bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleation and Formation of a Primary Clot in Insect Blood
Authors: Aprelev Pavel , Bruce Terri F. , Beard Charles E. , Adler Peter H. , Kornev Konstantin G. 
Published: March 2019

AbstractBlood clotting at wound sites is critical for preventing blood loss and invasion by microorganisms in multicellular animals, especially small insects vulnerable to dehydration. The mechanistic reaction of the clot is the first step in providing scaffolding for the formation of new epithelial and cuticular tissue. The clot, therefore, requires special materials properties. We have developed and used nano-rheological magnetic rotational spectroscopy with nanorods to quantitatively study nucleation of cell aggregates that occurs within fractions of a second. Using larvae of Manduca sexta, we discovered that clot nucleation is a two-step process whereby cell aggregation is the time-limiting step followed by rigidification of the aggregate. Clot nucleation and transformation of viscous blood into a visco-elastic aggregate happens in a few minutes, which is hundreds of times faster than wound plugging and scab formation. This discovery sets a time scale for insect clotting phenomena, establishing a materials metric for the kinetics of biochemical reaction cascades. Combined with biochemical and biomolecular studies, these discoveries can help design fast-working thickeners for vertebrate blood, including human blood, based on clotting principles of insect blood.
The genetic vulnerability to cisplatin ototoxicity: a systematic review
Authors: Tserga Evangelia , Nandwani Tara , Edvall Niklas K. , Bulla Jan , Patel Poulam , Canlon Barbara , Cederroth Christopher R. , Baguley David M. 
Published: March 2019

AbstractOtotoxicity is one of the major side-effects of platinum-based chemotherapy, in particular cisplatin (cis-diammine dichloroplatinum II). To our knowledge, no systematic review has previously provided a quantitative summary estimate of the impact of genetics upon the risk of developing hearing loss. We searched Embase, Medline, ASSIA, Pubmed, Scopus, and Web of Science, for studies documenting the genetic risk of ototoxicity in patients with cancer treated with cisplatin. Titles/abstracts and full texts were reviewed for inclusion. Meta-analytic estimates of risk (Odds Ratio) from the pooled data were calculated for studies that have been repeated twice or more. The search identified 3891 papers, of which 30 were included. The majority were retrospective (44%), ranging from n = 39 to n = 317, some including only patients younger than 25 years of age (33%), and some on both genders (80%). The most common cancers involved were osteosarcoma (53%), neuroblastoma (37%), prostate (17%) and reproductive (10%). Most studies performed genotyping, though only 5 studies performed genome-wide association studies. Nineteen single-nucleotide polymorphisms (SNPs) from 15 genes were repeated more than twice. Meta-analysis of group data indicated that rs1872328 on ACYP2, which plays a role in calcium homeostasis, increases the risk of ototoxicity by 4.61 (95% CI: 3.04–7.02; N = 696, p < 0.0001) as well as LRP2 rs4668123 shows a cumulated Odds Ratio of 3.53 (95% CI: 1.48–8.45; N = 118, p = 0.0059), which could not be evidenced in individual studies. Despite the evidence of heterogeneity across studies, these meta-analytic results from 30 studies are consistent with a view of a genetic predisposition to platinum-based chemotherapy mediated ototoxicity. These new findings are informative and encourage the genetic screening of cancer patients in order to identify patients with greater vulnerability of developing hearing loss, a condition having a potentially large impact on quality of life. More studies are needed, with larger sample size, in order to identify additional markers of ototoxic risk associated with platinum-based chemotherapy and investigate polygenic risks, where multiple markers may exacerbate the side-effects.
Active propagation of dendritic electrical signals in C. elegans
Authors: Shindou Tomomi , Ochi-Shindou Mayumi , Murayama Takashi , Saita Ei-ichiro , Momohara Yuto , Wickens Jeffery R. , Maruyama Ichiro N. 
Published: March 2019

AbstractActive propagation of electrical signals in C. elegans neurons requires ion channels capable of regenerating membrane potentials. Here we report regenerative depolarization of a major gustatory sensory neuron, ASEL. Whole-cell patch-clamp recordings in vivo showed supralinear depolarization of ASEL upon current injection. Furthermore, stimulation of animal’s nose with NaCl evoked all-or-none membrane depolarization in ASEL. Mutant analysis showed that EGL-19, the α1 subunit of L-type voltage-gated Ca2+ channels, is essential for regenerative depolarization of ASEL. ASEL-specific knock-down of EGL-19 by RNAi demonstrated that EGL-19 functions in C. elegans chemotaxis along an NaCl gradient. These results demonstrate that a natural substance induces regenerative all-or-none electrical signals in dendrites, and that these signals are essential for activation of sensory neurons for chemotaxis. As in other vertebrate and invertebrate nervous systems, active information processing in dendrites occurs in C. elegans, and is necessary for adaptive behavior.
Simulation of blast lung injury induced by shock waves of five distances based on finite element modeling of a three-dimensional rat
Authors: Yang Chang , Dong-hai Zhang , Ling-ying Liu , Yong-hui Yu , Yang Wu , Li-wei Zang , Rui-guo Han , Jia-ke Chai 
Published: March 2019

AbstractBlast lung injury (BLI) caused by both military and civilian explosions has become the main cause of death for blast injury patients. By building three-dimensional (3D) models of rat explosion regions, we simulated the surface pressure of the skin and lung. The pressure distributions were performed at 5 distances from the detonation center to the center of the rat. When the distances were 40 cm, 50 cm, 60 cm, 70 cm and 80 cm, the maximum pressure of the body surface were 634.77kPa, 362.46kPa, 248.11kPa, 182.13kPa and 109.29kPa and the surfaces lung pressure ranges were 928–2916 Pa, 733–2254 Pa, 488–1236 Pa, 357–1189 Pa and 314–992 Pa. After setting 6 virtual points placed on the surface of each lung lobe model, simulated pressure measurement and corresponding pathological autopsies were then conducted to validate the accuracy of the modeling. For the both sides of the lung, when the distance were 40 cm, 50 cm and 60 cm, the Pearson’s values showed strong correlations. When the distances were 70 cm and 80 cm, the Pearson’s values showed weak linear correlations. This computational simulation provided dynamic anatomy as well as functional and biomechanical information.
Application of Locked Nucleic Acid Oligonucleotides for siRNA Preclinical Bioanalytics
Authors: Thayer Mai B. , Lade Julie M. , Doherty David , Xie Fang , Basiri Babak , Barnaby Omar S. , Bala Noor S. , Rock Brooke M. 
Published: March 2019

AbstractDespite the exquisite potential of siRNA as a therapeutic, the mechanism(s) responsible for the robust indirect exposure-response relationships have not been fully elucidated. To understand the siRNA properties linked to potent activity, requires the disposition of siRNA to be characterized. A technical challenge in the characterization is the detection and quantitation of siRNA from biological samples. Described herein, a Locked Nucleic Acid (LNA) Hybridization-Ligation ECL ELISA was designed for ultra-sensitive quantification of both sense and antisense strands of siRNA independent of structural modifica-tions. This assay was applied to measure siRNA in serum and tissue homogenate in preclinical species. We observed rapid clearance of siRNA from the systemic circulation which contrasted the prolonged accumulation within the tissue. The assay was also able to distinguish and quantify free siRNA from RNA-induced silencing complex (RISC) and Argonaute 2 (Ago2) associated with therapeutic siRNA. We utilized an orthogonal method, LC-MS, to investigate 3′ exonuclease activity toward the antisense strand metabolism. Taken together, we have demonstrated that the LNA Hybridization-Ligation ECL ELISA is arobust analytical method with direct application to measuring the exposure of siRNA therapeutics seamlessly across biological matrices.
Platelet lysate outperforms FCS and human serum for co-culture of primary human macrophages and hMSCs
Authors: Tylek Tina , Schilling Tatjana , Schlegelmilch Katrin , Ries Maximilian , Rudert Maximilian , Jakob Franz , Groll Jürgen 
Published: March 2019

AbstractIn vitro co-cultures of different primary human cell types are pivotal for the testing and evaluation of biomaterials under conditions that are closer to the human in vivo situation. Especially co-cultures of macrophages and mesenchymal stem cells (MSCs) are of interest, as they are both present and involved in tissue regeneration and inflammatory reactions and play crucial roles in the immediate inflammatory reactions and the onset of regenerative processes, thus reflecting the decisive early phase of biomaterial contact with the host. A co-culture system of these cell types might thus allow for the assessment of the biocompatibility of biomaterials. The establishment of such a co-culture is challenging due to the different in vitro cell culture conditions. For human macrophages, medium is usually supplemented with human serum (hS), whereas hMSC culture is mostly performed using fetal calf serum (FCS), and these conditions are disadvantageous for the respective other cell type. We demonstrate that human platelet lysate (hPL) can replace hS in macrophage cultivation and appears to be the best option for co-cultivation of human macrophages with hMSCs. In contrast to FCS and hS, hPL maintained the phenotype of both cell types, comparable to that of their respective standard culture serum, as well as the percentage of each cell population. Moreover, the expression profile and phagocytosis activity of macrophages was similar to hS.
B-cell depletion induces a shift in self antigen specific B-cell repertoire and cytokine pattern in patients with bullous pemphigoid
Authors: Berkani Nicolas , Joly Pascal , Golinski Marie-Laure , Colliou Natacha , Lim Annick , Larbi Anis , Riou Gaetan , Caillot Frederique , Bernard Philippe , Bedane Christophe , Delaporte Emmanuel , Chaby Guillaume , Dompmartin Anne , Hertl Michael , Calbo Sebastien , Musette Philippe 
Published: March 2019

AbstractBullous Pemphigoid is the most common auto-immune bullous skin disease. It is characterized by the production of auto-antibodies directed against 2 proteins of the hemi-desmosome (BP180 and BP230). We assessed the efficacy and mechanisms of action of rituximab, an anti-CD20 monoclonal antibody, in 17 patients with severe and relapsing type of bullous pemphigoid. The phenotype, cytokine gene expression, and rearrangement of BP180-specific B-cell receptor genes were performed over 2 years following treatment. At the end of the study, 5 patients had died, 3 had withdrawn from the study, and 9 patients were in complete remission. The one- and two-year relapse rates were 44.1% (95% Confidence Interval (CI): 21.0–76.0%) and 66.5%, (95% CI: 38.4–91.4%), respectively. Phenotypic analyses confirmed dramatic B-cell depletion, which lasted for 9 to 12 months. The ELISA values of serum anti-BP180 antibodies and the frequency of BP180-specific circulating B cells decreased dramatically following treatment, which paralleled the improvement of skin lesions. During B-cell reconstitution, a polyclonal IgM repertoire appeared and a shift in the rearrangement of the B-cell receptor genes of BP180-specific circulating B cells was observed. Concurrently, we observed a decrease of IL-15, IL-6 and TNFα expressing BP180-specific B cells, and the emergence of IL-10 and IL-1RA-expressing BP180-specific IgM+ B cells in patients in complete remission off therapy, suggesting the functional plasticity of BP180-specific auto-immune B cells after rituximab treatment.
Near-zero metamaterial inspired UHF antenna for nanosatellite communication system
Authors: Alam Touhidul , Islam Mohammad Tariqul , Cho Mengu 
Published: March 2019

AbstractEpsilon-and-mu-near-zero (EMNZ) metamaterial structure inspired UHF antenna for nanosatellite has been proposed in this paper. The antenna consists of 3 × 2-unit cell array on the ground plane and a meander line radiating patch. Coaxial probe feeding technique has been obtained to excite the antenna. The meander line enables the antenna to resonate at lower UHF band and the metamaterial array is used to make the resonant frequency stable by reducing the coupling effect with metallic nanosatellite structure. The metamaterial structure exhibits EMNZ characteristics from 385 MHz to 488.5 MHz, which facilitates stable resonant frequency and higher antenna efficiency when embedded with nanosatellite structure. The proposed EMNZ inspired antenna has achieved measured impedance bandwidth (S11 < −10 dB) of 14.92 MHz (391 MHz–405.92 MHz). The perceptible novelty of this paper is the development of EMNZ metamaterial that significantly improves the UHF antenna’s operating frequency stability as well as efficiency for low earth orbit nanosatellite communications.
Cytohesin-3 is required for full insulin receptor signaling and controls body weight via lipid excretion
Authors: Jux Bettina , Gosejacob Dominic , Tolksdorf Felix , Mandel Christa , Rieck Michael , Namislo Angrit , Pfeifer Alexander , Kolanus Waldemar 
Published: March 2019

AbstractInsulin plays a central role in regulating metabolic homeostasis and guanine-nucleotide exchange factors of the cytohesin family have been suggested to be involved in insulin signal transduction. The Drosophila homolog of cytohesin-3, steppke, has been shown to be essential for insulin signaling during larval development. However, genetic evidence for the functional importance of cytohesin-3 in mammals is missing. We therefore analyzed the consequences of genetic cytohesin-3-deficiency on insulin signaling and function in young and aged mice, using normal chow or high-fat diet (HFD). Insulin-receptor dependent signaling events are significantly reduced in liver and adipose tissue of young cytohesin-3-deficient mice after insulin-injection, although blood glucose levels and other metabolic parameters remain normal in these animals. Interestingly, however, cytohesin-3-deficient mice showed a reduced age- and HFD-induced weight gain with a significant reduction of body fat compared to wild-type littermates. Furthermore, cytohesin-3-deficient mice on HFD displayed no alterations in energy expenditure, but had an increased lipid excretion instead, as well as a reduced expression of genes essential for bile acid synthesis. Our findings show for the first time that an intact cyth3 locus is required for full insulin signaling in mammals and might constitute a novel therapeutic target for weight reduction.
KBTBD11, a novel BTB-Kelch protein, is a negative regulator of osteoclastogenesis through controlling Cullin3-mediated ubiquitination of NFATc1
Authors: Narahara Shun , Sakai Eiko , Kadowaki Tomoko , Yamaguchi Yu , Narahara Haruna , Okamoto Kuniaki , Asahina Izumi , Tsukuba Takayuki 
Published: March 2019

AbstractKelch repeat and BTB domain-containing protein 11 (KBTBD11) is a member of the KBTBD subfamily of proteins that possess a BTB domain and Kelch repeats. Despite the presence of the Kbtbd11 gene in mammalian genomes, there are few reports about KBTBD11 at present. In this study, we identified the novel protein KBTBD11 as a negative regulator of osteoclast differentiation. We found that expression of KBTBD11 increased during osteoclastogenesis. Small-interfering-RNA-mediated knockdown of KBTBD11 enhanced osteoclast formation, and markedly increased the expression of several osteoclast marker genes compared with control cells. Conversely, KBTBD11 overexpression impaired osteoclast differentiation, and decreased the expression of osteoclast marker genes. Among six major signaling pathways regulating osteoclast differentiation, KBTBD11 predominantly influenced the nuclear factor of activated T cell cytoplasmic-1 (NFATc1) pathway. Mechanistically, KBTBD11 was found to interact with an E3 ubiquitin ligase, Cullin3. Further experiments involving immunoprecipitation and treatment with MG132, a proteasome inhibitor, showed that the KBTBD11–Cullin3 promotes ubiquitination and degradation of NFATc1 by the proteasome. Considering that NFATc1 is an essential factor for osteoclast differentiation, the KBTBD11 and Cullin3 probably regulate the levels of NFATc1 through the ubiquitin-proteasome degradation system. Thus, KBTBD11 negatively modulates osteoclast differentiation by controlling Cullin3-mediated ubiquitination of NFATc1.
A Mediterranean mesophotic coral reef built by non-symbiotic scleractinians
Authors: Corriero Giuseppe , Pierri Cataldo , Mercurio Maria , Nonnis Marzano Carlotta , Onen Tarantini Senem , Gravina Maria Flavia , Lisco Stefania , Moretti Massimo , De Giosa Francesco , Valenzano Eliana , Giangrande Adriana , Mastrodonato Maria , Longo Caterina , Cardone Frine 
Published: March 2019

AbstractThis is the first description of a Mediterranean mesophotic coral reef. The bioconstruction extended for 2.5 km along the Italian Adriatic coast in the bathymetric range −30/−55 m. It appeared as a framework of coral blocks mostly built by two scleractinians, Phyllangia americana mouchezii (Lacaze-Duthiers, 1897) and Polycyathus muellerae (Abel, 1959), which were able to edify a secondary substrate with high structural complexity. Scleractinian corallites were cemented by calcified polychaete tubes and organized into an interlocking meshwork that provided the reef stiffness. Aggregates of several individuals of the bivalve Neopycnodonte cochlear (Poli, 1795) contributed to the compactness of the structure. The species composition of the benthic community showed a marked similarity with those described for Mediterranean coralligenous communities and it appeared to be dominated by invertebrates, while calcareous algae, which are usually considered the main coralligenous reef-builders, were poorly represented. Overall, the studied reef can be considered a unique environment, to be included in the wide and diversified category of Mediterranean bioconstructions. The main reef-building scleractinians lacked algal symbionts, suggesting that heterotrophy had a major role in the metabolic processes that supported the production of calcium carbonate. The large amount of available suspended organic matter in the area could be the main nutritional source for these species, as already suggested in the literature referred to Mediterranean cold-water corals.
DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass
Authors: Gordon Scott M. , Neufeld Edward B. , Yang Zhihong , Pryor Milton , Freeman Lita A. , Fan Xiao , Kullo Iftikhar J. , Biesecker Leslie G. , Remaley Alan T. 
Published: March 2019

AbstractRegulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5b−/− mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of Dennd5b results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In humans, two independent exome sequencing studies reveal that a common DENND5B variant, p.(R52K), is correlated with body mass index. These studies establish an important role for DENND5B in post-Golgi chylomicron secretion and a subsequent influence on body composition and peripheral lipoprotein metabolism.
ALDH1A1 regulates postsynaptic μ–opioid receptor expression in dorsal striatal projection neurons and mitigates dyskinesia through transsynaptic retinoic acid signaling
Authors: Pan Jing , Yu Jia , Sun Lixin , Xie Chengsong , Chang Lisa , Wu Junbing , Hawes Sarah , Saez–Atienzar Sara , Zheng Wang , Kung Justin , Ding Jinhui , Le Weidong , Chen Shengdi , Cai Huaibin 
Published: March 2019

AbstractAldehyde dehydrogenase 1A1 (ALDH1A1), a retinoic acid (RA) synthase, is selectively expressed by the nigrostriatal dopaminergic (nDA) neurons that preferentially degenerate in Parkinson’s disease (PD). ALDH1A1–positive axons mainly project to the dorsal striatum. However, whether ALDH1A1 and its products regulate the activity of postsynaptic striatal neurons is unclear. Here we show that μ–type opioid receptor (MOR1) levels were severely decreased in the dorsal striatum of postnatal and adult Aldh1a1 knockout mice, whereas dietary supplement of RA restores its expression. Furthermore, RA treatment also upregulates striatal MOR1 levels and signaling and alleviates L-DOPA–induced dyskinetic movements in pituitary homeobox 3 (Pitx3)–deficient mice that lack of ALDH1A1–expressing nDA neurons. Therefore, our findings demonstrate that ALDH1A1–synthesized RA is required for postsynaptic MOR1 expression in the postnatal and adult dorsal striatum, supporting potential therapeutic benefits of RA supplementation in moderating L-DOPA–induced dyskinesia.
Discovery of natural product ovalicin sensitive type 1 methionine aminopeptidases: molecular and structural basis
Authors: Pillalamarri Vijaykumar , Arya Tarun , Haque Neshatul , Bala Sandeep Chowdary , Marapaka Anil Kumar , Addlagatta Anthony 
Published: March 2019

Abstract
Natural product ovalicin and its synthetic derivative TNP-470 have been extensively studied for their antiangiogenic property, and the later reached phase 3 clinical trials. They covalently modify the conserved histidine in Type 2 methionine aminopeptidases (MetAPs) at nanomolar concentrations. Even though a similar mechanism is possible in Type 1 human MetAP, it is inhibited only at millimolar concentration. In this study, we have discovered two Type 1 wild-type MetAPs (Streptococcus pneumoniae and Enterococcus faecalis) that are inhibited at low micromolar to nanomolar concentrations and established the molecular mechanism. F309 in the active site of Type 1 human MetAP (HsMetAP1b) seems to be the key to the resistance, while newly identified ovalicin sensitive Type 1 MetAPs have a methionine or isoleucine at this position. Type 2 human MetAP (HsMetAP2) also has isoleucine (I338) in the analogous position. Ovalicin inhibited F309M and F309I mutants of human MetAP1b at low micromolar concentration. Molecular dynamics simulations suggest that ovalicin is not stably placed in the active site of wild-type MetAP1b before the covalent modification. In the case of F309M mutant and human Type 2 MetAP, molecule spends more time in the active site providing time for covalent modification.