bluuebunny/crossref_metadata_2025 huggingface dataset:
Expending Role of Microsatellite Instability in Diagnosis and Treatment of Colorectal Cancers
Authors: Chang Liisa , Chang Minna , Chang Hanna M. , Chang Fuju
Published: July 2017

Background

Colorectal carcinomas with high-frequency microsatellite instability (MSI-H) account for 15% of all colorectal cancers, including 12% of sporadic cases and 3% of cancers associated with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome, HNPCC). Lynch syndrome is an autosomal dominant hereditary cancer syndrome, caused by germline mutations in mismatch repair genes, including MLH1, MSH2, MSH6 and PMS2.

Methods

Published articles from peer-reviewed journals were obtained from PubMed, Google Scholar and Clinicaltrials.gov. Based on the recent research data, we provide an update on the MSI testing, along with the evolving role of MSI in diagnosis, prognosis and treatment of colorectal cancers.

Results

Studies have led to significant advances in the molecular pathogenesis and clinicopathological characteristics of MSI-H colorectal cancers. Emerging evidence suggests that colorectal cancers with MSI-H show different outcome and treatment response from those with microsatellite stable (MSS) tumors. Therefore, MSI testing is essential not only in the genetic context, but it may also have important prognostic and predictive value of response to chemotherapy and immunotherapy.

Conclusions

Many experts and professional authorities have recommended a universal MSI testing in all individuals newly diagnosed with colorectal cancers.
Fertility Intentions and Residential Relocations
Authors: Vidal Sergi , Huinink Johannes , Feldhaus Michael
Published: July 2017

This research addresses the question of whether fertility intentions (before conception) are associated with residential relocations and the distance of the relocation. We empirically tested this using data from two birth cohorts (aged 24–28 and 34–38 in the first survey wave) of the German Family Panel (pairfam) and event history analysis. Bivariate analyses showed that coupled individuals relocated at a higher rate if they intended to have a(nother) child. We found substantial heterogeneity according to individuals’ age and parental status, particularly for outside-town relocations. Childless individuals of average age at family formation—a highly mobile group—relocated at a lower rate if they intended to have a child. In contrast, older individuals who already had children—the least-mobile group—relocated at a higher rate if they intended to have another child. Multivariate analyses show that these associations are largely due to adjustments in housing and other living conditions. Our results suggest that anticipatory relocations (before conception) to adapt to growing household size are importantly nuanced by the opportunities and rationales of couples to adjust their living conditions over the life course. Our research contributes to the understanding of residential mobility as a by-product of fertility decisions and, more broadly, evidences that intentions matter and need to be considered in the analysis of family life courses.
Devolution of Powers in Sarawak: A Dynamic Process of Redesigning Territorial Governance in a Federal System
Authors: HARDING Andrew
Published: July 2017

This article is based on a case study of the developing process of devolution of powers in Sarawak as an aspect of the operation of cooperative federalism in Malaysia. The argument developed is that devolution can be seen and used in conjunction with and in reinforcement of federalism, rather than being simply an alternative method of decentralizing powers. The study finds that this approach may be more promising than a more confrontational approach based on arguments around the fulfilment of the original federal bargain, and is also potentially more open-ended and creative (a process rather than an event), embracing issues within the federal bargain but also issues that are not dealt with in that bargain. The study is based on a unique opportunity to canvass the views of Sarawak leaders at the iteration of the devolution process.
Randomization Inference with Rainfall Data: Using Historical Weather Patterns for Variance Estimation
Authors: Cooperman Alicia Dailey
Published: July 2017

Many recent papers in political science and economics use rainfall as a strategy to facilitate causal inference. Rainfall shocks are as-if randomly assigned, but the assignment of rainfall by county is highly correlated across space. Since clustered assignment does not occur within well-defined boundaries, it is challenging to estimate the variance of the effect of rainfall on political outcomes. I propose using randomization inference with historical weather patterns from 73 years as potential randomizations. I replicate the influential work on rainfall and voter turnout in presidential elections in the United States by Gomez, Hansford, and Krause (2007) and compare the estimated average treatment effect (ATE) to a sampling distribution of estimates under the sharp null hypothesis of no effect. The alternate randomizations are random draws from national rainfall patterns on election and would-be election days, which preserve the clustering in treatment assignment and eliminate the need to simulate weather patterns or make assumptions about unit boundaries for clustering. I find that the effect of rainfall on turnout is subject to greater sampling variability than previously estimated using conventional standard errors.
Loss of cane and sugar yield resulting from Ceratovacuna lanigera Zehntner damage in cane-growing regions in China
Authors: Li W.F. , Zhang R.Y. , Huang Y.K. , Pu C.H. , Yin J. , Cang X.Y. , Shan H.L. , Wang X.Y. , Luo Z.M.
Published: July 2017

Ceratovacuna lanigera Zehntner is a major leaf pest of sugarcane. Widely distributed, it affects both the yield and quality of sugarcane in China. This study aimed to assess real yield and sugar yield losses, and the effect of C. lanigera damage on emergence of newly planted and ratoon cane under current production levels. Field experiments were carried out from 2014 to 2016 in Yunnan Province China. At maturity, plants were harvested and weighed to determine yield, and the effect on sugarcane quality and sucrose content analyzed. Real yield decreased by average of 46,185 kg hm−2 (range: 37,545–61,845 kg hm−2) in damaged versus undamaged areas, with an average yield loss rate of 35.9% (28.5–45.7%). Juice yield decreased by an average of 3.01% (2.4–4.13%) and sucrose content by 6.38% (5.48–8.16%). Juice brix decreased by an average of 7.66°BX (6.95–9.05°BX) and juice gravity purity by 12.35% (8.43–19.97%). In contrast, the reducing sugar content increased by an average of 1.21% (1.01–1.3%). Emergence rates of newly planted cane decreased by an average of 26.0% (24.7–27.3%). The emergence number of ratoon cane decreased by 66,834 hm2 (57,429–76,238 hm−2) and relative emergence loss rates of ratoon cane decreased by an average of 57.8% (57.6–58.0%). These findings confirm that C. lanigera damage severely affects sugarcane yield and quality in Yunnan Province. The results will help the implementation of effective control measures, thereby supporting sustainable development of the Chinese sugar industry.
Participation and Polemics: Angels from Origen to Augustine
Authors: Ployd Adam
Published: July 2017

When I shared an earlier draft of this article with a colleague who spends much more time in the modern theological world than I do, his reply was simple: “So, angels are a thing? And people want to talk about them?” Angels receive fairly short shrift in most twentieth- and twenty-first-century theology, but in late antique Christianity they certainly were “a thing,” if by “a thing” we mean an essential part of religious discourse, manifest in textual and material sources that testify to the significance of angels in theological speculation, popular piety, and ascetic practice.
Morphological and molecular characterization ofTarantobelus arachnicidagen. n., sp. n. (Nematoda, Rhabditida, Brevibuccidae), a parasitic nematode of tarantulas
Authors: Abolafia J. , Peña-Santiago R.
Published: July 2017

A new genus and new species,Tarantobelus arachnicida, was found in the oral opening of tarantula spiders bred in captivity in Poland. The new species is characterized by having a small body (0.77–0.95 mm long in females and 0.66–0.84 mm in males), cuticle poorly annulated by transverse incisures, lateral field inconspicuous, lips separated with small cuticular flaps topping each lip, stoma panagrolaimoid with gymnostom well developed with robust and refringent rhabdia, pharynx panagrolaimoid with isthmus slightly longer than the basal bulb, intestine with cardiac (anterior) and rectal (posterior) areas with narrower walls. Mature females with intestinal cells including needle crystal packs, excretory pore at isthmus level, female reproductive system panagrolaimoid with post-vulval sac 0.4–0.8 times the length of the corresponding body diameter and having very thick walls, vulva very prominent, female rectum 0.8–1.3 times the length of the anal body diameter, female tail conical with acute tip with phasmids at 58–62% of its length. Male tail conical with long and thin mucro, spicules ventrad bent having rounded manubrium and thick gubernaculum. Description, measurements and illustrations of the new species are provided. Molecular analyses show its relationship withBrevibuccaandCuticonema. On the other hand,Medibullaand its corresponding subfamily Medibullinae, previously in Osstellidae, are transferred to Panagrolaimidae, being Shahnematinae, the junior synonym of Medibullinae.Indocephalobus, recently proposed and located in the family Panagrolaimidae, is considered a junior synonym ofDiplogastrellus(Diplogasteromorpha), and its only species,I. zebrae, is considered a junior synonym ofD. gracilis. In addition, a key to identification of panagrolaimoid genera is included.
Shifts in habitat suitability and the conservation status of the Endangered Andean cat Leopardus jacobita under climate change scenarios
Authors: Bennett Magdalena , Marquet Pablo A. , Sillero-Zubiri Claudio , Marino Jorgelina
Published: July 2017

Organisms adapted to life at high elevations are particularly threatened by climate change, which can cause them to become isolated on mountain tops, yet their responses may vary according to their position in the food chain and their ecological flexibility. Predicting the future distributions of such organisms requires fine-tuned species-specific models. Building on a previous ecological niche model, we explored shifts in the suitability of habitats for the Endangered Andean cat Leopardus jacobita, and assessed how these will be represented within existing protected areas in the future. Using a robust set of presence records and corrected climate surfaces, we applied the Maxent algorithm to model habitat suitability for this carnivore and for its preferred prey, the mountain viscacha Lagidium viscacia. Our predictions indicate that the areas climatically suitable for Andean cats could contract by up to 30% by 2080 under the most pessimistic scenario, with an overall upwards shift of 225 m and a polewards displacement of 98–180 km. The predicted range contraction was more pronounced in the species’ core range, in the Bolivian and Peruvian Andes, whereas suitable conditions may increase in the southern range in Patagonia. Bolivia and Peru are predicted to suffer the most marked decline in habitat representativeness within protected areas. The southern range appears to be less vulnerable to climate change, offering opportunities for the conservation of this genetically distinct population. We discuss the value and limitations of using species distribution modelling to assess changes in the potential distribution and conservation status of this and other Andean species.
BUDGET ALLOCATIONS IN OPERATIONAL RISK MANAGEMENT
Authors: Xu Yuqian , Zhang Jiawei , Pinedo Michael
Published: July 2017

We consider a resource allocation model to analyze investment strategies for financial services firms in order to minimize their operational risk losses. A firm has to decide how much to invest in human resources and in infrastructure (information technology). The operational risk losses are a function of the activity level of the firm, of the amounts invested in personnel and in infrastructure, and of interaction effects between the amounts invested in personnel and infrastructure. We first consider a deterministic setting and show certain monotonicity properties of the optimal investments assuming general loss functions that are convex. We find that because of the interaction effects “economies of scale" may not hold in our setting, in contrast to a typical manufacturing environment. We then consider a general polynomial loss function in a stochastic setting with the number of transactions at the firm being a random variable. We characterize the asymptotic behaviors of the optimal investments in both heavy and light trading environments. We show that when the market is very liquid, that is, it is subject to heavy transaction volumes, it is optimal for a financial firm that is highly risk sensitive to use a balanced investment strategy. Both a heavier right tail of the distribution of transaction volume and a firm's risk sensitivity necessitate larger investments; in a heavy trading environment these two factors reinforce one another. However, in a light trading environment with the transaction volume having a heavy left tail the investment will be independent of the firm's sensitivity to risk.
MULTI-CLASS RESOURCE SHARING WITH PREEMPTIVE PRIORITIES
Authors: Mitrani Isi
Published: July 2017

Different virtual machines can share servers, subject to resource constraints. Incoming jobs whose resource requirements cannot be satisfied are queued and receive service according to a preemptive-resume scheduling policy. The problem is to evaluate a cost function, including holding and server costs, with a view to searching for the optimal number of servers. A model with two job types is analyzed exactly and the results are used to develop accurate approximations, which are then extended to more than two classes. Numerical examples and comparisons with simulations are presented.
Seamless Indoor-Outdoor Navigation based on GNSS, INS and Terrestrial Ranging Techniques
Authors: Jiang Wei , Li Yong , Rizos Chris , Cai Baigen , Shangguan Wei
Published: July 2017

We describe an integrated navigation system based on Global Navigation Satellite Systems (GNSS), an Inertial Navigation System (INS) and terrestrial ranging technologies that can support accurate and seamless indoor-outdoor positioning. To overcome severe multipath disturbance in indoor environments, Locata technology is used in this navigation system. Such a “Locata-augmented” navigation system can operate in different positioning modes in both indoor and outdoor environments. In environments where GNSS is unavailable, e.g. indoors, the proposed system is designed to operate in the Locata/INS “loosely-integrated” mode. On the other hand, in outdoor environments, all GNSS, Locata and INS measurements are available, and all useful information can be fused via a decentralised Federated Kalman filter. To evaluate the proposed system for seamless indoor-outdoor positioning, an indoor-outdoor test was conducted at a metal-clad warehouse. The test results confirmed that the proposed navigation system can provide continuous and reliable position and attitude solutions, with the positioning accuracy being better than five centimetres.
Eocene ungulate mammals from West Antarctica: implications from their fossil record and a new species
Authors: Gelfo Javier N. , López Guillermo M. , Santillana Sergio N.
Published: July 2017

Here we describe a new terrestrial mammal from the Eocene of Seymour Island (Isla Marambio) represented by a lower left third molar and assigned to a new species of Sparnotheriodontidae, an ungulate family with a broad palaeobiogeographical distribution in South America. The specimen was found in the Cucullaea I allomember of the La Meseta Formation, in a new mammalian locality (IAA 2/16).Notiolofos regueroisp. nov. shares a brachyodont, lophoselenodont and bicrescentic molar pattern withN. arquinotiensis, recorded for a stratigraphic sequence of 17.5 Ma in Antarctica. The criteria for the species differentiation are the absence of mesial and labial cingulids, the larger paraconid, the wider talonid basin, the accentuated distal projection of the hypoconulid, the centroconid development and the smaller size. Together with the astrapotherianAntarctodon sobrali, they represent the medium to large terrestrial mammals of the early Eocene Antarctic landscape that was mostly dominated by closed forests ofNothofagus. Dental wear facets and differences in their body mass are inferred and discussed as possible evidence of niche differentiation. Additionally, the presence of land mammals with Patagonian affinities in the Eocene of Antarctica reinforces the Cretaceous–Palaeocene presence of the Weddellian Isthmus, a functional land corridor between Antarctica and South America.
Creeping flow of a Herschel–Bulkley fluid with pressure-dependent material moduli
Authors: FUSI L. , ROSSO F.
Published: July 2017

We model the axisymmetric unidirectional flow of a Herschel–Bulkley fluid with rheological parameters that depend linearly on pressure. Adopting an appropriate scaling, we formulate the mathematical problem in cylindrical geometry exploiting an integral formulation for the momentum equation in the unyielded part. We prove that, under suitable assumptions on the data of the problem, explicit solutions can be determined. In particular, we determine the position of the yield surface together with the pressure and velocity profiles. With the aid of some plots, we finally discuss the dependence of the solution on the physical parameters of the problem.
Materiality and the urban: recent theses in archaeology and material culture and their importance for the study of urban history
Authors: FENNELLY KATHERINE
Published: July 2017

Half a century on from Ivor Noel Hume's reference to archaeology as the ‘handmaiden to history’, historical-period archaeology has come quite a way. From disparate origins, in anthropological approaches to material and rescue archaeology in North America, and industrial and buildings archaeology in Britain and Europe, the sub-discipline has coalesced into a structured approach to the recent past. Hume's comment is often misinterpreted as a critique of archaeology's supposed inferiority to history, yet his comment actually refers to the potential for archaeological material to inform historical narratives, fill in gaps and populate the histories of non-literate peoples with a material culture. Unfortunately, overlap between the two disciplines is still in relatively short supply. In light of the recent material turn in the humanities, however, as well as an increased interest amongst historians and geographers in engaging with material culture, archaeological approaches to artifacts, sites and built heritage are in a strong position to inform methods for examining the historical material environment. Collaboration is now not only necessary, but timely, and this review of theses is an attempt to further that potential for co-operation amongst those who study the past. The doctoral theses reviewed here explore changes and developments in the modern city from a material perspective, evidencing both the breadth of approaches and the potential for research in the arts and archaeological sciences to stimulate new studies across different disciplines.
A NONLINEAR ANALYSIS OF THE REAL EXCHANGE RATE–CONSUMPTION RELATIONSHIP
Authors: Pavlidis Efthymios G. , Paya Ivan , Peel David A.
Published: July 2017

A variety of international macroeconomic models predict a relationship between the real exchange rate and consumption. The empirical evidence in favor of such a relationship is limited, the so-calledBackus and Smith puzzle. In this paper, we extend the analysis to allow for nonlinear dynamics and volatility changes across exchange rate regimes. Our findings suggest that long-run relationships in line with standard international business cycle models do exist for many Organization for Economic Co-operation and Development (OECD) countries. Further, Monte Carlo experiments illustrate that the nonlinear models can generate the Backus and Smith and the exchange rate disconnect puzzles. In this paper, we also contribute to the nonlinear real exchange rate literature by establishing a theoretical relationship between volatility and persistence. In accordance with the theoretical results, our empirical findings suggest that the increase in volatility in the post-Bretton Woods era is associated with relatively fast mean reversion of the real rate toward its equilibrium value.
Professional caregivers' experiences with the Liverpool Care Pathway in dementia: An ethnographic study in a Dutch nursing home
Authors: Lemos Dekker Natashe , Gysels Marjolein , van der Steen Jenny T.
Published: July 2017

Objective:

There are few studies on how professional caregivers apply the Liverpool Care Pathway (LCP) in nursing home care for people with dementia. Further, despite critiques in the United Kingdom, the LCP continues to be used in the Netherlands, while, to the best of our knowledge, no studies have been conducted since its implementation. The purpose of the present study was to analyze professional caregivers' experiences with the LCP in this context.

Method:

This article draws on an ethnographic study. Data collection was based on 4 months of ethnographic fieldwork in 2015 in 11 psychogeriatric units of a nursing home in a rural area of the Netherlands. Data collection included participant observation and 25 semistructured audiotaped interviews with specialist elderly care physicians, nursing staff, and a nurse practitioner.

Results:

We found that professional caregivers appreciate the LCP as a communication tool and as a reminder of care goals. However, the document was deemed too complicated and to cause duplication of work. It was also reported that the LCP did not cover the complexity of care needs that emerge in practice. Actual care needs were prioritized over the LCP, which calls its contribution into question.

Significance of Results:

Overall, the LCP does not match the context of dementia care in the nursing home. While it could be argued that the LCP does not intend to replace good care, its benefits as a reminder and a communication tool need continued consideration in relation to the amount of work it requires as a bureaucratic obligation.
Phenotypic and genotypic richness of denitrifiers revealed by a novel isolation strategy
Authors: Lycus Pawel , Lovise Bøthun Kari , Bergaust Linda , Peele Shapleigh James , Reier Bakken Lars , Frostegård Åsa
Published: July 2017

Present-day knowledge on the regulatory biology of denitrification is based on studies of selected model organisms. These show large variations in their potential contribution to NO2−, NO, and N2O accumulation, attributed to lack of genes coding for denitrification reductases, but also to variations in their transcriptional regulation, as well as to post-transcriptional phenomena. To validate the relevance of these observations, there is a need to study a wider range of denitrifiers. We designed an isolation protocol that identifies all possible combinations of truncated denitrification chains (NO3−/NO2−/NO/N2O/N2). Of 176 isolates from two soils (pH 3.7 and 7.4), 30 were denitrifiers sensu stricto, reducing NO2− to gas, and five capable of N2O reduction only. Altogether, 70 isolates performed at least one reduction step, including two DNRA isolates. Gas kinetics and electron flow calculations revealed that several features with potential impact on N2O production, reported from model organisms, also exist in these novel isolates, including denitrification bet-hedging and control of NO2−/NO/N2O accumulation. Whole genome sequencing confirmed most truncations but also showed that phenotypes cannot be predicted solely from genetic potential. Interestingly, and opposed to the commonly observed inability to reduce N2O under acidic conditions, one isolate identified as Rhodanobacter reduced N2O only at low pH.
Escherichia coli FtsA forms lipid-bound minirings that antagonize lateral interactions between FtsZ protofilaments
Authors: Krupka Marcin , Rowlett Veronica W. , Morado Dustin , Vitrac Heidi , Schoenemann Kara , Liu Jun , Margolin William
Published: July 2017

Most bacteria divide using a protein machine called the divisome that spans the cytoplasmic membrane. Key divisome proteins on the membrane’s cytoplasmic side include tubulin-like FtsZ, which forms GTP-dependent protofilaments, and actin-like FtsA, which tethers FtsZ to the membrane. Here we present genetic evidence that in Escherichia coli, FtsA antagonizes FtsZ protofilament bundling in vivo. We then show that purified FtsA does not form straight polymers on lipid monolayers as expected, but instead assembles into dodecameric minirings, often in hexameric arrays. When coassembled with FtsZ on lipid monolayers, these FtsA minirings appear to guide FtsZ to form long, often parallel, but unbundled protofilaments, whereas a mutant of FtsZ (FtsZ*) with stronger lateral interactions remains bundled. In contrast, a hypermorphic mutant of FtsA (FtsA*) forms mainly arcs instead of minirings and enhances lateral interactions between FtsZ protofilaments. Based on these results, we propose that FtsA antagonizes lateral interactions between FtsZ protofilaments, and that the oligomeric state of FtsA may influence FtsZ higher-order structure and divisome function.
Association between allergic conditions and colorectal cancer risk/mortality: a meta-analysis of prospective studies
Authors: Ma Wangqian , Yang Jia , Li Peiwei , Lu Xinliang , Cai Jianting
Published: July 2017

We aimed to assess the association between allergic conditions and risk/mortality of colorectal cancer (CRC). A systematic literature search was conducted using Pubmed and Embase to identify relevant studies. Prospective studies assessing the association between allergic conditions and risk/mortality of CRC were included. Risk ratios (RRs) were pooled with either a fixed- or a random-effects model according to heterogeneity. A total of 515379 participants and 10345 CRC cases from 12 studies were included in the analysis of CRC risk, while four studies with 1484741 individuals and 30040 CRC deaths were included in the analysis of CRC mortality. The pooled RR for the association between allergic conditions and CRC risk was 0.88 (95% CI 0.83–0.92). The inverse association was observed both in colon cancer (pooled RR = 0.83, 95% CI 0.72–0.97) and rectal cancer (pooled RR = 0.83, 95% CI 0.74–0.93). Moreover, no gender difference was observed in the analysis of CRC risk (for males, pooled RR = 0.88, 95% CI 0.81–0.96; for females, pooled RR = 0.88, 95% CI 0.82–0.95). And allergic conditions were also found to be inversely associated with CRC mortality (pooled RR = 0.88, 95% CI 0.83–0.92). In conclusion, the current meta-analysis provides further evidence that allergic conditions were inversely associated with CRC risk and mortality.
Negative velocity fluctuations and non-equilibrium fluctuation relation for a driven high critical current vortex state
Authors: Bag Biplab , Shaw Gorky , Banerjee S. S. , Majumdar Sayantan , Sood A. K. , Grover A. K.
Published: July 2017

Under the influence of a constant drive the moving vortex state in 2H-NbS2 superconductor exhibits a negative differential resistance (NDR) transition from a steady flow to an immobile state. This state possesses a high depinning current threshold ($${{\boldsymbol{I}}}_{{\boldsymbol{c}}}^{{\boldsymbol{h}}}$$

I

c

h

) with unconventional depinning characteristics. At currents well above $${{\boldsymbol{I}}}_{{\boldsymbol{c}}}^{{\boldsymbol{h}}}$$

I

c

h

, the moving vortex state exhibits a multimodal velocity distribution which is characteristic of vortex flow instabilities in the NDR regime. However at lower currents which are just above $${{\boldsymbol{I}}}_{{\boldsymbol{c}}}^{{\boldsymbol{h}}}$$

I

c

h

, the velocity distribution is non-Gaussian with a tail extending to significant negative velocity values. These unusual negative velocity events correspond to vortices drifting opposite to the driving force direction. We show that this distribution obeys the Gallavotti-Cohen Non-Equilibrium Fluctuation Relation (GC-NEFR). Just above $${{\boldsymbol{I}}}_{{\boldsymbol{c}}}^{{\boldsymbol{h}}}$$

I

c

h

, we also find a high vortex density fluctuating driven state not obeying the conventional GC-NEFR. The GC-NEFR analysis provides a measure of an effective energy scale (E
eff
) associated with the driven vortex state. The E
eff
corresponds to the average energy dissipated by the fluctuating vortex state above $${{\boldsymbol{I}}}_{{\boldsymbol{c}}}^{{\boldsymbol{h}}}$$

I

c

h

. We propose the high E
eff
value corresponds to the onset of high energy dynamic instabilities in this driven vortex state just above $${{\boldsymbol{I}}}_{{\boldsymbol{c}}}^{{\boldsymbol{h}}}$$

I

c

h

.
3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation
Authors: Deng Yuan , Jiang Chuan , Li Cuidi , Li Tao , Peng Mingzheng , Wang Jinwu , Dai Kerong
Published: July 2017

Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.
Torque, but not FliL, regulates mechanosensitive flagellar motor-function
Authors: Chawla Ravi , Ford Katie M. , Lele Pushkar P.
Published: July 2017

The stator-complex in the bacterial flagellar motor is responsible for surface-sensing. It remodels in response to perturbations in viscous loads, recruiting additional stator-units as the load increases. Here, we tested a hypothesis that the amount of torque generated by each stator-unit modulates its association with the rotor. To do this, we measured stator-binding to the rotor in mutants in which motors reportedly develop lower torque compared to wildtype motors. First, we employed a strain lacking fliL. Contrary to earlier reports, measurements indicated that the torque generated by motors in the fliL strain was similar to that in the wildtype, at high loads. In these motors, stator-binding was unchanged. Next, experiments with a paralyzed strain indicated that the stator-binding was measurably weaker when motors were unable to generate torque. An analytical model was developed that incorporated an exponential dependence of the unit’s dissociation rate on the force delivered to the rotor. The model provided accurate fits to measurements of stator-rotor binding over a wide range of loads. Based on these results, we propose that the binding of each stator-unit is enhanced by the force it develops. Furthermore, FliL does not play a significant role in motor function in E. coli.
Cognitive brain responses during circadian wake-promotion: evidence for sleep-pressure-dependent hypothalamic activations
Authors: Reichert Carolin F. , Maire Micheline , Gabel Virginie , Viola Antoine U. , Götz Thomas , Scheffler Klaus , Klarhöfer Markus , Berthomier Christian , Strobel Werner , Phillips Christophe , Salmon Eric , Cajochen Christian , Schmidt Christina
Published: July 2017

The two-process model of sleep-wake regulation posits that sleep-wake-dependent homeostatic processes interact with the circadian timing system to affect human behavior. The circadian timing system is fundamental to maintaining stable cognitive performance, as it counteracts growing homeostatic sleep pressure during daytime. Using magnetic resonance imaging, we explored brain responses underlying working memory performance during the time of maximal circadian wake-promotion under varying sleep pressure conditions. Circadian wake-promoting strength was derived from the ability to sleep during an evening nap. Hypothalamic BOLD activity was positively linked to circadian wake-promoting strength under normal, but not under disproportionally high or low sleep pressure levels. Furthermore, higher hypothalamic activity under normal sleep pressure levels predicted better performance under sleep loss. Our results reappraise the two-process model by revealing a homeostatic-dose-dependent association between circadian wake-promotion and cognition-related hypothalamic activity.
Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery
Authors: Yu-Wai-Man Cynthia , Owen Nicholas , Lees Jonathan , Tagalakis Aristides D. , Hart Stephen L. , Webster Andrew R. , Orengo Christine A. , Khaw Peng T.
Published: July 2017

Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibrotic and 7 non-fibrotic conjunctival fibroblast cell lines from patients with and without previous glaucoma surgery, respectively. The patients were matched for ethnicity and age. We identified 246 genes that were differentially expressed by over two-fold and p < 0.05, of which 46 genes were upregulated and 200 genes were downregulated in the fibrotic cell lines compared to the non-fibrotic cell lines. We also carried out detailed gene ontology, KEGG, disease association, pathway commons, WikiPathways and protein network analyses, and identified distinct pathways linked to smooth muscle contraction, inflammatory cytokines, immune mediators, extracellular matrix proteins and oncogene expression. We further validated 11 genes that were highly upregulated or downregulated using real-time quantitative PCR and found a strong correlation between the RNA-Seq and qPCR results. Our study demonstrates that there is a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery and provides new insights into the mechanistic pathways driving the complex fibrotic process in the eye and other tissues.
Magnetic anisotropy control by applying an electric field to the side surface of ferromagnetic films
Authors: Terada Hiroshi , Ohya Shinobu , Anh Le Duc , Iwasa Yoshihiro , Tanaka Masaaki
Published: July 2017

Reducing the power consumption necessary for magnetization reversal is one of the most crucial issues facing spintronics devices. Electric field control of the magnetic anisotropy of ferromagnetic thin films is a promising method to solve this problem. However, the electric field is believed to be effective only within several nanometres of the surface in ferromagnetic metals because of its short Thomas-Fermi screening length, which prevents its practical application to devices. Herein, we successfully modulate the magnetic anisotropy of the entire region of the ferromagnetic layers in the elongated mesas of vertical spin field-effect transistors with widths as large as ~500 nm by applying an electric field to the side surface of the metallic GaMnAs-based mesas through an electric double layer. Our results will open up a new pathway for spintronics devices with ultra-low power consumption.
Cellular uptake pathways of sepiolite nanofibers and DNA transfection improvement
Authors: Castro-Smirnov Fidel Antonio , Ayache Jeanne , Bertrand Jean-Rémi , Dardillac Elodie , Le Cam Eric , Piétrement Olivier , Aranda Pilar , Ruiz-Hitzky Eduardo , Lopez Bernard S.
Published: July 2017

Sepiolite is a nanofibrous natural silicate that can be used as a nanocarrier because it can be naturally internalized into mammalian cells, due to its nano-size dimension. Therefore, deciphering the mechanisms of sepiolite cell internalization constitutes a question interesting biotechnology, for the use of sepiolite as nanocarrier, as well as environmental and public health concerns. Though it is low, the perfectly stable and natural intrinsic fluorescence of sepiolite nanofibers allows to follow their fate into cells by specifically sensitive technics. By combining fluorescence microscopy (including confocal analysis), time-lapse video microscopy, fluorescence activated cell sorting and transmission electron microscopy, we show that sepiolite can be spontaneously internalized into mammalian cells through both non-endocytic and endocytic pathways, macropinocytosis being one of the main pathways. Interestingly, exposure of the cells to endocytosis inhibitors, such as chloroquine, two-fold increase the efficiency of sepiolite-mediated gene transfer, in addition to the 100-fold increased resulting from sepiolite sonomechanical treatment. As sepiolite is able to bind various biological molecules, this nanoparticulate silicate could be a good candidate as a nanocarrier for simultaneous vectorization of diverse biological molecules.
Investigation of the Changes in the Power Distribution in Resting-State Brain Networks Associated with Pure Conduct Disorder
Authors: Zhang Jiang , Zhou Jiansong , Lu Fengmei , Chen Liangyin , Huang Yunzhi , Chen Huafu , Xiang Yutao , Yang Gang , Yuan Zhen
Published: July 2017

Conduct disorder (CD) is a psychiatric disorder in children and adolescence. To investigate changes in the power distribution in brain networks between CD and typically developing (TD) groups, resting-state functional magnetic resonance imaging (rsfMRI) data of thirty-six subjects were first recorded, and then the data were preprocessed using DPARSF and SPM8. Meanwhile, the power of the blood oxygenation level-dependent (BOLD) signals of ninety brain regions was acquired using the integral of the Welch power spectral density (PSD). Additionally, the powers of the brain regions that reached significance (p < 0.05) were extracted using the bootstrap statistics, in which the standardized z-scores of the powers were used as a reference. The results of the analysis of the changes in power exhibited that there were significant power differences in some pairs of brain regions between the CD and TD groups, indicating a change in the power distribution. In addition, the results also suggest that the total power consumption of brain networks in CD patients is less than that observed in the TD group. Consequently, the study provided a paradigm for establishing quantifiable indicators via the power spectrum approach for the comparison and analysis of the BOLD signal power between CD patients and healthy controls.
Transcriptome Analysis of Rice Seedling Roots in Response to Potassium Deficiency
Authors: Zhang Xiaoqin , Jiang Hua , Wang Hua , Cui Jun , Wang Jiahui , Hu Jiang , Guo Longbiao , Qian Qian , Xue Dawei
Published: July 2017

Rice is one of the most important food crops in the world, and its growth, development, yield, and grain quality are susceptible to a deficiency of the macronutrient potassium (K+). The molecular mechanism for K+deficiency tolerance remains poorly understood. In this study, K+deficient conditions were employed to investigate the resulting changes in the transcriptome of rice seedling roots. Using ribonucleic acid sequencing (RNA-Seq) and analysis, a total of 805 differentially expressed genes were obtained, of which 536 genes were upregulated and 269 were downregulated. Gene functional classification showed that the expression of genes involved in nutrient transport, protein kinases, transcription processes, and plant hormones were particularly altered in the roots. Although these changes were significant, the expression of most genes remained constant even in K+-deficient conditions. Interestingly, when our RNA-Seq results were compared to public microarray data, we found that most of the genes that were differentially expressed in low K+conditions also exhibited changes in expression in other environmental stress conditions.
Plk1 phosphorylation of CAP-H2 triggers chromosome condensation by condensin II at the early phase of mitosis
Authors: Kagami Yuya , Ono Masaya , Yoshida Kiyotsugu
Published: July 2017

Condensin complexes play crucial roles in chromosome condensation that is a fundamental process to establish the “rod-like” shape of chromosome structure in mitosis. Failure of the chromosome assembly causes chromosome segregation errors and subsequent genomic instability. However, a molecular mechanism that controls condensin function for the chromosomal organization has not been fully understood. Here, we show that the abundance of CAP-H2, one of the condensin II subunits, is fluctuated during the cell cycle in accordance with Plk1 kinase activity. Inhibition of Plk1 leads to Cdc20-mediated degradation of CAP-H2 in mitosis. Plk1 phosphorylation of CAP-H2 at Ser288 is required for the accumulation of CAP-H2 and accurate chromosomal condensation during prophase. These findings suggest that Plk1 phosphorylation regulates condensin II function by modulating CAP-H2 expression levels to facilitate proper mitotic chromosome organization.
Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab
Authors: Lee Hyun Tae , Lee Ju Yeon , Lim Heejin , Lee Sang Hyung , Moon Yu Jeong , Pyo Hyo Jeong , Ryu Seong Eon , Shin Woori , Heo Yong-Seok
Published: July 2017

In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents. Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 antibodies provides a better understanding of the mechanism of PD-L1 blockade as well as new insights into the rational design of improved anti-PD-L1 therapeutics.
CDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson’s disease model
Authors: Jiao Feng-Juan , Wang Qing-Zhi , Zhang Pei , Yan Jian-Guo , Zhang Zheng , He Feng , Zhang Qian , Lv Ze-Xi , Peng Xiang , Cai Hong-Wei , Tian Bo
Published: July 2017

Parkinson’s disease (PD) is an irreversible and progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta. Growing evidence indicates that endoplasmic reticulum stress is a hallmark of PD; however, its exact contribution to the disease process remains poorly understood. Here, we used molecular biology methods and RNA-Seq analysis to explored an unexpected role of spliced X-Box binding protein 1 (XBP1s) in the nervous system. In this study, we determined that the IRE1α/XBP1 pathway is activated in MPP+-treated neurons. Furthermore, XBP1s was identified as a substrate of CDK5 and that the phosphorylation of XBP1s at the Ser61 residue enhances its nuclear migration, whereas mutation of the residue to alanine substantially reduces its nuclear translocation and activity. Importantly, phosphorylated XBP1s acts as a nuclear transcription factor for multiple target genes, including metabolic-related genes, FosB, and non-coding RNAs. Our findings confirm that the IRE1α/XBP1 pathway is activated in PD, and reveal a novel role of XBP1s in the pathogenesis of PD. This pathway may be a new therapeutic strategy for PD.
Elemental compositions of lichens from Duolun County, Inner Mongolia, China: Origin, road effect and species difference
Authors: Liu Hua-Jie , Wang Jing-Gong , Xia Yu , Yang Meng-Jie , Liu Si-Wa , Zhao Liang-Cheng , Guo Xiu-Ping , Jiang Yun-Jun , Li Xin , Wu Qing-Feng , Fang Shi-Bo
Published: July 2017

To assess the response of lichen elemental compositions to road traffic and species difference in the context of high dust input and anthropogenic emissions, two foliose epiphytic lichens (Phaeophyscia hirtuosa, PHh; Candelaria fibrosa, CAf) were sampled near a road adjacent to Dolon Nor Town (Duolun County, Inner Mongolia, China). Twenty elements (Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, P, Pb, Sb, Sr, Ti, V and Zn) in lichen and surface soil samples were analysed using inductively coupled plasma mass spectrometer (ICP-MS). The results demonstrate that lichen elemental compositions are highly influenced by both their natural environment and anthropogenic input. Windblown dust associated with sand dunes and degraded/desertified steppes represents the predominant source of lichen elements. Road traffic can enhance the lichen elemental burden by increasing the number of soil particles. Anthropogenic emissions from the town and road traffic have also led to the enrichment of Cd and Zn in lichens. PHh was higher than CAf in concentrations of 14 terrigenous metals. Both lichens are applicable to biomonitoring of atmospheric element deposition and, in most cases, yield comparable results.
Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine
Authors: Aladegbami Bola , Barron Lauren , Bao James , Colasanti Jason , Erwin Christopher R. , Warner Brad W. , Guo Jun
Published: July 2017

Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished. After massive small bowel resection, tuft cells and Tm were diminished due to the diet used postoperatively. The elimination of Tm and subsequent re-infection of mice with Tm led to type 2 immune response only in WT, but Tm colonization in both WT and Raptor deficient mice. When intestinal organoids were stimulated with IL-4, tuft cells and IL-25 were induced in both WT and Raptor deficient organoids. In summary, our study reveals that enterocyte specific Raptor is required for initiating a type 2 immune response which appears to function through the regulation of mTORC1 activity.