bluuebunny/crossref_metadata_2025 huggingface dataset:
Accumulation of Flavonoid Glycosides and UFGT Gene Expression in Mulberry Leaves (Morus alba L.) before and after Frost
Authors: Yu Xiaofeng , Zhu Yiling , Fan Jingyi , Wang Dujun , Gong Xiaohui , Ouyang Zhen
Published: March 2017

In order to determine the molecular mechanism underlying the influence of frost on chemical changes in mulberry leaves, the UFGT activity, expression level, and accumulation of flavonoid glycosides in mulberry leaves (Morus alba L.) were studied. The expression of UFGT gene was investigated by quantitative real‐time PCR (qRT‐PCR) and the UFGT activity, accumulation of flavonoid glycosides was studied by high performance liquid chromatography. Then, the correlation between the expression level of UFGT, the UFGT activity, and the flavonoid glycosides accumulation with temperature was explored. The accumulation of isoquercitrin and astragalin is significantly positively correlated with UFGT gene expression and UFGT activity. On the contrary, the average temperature was significantly negatively correlated with the level of UFGT gene expression and UFGT activity. The results show that after frost, low temperature can induce the expression of UFGT gene in mulberry leaves, resulting in the accumulation of flavonoid glycosides.
Chemical Composition, Antibacterial, Antibiofilm and Synergistic Properties of Essential Oils from Eucalyptus globulus Labill. and Seven Mediterranean Aromatic Plants
Authors: Vieira Maria , Bessa Lucinda J. , Martins M. Rosário , Arantes Sílvia , Teixeira António P. S. , Mendes Ângelo , Martins da Costa Paulo , Belo Anabela D. F.
Published: March 2017

Essential oils (EOs) from Eucalyptus globulus Labill. ssp. globulus and from Mediterranean autochthonous aromatic plants – Thymus mastichina L., Mentha pulegium L., Rosmarinus officinalis L., Calamintha nepeta (L.) Savi ssp. nepeta, Cistus ladanifer L., Foeniculum vulgare L., Dittrichia viscosa (L.) Greuter ssp. viscosa – were extracted by hydrodistillation and characterized by GC‐FID and NMR spectroscopy. EOs were evaluated for antimicrobial properties against several bacterial strains, using diverse methods, namely, the agar disc‐diffusion method, the microdilution method, the crystal violet assay and the Live/Dead staining for assessment of biofilm formation. Potential synergy was assessed by a checkerboard method. EOs of R. officinalis and C. ladanifer showed a predominance in monoterpene hydrocarbons (> 60%); EOs of C. nepeta, M. pulegium, T. mastichina, E. globulus and F. vulgare were rich in oxygenated monoterpenes (62 – 96%) whereas EO of D. viscosa was mainly composed of oxygenated sesquiterpenes (54%). All EOs showed antimicrobial activity; M. pulegium and E. globulus generally had the strongest antimicrobial activity. EO of C. nepeta was the most promising in hampering the biofilm formation. The combinations D. viscosa/C. nepeta and E. globulus/T. mastichina were synergistic against Staphylococcus aureus. These results support the notion that EOs from the aromatic plants herein reported should be further explored as potential pharmaceuticals and/or food preservatives.
A Fungal N‐Dimethylallyltryptophan Metabolite from Fusarium fujikuroi
Authors: Arndt Birgit , Janevska Slavica , Schmid Robin , Hübner Florian , Tudzynski Bettina , Humpf Hans‐Ulrich
Published: March 2017

The range of secondary metabolites (SMs) produced by the rice pathogen Fusarium fujikuroi is quite broad. Several polyketides, nonribosomal peptides and terpenes have been identified. However, no products of dimethylallyltryptophan synthases (DMATSs) have been elucidated, although two putative DMATS genes are present in the F. fujikuroi genome. In this study, the in vivo product derived from one of the DMATSs (DMATS1, FFUJ_09179) was identified with the help of the software MZmine 2. Detailed structure elucidation showed that this metabolite is a reversely N‐prenylated tryptophan with a rare form of prenylation. Further identified products probably resulted from side reactions of DMATS1. The genes adjacent to DMATS1 were analyzed; this showed no influence on the biosynthesis of the product.
Prevalence and clinical significance of left bundle branch block according to classical or strict definition criteria in permanent pacemaker patients
Authors: Mazza Andrea , Bendini Maria Grazia , De Cristofaro Raffaele , Lovecchio Mariolina , Valsecchi Sergio , Leggio Massimo , Boriani Giuseppe
Published: March 2017

Background

Previous studies have shown that the presence of left bundle branch block (LBBB) is associated with an increased risk of cardiac mortality and heart failure (HF). Recently, new criteria to define strict LBBB have been proposed: QRS duration ≥140 ms for men and ≥130 ms for women, along with mid‐QRS notching or slurring in ≥2 contiguous leads.

Hypothesis

We assessed the prevalence and prognostic significance of LBBB according to classical (QRS duration ≥120ms) and strict criteria in permanent pacemaker patients.

Methods

We retrospectively enrolled 723 consecutive patients who had undergone single‐ or dual‐chamber pacemaker implantation at the study center from July 2002 to December 2014. Patients with a left ventricular ejection fraction ≤35% or a prior diagnosis of HF were excluded.

Results

LBBB was reported in 54 (7%) patients, and strict‐LBBB in 15 (2%) patients. During a median follow‐up of 48 months (range, 18–92 months), 147 (20%) patients reached the combined endpoint of death or HF hospitalization. Patients with LBBB and those with strict‐LBBB displayed significantly higher rates of death or HF hospitalization (log‐rank test, all P < 0.0001). In particular, strict‐LBBB was associated with the worst outcome. The presence of LBBB according to classical definition criteria (hazard ratio [HR] = 1.98, confidence interval [CI]: 1.23‐3.19, P = 0.005) and to strict criteria (HR = 2.20; CI: 1.04‐4.65; P = 0.039) were both confirmed as independent predictors of death or HF hospitalization after adjustment for relevant clinical covariates.

Conclusions

Among patients who had undergone standard pacemaker implantation, the prevalence of LBBB was 7% according to classical definition criteria and 2% according to strict criteria. The presence of LBBB, and particularly of strict‐LBBB, at the baseline predicted a poor outcome in terms of death or HF hospitalization.
Alcohol and cardiovascular disease in the geriatric population
Authors: Kalla Aditi , Figueredo Vincent M.
Published: March 2017

There has been little focus on the effects of alcohol on the elderly. Although the cardiovascular benefits of moderate alcohol consumption could be of the greatest benefit in this group, so might be the detrimental effects of abuse. In this article, we review available data on the effects of alcohol consumption on cardiovascular disease, cardiomyopathy, arrhythmias, hypertension, and vascular function in older adults. Alcohol consumption has increased in the US population age 65 years and older in the last decade, as has monthly heavy episodic drinking in older alcohol consumers. Studies of alcohol consumption in older subjects suggest that consumption in moderation does not increase the risk of heart failure, hypertension, or atrial arrhythmias, and may in fact improve vascular function and reduce cardiovascular disease events. As in younger subjects, heavy consumption, or abuse of alcohol, negates any potential protective cardiovascular effects, increasing the incidence of heart failure and hypertension. Although alcohol consumed in moderation does not appear harmful in the elderly population, heavier consumption exacerbates hypertension and increases the incidence of heart failure.
Urinary [TIMP‐2] × [IGFBP7] for risk prediction of acute kidney injury in decompensated heart failure
Authors: Schanz Moritz , Shi Jing , Wasser Christoph , Alscher Mark Dominik , Kimmel Martin
Published: March 2017

Background

In acute decompensated heart failure (ADHF) the risk of acute kidney injury (AKI) is high. Early detection of patients at risk for AKI is important. We tested urinary [TIMP‐2] × [IGFBP7], a new US Food and Drug Administration–cleared test to assess AKI risk, in a cohort of hospitalized ADHF patients.

Hypothesis

In patients with ADHF, urinary [TIMP‐2] × [IGFBP7] is associated with moderate to severe AKI and related to increased mortality.

Methods

We enrolled 400 patients in the emergency department at Robert‐Bosch Hospital, Stuttgart, Germany. We examined the predictive ability of urinary [TIMP‐2] × [IGFBP7] (units: [ng/mL]2/1000) for development of AKI stage 2 or 3 within 24 hours of sample collection in patients with ADHF. Operating characteristics were determined for the validated cutoffs of 0.3 and 2.0.

Results

Forty patients had ADHF upon presentation and sufficient data for AKI staging. 27.5% developed AKI stage 2–3 within 7 days. Urinary [TIMP‐2] × [IGFBP7] discriminated for AKI stage 2–3 over the first day with an area under the ROC curve of 0.84 (95% confidence interval: 0.72‐0.93) and over 7 days with an AUC of 0.77 (95% confidence interval: 0.65‐0.88). For the first day, sensitivity was 86% at the 0.3 cutoff and specificity was 95% at the 2.0 cutoff for prediction of AKI stage 2–3. There was a trend (P = 0.08) for higher mortality in patients with urinary [TIMP‐2] × [IGFBP7] >2.0 and AKI 2–3.

Conclusions

Urinary [TIMP‐2] × [IGFBP7] is a promising marker for AKI risk assessment in patients with ADHF.
The role of thyroid hormones in acute coronary syndromes: Prognostic value of alterations in thyroid hormones
Authors: Lamprou Vasileios , Varvarousis Dimitrios , Polytarchou Kali , Varvarousi Giolanda , Xanthos Theodoros
Published: March 2017

The prognosis of acute coronary syndromes (ACS) is affected by many factors. Normal thyroid homeostasis is known to alter during various critical illnesses, a condition that has been shown to correlate with the severity of the disease and increased mortality. The purpose of this article is to review literature to emphasize the considerable association of thyroid function with the cardiovascular system and summarize all existing evidence with regard to the role of thyroid hormones alterations duringACS. The electronic databases ofPubMed, Medline, Scopus, and Cochrane were searched for relevant literature and studies. Alterations in thyroid hormone plasma concentrations, especially low triiodothyronine (T3) levels, represent a hormonal imbalance that is not uncommon among patients suffering an acute coronary event. Many studies have identified this abnormal thyroid hormonal status to be related to worse prognosis. Although further large‐scale clinical trials are needed, the lowT3syndrome manifesting in patients duringACSmight be useful in prognostic stratification.
REGOSARC: Regorafenib versus placebo in doxorubicin‐refractory soft‐tissue sarcoma—A quality‐adjusted time without symptoms of progression or toxicity analysis
Authors: Berry Vincent , Basson Laurent , Bogart Emilie , Mir Olivier , Blay Jean‐Yves , Italiano Antoine , Bertucci François , Chevreau Christine , Clisant‐Delaine Stéphanie , Liegl‐Antzager Bernadette , Tresch‐Bruneel Emmanuelle , Wallet Jennifer , Taieb Sophie , Decoupigny Emilie , Le Cesne Axel , Brodowicz Thomas , Penel Nicolas
Published: March 2017

BACKGROUND

In a placebo‐controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression‐free survival (PFS) for patients with doxorubicin‐pretreated advanced nonadipocytic sarcoma. A quality‐adjusted time without symptoms of progression or toxicity (Q‐TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit.

METHODS

In the base‐case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse. The time spent in each state was weighted with a health‐state utility associated with that state and was summed to calculate the Q‐TWiST. The stability of the base‐case analysis was explored with several sensitivity analyses.

RESULTS

In nonadipocytic sarcoma, the PFS was (4.0 months [2.6‐5.5 months] with regorafenib vs 1.0 month [0.9‐1.8 months] with a placebo; hazard ratio, 0.36 [0.25‐0.53]; P < .0001); the OS was 13.4 months (8.6‐17.3 months) with regorafenib and 9.0 months (6.8‐12.5 months) with a placebo (hazard ratio, 0.67 [0.44‐1.02]). With the classic definition of TOX (including all grade 3 and 4 clinical adverse events), the Q‐TWiSTs were 8.0 months (7.0‐9.0 months) with regorafenib and 5.7 months (4.9‐6.4 months) with a placebo (P < .001).

CONCLUSIONS

For patients with doxorubicin‐pretreated soft‐tissue sarcoma, regorafenib significantly improved quality‐adjusted survival in comparison with a placebo. Cancer 2017;123:2294–2302. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Q‐TWiST: What really matters to the cancer patient?
Authors: Husson Olga , Jones Robin L.
Published: March 2017

The quality‐adjusted time without symptoms of disease or toxicity method improves on the current benchmarks of overall and progression‐free survival by adding adverse events and utility coefficients to account for patients' quality of life. This will provide patients and their caregivers with additional information critical to making treatment decisions.

See also pages 2294‐302.
Iron‐Based Electrodes Meet Water‐Based Preparation, Fluorine‐Free Electrolyte and Binder: A Chance for More Sustainable Lithium‐Ion Batteries?
Authors: Valvo Mario , Liivat Anti , Eriksson Henrik , Tai Cheuk‐Wai , Edström Kristina
Published: March 2017

Environmentally friendly and cost‐effective Li‐ion cells are fabricated with abundant, non‐toxic LiFePO4 cathodes and iron oxide anodes. A water‐soluble alginate binder is used to coat both electrodes to reduce the environmental footprint. The critical reactivity of LiPF6‐based electrolytes toward possible traces of H2O in water‐processed electrodes is overcome by using a lithium bis(oxalato)borate (LiBOB) salt. The absence of fluorine in the electrolyte and binder is a cornerstone for improved cell chemistry and results in stable battery operation. A dedicated approach to exploit conversion‐type anodes more effectively is also disclosed. The issue of large voltage hysteresis upon conversion/de‐conversion is circumvented by operating iron oxide in a deeply lithiated Fe/Li2O form. Li‐ion cells with energy efficiencies of up to 92 % are demonstrated if LiFePO4 is cycled versus such anodes prepared through a pre‐lithiation procedure. These cells show an average energy efficiency of approximately 90.66 % and a mean Coulombic efficiency of approximately 99.65 % over 320 cycles at current densities of 0.1, 0.2 and 0.3 mA cm−2. They retain nearly 100 % of their initial discharge capacity and provide an unmatched operation potential of approximately 2.85 V for this combination of active materials. No occurrence of Li plating was detected in three‐electrode cells at charging rates of approximately 5C. Excellent rate capabilities of up to approximately 30C are achieved thanks to the exploitation of size effects from the small Fe nanoparticles and their reactive boundaries.
Transverse motion of a plasma column in a sheet plasma
Authors: Onda Takuya , Kajita Shin , Iijima Takaaki , Tonegawa Akira , Ohno Noriyasu , Tanaka Hirohiko
Published: March 2017

In this paper, we show the dynamic behaviors of a sheet plasma and the corresponding release of blob‐like plasmas to the periphery of the sheet based on observation with a high‐speed camera. We found that the plasma column moves in a transverse direction reciprocally when injecting a small amount of Ar gas to the He plasma from the plasma source region. The motion continued periodically at a frequency of ∼5 kHz. The frequency of the plasma column motion decreased with increasing Ar gas flow rate and increasing magnetic field. The mechanism of the transverse motion is discussed. Furthermore, in response to the reciprocating motion, release of a blob‐like plasma was observed. The differences in the behavior of the released plasma compared with the other linear devices are discussed.
Seasonal and temperature‐related movement of Colorado River cutthroat trout in a low‐elevation, Rocky Mountain stream
Authors: Hodge Brian W. , Battige Kyle D. , Rogers Kevin B.
Published: March 2017

Mobile species will migrate considerable distances to find habitats suitable for meeting life history requirements, and stream‐dwelling salmonids are no exception. In April–October 2014, we used radio‐telemetry to examine habitat use and movement of 36 Colorado River cutthroat trout Oncorhynchus clarkii pleuriticus (CRCT) in a 14.9‐km fragment of Milk Creek, a relatively low‐elevation stream in the Rocky Mountains (Colorado). We also used a network of data loggers to track stream temperature across time and space. Our objectives were to (1) characterize distribution and movement of CRCT, (2) evaluate seasonal differences in distribution and movement of CRCT, and (3) explore the relationship between stream temperature and distribution and movement of CRCT. During the course of our study, median range of CRCT was 4.81 km (range = 0.14–10.94) and median total movement was 5.94 km (range = 0.14–26.02). Median location of CRCT was significantly further upstream in summer than in spring, whereas range and movement of CRCT were greater in spring than in summer. Twenty‐six of the 27 CRCT tracked through mid‐June displayed a potamodromous (freshwater migratory) life history, migrating 1.8–8.0 km upstream during the spring spawning season. Four of the seven CRCT tracked through July migrated >1.4 km in summer. CRCT selected relatively cool reaches during summer months, and early‐summer movement was positively correlated with mean stream temperature. Study fish occupied stream segments in spring and fall that were thermally unsuitable, if not lethal, to the species in summer. Although transmitter loss limited the scope of inference, our findings suggest that preferred habitat is a moving target in Milk Creek, and that CRCT move to occupy that target. Because mobile organisms move among complementary habitats and exploit seasonally‐unsuitable reaches, we recommend that spatial and temporal variability be accounted for in delineations of distributional boundaries.
Measurement of troponin and natriuretic peptides shortly after admission in patients with heart failure—does it add useful prognostic information? An analysis of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Studies (VERITAS)
Authors: Cleland John G.F. , Teerlink John R. , Davison Beth A. , Shoaib Ahmad , Metra Marco , Senger Stefanie , Milo Olga , Cotter Gad , Bourge Robert C. , Parker John D. , Jondeau Guillaume , Krum Henry , O'Connor Christopher M. , Torre‐Amione Guillermo , van Veldhuisen Dirk J. , McMurray John J.V. ,   for the VERITAS Investigators
Published: March 2017

Objective

Plasma concentrations of B‐type natriuretic peptide (BNP) and troponin are often measured for diagnostic purposes when patients are admitted with heart failure, but their prognostic value when measured soon after admission is uncertain. We aimed to investigate the added prognostic value of admission measurements of BNP and troponins in patients with acute heart failure.

Methods and results

Multivariable prognostic models for death or any worsening heart failure (WHF) or rehospitalization for WHF by 30 days, 30‐day death or rehospitalization for WHF, and 90‐day mortality were constructed using baseline data from the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Studies (VERITAS) including BNP and troponin I. Of 1347 patients, the median (interquartile range) value of BNP was 422 (156–945) pg/mL and 855 (63%) had measurable troponin I. By 30 days, 432 patients had died or experienced WHF. Clinical variables had only moderate predictive performance that was not substantially improved by BNP or troponin I (c‐indices 0.6528 and 0.6595, respectively). By 30 days, 150 patients died or were rehospitalized for WHF. The c‐index using clinical variables (0.6855) was not improved by adding biomarkers. By 90 days, 135 patients had died. The c‐index for mortality was somewhat better than for composite outcomes (0.7394) but improved little with biomarkers (0.7461).

Conclusion

Routine clinical data recorded at the time of admission in patients with acute heart failure are poor at predicting recurrent admissions but somewhat better at predicting mortality. Neither BNP nor troponin measured at admission improved predictions; measurement closer to discharge, or of other novel biomarkers, might perform differently.
Negative regulators of the RIG‐I‐like receptor signaling pathway
Authors: Quicke Kendra M. , Diamond Michael S. , Suthar Mehul S.
Published: March 2017

Upon recognition of specific molecular patterns on microbes, host cells trigger an innate immune response, which culminates in the production of type I interferons, proinflammatory cytokines and chemokines, and restricts pathogen replication and spread within the host. At each stage of this response, there are stimulatory and inhibitory signals that regulate the magnitude, quality, and character of the response. Positive regulation promotes an antiviral state to control and eventually clear infection, whereas negative regulation dampens inflammation and prevents immune‐mediated tissue damage. An overexuberant innate response can lead to cell and tissue destruction, and the development of spontaneous autoimmunity. The retinoic acid‐inducible gene I (RIG‐I)‐like receptors (RLRs), RIG‐I and melanoma differentiation‐associated gene 5 (MDA5), belong to a family of cytosolic host RNA helicases that recognize distinct nonself RNA signatures and trigger innate immune responses against several RNA viruses by signaling through the essential adaptor protein mitochondrial antiviral signaling (MAVS). The RLR signaling pathway is tightly regulated to maximize antiviral immunity and minimize immune‐mediated pathology. This review highlights contemporary findings on negative regulators of the RLR signaling pathway, with specific focus on the proteins and biological processes that directly regulate RIG‐I, MDA5 and MAVS signaling function.
Deficiency in IRAK4 activity attenuates manifestations of murine Lupus
Authors: Murphy Michael , Pattabiraman Goutham , Manavalan Tissa T. , Medvedev Andrei E.
Published: March 2017

Interleukin‐1 receptor‐associated kinase (IRAK) 4 mediates host defense against infections. As an active kinase, IRAK4 elicits full spectra of myeloid differentiation primary response protein (MyD) 88‐dependent responses, while kinase‐inactive IRAK4 induces a subset of cytokines and negative regulators whose expression is not regulated by mRNA stability. IRAK4 kinase activity is critical for resistance against Streptococcus pneumoniae, but its involvement in autoimmunity is incompletely understood. In this study, we determined the role of IRAK4 kinase activity in murine lupus. Lupus development in BXSB mice expressing the Y chromosome autoimmunity accelerator (Yaa) increased basal and Toll‐like receptor (TLR) 4/7‐induced phosphorylation of mitogen‐activated protein kinases, p65 nuclear factor‐κB (NF‐κB), enhanced tumor necrosis factor (TNF)‐α and C‐C motif chemokine ligand (CCL) 5 gene expression in splenic macrophages, but decreased levels of Toll‐interacting protein and IRAK‐M, without affecting IRAK4 or IRAK1 expression. Mice harboring kinase‐inactive IRAK4 on the lupus‐prone Yaa background manifested blunted TLR signaling in macrophages and reduced glomerulonephritis, splenomegaly, serum anti‐nuclear antibodies, numbers of splenic macrophages, total and TNF‐α+ dendritic cells, activated T‐ and B‐lymphocytes, and lower TNF‐α expression in macrophages compared with lupus‐prone mice with functional IRAK4. Thus, IRAK4 kinase activity contributes to murine lupus and could represent a new therapeutic target.
Generation of precursor, immature, and mature murine B1‐cell lines from c‐myc/bcl‐xL‐overexpressing pre‐BI cells
Authors: Wolf Inge , Bouquet Corinne , Naumann Friederike , Melchers Fritz
Published: March 2017

Deregulated expression of c‐myc and bcl‐xL is long known to generate transformed B cells in humans and mice. We overexpressed these genes to induce in vitro and in vivo differentiation of fetal liver‐derived mouse pre‐BI cells to B1‐lineage pre‐BII‐like, immature and mature B‐cell lines, and to Ig‐secreting cells. In vitro, doxycycline‐controlled c‐myc/bcl‐xL‐overexpressing CD19+CD93+c‐kikt+IgM− pre‐BI cells differentiate to and survive as CD19+CD93+c‐kit−IgM+ immature B1 cells. Timed CpG stimulation of these oncogene‐overexpressing pre‐B or immature B1 cells generates either CD19+CD93lowc‐kit−IgM−SLC− pre‐BII‐like or IgM+MHCII+CD73+CD80+CD40+ mature B1‐cell lines and IgM‐secreting B1 cells in vitro and fixes their state of differentiation. All cell lines are clonable, but a majority of immature and mature B1‐cell clones eventually reach a nonproliferating, surviving G0‐state. Transplanted in vivo, c‐myc/bcl‐xL‐overexpressing pre‐B cells expand to mature B1 cells, and to IgM‐ and IgA‐secreting plasmablasts and plasma cells. Within 2 months, plasmablasts have expanded most prominently in BM and spleen, indicating that the host selectively expanded development of these transformed plasma cells. The sIgM+ B1‐cell lines and clones offer the possibility to study their roles in the development of B1‐Ab repertoires, of B1‐cell‐mediated autoimmune diseases and of B1‐cell malignancies.
Direct Regioselective Alkylation of Non‐Basic Heterocycles with Alcohols and Cyclic Ethers through a Dehydrogenative Cross‐Coupling Reaction under Metal‐Free Conditions
Authors: Kianmehr Ebrahim , Fardpour Maryam , Khan Khalid Mohammed
Published: March 2017

A metal‐free, simple, and highly efficient method for the direct alkylation of non‐basic heterocycles and basic ones with various alcohols and cyclic ethers has been developed based on an oxidative C–H activation process. The corresponding products were generated through a dehydrogenative C–C cross‐coupling reaction in the presence of di‐tert‐butyl peroxide in good to high yields.
Thermophilic microorganisms in arable land around medieval archaeological sites in Northern Caucasus, Russia: Novel evidence of past manuring practices
Authors: Chernysheva Elena , Korobov Dmitry , Borisov Alexander
Published: March 2017

Thermophilic microorganisms in the soils of medieval cultivated fields located within the Kislovodsk Basin (Northern Caucasus, Russia) were selected as a means for the reconstruction of manuring practices. Thermophilic bacteria are specific groups of microorganisms that develop in manure during the composting process when temperatures reach 60–70°C. The abundance of this type of bacteria in soils depends greatly on the intensity of farming practices. In medieval cultivated soils (Alanic Culture, A.D. 500–800), high numbers of thermophilic bacteria were observed, indicating the long‐term use of manure. In arable lands near Alanic settlements, the abundance of thermophilic bacteria decreased significantly with distance from the sites. The highest abundance of thermophilic bacteria was observed in the 500 m zone adjacent to the sites. Moreover, the highest concentration of thermophilic microorganisms was found in the soil within an Alanic corral. We suggest that dung accumulated in the paddock for a long time. Abundance of thermophilic microorganisms at archaeological sites could be used as a new indicator of the application of decomposed manure to ancient and medieval arable soils.
Dynamics of Celtic fields—A geoarchaeological investigation of Øster Lem Hede, Western Jutland, Denmark
Authors: Nielsen Nina Helt , Dalsgaard Kristian
Published: March 2017

Celtic fields are the most widespread type of prehistoric field systems in northwestern Europe. Many questions remain regarding their formation and use, but these may potentially be answered through geoarchaeological investigations. The aim of this study is to contribute to the understanding of the formation of the field systems, the formation of the banks and lynchets demarcating the fields, and the prehistoric land use through geoarchaeological investigations of Øster Lem Hede, one of the best preserved Celtic fields in Denmark. Four trenches dug through selected field boundaries were sampled for geochemical, particle size, thin section, and pollen analyses, as well as radiocarbon and optically stimulated luminescence (OSL) dating. OSL dates show that the investigated banks were formed in the late Bronze Age/early Iron Age (oldest dates: c. 600 ± 140 B.C.), but cultivation predating the field system is also indicated. Particle size and multielement analyses indicate that the banks formed through accumulation of soil from the fields. Dynamic alterations of the layout and field boundaries in the form of added banks and temporarily discontinued boundaries were identified. Geochemistry, pollen, and microscopic inclusions in the soil indicate that the fields were amended with household waste, animal manure, and material from wetlands and heathland. Several different crops were grown including barley, flax, and spurry but also rye appears to have been present in the 2.500‐year‐old fields.
Functional brain segmentation using inter‐subject correlation in fMRI
Authors: Kauppi Jukka‐Pekka , Pajula Juha , Niemi Jari , Hari Riitta , Tohka Jussi
Published: March 2017

The human brain continuously processes massive amounts of rich sensory information. To better understand such highly complex brain processes, modern neuroimaging studies are increasingly utilizing experimental setups that better mimic daily‐life situations. A new exploratory data‐analysis approach, functional segmentation inter‐subject correlation analysis (FuSeISC), was proposed to facilitate the analysis of functional magnetic resonance (fMRI) data sets collected in these experiments. The method provides a new type of functional segmentation of brain areas, not only characterizing areas that display similar processing across subjects but also areas in which processing across subjects is highly variable. FuSeISC was tested using fMRI data sets collected during traditional block‐design stimuli (37 subjects) as well as naturalistic auditory narratives (19 subjects). The method identified spatially local and/or bilaterally symmetric clusters in several cortical areas, many of which are known to be processing the types of stimuli used in the experiments. The method is not only useful for spatial exploration of large fMRI data sets obtained using naturalistic stimuli, but also has other potential applications, such as generation of a functional brain atlases including both lower‐ and higher‐order processing areas. Finally, as a part of FuSeISC, a criterion‐based sparsification of the shared nearest‐neighbor graph was proposed for detecting clusters in noisy data. In the tests with synthetic data, this technique was superior to well‐known clustering methods, such as Ward's method, affinity propagation, and K‐means
. Hum Brain Mapp 38:2643–2665, 2017. © 2017 Wiley Periodicals, Inc.
Assessing global transitions in human development and colorectal cancer incidence
Authors: Fidler Miranda M , Bray Freddie , Vaccarella Salvatore , Soerjomataram Isabelle
Published: March 2017

Colorectal cancer incidence has paralleled increases in human development across most countries. Yet, marked decreases in incidence are now observed in countries that have attained very high human development. Thus, in this study, we explored the relationship between human development and colorectal cancer incidence, and in particular assessed whether national transitions to very high human development are linked to temporal patterns in colorectal cancer incidence. For these analyses, we utilized the Human Development Index (HDI) and annual incidence data from regional and national cancer registries. Truncated (30–74 years) age‐standardized incidence rates were calculated. Yearly incidence rate ratios and HDI ratios, before and after transitioning to very high human development, were also estimated. Among the 29 countries investigated, colorectal cancer incidence was observed to decrease after reaching the very high human development threshold for 12 countries; decreases were also observed in a further five countries, but the age‐standardized incidence rates remained higher than that observed at the threshold. Such declines or stabilizations are likely due to colorectal cancer screening in some populations, as well as varying levels of exposure to protective factors. In summary, it appears that there is a threshold at which human development predicts a stabilization or decline in colorectal cancer incidence, though this pattern was not observed for all countries assessed. Future cancer planning must consider the increasing colorectal cancer burden expected in countries transitioning towards higher levels of human development, as well as possible declines in incidence among countries reaching the highest development level.
Tolosa–Hunt syndrome presenting during pregnancy following progesterone administration
Authors: Litwin Charles E. , Leung Annie S.O.
Published: March 2017

A patient experienced Tolosa–Hunt syndrome during pregnancy; progesterone administration was identified as the potential cause. Healthcare providers should be aware of this potential complication.
Basis of bone metabolism around dental implants during osseointegration and peri‐implant bone loss
Authors: Insua Angel , Monje Alberto , Wang Hom‐Lay , Miron Richard J.
Published: March 2017

Despite the growing number of publications in the field of implant dentistry, there are limited studies to date investigating the biology and metabolism of bone healing around dental implants and their implications in peri‐implant marginal bone loss. The aim of this review article is to provide a thorough understanding of the biological events taking place during osseointegration and the subsequent early and late phases of bone remodeling around dental implants. An update on the coupling mechanism occurring during bone resorption‐bone remodeling is provided, focused on the relevance of the osteocytes, bone lining cells and immune cells during bone maintenance. An electronic and manual literature search was conducted by three independent reviewers in several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Oral Health Group Trials Register databases for articles up to September 2016 with no language restriction. Local bone metabolism is subject to signals from systemic calcium‐phosphate homeostasis and bone remodeling. Three areas of interest were reviewed due to recent reported compromises in bone healing including the putative effects of (1) cholesterol, (2) hyperlipidemia, and (3) low vitamin D intake. Moreover, the prominent influence of osteocytes and immune cells is discussed as being key regulators during dental implant osseointegration and maintenance. These cells are of crucial importance in the presence of biofilm accumulation and their associated byproducts that leads to hard and soft tissue breakdown; the so called peri‐implantitis. Factors that could negatively impact osteoclastogenesis or osteal macrophage activation should be monitored in future research including implant placement/torque protocols, bone characteristics, as well as meticulous maintenance programs to favor osseointegration and future long‐term stability and success of dental implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2075–2089, 2017.
Three‐dimensional carbon nanotube scaffolds for long‐term maintenance and expansion of human mesenchymal stem cells
Authors: Lalwani Gaurav , D'agati Michael , Gopalan Anu , Patel Sunny C. , Talukdar Yahfi , Sitharaman Balaji
Published: March 2017

Expansion of mesenchymal stem cells (MSCs) and maintenance of their self‐renewal capacity in vitro requires specialized robust cell culture systems. Conventional approaches using animal‐derived or artificial matrices and a cocktail of growth factors have limitations such as consistency, scalability, pathogenicity, and loss of MSC phenotype. Herein, we report the use of all‐carbon 3‐D single‐ and multiwalled carbon nanotube scaffolds (SWCNTs and MWCNTs) as artificial matrices for long‐term maintenance and expansion of human MSCs. Three‐dimensional SWCNT and MWCNT scaffolds were fabricated using a novel radical initiated thermal cross‐linking method that covalently cross‐links CNTs to form 3‐D macroporous all‐carbon architectures. Adipose‐derived human MSCs showed good cell viability, attachment, proliferation, and infiltration in MWCNT and SWCNT scaffolds comparable to poly(lactic‐co‐glycolic) acid (PLGA) scaffolds (baseline control). ADSCs retained stem cell phenotype after 30 days and satisfied the International Society for Cellular Therapy's (ISCT) minimal criteria for MSCs. Post expansion, (1) ADSCs showed in vitro adherence to tissue culture polystyrene (TCPS); (2) MSC surface antigen expression [CD14(−), CD19(−), CD34(−), CD45(−), CD73(+), CD90(+), CD105(+)]; and (3) trilineage differentiation into osteoblasts, adipocytes, and chondrocytes. Results show that cross‐linked 3‐D MWCNTs and SWCNTs scaffolds are suitable for ex vivo expansion and maintenance of MSCs for therapeutic applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1927–1939, 2017.
Thiol surface functionalization via continuous phase plasma polymerization of allyl mercaptan, with subsequent maleimide‐linked conjugation of collagen
Authors: Stynes Gil D. , Gengenbach Thomas R. , Kiroff George K. , Morrison Wayne A. , Kirkland Mark A.
Published: March 2017

Thiol groups can undergo a large variety of chemical reactions and are used in solution phase to conjugate many bioactive molecules. Previous research on solid substrates with continuous phase glow discharge polymerization of thiol‐containing monomers may have been compromised by oxidation. Thiol surface functionalization via glow discharge polymerization has been reported as requiring pulsing. Herein, continuous phase glow discharge polymerization of allyl mercaptan (2‐propene‐1‐thiol) was used to generate significant densities of thiol groups on a mixed macrodiol polyurethane and tantalum. Three general classes of chemistry are used to conjugate proteins to thiol groups, with maleimide linkers being used most commonly. Here the pH specificity of maleimide reactions was used effectively to conjugate surface‐bound thiol groups to amine groups in collagen. XPS demonstrated surface‐bound thiol groups without evidence of oxidation, along with the subsequent presence of maleimide and collagen. Glow discharge reactor parameters were optimized by testing the resistance of bound collagen to degradation by 8 M urea. The nature of the chemical bonding of collagen to surface thiol groups was effectively assessed by colorimetric assay (ELISA) of residual collagen after incubation in 8 M urea over 8 days and after incubation with keratinocytes over 15 days. The facile creation of useable solid‐supported thiol groups via continuous phase glow discharge polymerization of allyl mercaptan opens a route for attaching a vast array of bioactive molecules. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1940–1948, 2017.
Theoretical approaches for predicting the color of rigid dyes in solution
Authors: Di Tommaso Stefania , Bousquet Diane , Moulin Delphine , Baltenneck Frédéric , Riva Priscilla , David Hervé , Fadli Aziz , Gomar Jérôme , Ciofini Ilaria , Adamo Carlo
Published: March 2017

Aiming at developing an affordable and easily implementable computational protocol for routine prediction of spectral properties of rigid molecular dyes, density functional theory, and time‐dependent density functional theory were used in conjunction with a vibronic coupling scheme for band shape estimate. To predict the perceived color of molecules in solution, a model has been setup linking the UV‐vis spectra predicted at ab initio level to the L*a*b* colorimetric parameters. The results show that a mixed protocol, implying the use of a global hybrid functional for the prediction of adiabatic energy differences and a range separated hybrid for the prediction of potential energy curvature, allows perceived colors to be quantitatively predicted, as demonstrated by the comparison of L*a*b* colorimetric parameters obtained from computed and experimental spectra. © 2017 Wiley Periodicals, Inc.
FFLUX: Transferability of polarizable machine‐learned electrostatics in peptide chains
Authors: Fletcher Timothy L. , Popelier Paul L. A.
Published: March 2017

The fully polarizable, multipolar, and atomistic force field protein FFLUX is being built from machine learning (i.e., kriging) models, each of which predicts an atomic property. Each atom of a given protein geometry needs to be assigned such a kriging model. Such a knowledgeable atom needs to be informed about a sufficiently large environment around it. The resulting complexity can be tackled by collecting the 20 natural amino acids into a few groups. Using substituted deca‐alanines, we present the proof‐of‐concept that a given atom's charge can be modeled by a few kriging models only. © 2017 Wiley Periodicals, Inc.
Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases
Authors: Arosarena Oneida A. , Barr Eric W. , Thorpe Ryan , Yankey Hilary , Tarr Joseph T. , Safadi Fayez F.
Published: March 2017

Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP‐10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP‐9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP‐10 expression in UMSCC12 cells (p = 0.0001), and MMP‐3 (p = 0.0005) and ‐9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP‐2 (p = 0.0408) and MMP‐9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP‐2 (p = 0.0023) and ‐9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion.
Physiological state as transferable operating criterion to improve recombinant protein production in Pichia pastoris through oxygen limitation
Authors: Garcia‐Ortega Xavier , Valero Francisco , Montesinos‐Seguí José Luis
Published: March 2017

BACKGROUND

The yeast Pichia pastoris is widely used as a production platform for secreted recombinant protein. The application of oxygen‐limiting conditions leads to an important increase in protein specific productivity driven by the GAP promoter.

RESULTS

The physiological and metabolic adaptation of the host to a wide range of oxygen availability has been systematically studied in glucose‐limited chemostat cultivations producing an antibody fragment (Fab). A weighty increase of up to 3‐fold of the specific Fab production rate (qFab) and Fab yield (YPX) has been achieved for the optimal conditions. Besides the remarkable increase on both Fab yield and productivity, as a consequence of the metabolic shift from respiratory to respiro‐fermentative pathways, a decrease on biomass yield and generation of several secreted by‐products have been observed.

CONCLUSION

The accurate system characterization achieved throughout the bioprocess specific rates and the monitoring of cell physiology allowed the determination of the optimal conditions to enhance bioprocess efficiency. This work also presents a versatile approach based on the physiological state of the yeast that can be used to implement the desired oxygen‐limiting conditions to fermentations set‐ups with different oxygen transfer capacities, alternative operating modes, and even for the production of other proteins of interest. © 2017 Society of Chemical Industry
A New Class of Graphs That Satisfies the Chen‐Chvátal Conjecture
Authors: Aboulker P. , Matamala M. , Rochet P. , Zamora J.
Published: March 2017

A well‐known combinatorial theorem says that a set of n non‐collinear points in the plane determines at least n distinct lines. Chen and Chvátal conjectured that this theorem extends to metric spaces, with an appropriated definition of line. In this work, we prove a slightly stronger version of Chen and Chvátal conjecture for a family of graphs containing chordal graphs and distance‐hereditary graphs.
Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care
Authors: Wang Yi , Spincemaille Pascal , Liu Zhe , Dimov Alexey , Deh Kofi , Li Jianqi , Zhang Yan , Yao Yihao , Gillen Kelly M. , Wilman Alan H. , Gupta Ajay , Tsiouris Apostolos John , Kovanlikaya Ilhami , Chiang Gloria Chia‐Yi , Weinsaft Jonathan W. , Tanenbaum Lawrence , Chen Weiwei , Zhu Wenzhen , Chang Shixin , Lou Min , Kopell Brian H. , Kaplitt Michael G. , Devos David , Hirai Toshinori , Huang Xuemei , Korogi Yukunori , Shtilbans Alexander , Jahng Geon‐Ho , Pelletier Daniel , Gauthier Susan A. , Pitt David , Bush Ashley I. , Brittenham Gary M. , Prince Martin R.
Published: March 2017

Quantitative susceptibility mapping (QSM) has enabled magnetic resonance imaging (MRI) of tissue magnetic susceptibility to advance from simple qualitative detection of hypointense blooming artifacts to precise quantitative measurement of spatial biodistributions. QSM technology may be regarded to be sufficiently developed and validated to warrant wide dissemination for clinical applications of imaging isotropic susceptibility, which is dominated by metals in tissue, including iron and calcium. These biometals are highly regulated as vital participants in normal cellular biochemistry, and their dysregulations are manifested in a variety of pathologic processes. Therefore, QSM can be used to assess important tissue functions and disease. To facilitate QSM clinical translation, this review aims to organize pertinent information for implementing a robust automated QSM technique in routine MRI practice and to summarize available knowledge on diseases for which QSM can be used to improve patient care. In brief, QSM can be generated with postprocessing whenever gradient echo MRI is performed. QSM can be useful for diseases that involve neurodegeneration, inflammation, hemorrhage, abnormal oxygen consumption, substantial alterations in highly paramagnetic cellular iron, bone mineralization, or pathologic calcification; and for all disorders in which MRI diagnosis or surveillance requires contrast agent injection. Clinicians may consider integrating QSM into their routine imaging practices by including gradient echo sequences in all relevant MRI protocols.

Level of Evidence: 1

Technical Efficacy: Stage 5

J. Magn. Reson. Imaging 2017;46:951–971.