictive models consisting of routinely available laboratory parameters to predict the presence of Gram-positive or Gram-negative bacteremia. Major machine learning algorithms were screened for their capacity to maximize the area under the receiver operating characteristic curve (ROC-AUC) for discriminating between Gram-positive and Gram-negative cases. Data from 23,765 patients with clinically suspected bacteremia were screened and 1,180 bacteremic patients were included in the study. A relative predominance of Gram-negative bacteremia (54.0%), which was more pronounced in females (59.1%), was observed. The final model achieved 0.675 ROC-AUC resulting in 44.57% sensitivity and 79.75% specificity. Various parameters presented a significant difference between both genders. In gender-specific models, the discriminatory potency was slightly improved. The results of this study do not support the use of surrogate laboratory parameters for predicting classes of causative pathogens. In this patient cohort, gender-specific differences in various laboratory parameters were observed, indicating differences in the host response between genders.
Non-periodic outbreaks of recurrent epidemics and its network modelling
Authors: Zheng Muhua , Wang Chaoqing , Zhou Jie , Zhao Ming , Guan Shuguang , Zou Yong , Liu Zonghua
Published: November 2015

The study of recurrent epidemic outbreaks has been attracting great attention for decades, but its underlying mechanism is still under debate. Based on a large number of real data from different cities, we find that besides the seasonal periodic outbreaks of influenza, there are also non-periodic outbreaks, i.e. non-seasonal or non-annual behaviors. To understand how the non-periodicity shows up, we present a network model of SIRS epidemic with both time-dependent infection rate and a small possibility of persistent epidemic seeds, representing the influences from the larger annual variation of environment and the infection generated spontaneously in nature, respectively. Our numerical simulations reveal that the model can reproduce the non-periodic outbreaks of recurrent epidemics with the main features of real influenza data. Further, we find that the recurrent outbreaks of epidemic depend not only on the infection rate but also on the density of susceptible agents, indicating that they are both the necessary conditions for the recurrent epidemic patterns with non-periodicity. A theoretical analysis based on Markov dynamics is presented to explain the numerical results. This finding may be of significance to the control of recurrent epidemics.
Expression profiling of prostate cancer tissue delineates genes associated with recurrence after prostatectomy
Authors: Mortensen Martin Mørck , Høyer Søren , Lynnerup Anne-Sophie , Ørntoft Torben Falck , Sørensen Karina Dalsgaard , Borre Michael , Dyrskjøt Lars
Published: November 2015

Prostate cancer is a leading cause of cancer death amongst males. The main clinical dilemma in treating prostate cancer is the high number of indolent cases that confer a significant risk of overtreatment. In this study, we have performed gene expression profiling of tumor tissue specimens from 36 patients with prostate cancer to identify transcripts that delineate aggressive and indolent cancer. Key genes were validated using previously published data and by tissue microarray analysis. Two molecular subgroups were identified with a significant overrepresentation of tumors from patients with biochemical recurrence in one of the groups. We successfully validated key transcripts association with recurrence using two publically available datasets totaling 669 patients. Twelve genes were found to be independent predictors of recurrence in multivariate logistical regression analysis. SFRP4 gene expression was consistently up regulated in patients with recurrence in all three datasets. Using an independent cohort of 536 prostate cancer patients we showed SFRP4 expression to be an independent predictor of recurrence after prostatectomy (HR = 1.35; p = 0.009). We identified SFRP4 to be associated with disease recurrence. Prospective studies are needed in order to assess the clinical usefulness of the identified key markers in this study.