bluuebunny/crossref_metadata_2025 huggingface dataset:
Lignin composition is more important than content for maize stem cell wall degradation
Authors: He Yuan , Mouthier Thibaut MB , Kabel Mirjam A , Dijkstra Jan , Hendriks Wouter H , Struik Paul C , Cone John W
Published: August 2017

BACKGROUND

The relationship between the chemical and molecular properties – in particular the (acid detergent) lignin (ADL) content and composition expressed as the ratio between syringyl and guaiacyl compounds (S:G ratio) – of maize stems and in vitro gas production was studied in order to determine which is more important in the degradability of maize stem cell walls in the rumen of ruminants. Different internodes from two contrasting maize cultivars (Ambrosini and Aastar) were harvested during the growing season.

RESULTS

The ADL content decreased with greater internode number within the stem, whereas the ADL content fluctuated during the season for both cultivars. The S:G ratio was lower in younger tissue (greater internode number or earlier harvest date) in both cultivars. For the gas produced between 3 and 20 h, representing the fermentation of cell walls in rumen fluid, a stronger correlation (R2 = 0.80) was found with the S:G ratio than with the ADL content (R2 = 0.68). The relationship between ADL content or S:G ratio and 72‐h gas production, representing total organic matter degradation, was weaker than that with gas produced between 3 and 20 h.

CONCLUSION

The S:G ratio plays a more dominant role than ADL content in maize stem cell wall degradation. © 2017 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Advances in organic–inorganic hybrid sorbents for the extraction of organic and inorganic pollutants in different types of food and environmental samples
Authors: Ng Nyuk‐Ting , Kamaruddin Amirah Farhan , Wan Ibrahim Wan Aini , Sanagi Mohd Marsin , Abdul Keyon Aemi S.
Published: August 2017

The efficiency of the extraction and removal of pollutants from food and the environment has been an important issue in analytical science. By incorporating inorganic species into an organic matrix, a new material known as an organic–inorganic hybrid material is formed. As it possesses high selectivity, permeability, and mechanical and chemical stabilities, organic–inorganic hybrid materials constitute an emerging research field and have become popular to serve as sorbents in various separaton science methods. Here, we review recent significant advances in analytical solid‐phase extraction employing organic–inorganic composite/nanocomposite sorbents for the extraction of organic and inorganic pollutants from various types of food and environmental matrices. The physicochemical characteristics, extraction properties, and analytical performances of sorbents are discussed; including morphology and surface characteristics, types of functional groups, interaction mechanism, selectivity and sensitivity, accuracy, and regeneration abilities. Organic–inorganic hybrid sorbents combined with extraction techniques are highly promising for sample preparation of various food and environmental matrixes with analytes at trace levels.
Adjuvant chemoradiation does not improve survival in elderly patients with high‐risk resected head and neck cancer
Authors: Giacalone Nicholas J. , Qureshi Muhammad M. , Mak Kimberley S. , Kirke Diana , Patel Sagar A. , Shah Bhartesh A. , Salama Andrew R. , Jalisi Scharukh , Truong Minh Tam
Published: August 2017

Objectives/Hypothesis

Randomized trials have demonstrated that adjuvant chemoradiotherapy (CRT) confers an overall survival (OS) benefit over adjuvant radiation therapy (RT) alone in patients with resected head and neck squamous cell carcinoma (HNSCC) with adverse pathologic features (positive surgical margins [SM+] and/or extracapsular extension [ECE]). Whether this OS benefit exists in an elderly population remains unknown.

Study Design

Retrospective database study.

Methods

Using the National Cancer Database, we identified 1,686 elderly patients (age ≥70 years) with resected HNSCC with SM+ and/or ECE, who received adjuvant CRT (491 patients, 29%) or adjuvant RT alone (1,195 patients, 71%) between 1998 and 2011. Three‐year survival rates were estimated using the Kaplan‐Meier method both before and after propensity score matching (PSM). Crude and adjusted hazard ratios (HR) with 95% confidence intervals (CI) were computed using Cox regression modeling.

Results

Median follow‐up was 23.5 and 42.8 months for all and surviving patients, respectively. Three‐year OS was 50.7% and 44.4% among patients receiving adjuvant CRT and RT alone, respectively (P = .002). On multivariate analysis, there was no significant improvement in OS with adjuvant CRT relative to adjuvant RT alone (HR: 0.88, 95% CI: 0.73‐1.06). Similarly, a PSM cohort showed no significant difference in the 3‐year OS for patients receiving adjuvant CRT versus adjuvant RT alone (48.8% and 50.9%, respectively; P = .839).

Conclusions

Although the addition of chemotherapy to adjuvant RT has been proven effective in randomized trials of patients with resected HNSCC with SM+ or ECE, it may be less efficacious in an elderly patient population treated outside of a controlled trial setting.

Level of Evidence

2c. Laryngoscope, 128:831–840, 2018
Corrosion behaviour of 2205 duplex stainless steel in pure cultures of sulphate reducing bacteria: SEM studies, electrochemical characterisation and biochemical analyses
Authors: Dec W. , Jaworska‐Kik M. , Simka W. , Michalska J.
Published: August 2017

The paper presents the results on biofilm formation induced by pure Desulfovibrio desulfuricans strains and its effect on corrosion behaviour of 2205 duplex stainless steel (DSS). Biofilm formation and damage process stimulated by D. desulfuricans strains are analysed with reference to their metabolic activity and to the surface characterisation of structure and configuration of the biofilm. Electrochemical techniques are applied to monitor bacterial attachment to the steel surface and to determine the influence of bacteria on the passivity and corrosion resistance of 2205 DSS. The obtained results prove that 2205 DSS is rapidly colonised by D. desulfuricans and that the biofilms formed affect its corrosion resistance. Bacterial activity leads to the more noble corrosion potential values and to the increased current densities on the potentiodynamic polarisation curves. SEM observations reveal micropits as well as signs of crevice attack on the steel surface.
Characterization of Adsorbed Polymer Layers: Preparation, Determination of the Adsorbed Amount and Investigation of the Kinetics of Irreversible Adsorption
Authors: Nieto Simavilla David , Panagopoulou Anna , Napolitano Simone
Published: August 2017

Irreversibly adsorbed polymer layers represent an intriguing new class of materials with unexpected properties, strongly deviating from what observed in unbounded polymer melts. These extremely thin layers (thickness < few tens of nanometers) are obtained via a short list of successive steps, easily reproducible in a laboratory environment: a polymer melt is placed in contact with an adsorbing substrate and non‐adsorbed chains are washed away by soaking the sample in a good solvent. Importantly, tuning the thickness of the adsorbed layer, an operational parameter equivalent to the number of chains adsorbed on a unit surface, allows modifying the performance of polymer coatings without affecting the interfacial chemistry. Here, after providing an introduction to the kinetics of irreversible adsorption, we discuss on the most commonly used methods to determine the thickness of adsorbed layers. We conclude with a brief perspective on future possible applications of adsorbed layers.
Discounted average degree density metric and new algorithms for the densest subgraph problem
Authors: Yanagisawa Hiroki , Hara Satoshi
Published: August 2017

Detecting the densest subgraph is one of the most important problems in graph mining and has a variety of applications. Although there are many possible metrics for subgraph density, there is no consensus on which density metric we should use. In this article, we suggest a new density metric, the discounted average degree, which has some desirable properties of the subgraph's density. We also show how to obtain an optimum densest subgraph for small graphs with respect to several density metrics, including our new density metric, by using mixed integer programming. Finally, we develop a new heuristic algorithm to quickly obtain a good approximate solution for large graphs. Our computational experiments on real‐world graphs showed that our new heuristic algorithm outperformed other heuristics in terms of the quality of the solutions. © 2017 Wiley Periodicals, Inc. NETWORKS, Vol. 71(1), 3–15 2018
Cucurbituril‐mediated immobilization of fluorescent proteins on supramolecular biomaterials
Authors: Goor Olga J. G. M. , Bosmans Ralph P. G. , Brunsveld Luc , Dankers Patricia Y. W.
Published: August 2017

The reversible introduction of functionality at material surfaces is of interest for the development of functional biomaterials. In particular, the use of supramolecular immobilization strategies facilitates mild reaction and processing conditions, as compared to other covalent analogues. Here, the engineering of multicomponent supramolecular materials, beyond the use of a single supramolecular entity is proposed. Cucurbit[8]uril (Q8) mediated host–guest chemistry is combined with hydrogen bonding supramolecular 2‐ureido‐4‐pyrimidinone (UPy)‐based materials. The modular incorporation of a UPy‐additive that presents one guest to incorporate into the Q8 host allows for selective supramolecular functionalization at the water–polymer material interface. Supramolecular ternary complex formation at the material surface was studied by X‐ray photoelectron spectroscopy, which as a result of large overlap in atomic composition of the different components showed minor changes is surface composition upon complex formation. Surface MALDI‐ToF MS measurements revealed useful insights in the formation of complexes. Protein immobilization was monitored using both fluorescence spectroscopy and quartz crystal microbalance with dissipation monitoring, which successfully demonstrated ternary complex formation. Although proteins could selectively be immobilized onto the surfaces, control of the system's stability remains a challenge as a result of the dynamicity of the host–guest assembly. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3607–3616
Conformational heterogeneity in the Hsp70 chaperone‐substrate ensemble identified from analysis of NMR‐detected titration data
Authors: Sekhar Ashok , Nagesh Jayashree , Rosenzweig Rina , Kay Lewis E.
Published: August 2017

The Hsp70 chaperone system plays a critical role in cellular homeostasis by binding to client protein molecules. We have recently shown by methyl‐TROSY NMR methods that the Escherichia coli Hsp70, DnaK, can form multiple bound complexes with a small client protein, hTRF1. In an effort to characterize the interactions further we report here the results of an NMR‐based titration study of hTRF1 and DnaK, where both molecular components are monitored simultaneously, leading to a binding model. A central finding is the formation of a previously undetected 3:1 hTRF1‐DnaK complex, suggesting that under heat shock conditions, DnaK might be able to protect cytosolic proteins whose net concentrations would exceed that of the chaperone. Moreover, these results provide new insight into the heterogeneous ensemble of complexes formed by DnaK chaperones and further emphasize the unique role of NMR spectroscopy in obtaining information about individual events in a complex binding scheme by exploiting a large number of probes that report uniquely on distinct binding processes.
Analysis of IgG kinetic stability by differential scanning calorimetry, probe fluorescence and light scattering
Authors: Nemergut Michal , Žoldák Gabriel , Schaefer Jonas V. , Kast Florian , Miškovský Pavol , Plückthun Andreas , Sedlák Erik
Published: August 2017

Monoclonal antibodies of the immunoglobulin G (IgG) type have become mainstream therapeutics for the treatment of many life‐threatening diseases. For their successful application in the clinic and a favorable cost‐benefit ratio, the design and formulation of these therapeutic molecules must guarantee long‐term stability for an extended period of time. Accelerated stability studies, e.g., by employing thermal denaturation, have the great potential for enabling high‐throughput screening campaigns to find optimal molecular variants and formulations in a short time. Surprisingly, no validated quantitative analysis of these accelerated studies has been performed yet, which clearly limits their application for predicting IgG stability. Therefore, we have established a quantitative approach for the assessment of the kinetic stability over a broad range of temperatures. To this end, differential scanning calorimetry (DSC) experiments were performed with a model IgG, testing chaotropic formulations and an extended temperature range, and they were subsequently analyzed by our recently developed three‐step sequential model of IgG denaturation, consisting of one reversible and two irreversible steps. A critical comparison of the predictions from this model with data obtained by an orthogonal fluorescence probe method, based on 8‐anilinonaphthalene‐1‐sulfonate binding to partially unfolded states, resulted in very good agreement. In summary, our study highlights the validity of this easy‐to‐perform analysis for reliably assessing the kinetic stability of IgGs, which can support accelerated formulation development of monoclonal antibodies by ranking different formulations as well as by improving colloidal stability models.
Optical Investigation of On‐Surface Synthesized Armchair Graphene Nanoribbons
Authors: Zhao Shen , Borin Barin Gabriela , Rondin Loïc , Raynaud Christophe , Fairbrother Andrew , Dumslaff Tim , Campidelli Stéphane , Müllen Klaus , Narita Akimitsu , Voisin Christophe , Ruffieux Pascal , Fasel Roman , Lauret Jean‐Sébastien
Published: August 2017

On‐surface synthesized N = 9‐armchair graphene nanoribbons (AGNRs) are investigated by Raman spectroscopy and AFM/micro photoluminescence measurements. In order to perform the optical experiments, the AGNR film is transferred on a glass substrate through a non‐membrane method. The Raman spectroscopy shows the radial breathing‐like mode characteristic of the 1D nature of GNRs, proving the efficiency of the transfer method. Then, the results of combined AFM/micro photoluminescence measurements are discussed. First, the observation of high‐order Raman lines suggests the 1D nature of the electron–phonon coupling in GNR, similar to the case of carbon nanotubes. Secondly, the origin of the broad luminescence line is discussed in comparison with the predicted gap energy of the 9‐AGNR. Due to its width and energy range, the emission is interpreted as arising from defect sites, missing phenyl rings for instance, that occur during the synthesis of these specific armchair nanoribbons.
Interaction of solitons on 2‐dimensional branched π‐electron surface of graphene ribbons
Authors: Sendiuk Volodymyr A. , Pavlenko Elena L. , Dmytrenko Oksana P. , Kulish Mykola P. , Viniychuk Oleksandr O. , Prostota Yaroslav O. , Kachkovsky Olexiy D.
Published: August 2017

We have performed quantum‐mechanical study of charge distribution on the carbon atoms of two‐dimensional conjugated system of the model graphene ribbon. The study shows that charges in the quasi‐two dimensional conjugated system of the graphene ribbon are not localized on separate carbon atoms, but form one‐dimensional solitonic charge waves along zig‐zag sides. There are two solitonic charge waves in the dication or dication due to generation of own soliton by each charge; the first soliton in the acene chain is located on one side while the second one is positioned on the opposite side. The shapes of the solitonic waves in the graphene ribbon are similar to ones in one‐dimensional conjugated systems. Similarly, in the ionic two‐dimensional collective systems of π‐electrons two splitted solitonic levels are generated; lengthening of the chain leads to convergence of the levels. The widening of graphene ribbon (y‐expansion of two‐dimensional conjugated system is accompanied with recession of both solitons to outer sides, so amplitudes of the solitons on the inner sides regularly decrease under widening of the model graphene ribbon; the charges on the inner carbon atoms converge to zero.
The cranial morphology, phylogenetic position and biogeography of the upper Permian dicynodontCompsodon helmoedivan Hoepen (Therapsida, Anomodontia)
Authors: Angielczyk Kenneth D. , Kammerer Christian F.
Published: August 2017

Compsodon helmoediis an obscure dicynodont originally described based on a single specimen from the upper Permian of the Karoo Basin. The discovery of three new specimens ofCompsodonfrom the Luangwa Basin of Zambia and two additional specimens from South African museum collections facilitates a reassessment of its cranial morphology and phylogenetic position.Compsodonis diagnosed by an autapomorphic secondary palate morphology: medial depression at anterior end of premaxillary secondary palate; medial anterior palatal ridges absent; lateral anterior palatal ridges prominent and extend to posterior end of secondary palate; Y‐shaped anterior end of posterior median palatal ridge; embayment of palatal rim anterior to caniniform process divided into two depressions by a posteromedially‐trending ridge. Other important characters include the presence of maxillary ‘postcanines’ and a postcaniniform keel; long interpterygoid vacuity; palatine pad smooth and pierced by a foramen; pineal foramen flanked by swollen eminences of parietals; parietals fused and narrowly exposed between broad postorbitals on dorsal surface of skull; and pocket‐like depression on lateral surface of maxilla. Phylogenetic analysis demonstrates thatCompsodonis a member of Emydopoidea, but underscores major outstanding problems in our understanding of Permian dicynodont phylogeny that require further attention. The cranial morphology ofCompsodonconverges on that of cryptodonts likeTropidostoma, and as such represents a unique emydopoid morphotype. The stratigraphic range ofCompsodonprobably spans the upperCistecephalusand lowerDaptocephalusassemblage zones, and its presence in South Africa and Zambia reinforces a pattern of small Permian dicynodonts with wide geographical ranges in southern Gondwana.
The Wnt5a Receptor, Receptor Tyrosine Kinase-Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation
Authors: Dickinson Sally C. , Sutton Catherine A. , Brady Kyla , Salerno Anna , Katopodi Theoni , Williams Rhys L. , West Christopher C. , Evseenko Denis , Wu Ling , Pang Suzanna , Ferro de Godoy Roberta , Goodship Allen E. , Péault Bruno , Blom Ashley W. , Kafienah Wael , Hollander Anthony P.
Published: August 2017

Multipotent mesenchymal stem cells (MSCs) have enormous potential in tissue engineering and regenerative medicine. However, until now, their development for clinical use has been severely limited as they are a mixed population of cells with varying capacities for lineage differentiation and tissue formation. Here, we identify receptor tyrosine kinase-like orphan receptor 2 (ROR2) as a cell surface marker expressed by those MSCs with an enhanced capacity for cartilage formation. We generated clonal human MSC populations with varying capacities for chondrogenesis. ROR2 was identified through screening for upregulated genes in the most chondrogenic clones. When isolated from uncloned populations, ROR2+ve MSCs were significantly more chondrogenic than either ROR2–ve or unfractionated MSCs. In a sheep cartilage-repair model, they produced significantly more defect filling with no loss of cartilage quality compared with controls. ROR2+ve MSCs/perivascular cells were present in developing human cartilage, adult bone marrow, and adipose tissue. Their frequency in bone marrow was significantly lower in patients with osteoarthritis (OA) than in controls. However, after isolation of these cells and their initial expansion in vitro, there was greater ROR2 expression in the population derived from OA patients compared with controls. Furthermore, osteoarthritis-derived MSCs were better able to form cartilage than MSCs from control patients in a tissue engineering assay. We conclude that MSCs expressing high levels of ROR2 provide a defined population capable of predictably enhanced cartilage production.
Impact of Abdominal Wall Hernias and Repair on Patient Quality of Life
Authors: Cherla Deepa V. , Moses Maya L. , Viso Cristina P. , Holihan Julie L. , Flores‐Gonzalez Juan R. , Kao Lillian S. , Ko Tien C. , Liang Mike K.
Published: August 2017

Background

The modified Activities Assessment Scale (AAS) is a 13‐question abdominal wall quality of life (AW‐QOL) survey validated in patients undergoing ventral hernia repair (VHR). No studies have assessed AW‐QOL among individuals without abdominal wall pathology. The minimal clinically important difference (MCID) of the modified AAS and its implications for the threshold at which VHR should be offered also remain unknown. Our objectives were to (1) establish the AW‐QOL of patients with a clinical abdominal wall hernia versus those with no hernia, (2) determine the MCID of the modified AAS, and (3) identify the baseline quality of life (QOL) score at which patients derive little clinical benefit from VHR.

Methods

Patient‐centered outcomes data for all patients presenting to General Surgery and Hernia Clinics October–December 2016 at a single safety‐net institution were collected via a prospective, cross‐sectional observational study design. Primary outcome was QOL measured using the modified AAS. Secondary outcome was the MCID.

Results

Patients with no hernia had modified AAS scores of 81.6 (50.4–94.4), while patients with a clinically apparent hernia had lower modified AAS scores of 31.4 (12.6–58.7) (p < 0.001). The MCID threshold was 7.6 for a “slight” change and 14.9 for “definite” change. Above a modified AAS score of 81, the risk of worsening a patient’s QOL by surgery is higher than the chances of improvement.

Conclusions

VHR can improve 1‐year postsurgical AW‐QOL to levels similar to that of the general population. The MCID of the modified AAS is 7.6 points. Patients with high baseline scores should be counseled about the lack of potential benefit in QOL from elective VHR.
Racial and Ethnic Variation in Health-Related Quality of Life Scores Prior to Prostate Cancer Treatment
Authors: Reading Stephanie R. , Porter Kimberly R. , Slezak Jeffrey M. , Harrison Teresa N. , Gelfond Joy S. , Chien Gary W. , Jacobsen Steven J.
Published: August 2017

Introduction

Many men diagnosed with prostate cancer are concerned with how the disease and its course of treatment could affect their health-related quality of life (HRQOL). To aid in the decision-making process on a course of treatment and to better understand how these treatments can affect HRQOL, knowledge of pretreatment HRQOL is essential.

Aims

To assess the racial and ethnic variations in HRQOL scores in men newly diagnosed with prostate cancer before electing a course of treatment.

Methods

Male members of the Kaiser Permanente of Southern California health plan who were newly diagnosed with prostate cancer completed the five-domain specific Expanded Prostate Index Composite–26 (EPIC-26) HRQOL questionnaire from March 1, 2011 through August 31, 2013 (N = 2,579). Domain scores were compared across racial and ethnic subgroups and multiple logistic regression analyses were used to assess the association after adjusting for sociodemographic and clinical characteristics.

Main Outcome Measures

The five EPIC-26 domain scores (sexual, bowel, hormonal, urinary incontinence, and urinary irritation and obstruction).

Results

Results from the fully adjusted analyses indicated that non-Hispanic black men were more likely to be above the sample median on the sexual (odds ratio [OR] = 1.43, 95% CI = 1.09–1.88), hormonal (OR = 1.35, 95% CI = 1.03–1.77), and urinary irritation and obstruction (OR = 1.34, 95% CI = 1.03–1.74) domains compared with non-Hispanic white men. The Asian or Pacific Islander men were less likely to be above the sample median on the sexual domain (OR = 0.60, 95% CI = 0.44–0.83) compared with non-Hispanic white men. No additional statistically significant differences were identified.

Conclusions

Within an integrated health care organization, we found minimal racial and ethnic differences, aside from sexual function, in pretreatment HRQOL in men newly diagnosed with prostate cancer. These findings provide important insight with which to interpret HRQOL changes in men newly diagnosed with prostate cancer during and after prostate cancer treatment.
Marketing and Pricing Risk in Marine Insurance in Sixteenth-Century Antwerp
Authors: Puttevils Jeroen , Deloof Marc
Published: August 2017

Drawing on a set of insurance contracts brokered in Antwerp in 1562–1563, we demonstrate that by that time Antwerp hosted a sophisticated, large, and international market for marine insurance in which small and large traders could acquire and sell insurance, backed by the intermediation of a large broker, Juan Henriquez who functioned as an open-access institution. Using information from Henriquez's ledgers which was also available to underwriters, we find that insurance premiums reflected the underlying risk and that agents were able to determine the effect of different contract parameters.
European Trade, Colonialism, and Human Capital Accumulation in Senegal, Gambia and Western Mali, 1770–1900
Authors: Cappelli Gabriele , Baten Joerg
Published: August 2017

We trace the development of human capital in today's Senegal, Gambia, and Western Mali between 1770 and 1900. European trade, slavery, and early colonialism were linked to human capital formation, but this connection appears to have been heterogeneous. The contact with the Atlantic slave trade increased regional divergence, as the coast of Senegambia developed more quickly than inner areas. This pattern was affected by French early colonialism and by the reaction of different West African populations to the economic incentives provided by foreign demand for agricultural products. The peanut trade since the mid-nineteenth century further amplified regional economic inequalities.
On-the-Ground Measurements Overestimate Earth’s Albedo
Authors: Shultz David
Published: August 2017

Weather stations can be used to calibrate and validate albedo measurements from satellites, but they fail to account for variability across landscapes, overestimating how reflective our planet is.
Apoptotic resistance of human skin mast cells is mediated by Mcl-1
Authors: Hazzan Tarek , Eberle Jürgen , Worm Margitta , Babina Magda
Published: August 2017

Mast cells (MCs) are major effector cells of allergic reactions and contribute to multiple other pathophysiological processes. MCs are long-lived in the tissue microenvironment, in which they matured, but it remains ill-defined how longevity is established by the natural habitat, as research on human MCs chiefly employs cells generated and expanded in culture. In this study, we report that naturally differentiated skin MCs exhibit substantial resilience to cell death with considerable portions surviving up to 3 days in the complete absence of growth factors (GF). This was evidenced by kinetic resolution of membrane alterations (Annexin-V, YoPro), DNA degradation (propidium iodide), mitochondrial membrane disruption (Depsipher), and Caspase-3 activity. Because of the high basal survival, further protection by SCF was modest. Conversely, survival was severely compromised by staurosporine, implying functional caspase machinery. Contrary to the resistance of freshly purified MCs, their culture-expanded counterpart readily underwent cell death upon GF deprivation. Searching for the molecular underpinnings explaining the difference, we identified Mcl-1 as a critical protector. In fact, silencing Mcl-1 by RNAi led to impaired survival in skin MCs ex vivo, but not their cultured equivalent. Therefore, MCs matured in the skin have not only higher expression of Mcl-1 than proliferating MCs, but also greater reliance on Mcl-1 for their survival. Collectively, we report that human skin MCs display low susceptibility to cell death through vast expression of Mcl-1, which protects from mortality and may contribute to MC longevity in the tissue.
Enriched housing promotes post-stroke functional recovery through astrocytic HMGB1-IL-6-mediated angiogenesis
Authors: Chen Jia-Yi , Yu Yuan , Yuan Yin , Zhang Yu-Jing , Fan Xue-Peng , Yuan Shi-Ying , Zhang Jian-Cheng , Yao Shang-Long
Published: August 2017

Enriched environment (EE) is shown to promote angiogenesis, neurogenesis and functional recovery after ischemic stroke. However, the underlying mechanisms remain unclear. C57BL/6 mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion, after which mice were housed in either standard environment (SE) or EE. Here we found that post-ischemic EE exhibited decreased depression and anxiety-like behavior, and promoted angiogenesis and functional recovery compared to SE mice. EE mice treated with high-mobility group box-1 (HMGB1) inhibitor glycyrrhizin had an increased post-stroke depression and anxiety-like behavior, and the angiogenesis and functional recovery were decreased. HMGB1 and interleukin-6 (IL-6) expression in astrocyte were increased in EE mice. EE mice treated with glycyrrhizin decreased, whereas EE mice treated with recombinant HMGB1 (rHMGB1) increased the levels of IL-6 and p-AKT. Blockade of IL-6 with anti-IL-6-neutralizing antibody in EE mice attenuated EE-mediated angiogenesis and functional recovery. Furthermore, our in vitro data revealed that in primary astrocyte cultures rHMGB1 promoted the expression of IL-6 in activated astrocytes. PI3K/AKT signaling pathway was involved in HMGB1-mediated expression of astrocytic IL-6. Thus, our results reveal a previously uncharacterized property of HMGB1/IL-6 signaling pathway in EE-mediated angiogenesis and functional recovery after ischemic stroke.
Dimerization in tailoring uptake efficacy of the HSV-1 derived membranotropic peptide gH625
Authors: Falanga Annarita , Valiante Salvatore , Galdiero Emilia , Franci Gianluigi , Scudiero Olga , Morelli Giancarlo , Galdiero Stefania
Published: August 2017

gH625 constitutes a promising delivery vehicle for the transport of therapeutic biomacromolecules across membrane barriers. We report an application of multivalency to create a complex nanosystem for delivery and to elucidate the mechanism of peptide-lipid bilayer interactions. Multivalency may offer a route to enhance gH625 cellular uptake as demonstrated by results obtained on dimers of gH625 by fluorescence spectroscopy, circular dichroism, and surface plasmon resonance. Moreover, using both phase contrast and light sheet fluorescence microscopy we were able to characterize and visualize for the first time the fusion of giant unilamellar vesicles caused by a membranotropic peptide.
Cancer-targeted Nucleic Acid Delivery and Quantum Dot Imaging Using EGF Receptor Aptamer-conjugated Lipid Nanoparticles
Authors: Kim Min Woo , Jeong Hwa Yeon , Kang Seong Jae , Choi Moon Jung , You Young Myoung , Im Chan Su , Lee Tae Sup , Song In Ho , Lee Chang Gun , Rhee Ki-Jong , Lee Yeon Kyung , Park Yong Serk
Published: August 2017

Co-application of fluorescent quantum dot nanocrystals and therapeutics has recently become a promising theranostic methodology for cancer treatment. We developed a tumor-targeted lipid nanocarrier that demonstrates notable efficacy in gene delivery as well as tumor bio-imaging. Coupling of aptamer molecules against the EGF receptor (EGFR) to the distal termini of lipid nanoparticles provided the carrier with tumor-specific recognition capability. The cationic lipid component, referred to as O,O’-dimyristyl-N-lysyl glutamate (DMKE), was able to effectively complex with anionic small-interfering RNA (siRNA). The hydrophobic quantum dots (Q-dots) were effectively incorporated in hydrophobic lipid bilayers at an appropriate Q-dot to lipid ratio. In this study, we optimized the liposomal formula of aptamer-conjugated liposomes containing Q-dots and siRNA molecules (Apt-QLs). The anti-EGFR Apt-QLs exhibited remarkable EGFR-dependent siRNA delivery as well as fluorescence imaging, which were analyzed in cultured cancer cells and tumor xenografts in mice. These results imply that the formulation of Apt-QLs could be widely utilized as a carrier for tumor-directed gene delivery and bio-imaging.
Optimal Translation Along a Circular mRNA
Authors: Zarai Yoram , Ovseevich Alexander , Margaliot Michael
Published: August 2017

The ribosome flow model on a ring (RFMR) is a deterministic model for ribosome flow along a circularized mRNA. We derive a new spectral representation for the optimal steady-state production rate and the corresponding optimal steady-state ribosomal density in the RFMR. This representation has several important advantages. First, it provides a simple and numerically stable algorithm for determining the optimal values even in very long rings. Second, it enables efficient computation of the sensitivity of the optimal production rate to small changes in the transition rates along the mRNA. Third, it implies that the optimal steady-state production rate is a strictly concave function of the transition rates. Maximizing the optimal steady-state production rate with respect to the rates under an affine constraint on the rates thus becomes a convex optimization problem that admits a unique solution. This solution can be determined numerically using highly efficient algorithms. This optimization problem is important, for example, when re-engineering heterologous genes in a host organism. We describe the implications of our results to this and other aspects of translation.
A neuropeptide, Substance-P, directly induces tissue-repairing M2 like macrophages by activating the PI3K/Akt/mTOR pathway even in the presence of IFNγ
Authors: Lim Ji Eun , Chung Eunkyung , Son Youngsook
Published: August 2017

Macrophage polarization plays an important role in tissue damage and repair. In this study, we show that Substance-P (SP) can directly induce M2 polarization of inflammatory macrophages. SP induced the differentiation of GM-CSF-differentiated pro-inflammatory macrophages into alternatively activated phagocytic M2 like macrophages (M2SP) through direct activation of the PI3K/Akt/mTOR/S6kinase pathway and induction of Arginase-1, CD163, and CD206, all of which were nullified by pretreatment with the neurokinin-1 receptor (NK-1R) antagonist RP67580 and specific signaling pathway inhibitors. M2SP were distinct from IL-4/IL-13-induced M2a and IL-10-induced M2c subtypes; they did not show STAT activation and exhibited high phagocytic and endothelial adhesive activity. Furthermore, SP had a dominant effect on M2 polarization over Interferon gamma (IFNγ), a potent M1-skewing cytokine, and effectively induced the M2 phenotype in monocytes and the human THP-1 cell line. Finally, adoptively transferred M2SP migrated to a spinal cord injury (SCI) lesion site and improved functional recovery. Collectively, our findings show that SP, a neuropeptide, plays a role as a novel cytokine by inducing tissue-repairing M2SP macrophages and thus may be developed for pharmacological intervention in diseases involving chronic inflammation and acute injury.
An informatics guided classification of miscible and immiscible binary alloy systems
Authors: Zhang R. F. , Kong X. F. , Wang H. T. , Zhang S. H. , Legut D. , Sheng S. H. , Srinivasan S. , Rajan K. , Germann T. C.
Published: August 2017

The classification of miscible and immiscible systems of binary alloys plays a critical role in the design of multicomponent alloys. By mining data from hundreds of experimental phase diagrams, and thousands of thermodynamic data sets from experiments and high-throughput first-principles (HTFP) calculations, we have obtained a comprehensive classification of alloying behavior for 813 binary alloy systems consisting of transition and lanthanide metals. Among several physics-based descriptors, the slightly modified Pettifor chemical scale provides a unique two-dimensional map that divides the miscible and immiscible systems into distinctly clustered regions. Based on an artificial neural network algorithm and elemental similarity, the miscibility of the unknown systems is further predicted and a complete miscibility map is thus obtained. Impressively, the classification by the miscibility map yields a robust validation on the capability of the well-known Miedema’s theory (95% agreement) and shows good agreement with the HTFP method (90% agreement). Our results demonstrate that a state-of-the-art physics-guided data mining can provide an efficient pathway for knowledge discovery in the next generation of materials design.
Solvent Assisted Tuning of Morphology of a Peptide-Perylenediimide Conjugate: Helical Fibers to Nano-Rings and their Differential Semiconductivity
Authors: Ahmed Sahnawaz , Pramanik Bapan , Sankar K. N. Amba , Srivastava Abhinav , Singha Nilotpal , Dowari Payel , Srivastava Arpita , Mohanta Kallol , Debnath Ananya , Das Debapratim
Published: August 2017

Understanding the regulatory factors of self-assembly processes is a necessity in order to modulate the nano-structures and their properties. Here, the self-assembly mechanism of a peptide-perylenediimide (P-1) conjugate in mixed solvent systems of THF/water is studied and the semiconducting properties are correlated with the morphology. In THF, right handed helical fibers are formed while in 10% THF-water, the morphology changes to nano-rings along with a switch in the helicity to left-handed orientation. Experimental results combined with DFT calculations reveal the critical role of thermodynamic and kinetic factors to control these differential self-assembly processes. In THF, P-1 forms right handed helical fibers in a kinetically controlled fashion. In case of 10% THF-water, the initial nucleation of the aggregate is controlled kinetically. Due to differential solubility of the molecule in these two solvents, elongation of the nuclei into fibers is restricted after a critical length leading to the formation of nano-rings which is governed by the thermodynamics. The helical fibers show superior semi-conducting property to the nano-rings as confirmed by conducting-AFM and conventional I-V characteristics.
Retinal cell death dependent reactive proliferative gliosis in the mouse retina
Authors: Sardar Pasha Sheik Pran Babu , Münch Robert , Schäfer Patrick , Oertel Peter , Sykes Alex M. , Zhu Yiqing , Karl Mike O.
Published: August 2017

Neurodegeneration is a common starting point of reactive gliosis, which may have beneficial and detrimental consequences. It remains incompletely understood how distinctive pathologies and cell death processes differentially regulate glial responses. Müller glia (MG) in the retina are a prime model: Neurons are regenerated in some species, but in mammals there may be proliferative disorders and scarring. Here, we investigated the relationship between retinal damage and MG proliferation, which are both induced in a reproducible and temporal order in organotypic culture of EGF-treated mouse retina: Hypothermia pretreatment during eye dissection reduced neuronal cell death and MG proliferation; stab wounds increased both. Combined (but not separate) application of defined cell death signaling pathway inhibitors diminished neuronal cell death and maintained MG mitotically quiescent. The level of neuronal cell death determined MG activity, indicated by extracellular signal-regulated kinase (ERK) phosphorylation, and proliferation, both of which were abolished by EGFR inhibition. Our data suggest that retinal cell death, possibly either by programmed apoptosis or necrosis, primes MG to be able to transduce the EGFR–ERK activity required for cell proliferation. These results imply that cell death signaling pathways are potential targets for future therapies to prevent the proliferative gliosis frequently associated with certain neurodegenerative conditions.
Intrinsic brain connectivity after partial sleep deprivation in young and older adults: results from the Stockholm Sleepy Brain study
Authors: Nilsonne Gustav , Tamm Sandra , Schwarz Johanna , Almeida Rita , Fischer Håkan , Kecklund Göran , Lekander Mats , Fransson Peter , Åkerstedt Torbjörn
Published: August 2017

Sleep deprivation has been reported to affect intrinsic brain connectivity, notably reducing connectivity in the default mode network. Studies to date have however shown inconsistent effects, in many cases lacked monitoring of wakefulness, and largely included young participants. We investigated effects of sleep deprivation on intrinsic brain connectivity in young and older participants. Participants aged 20–30 (final n = 30) and 65–75 (final n = 23) years underwent partial sleep deprivation (3 h sleep) in a cross-over design, with two 8-minutes eyes-open resting state functional magnetic resonance imaging (fMRI) runs in each session, monitored by eye-tracking. We assessed intrinsic brain connectivity using independent components analysis (ICA) as well as seed-region analyses of functional connectivity, and also analysed global signal variability, regional homogeneity, and the amplitude of low-frequency fluctuations. Sleep deprivation caused increased global signal variability. Changes in investigated resting state networks and in regional homogeneity were not statistically significant. Younger participants had higher connectivity in most examined networks, as well as higher regional homogeneity in areas including anterior and posterior cingulate cortex. In conclusion, we found that sleep deprivation caused increased global signal variability, and we speculate that this may be caused by wake-state instability.
Virtual histological assessment of the prenatal life history and age at death of the Upper Paleolithic fetus from Ostuni (Italy)
Authors: Nava Alessia , Coppa Alfredo , Coppola Donato , Mancini Lucia , Dreossi Diego , Zanini Franco , Bernardini Federico , Tuniz Claudio , Bondioli Luca
Published: August 2017

The fetal remains from the Ostuni 1 burial (Italy, ca 27 ka) represent a unique opportunity to explore the prenatal biological parameters, and to reconstruct the possible patho-biography, of a fetus (and its mother) in an Upper Paleolithic context. Phase-contrast synchrotron X-ray microtomography imaging of two deciduous tooth crowns and microfocus CT measurements of the right hemimandible of the Ostuni 1b fetus were performed at the SYRMEP beamline and at the TomoLab station of the Elettra - Sincrotrone laboratory (Trieste, Italy) in order to refine age at death and to report the enamel developmental history and dental tissue volumes for this fetal individual. The virtual histology allowed to estimate the age at death of the fetus at 31–33 gestational weeks. Three severe physiological stress episodes were also identified in the prenatal enamel. These stress episodes occurred during the last two months and half of pregnancy and may relate to the death of both individuals. Compared with modern prenatal standards, Os1b’s skeletal development was advanced. This cautions against the use of modern skeletal and dental references for archaeological finds and emphasizes the need for more studies on prenatal archaeological skeletal samples.
Altered expression of Tumor Necrosis Factor Alpha -Induced Protein 3 correlates with disease severity in Ulcerative Colitis
Authors: Majumdar Ishani , Ahuja Vineet , Paul Jaishree
Published: August 2017

Ulcerative colitis (UC), an inflammatory disorder of the colon arises from dysregulated immune response towards gut microbes. Transcription factor NFκB is a major regulatory component influencing mucosal inflammation. We evaluated expression of Tumor Necrosis Factor Alpha Induced Protein3 (TNFAIP3), the inhibitor of NFκB activation and its associated partners ITCH, RNF11 and Tax1BP1 in inflamed mucosa of UC patients. We found highly significant up-regulated mRNA expression of TNFAIP3 that negatively correlated with disease activity in UC. mRNA levels of ITCH, RNF11 and Tax1BP1 were significantly down-regulated. Significant positive correlation with disease activity was noted for Tax1BP1. All four genes showed significant down-regulation at protein level. mRNA levels of inducers of TNFAIP3 expression, NFκB p65 subunit and MAST3 was determined. There was significant increase in p65 mRNA expression and down-regulated MAST3 expression. This suggested that increase in NFκB expression regulates TNFAIP3 levels. Deficiency of TNFAIP3 expression resulted in significant up-regulation of NFκB p65 sub-unit as well as its downstream genes such as iNOS, an inflammatory marker, inhibitors of apoptosis like cIAP2 and XIAP and mediators of anti-apoptotic signals TRAF1 and TRAF2. Taken together, decreased expression of TNFAIP3 and its partners contribute to inflammation and up-regulation of apoptosis inhibitors that may create microenvironment for colorectal cancer.
A preclinical model for identifying rats at risk of alcohol use disorder
Authors: Jadhav Kshitij S. , Magistretti Pierre J. , Halfon Olivier , Augsburger Marc , Boutrel Benjamin
Published: August 2017

Alcohol use is one of the world’s leading causes of death and disease, although only a small proportion of individuals develop persistent alcohol use disorder (AUD). The identification of vulnerable individuals prior to their chronic intoxication remains of highest importance. We propose here to adapt current methodologies for identifying rats at risk of losing control over alcohol intake by modeling diagnostic criteria for AUD: inability to abstain during a signaled period of reward unavailability, increased motivation assessed in a progressive effortful task and persistent alcohol intake despite aversive foot shocks. Factor analysis showed that these three addiction criteria loaded on one underlying construct indicating that they represent a latent construct of addiction trait. Further, not only vulnerable rats displayed higher ethanol consumption, and higher preference for ethanol over sweetened solutions, but they also exhibited pre-existing higher anxiety as compared to resilient rats. In conclusion, the present preclinical model confirms that development of an addiction trait not only requires prolonged exposure to alcohol, but also depends on endophenotype like anxiety that predispose a minority of individuals to lose control over alcohol consumption.
A Model of Exposure to Extreme Environmental Heat Uncovers the Human Transcriptome to Heat Stress
Authors: Bouchama Abderrezak , Aziz Mohammad Azhar , Mahri Saeed Al , Gabere Musa Nur , Dlamy Meshan Al , Mohammad Sameer , Abbad Mashael Al , Hussein Mohamed
Published: August 2017

The molecular mechanisms by which individuals subjected to environmental heat stress either recover or develop heat-related complications are not well understood. We analysed the changes in blood mononuclear gene expression patterns in human volunteers exposed to extreme heat in a sauna (temperature of 75.7 ± 0.86 °C). Our analysis reveals that expression changes occur rapidly with no significant increase in core temperature and continue to amplify one hour after the end of heat stress. The reprogramed transcriptome was predominantly inhibitory, as more than two-thirds of the expressed genes were suppressed. The differentially expressed genes encoded proteins that function in stress-associated pathways; including proteostasis, energy metabolism, cell growth and proliferation, and cell death, and survival. The transcriptome also included mitochondrial dysfunction, altered protein synthesis, and reduced expression of genes -related to immune function. The findings reveal the human transcriptomic response to heat and highlight changes that might underlie the health outcomes observed during heat waves.