bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designed Macrocyclic Peptides as Nanomolar Amyloid Inhibitors Based on Minimal Recognition Elements
Authors: Spanopoulou Anna , Heidrich Luzia , Chen Hong‐Ru , Frost Christina , Hrle Dean , Malideli Eleni , Hille Kathleen , Grammatikopoulos Alexandros , Bernhagen Jürgen , Zacharias Martin , Rammes Gerhard , Kapurniotu Aphrodite 
Published: June 2018

AbstractAmyloid self‐assembly is linked to the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes (T2D), but so far, no anti‐amyloid compound has reached the clinic. Macrocyclic peptides belong to the most attractive drug candidates. Herein we present macrocyclic peptides (MCIPs) designed using minimal IAPP‐derived recognition elements as a novel class of nanomolar amyloid inhibitors of both Aβ40(42) and IAPP or Aβ40(42) alone and show that chirality controls inhibitor selectivity. Sequence optimization led to the discovery of an Aβ40(42)‐selective MCIP exhibiting high proteolytic stability in human plasma and human blood–brain barrier (BBB) crossing ability in a cell model, two highly desirable properties for anti‐amyloid AD drugs. Owing to their favorable properties, MCIPs should serve as leads for macrocyclic peptide‐based anti‐amyloid drugs and scaffolds for the design of small‐molecule peptidomimetics for targeting amyloidogenesis in AD or in both AD and T2D.
Serpin A1 and the modulation of type I collagen turnover: Effect of the C‐terminal peptide 409–418 (SA1‐III) in human dermal fibroblasts
Authors: Cipriani Caterina , Pascarella Simona , Errante Fosca , Menicacci Beatrice , Magnelli Lucia , Mocali Alessandra , Rovero Paolo , Giovannelli Lisa 
Published: June 2018

AbstractThe pharmacological modulation of collagen turnover is a strategy potentially useful in different skin conditions. The serine protease inhibitor Serpin A1 and portions of its C‐terminal region have been investigated as collagen modulators. To clarify the mechanisms by which the C‐terminal 409–418 peptide SA1‐III increases extracellular type I collagen levels, to compare its activities range with that of the originator molecule Serpin A1, and to evaluate its efficacy in primary cultures from adult and aged human subjects. The different forms of type I collagen were analyzed by means of western blot in cell lysates and cell‐conditioned media of primary human dermal fibroblasts obtained from subjects of different ages. Gelatin zymography was used to investigate the degrading enzymes. Cell viability and in vitro wound healing tests were used to evaluate cell proliferation. The SA1‐III peptide increased extracellular collagen levels by reducing degradation, with no effect on cellular biosynthesis or cell proliferation mechanisms. A reduced level of MMP‐2 and MMP‐9 was also found in cell media upon peptide treatment. No peptide effect was detected on inflammatory mediators gene expression in resting and LPS‐stimulated fibroblasts, or in the wound healing test. The SA1‐III peptide is a good collagen modulator candidate, protecting collagen against degradation without detectable actions on biosynthesis, acting at reasonably low concentrations, and non‐interfering with cell proliferation. It is effective in primary fibroblasts from young and aged subjects. These effects can prove useful in pathological and physiological skin conditions in which collagen degradation is excessive compared to the synthetic capacity.
Rational Design of Alkali‐Resistant NO Reduction Catalysts using a Stable Hexagonal V‐Doped MoO3 Support for Alkali Trapping
Authors: Liu Xiaona , Gao Jiayi , Chen Yaxin , Li Chao , Chen Junxiao , Qu Weiye , Chen Xin , Ma Zhen , Tang Xingfu 
Published: June 2018

AbstractTo avoid alkali poisoning in the selective catalytic reduction (SCR) of NOx with NH3, it is desirable to design SCR catalysts with abundant alkali‐trapping sites spatially separated from catalytically active sites. Here we develop such a catalyst with strong resistance against alkali poisoning by using hexagonal vanadium‐doped MoO3 (V‐HMoO) with alkali‐trapping tunnels as a catalyst support. Although pure HMoO also possesses strong alkali resistance due to size‐suitable tunnels, active Mo5+ ions on the framework make HMoO thermally unstable, and hence pure HMoO is not able to be used as a suitable support for SCR in a normal operating temperature window of 280–420 °C. We substitute the active Mo5+ by stable V5+ due to its fully unoccupied electron configuration to achieve a thermally stable V‐HMoO support, as confirmed by various characterization results. After loading active V2O5 onto the V‐HMoO support, the catalyst shows high SCR activity with excellent alkali resistance due to the alkali trapping function of V‐HMoO. This work may give a strategy to design stable alkali‐trapping SCR catalysts in general.
The mechanosensory‐motor apparatus of antennae in the Oleander hawk moth (Daphnis nerii, Lepidoptera)
Authors: Sant Harshada H. , Sane Sanjay P. 
Published: June 2018

AbstractInsect antennae are sensory organs of great importance because they can sense diverse environmental stimuli. In addition to serving as primary olfactory organs of insects, antennae also sense a wide variety of mechanosensory stimuli, ranging from low‐frequency airflow or gravity cues to high‐frequency antennal vibrations due to sound, flight or touch. The basal segments of the antennae house multiple types of mechanosensory structures that prominently include the sensory hair plates, or Böhm's bristles, which measure the gross extent of antennal movement, and a ring of highly sensitive scolopidial neurons, collectively called the Johnston's organs, which record subtle flagellar vibrations. To fulfill their multifunctional mechanosensory role, the antennae of insects must actively move thereby enhancing their ability to sense various cues in the surrounding environment. This tight coupling between antennal mechanosensory function and antennal movements means that the underlying mechanosensory‐motor apparatus constitutes a highly tuned feedback‐controlled system. Our study aims to explore how the sensory and motor components of this system are configured to enable such functional versatility. We describe antennal mechanosensory neurons, their central projections in the brain relative to antennal motor neurons and the internal morphology of various antennal muscles that actuate the basal segments of the antenna. We studied these in the Oleander hawk moth (Daphnis nerii) using a combination of techniques such as neural dye fills, confocal microscopy, scanning electron microscopy and X‐ray tomography. Our study thus provides a detailed anatomical picture of the antennal mechanosensory‐motor apparatus, which in turn provides key insights into its multifunctional role.
Magnetically aligned straight depolarization canals and the rolling Hough transform
Authors: Jelić Vibor , Prelogović David , Haverkorn Marijke , Remeijn Jur , Klindžić Dora 
Published: June 2018

Aims. We aim to characterize the properties of the straight depolarization canals detected in the Low Frequency Array (LOFAR) polarimetric observations of a field centered on the extragalactic source 3C 196. We also compare the canal orientations with magnetically aligned HI filaments and the magnetic field probed by polarized dust emission.
Methods. We used the rolling Hough transform (RHT) to identify and characterize the orientation of the straight depolarization canals in radio polarimetric data and the filaments in HI data.
Results. The majority of the straight depolarization canals and the Hi filaments are inclined by ~10° with respect to the Galactic plane and are aligned with the plane-of-sky magnetic field orientation probed by the Planck dust polarization data. The other distinct orientation, of −65° with respect to the Galactic plane, is associated with the orientation of a bar-like structure observed in the 3C 196 field at 350 MHz.
Conclusions. An alignment between three distinct tracers of the (local) interstellar medium (ISM) suggests that an ordered magnetic field plays a crucial role in confining different ISM phases. The majority of the straight depolarization canals are a result of a projection of the complicated 3D distribution of the ISM. The RHT analysis is a robust method for identifying and characterizing the straight depolarization canals observed in radio-polarimetric data.
Distal-to-Snuffbox Arteriovenous Fistula
Authors: Maharaj Dale , Baksh Rayaad , Oladiran Adedapo , Budhoo Emerson , Ramdass Michael 
Published: June 2018

AbstractThe dogma for optimal arteriovenous fistula (AVF) creation is based on starting as distally as possible on the upper limb and progressing proximally. We herein present our findings of an AVF that is as distal as possible on the hand. To document primary patency rates of the distal-to-snuffbox AVF. A 10-year prospective study (2006–2016) involving 31 patients whose distal cephalic vein diameter was ≥3 mm with a normal Allen's test was conducted. Patients were excluded if the radial artery in the wrist was highly calcified, the cephalic vein did not dilate more than 3 mm with proximal compression, and there was previously failed AVF of the limb or previous trauma to the limb. The procedure was performed under local anesthetic, and the anastomosis performed with a 6.0 polypropylene suture in an end-to-side fashion. Thirty-one patients with end-stage renal disease underwent distal vascular access using the distal-to-snuffbox (Hitchhiker's) AVF (HAVF). During follow-up, eight patients died with an adequately functioning HAVF. The primary patency rates at 12, 24, 48, and 60 months were 90, 87, 85, and 82%, respectively. Failure occurred in six (19%) cases over the follow-up period, two in the first 2 weeks and four over a span of 60 months.
Conclusion The creation of radiocephalic AVFs in the first web space, distal to the tendon of the extensor pollicis longus, serves as a viable option with acceptable success rates. This allows the surgeon more options with proper patient selection for this procedure.
Heart specific PGC-1α deletion identifies metabolome of cardiac restricted metabolic heart failure
Authors: Kärkkäinen Olli , Tuomainen Tomi , Mutikainen Maija , Lehtonen Marko , Ruas Jorge L , Hanhineva Kati , Tavi Pasi 
Published: June 2018

Abstract

Aims
Heart failure (HF) is associated with drastic changes in metabolism leading to a cardiac energy deficiency well as maladaptive changes in multiple other tissues. It is still unclear which of these changes originates from cardiomyocyte metabolic remodelling or whether they are induced secondarily by systemic factors. Our aim here was to induce cardiac restricted metabolic changes mimicking those seen in HF and to characterize the associated metabolite changes in the heart, circulation, and peripheral tissues.

Methods and results
We generated a cardiac specific PGC-1α knockout mice (KO) to specifically induce metabolic dysregulation typically accompanied by HF and performed a non-targeted LC-MS metabolite profiling analysis of heart, plasma, liver, and skeletal muscle to identify metabolites associated with cardiac specific metabolic remodelling. The KO animals developed a progressive cardiomyopathy with cardiac dilatation leading to fatal HF. At 17 weeks of age, when significant remodelling had occurred but before the onset of HF, isolated PGC-1α deficient cardiomyocytes had suppressed glucose and fatty acid oxidation as well as blunted anaerobic metabolism. KO hearts displayed a distinctive metabolite profile with 92 significantly altered molecular features including metabolite changes in energy metabolism, phospholipid metabolism, amino acids, and oxidative stress signalling. Some of the metabolite changes correlated with the specific parameters of cardiac function. We did not observe any significant alterations in the metabolomes of the other measured tissues or in plasma.

Conclusions
Heart specific PGC-1α KO induces metabolic, functional, and structural abnormalities leading to dilating cardiomyopathy and HF. The metabolic changes were limited to the cardiac tissue indicating that cardiomyocyte metabolic remodelling is not sufficient to evoke the body wide metabolic alterations usually associated with HF.
Combinatorics of Generalized Exponents
Authors: Lecouvey Cédric , Lenart Cristian 
Published: June 2018

Abstract
We give a purely combinatorial proof of the positivity of the stabilized forms of the generalized exponents associated to each classical root system. In finite type $A_{n-1}$, we rederive the description of the generalized exponents in terms of crystal graphs without using the combinatorics of semistandard tableaux or the charge statistic. In finite type $C_{n}$, we obtain a combinatorial description of the generalized exponents based on the so-called distinguished vertices in crystals of type $A_{2n-1}$, which we also connect to symplectic King tableaux. This gives a combinatorial proof of the positivity of Lusztig $t$-analogs associated to zero-weight spaces in the irreducible representations of symplectic Lie algebras. We also present three applications of our combinatorial formula and discuss some implications to relating two type $C$ branching rules. Our methods are expected to extend to the orthogonal types.
Connectome preprocessing by Consensus Clustering increases separability in group neuroimaging studies
Authors: Rasero Javier , Cortes Jesus M , Marinazzo Daniele , Stramaglia Sebastiano 
Published: June 2018

AbstractOne of the biggest challenges in preprocessing pipelines for neuroimaging data is to increase the signal-to-noise ratio of the data which will be used for subsequent analyses. In the same line, we suggest in the present work that the application of consensus clustering for brain connectivity matrices to find subgroups of subjects can be a valid additional”connectome processing” step helpful to reduce intra-group variability and therefore increase the separability of distinct classes. In addition, by partitioning the data before any group comparison, we demonstrate that unique regions within each cluster arise and bring new information that could be relevant from a clinical point of view.
Unaltered prion disease in mice lacking developmental endothelial locus-1 (Del-1)
Authors: Zhu Caihong , Li Zhihao , Li Bei , Pfammatter Manuela , Aguzzi Adriano 
Published: June 2018

AbstractProgression of prion diseases is driven by the accumulation of prions in the brain. Ablation of microglia or deletion of the eat-me-signal milk-fat globule EGF factor VIII (Mfge8) accelerate prion pathogenesis, suggesting that microglia defends the brain by phagocytosing prions. Like Mfge8, Developmental endothelial locus-1 (Del-1) is a secreted protein that acts as an opsonin bridging phagocytes and apoptotic cells to facilitate phagocytosis. We therefore asked whether Del-1 might play a role in controlling prion pathogenesis. We first determined the expression pattern of Del-1 in mice, and found that the brain expresses the highest level of Del-1. In mouse brains, Del-1 was mainly expressed by neurons. We then assessed the anti-inflammatory and phagocytosis-promoting functions of Del-1 in prion disease, and determined whether Del-1 complements Mfge8 in prion clearance in mice with a C57BL/6J genetic background. We found that Del-1 deficiency did not change prion disease progression and lesion patterns. Also, prion clearance and PrPSc deposition were unaltered in Del-1 deficient mice. Additionally, prioninduced neuroinflammation was not affected by Del-1 deficiency. We conclude that Del-1 is not a major determinant of prion pathogenesis in this context.
Proviral sequencing suggests the majority of the HIV reservoir is expressed over time but significant decay is obscured by clonal expansion
Authors: Rita Pinzone Marilia , VanBelzen D. Jake , Weissman Sam , Bertuccio Maria Paola , Cannon LaMont , Hwang Wei-Ting , Sherman Brad , O’Doherty Una 
Published: June 2018

AbstractAfter initiating antiretroviral therapy (ART), a rapid decline in plasma viremia is followed by reservoir stabilization. Viral outgrowth assay suggests the reservoir continues to decline slowly, but variation over time and among individuals complicates our understanding of selective pressures during ART. We used full-length sequencing to study more than 800 HIV proviruses of two subjects on ART at four time points over nine years to investigate the selection pressures influencing the dynamics of the reservoir. We found that intact as well as defective proviruses capable of significant protein expression decrease over time. Moreover, proviruses lacking genetic elements to promote viral protein expression, yet containing strong splice donor sequences increase relative to other defectives over time, especially among clones. Our work suggests that HIV expression occurs to a significant extent during ART and results in HIV clearance, but this is obscured by clones generated by donor splice site-enhanced clonal expansion.
Maternal group 2 innate lymphoid cells contribute to fetal growth and protection from endotoxin-induced abortion in mice
Authors: Balmas Elisa , Rana Batika MJ , Hamilton Russell S , Shreeve Norman , Kieckbusch Jens , Aye Irving , Hawkes Delia A , Trotter Sophie , López-Tello Jorge , Yong Hannah EJ , Valenti Salvatore , Sferruzi-Perri Amanda N , Gaccioli Francesca , McKenzie Andrew NJ , Colucci Francesco 
Published: June 2018

AbstractGroup 2 innate lymphoid cells (ILC2s) adapt to tissue physiology and contribute to immunity, inflammatory pathology and metabolism. We show that mouse uterine ILC2s have a heightened type-2 gene signature and expand during pregnancy. Indeed, maternal ILC2s promote fetal growth and protect against fetal mortality upon systemic endotoxin challenge. Absence of ILC2s leads to utero-placental abnormalities, including poor vascular remodelling, increasedIl1band decreasedIl4, Il5, andIl13gene expression, and reduced alternative activation of dendritic cells (DCs) and macrophages. Placentas exhibit signs of adaptation to stress, including larger maternal blood spaces and increased expression of nutrient transporter genes. Endotoxin induces the expansion of IL-1β-producing uterine DCs and, in response, more uterine ILC2s produce IL-4, IL-5 and IL-13. In a protective feedback mechanism, these cytokines suppress IL-1β-producing DCs, in line with a protective role of uILC2s against endotoxin-induced abortion. Uterine ILC2s emerge as pivotal for both normal and complicated pregnancies.
Towards a universal structural and energetic model for prokaryotic promoters
Authors: Mishra A. , Siwach P. , Misra P. , Jayaram B. , Bansal M. , Olson W.K. , Thayer K.M. , Beveridge D.L. 
Published: June 2018

AbstractWith almost no consensus promoter sequence in prokaryotes, recruitment of RNA polymerase (RNAP) to precise transcriptional start sites (TSSs) has remained an unsolved puzzle. Uncovering the underlying mechanism is critical for understanding the principle of gene regulation. We attempted to search the hidden code in ~16500 promoters, of twelve prokaryotes representing two kingdoms, in their structure and energetics. Twenty eight fundamental parameters of DNA structure including backbone angles, base pair axis, inter base pair and intra base pair parameters were used and information was extracted from X-ray crystallography (XRC) data. Three parameters (solvation energy, hydrogen bond energy and stacking energy) were selected for creating energetics profiles using in-house programs. DNA was found to be inherently designed to undergo a change in every parameter undertaken, from some distance upstream of TSSs to adopt a signature state at these locations in all prokaryotes. These signature states might be the universal hidden codes recognised by RNAP. This observation was reiterated when randomly selected promoter sequences (with little sequence conservation) were subjected to structure generation; all developed into very similar three dimensional structures, quite distinct from those of conventional B-DNA and coding sequences. Fine structural details at important motifs (viz. −11, −35, −75 positions relative to TSS) of promoters reveal novel and pointed insights for RNAP interaction at these locations; it could be correlated that how some particular structural changes at −11 region may allow insertion of RNAP amino acids in inter-base pair space as well as facilitate the flipping out of bases from DNA duplex.
Mito-nuclear effects uncovered in admixed populations
Authors: Zaidi Arslan A. , Makova Kateryna D. 
Published: June 2018

AbstractTo function properly, mitochondria utilize products of 37 and >1,000 genes encoded by the mitochondrial and nuclear genomes, respectively, which should be compatible with each other. Discordance between mitochondrial and nuclear genetic ancestry could contribute to phenotypic variation in admixed populations. Here we explored potential mito-nuclear incompatibility in six admixed human populations from the Americas: African Americans, African Caribbeans, Colombians, Mexicans, Peruvians, and Puerto Ricans. For individuals in these populations, we determined nuclear genome proportions derived from Africans, Europeans, and Native Americans, the geographic origins of the mitochondrial DNA (mtDNA), as well as mtDNA copy number in lymphoblastoid cell lines. By comparing nuclear vs. mitochondrial ancestry in admixed populations, we show that, first, mtDNA copy number decreases with increasing discordance between nuclear and mitochondrial DNA ancestry, in agreement with mito-nuclear incompatibility. The direction of this effect is consistent across mtDNA haplogroups of different geographic origins. This observation suggests suboptimal regulation of mtDNA replication when its components are encoded by nuclear and mtDNA genes with different ancestry. Second, while most populations analyzed exhibit no such trend, in Puerto Ricans and African Americans we find a significant enrichment of ancestry at nuclear-encoded mitochondrial genes towards the source populations contributing the most prevalent mtDNA haplogroups (Native American and African, respectively). This likely reflects compensatory effects of selection in recovering mito-nuclear interactions optimized in the source populations. Our results provide the first evidence of mito-nuclear effects in human admixed populations and we discuss its implications for human health and disease.
Laminin α1 orchestrates VEGFA functions in the ecosystem of colorectal carcinoma
Authors: Mammadova‐Bach Elmina , Rupp Tristan , Spenlé Caroline , Jivkov Ivo , Shankaranarayanan Pattabhiraman , Klein Annick , Pisarsky Laura , Méchine‐Neuville Agnès , Cremel Gérard , Kedinger Michèle , De Wever Olivier , Ambartsumian Noona , Robine Sylvie , Pencreach Erwan , Guenot Dominique , Simon‐Assmann Patricia , Goetz Jacky G. , Orend Gertraud , Lefebvre Olivier 
Published: June 2018

Background InformationTumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma.ResultsBy employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumor‐stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth. The underlying mechanism involves attraction of carcinoma‐associated fibroblasts by LMα1, VEGFA expression triggered by the complex integrin α2β1‐CXCR4 and binding of VEGFA to LM‐111, which in turn promotes angiogenesis, tumor cell survival and proliferation. A gene signature comprising LAMA1, ITGB1, ITGA2, CXCR4 and VEGFA has negative predictive value in colon cancer.ConclusionsTogether, we have identified VEGFA, CXCR4 and α2β1 integrin downstream of LMα1 in colon cancer as of bad prognostic value for patient survival.SignificanceThis information opens novel opportunities for diagnosis and treatment of colon cancer.