bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel method for visualizing and tracking endogenous mRNA in a specific cell population in pathological neovascularization
Authors: Uddin Md Imam , Kilburn Tyler C. , Jamal Sara Z. , Duvall Craig L. , Penn John S.
Published: January 2021

Diabetic retinopathy, retinopathy of prematurity and retinal vein occlusion are potentially blinding conditions largely due to their respective neovascular components. The development of real-time in vivo molecular imaging methods, to assess levels of retinal neovascularization (NV), would greatly benefit patients afflicted with these conditions. mRNA hybridization techniques offer a potential method to image retinal NV. The success of these techniques hinges on the selection of a target mRNA whose tissue levels and spatial expression patterns correlate closely with disease burden. Using a model of oxygen-induced retinopathy (OIR), we previously observed dramatic increases in retinal endoglin that localized to neovascular structures (NV), directly correlating with levels of neovascular pathology. Based on these findings, we have investigated Endoglin mRNA as a potential marker for imaging retinal NV in OIR mice. Also of critical importance, is the application of innovative technologies capable of detecting mRNAs in living systems with high sensitivity and specificity. To detect and visualize endoglin mRNA in OIR mice, we have designed and synthesized a novel imaging probe composed of short-hairpin anti-sense (AS) endoglin RNA coupled to a fluorophore and black hole quencher (AS-Eng shRNA). This assembly allows highly sensitive fluorescence emission upon hybridization of the AS-Eng shRNA to cellular endoglin mRNA. The AS-Eng shRNA is further conjugated to a diacyl-lipid (AS-Eng shRNA–lipid referred to as probe). The lipid moiety binds to serum albumin facilitating enhanced systemic circulation of the probe. OIR mice received intraperitoneal injections of AS-Eng shRNA–lipid. Ex vivo imaging of their retinas revealed specific endoglin mRNA dependent fluorescence superimposed on neovascular structures. Room air mice receiving AS-Eng shRNA–lipid and OIR mice receiving a non-sense control probe showed little fluorescence activity. In addition, we found that cells in neovascular lesions labelled with endoglin mRNA dependent fluorescence, co-labelled with the macrophage/microglia-associated marker IBA1. Others have shown that cells expressing macrophage/microglia markers associate with retinal neovascular structures in proportion to disease burden. Hence we propose that our probe may be used to image and to estimate the levels of retinal neovascular disease in real-time in living systems.
Bioinspired antireflective flexible films with optimized mechanical resistance fabricated by roll to roll thermal nanoimprint
Authors: Jacobo-Martín Alejandra , Rueda Mario , Hernández Jaime J. , Navarro-Baena Iván , Monclús Miguel A. , Molina-Aldareguia Jon M. , Rodríguez Isabel
Published: January 2021

This work describes the fabrication process of moth eye antireflective poly (methyl methacrylate) transparent films via roll to roll thermal nanoimprint lithography. The process parameters are investigated and adjusted in order to obtain from a single moth-eye structured mold, a range of antireflective topographies that gradually vary their geometry from protruding to intruding nanocones. A correlation between the process parameters with the optical and mechanical properties of the films is established to illustrate the influence of the processing parameters and serve as guideline to produce antireflective flexible films with balanced properties and optimized performance adequate to the application environment. A finite element model is described predicting the mechanical behavior of the moth-eye PMMA imprinted nanostructures.
Foraging niche partitioning in sympatric seabird populations
Authors: Petalas Christina , Lazarus Thomas , Lavoie Raphael A. , Elliott Kyle H. , Guigueno Mélanie F.
Published: January 2021

Sympatric species must sufficiently differentiate aspects of their ecological niche to alleviate complete interspecific competition and stably coexist within the same area. Seabirds provide a unique opportunity to understand patterns of niche segregation among coexisting species because they form large multi-species colonies of breeding aggregations with seemingly overlapping diets and foraging areas. Recent biologging tools have revealed that colonial seabirds can differentiate components of their foraging strategies. Specifically, small, diving birds with high wing-loading may have small foraging radii compared with larger or non-diving birds. In the Gulf of St-Lawrence in Canada, we investigated whether and how niche differentiation occurs in four incubating seabird species breeding sympatrically using GPS-tracking and direct field observations of prey items carried by adults to chicks: the Atlantic puffin (Fratercula arctica), razorbill (Alca torda), common murre (Uria aalge), and black-legged kittiwake (Rissa tridactyla). Although there was overlap at foraging hotspots, all species differentiated in either diet (prey species, size and number) or foraging range. Whereas puffins and razorbills consumed multiple smaller prey items that were readily available closer to the colony, murres selected larger more diverse prey that were accessible due to their deeper diving capability. Kittiwakes compensated for their surface foraging by having a large foraging range, including foraging largely at a specific distant hotspot. These foraging habitat specialisations may alleviate high interspecific competition allowing for their coexistence, providing insight on multispecies colonial living.
Dense cellular segmentation for EM using 2D–3D neural network ensembles
Authors: Guay Matthew D. , Emam Zeyad A. S. , Anderson Adam B. , Aronova Maria A. , Pokrovskaya Irina D. , Storrie Brian , Leapman Richard D.
Published: January 2021

Biologists who use electron microscopy (EM) images to build nanoscale 3D models of whole cells and their organelles have historically been limited to small numbers of cells and cellular features due to constraints in imaging and analysis. This has been a major factor limiting insight into the complex variability of cellular environments. Modern EM can produce gigavoxel image volumes containing large numbers of cells, but accurate manual segmentation of image features is slow and limits the creation of cell models. Segmentation algorithms based on convolutional neural networks can process large volumes quickly, but achieving EM task accuracy goals often challenges current techniques. Here, we define dense cellular segmentation as a multiclass semantic segmentation task for modeling cells and large numbers of their organelles, and give an example in human blood platelets. We present an algorithm using novel hybrid 2D–3D segmentation networks to produce dense cellular segmentations with accuracy levels that outperform baseline methods and approach those of human annotators. To our knowledge, this work represents the first published approach to automating the creation of cell models with this level of structural detail.
Arabidopsis REI-LIKE proteins activate ribosome biogenesis during cold acclimation
Authors: Cheong Bo Eng , Beine-Golovchuk Olga , Gorka Michal , Ho William Wing Ho , Martinez-Seidel Federico , Firmino Alexandre Augusto Pereira , Skirycz Aleksandra , Roessner Ute , Kopka Joachim
Published: January 2021

Arabidopsis REIL proteins are cytosolic ribosomal 60S-biogenesis factors. After shift to 10 °C,reilmutants deplete and slowly replenish non-translating eukaryotic ribosome complexes of root tissue, while controlling the balance of non-translating 40S- and 60S-subunits.Reilmutations respond by hyper-accumulation of non-translating subunits at steady-state temperature; after cold-shift, a KCl-sensitive 80S sub-fraction remains depleted. We infer that Arabidopsis may buffer fluctuating translation by pre-existing non-translating ribosomes before de novo synthesis meets temperature-induced demands.Reil1 reil2double mutants accumulate 43S-preinitiation and pre-60S-maturation complexes and alter paralog composition of ribosomal proteins in non-translating complexes. With few exceptions, e.g. RPL3B and RPL24C, these changes are not under transcriptional control. Our study suggests requirement of de novo synthesis of eukaryotic ribosomes for long-term cold acclimation, feedback control ofNUC2andeIF3C2transcription and links new proteins, AT1G03250, AT5G60530, to plant ribosome biogenesis. We propose that Arabidopsis requires biosynthesis of specialized ribosomes for cold acclimation.
Hydrogen bond dynamics of interfacial water molecules revealed from two-dimensional vibrational sum-frequency generation spectroscopy
Authors: Ojha Deepak , Kühne Thomas D.
Published: January 2021

Vibrational sum-frequency generation (vSFG) spectroscopy allows the study of the structure and dynamics of interfacial systems. In the present work, we provide a simple recipe, based on a narrowband IR pump and broadband vSFG probe technique, to computationally obtain the two-dimensional vSFG spectrum of water molecules at the air–water interface. Using this technique, to study the time-dependent spectral evolution of hydrogen-bonded and free water molecules, we demonstrate that at the interface, the vibrational spectral dynamics of the free OH bond is faster than that of the bonded OH mode.
Resuscitation from hemorrhagic shock after traumatic brain injury with polymerized hemoglobin
Authors: Muller Cynthia R. , Courelli Vasiliki , Lucas Alfredo , Williams Alexander T. , Li Joyce B. , Dos Santos Fernando , Cuddington Clayton T. , Moses Savannah R. , Palmer Andre F. , Kistler Erik B. , Cabrales Pedro
Published: January 2021

Traumatic brain injury (TBI) is often accompanied by hemorrhage, and treatment of hemorrhagic shock (HS) after TBI is particularly challenging because the two therapeutic treatment strategies for TBI and HS often conflict. Ischemia/reperfusion injury from HS resuscitation can be exaggerated by TBI-induced loss of autoregulation. In HS resuscitation, the goal is to restore lost blood volume, while in the treatment of TBI the priority is focused on maintenance of adequate cerebral perfusion pressure and avoidance of secondary bleeding. In this study, we investigate the responses to resuscitation from severe HS after TBI in rats, using fresh blood, polymerized human hemoglobin (PolyhHb), and lactated Ringer’s (LR). Rats were subjected to TBI by pneumatic controlled cortical impact. Shortly after TBI, HS was induced by blood withdrawal to reduce mean arterial pressure (MAP) to 35–40 mmHg for 90 min before resuscitation. Resuscitation fluids were delivered to restore MAP to ~ 65 mmHg and animals were monitored for 120 min. Increased systolic blood pressure variability (SBPV) confirmed TBI-induced loss of autoregulation. MAP after resuscitation was significantly higher in the blood and PolyhHb groups compared to the LR group. Furthermore, blood and PolyhHb restored diastolic pressure, while this remained depressed for the LR group, indicating a loss of vascular tone. Lactate increased in all groups during HS, and only returned to baseline level in the blood reperfused group. The PolyhHb group possessed lower SBPV compared to LR and blood groups. Finally, sympathetic nervous system (SNS) modulation was higher for the LR group and lower for the PolyhHb group compared to the blood group after reperfusion. In conclusion, our results suggest that PolyhHb could be an alternative to blood for resuscitation from HS after TBI when blood is not available, assuming additional testing demonstrate similar favorable results. PolyhHb restored hemodynamics and oxygen delivery, without the logistical constraints of refrigerated blood.
Redirecting substrate regioselectivity using engineered ΔN123-GBD-CD2 branching sucrases for the production of pentasaccharide repeating units of S. flexneri 3a, 4a and 4b haptens
Authors: Benkoulouche Mounir , Ben Imeddourene Akli , Barel Louis-Antoine , Le Heiget Guillaume , Pizzut Sandra , Kulyk Hanna , Bellvert Floriant , Bozonnet Sophie , Mulard Laurence A. , Remaud-Siméon Magali , Moulis Claire , André Isabelle
Published: January 2021

The (chemo-)enzymatic synthesis of oligosaccharides has been hampered by the lack of appropriate enzymatic tools with requisite regio- and stereo-specificities. Engineering of carbohydrate-active enzymes, in particular targeting the enzyme active site, has notably led to catalysts with altered regioselectivity of the glycosylation reaction thereby enabling to extend the repertoire of enzymes for carbohydrate synthesis. Using a collection of 22 mutants of ΔN123-GBD-CD2 branching sucrase, an enzyme from the Glycoside Hydrolase family 70, containing between one and three mutations in the active site, and a lightly protected chemically synthesized tetrasaccharide as an acceptor substrate, we showed that altered glycosylation product specificities could be achieved compared to the parental enzyme. Six mutants were selected for further characterization as they produce higher amounts of two favored pentasaccharides compared to the parental enzyme and/or new products. The produced pentasaccharides were shown to be of high interest as they are precursors of representative haptens of Shigella flexneri serotypes 3a, 4a and 4b. Furthermore, their synthesis was shown to be controlled by the mutations introduced in the active site, driving the glucosylation toward one extremity or the other of the tetrasaccharide acceptor. To identify the molecular determinants involved in the change of ΔN123-GBD-CD2 regioselectivity, extensive molecular dynamics simulations were carried out in combination with in-depth analyses of amino acid residue networks. Our findings help to understand the inter-relationships between the enzyme structure, conformational flexibility and activity. They also provide new insight to further engineer this class of enzymes for the synthesis of carbohydrate components of bacterial haptens.
Reduced hippocampal subfield volumes and memory performance in preterm children with and without germinal matrix-intraventricular hemorrhage
Authors: Fernández de Gamarra-Oca Lexuri , Zubiaurre-Elorza Leire , Junqué Carme , Solana Elisabeth , Soria-Pastor Sara , Vázquez Élida , Delgado Ignacio , Macaya Alfons , Ojeda Natalia , Poca Maria A.
Published: January 2021

Preterm newborns with germinal matrix-intraventricular hemorrhage (GM-IVH) are at a higher risk of evidencing neurodevelopmental alterations. Present study aimed to explore the long-term effects that GM-IVH have on hippocampal subfields, and their correlates with memory. The sample consisted of 58 participants, including 36 preterm-born (16 with GM-IVH and 20 without neonatal brain injury), and 22 full-term children aged between 6 and 15 years old. All participants underwent a cognitive assessment and magnetic resonance imaging study. GM-IVH children evidenced lower scores in Full Intelligence Quotient and memory measures compared to their low-risk preterm and full-term peers. High-risk preterm children with GM-IVH evidenced significantly lower total hippocampal volumes bilaterally and hippocampal subfield volumes compared to both low-risk preterm and full-term groups. Finally, significant positive correlations between memory and hippocampal subfield volumes were only found in preterm participants together; memory and the right CA-field correlation remained significant after Bonferroni correction was applied (p = .002). In conclusion, memory alterations and both global and regional volumetric reductions in the hippocampus were found to be specifically related to a preterm sample with GM-IVH. Nevertheless, results also suggest that prematurity per se has a long-lasting impact on the association between the right CA-field volume and memory during childhood.
Acute environmental temperature variation affects brain protein expression, anxiety and explorative behaviour in adult zebrafish
Authors: Nonnis S. , Angiulli E. , Maffioli E. , Frabetti F. , Negri A. , Cioni C. , Alleva E. , Romeo V. , Tedeschi G. , Toni M.
Published: January 2021

This study investigated the effect of 4-d acute thermal treatments at 18 °C, 26 °C (control) and 34 °C on the nervous system of adult zebrafish (Danio rerio) using a multidisciplinary approach based on behavioural tests and brain proteomic analysis. The behavioural variations induced by thermal treatment were investigated using five different tests, the novel tank diving, light and dark preference, social preference, mirror biting, and Y-Maze tests, which are standard paradigms specifically tailored for zebrafish to assess their anxiety-like behaviour, boldness, social preference, aggressiveness, and explorative behaviour, respectively. Proteomic data revealed that several proteins involved in energy metabolism, messenger RNA translation, protein synthesis, folding and degradation, cytoskeleton organisation and synaptic vesiculation are regulated differently at extreme temperatures. The results showed that anxiety-like behaviours increase in zebrafish at 18 °C compared to those at 26 °C or 34 °C, whereas anxiety-related protein signalling pathways are downregulated. Moreover, treatments at both 18 °C and 34 °C affect the exploratory behaviour that appears not to be modulated by past experiences, suggesting the impairment of fish cognitive abilities. This study is the continuation of our previous work on the effect of 21-d chronic treatment at the same constant temperature level and will enable the comparison of acute and chronic treatment effects on the nervous system function in adult zebrafish.
RETRACTED ARTICLE: Sulforaphane induces S-phase
arrest and apoptosis via p53-dependent manner in gastric cancer cells
Authors: Wang Yuan , Wu Huazhang , Dong Nannan , Su Xu , Duan Mingxiu , Wei Yaqin , Wei Jun , Liu Gaofeng , Peng Qingjie , Zhao Yunli
Published: January 2021

Sulforaphane (SFN) extracted from broccoli sprout has previously been
investigated for its potential properties in cancers, however, the underlying mechanisms
of the anticancer activity of SFN remain not fully understood. In the present study, we
investigate the effects of SFN on cell proliferation, cell cycle, cell apoptosis, and
also the expression of several cell cycle and apoptosis-related genes by MTT assay, flow
cytometry and western blot analysis in gastric cancer (GC) cells. The results showed
that SFN could impair the colony-forming ability in BGC-823 and MGC-803 cell lines
compared with the control. In addition, SFN significantly suppressed cell proliferation
by arresting the cell cycle at the S phase and enhancing cell apoptosis in GC cells in a
dose-dependent manner. Western blot results showed that SFN treatment significantly
increased the expression levels of p53, p21 and decreased CDK2 expression, which
directly regulated the S phase transition. The Bax and cleaved-caspase-3 genes involved
in apoptosis executive functions were significantly increased in a dose-dependent manner
in BGC-823 and MGC-803 cells. These results suggested that SFN-induced S phase cell
cycle arrest and apoptosis through p53-dependent manner in GC cells, which suggested
that SFN has a potential therapeutic application in the treatment and prevention of
GC.
Interactions between two QTLs for time to anthesis on spike development and fertility in wheat
Authors: Basavaraddi Priyanka A. , Savin Roxana , Wingen Luzie U. , Bencivenga Stefano , Przewieslik-Allen Alexandra M. , Griffiths Simon , Slafer Gustavo A.
Published: January 2021

Earliness per se (Eps) genes are reported to be important in fine-tuning flowering time in wheat independently of photoperiod (Ppd) and vernalisation (Vrn). Unlike Ppd and Vrn genes, Eps have relatively small effects and their physiological effect along with chromosomal position are not well defined. We evaluated eight lines derived from crossing two vernalisation insensitive lines, Paragon and Baj (late and early flowering respectively), to study the detailed effects of two newly identified QTLs, Eps-7D and Eps-2B and their interactions under field conditions. The effect of both QTLs was minor and was affected by the allelic status of the other. While the magnitude of effect of these QTLs on anthesis was similar, they are associated with very different profiles of pre-anthesis development which also depends on their interaction. Eps-7D affected both duration before and after terminal spikelet while not affecting final leaf number (FLN) so Eps-7D-early had a faster rate of leaf appearance. Eps-2B acted more specifically in the early reproductive phase and slightly altered FLN without affecting the leaf appearance rate. Both QTLs affected the spike fertility by altering the rate of floret development and mortality. The effect of Eps-2B was very small but consistent in that -late allele tended to produce more fertile florets.
Pareto-based evaluation of national responses to COVID-19 pandemic shows that saving lives and protecting economy are non-trade-off objectives
Authors: Kochańczyk Marek , Lipniacki Tomasz
Published: January 2021

Countries worldwide have adopted various strategies to minimize the socio-economic impact of the ongoing COVID-19 pandemic. Stringency of imposed measures universally reflects the standpoint from which protecting public health and avoiding damage to economy are seen as contradictory objectives. Based on epidemic trajectories of 25 highly developed countries and 10 US states in the (mobility reduction)–(reproduction number) plane we showed that delay in imposition of nation-wide quarantine elevates the number of infections and deaths, surge of which inevitably has to be suppressed by stringent and sustained lockdown. As a consequence, cumulative mobility reduction and population-normalized cumulative number of COVID-19-associated deaths are significantly correlated and this correlation increases with time. Overall, we demonstrated that, as long as epidemic suppression is the aim, the trade-off between the death toll and economic loss is illusory: high death toll correlates with deep and long-lasting lockdown causing a severe economic downturn.
Grammatical category and the neural processing of phrases
Authors: Burroughs Amelia , Kazanina Nina , Houghton Conor
Published: January 2021

The interlocking roles of lexical, syntactic and semantic processing in language comprehension has been the subject of longstanding debate. Recently, the cortical response to a frequency-tagged linguistic stimulus has been shown to track the rate of phrase and sentence, as well as syllable, presentation. This could be interpreted as evidence for the hierarchical processing of speech, or as a response to the repetition of grammatical category. To examine the extent to which hierarchical structure plays a role in language processing we recorded EEG from human participants as they listen to isochronous streams of monosyllabic words. Comparing responses to sequences in which grammatical category is strictly alternating and chosen such that two-word phrases can be grammatically constructed——or is absent——showed cortical entrainment at the two-word phrase rate was only present in the grammatical condition. Thus, grammatical category repetition alone does not yield entertainment at higher level than a word. On the other hand, cortical entrainment was reduced for the mixed-phrase condition that contained two-word phrases but no grammatical category repetition——which is not what would be expected if the measured entrainment reflected purely abstract hierarchical syntactic units. Our results support a model in which word-level grammatical category information is required to build larger units.
Genome-wide comparative analyses reveal selection signatures underlying adaptation and production in Tibetan and Poll Dorset sheep
Authors: Zhang Yingyue , Xue Xianglan , Liu Yue , Abied Adam , Ding Yangyang , Zhao Shengguo , Wang Wenqiang , Ma Liqing , Guo Jijun , Guan Weijun , Pu Yabin , Mwacharo Joram M. , Han Jianlin , Ma Yuehui , Zhao Qianjun
Published: January 2021

The identification of genome-wide selection signatures can provide insights on the mechanisms of natural and/or artificial selection and uncover genes related to biological functions and/or phenotypes. Tibetan sheep are an important livestock in Tibet, providing meat and wool for Tibetans who are renown for breeding livestock that adapt well to high altitudes. Using whole-genome sequences with an effective sequencing depth of 5×, we investigated the genomic diversity and structure and, identified selection signatures of White Tibetan, Oula and Poll Dorset sheep. We obtained 30,163,679 Single Nucleotide Polymorphisms (SNPs) and 5,388,372 indels benchmarked against the ovine Oar_v4.0 genome assembly. Next, using FST, ZHp and XP-EHH approaches, we identified selection signatures spanning a set of candidate genes, including HIF1A, CAPN3, PRKAA1, RXFP2, TRHR and HOXA10 that are associated with pathways and GO categories putatively related to hypoxia responses, meat traits and disease resistance. Candidate genes and GO terms associated with coat color were also identified. Finally, quantification of blood physiological parameters, revealed higher levels of mean corpuscular hemoglobin measurement and mean corpuscular hemoglobin concentration in Tibetan sheep compared with Poll Dorset, suggesting a greater oxygen-carrying capacity in the Tibetan sheep and thus better adaptation to high-altitude hypoxia. In conclusion, this study provides a greater understanding of genome diversity and variations associated with adaptive and production traits in sheep.
Nanooptical elements for visual verification
Authors: Goncharsky Alexander , Goncharsky Anton , Melnik Dmitry , Durlevich Svyatoslav
Published: January 2021

This paper focuses on the development of flat diffractive optical elements (DOEs) for protecting banknotes, documents, plastic cards, and securities against counterfeiting. A DOE is a flat diffractive element whose microrelief, when illuminated by white light, forms a visual image consisting of several symbols (digits or letters), which move across the optical element when tilted. The images formed by these elements are asymmetric with respect to the zero order. To form these images, the microrelief of a DOE must itself be asymmetric. The microrelief has a depth of ~ 0.3 microns and is shaped with an accuracy of ~ 10–15 nm using electron-beam lithography. The DOEs developed in this work are securely protected against counterfeiting and can be replicated hundreds of millions of times using standard equipment meant for the mass production of relief holograms.
Integrating inflammatory serum biomarkers into a risk calculator for prostate cancer detection
Authors: Jalali Amirhossein , Kitching Michael , Martin Kenneth , Richardson Ciaran , Murphy Thomas Brendan , FitzGerald Stephen Peter , Watson Ronald William , Perry Antoinette Sabrina
Published: January 2021

Improved prostate cancer detection methods would avoid over-diagnosis of clinically indolent disease informing appropriate treatment decisions. The aims of this study were to investigate the role of a panel of Inflammation biomarkers to inform the need for a biopsy to diagnose prostate cancer. Peripheral blood serum obtained from 436 men undergoing transrectal ultrasound guided biopsy were assessed for a panel of 18 inflammatory serum biomarkers in addition to Total and Free Prostate Specific Antigen (PSA). This panel was integrated into a previously developed Irish clinical risk calculator (IPRC) for the detection of prostate cancer and high-grade prostate cancer (Gleason Score ≥ 7). Using logistic regression and multinomial regression methods, two models (Logst-RC and Multi-RC) were developed considering linear and nonlinear effects of the panel in conjunction with clinical and demographic parameters for determination of the two endpoints. Both models significantly improved the predictive ability of the clinical model for detection of prostate cancer (from 0.656 to 0.731 for Logst-RC and 0.713 for Multi-RC) and high-grade prostate cancer (from 0.716 to 0.785 for Logst-RC and 0.767 for Multi-RC) and demonstrated higher clinical net benefit. This improved discriminatory power and clinical utility may allow for individualised risk stratification improving clinical decision making.
Association of Behçet disease with psoriasis and psoriatic arthritis
Authors: Hahn Hyung Jin , Kwak Sang Gyu , Kim Dong-Kyu , Kim Jong-Yeup
Published: January 2021

Behçet disease (BD) is a debilitating multi-systemic vasculitis with a litany of muco-cutaneous manifestations and potentially lethal complications. Meanwhile, psoriasis (PSO) is a cutaneous and systemic inflammatory disorder marked by hyperplastic epidermis and silvery scales, which may be accompanied by a distinct form of arthropathy called psoriatic arthritis (PsA). While the clinical pictures of these two are quite different, they feature some important similarities, most of which may stem from the autoinflammatory components of BD and PSO. Therefore, the aim of this study was to investigate the prospective link between BD and cutaneous and articular manifestations of psoriasis. BD, PSO, and PsA cohorts were extracted using the National Health Insurance Service of Korea database. Using χ2 tests, prevalence of PSO and PsA with respect to BD status was analysed. Relative to non-BD individuals, those with personal history of BD were nearly three times more likely to be diagnosed with PSO. The adjusted odds ratio (aOR) was 2.36 [95% confidence interval (CI), 1.91–2.93, p < 0.001]. Elevated PSO risk was more pronounced in the male BD cohort (aOR = 1.19, 95% CI 1.16–1.23, p < 0.001). In age-group sub-analysis, individuals over 65 years with PSO were one and a half times more likely to be affected with BD, relative to those under 65. The adjusted OR for the older group was 1.51 (95% CI 1.43–1.59, p < 0.001). BD individuals with “healthy” body weight were significantly less likely to be affected by PSO (aOR = 0.59, 95% CI 0.57–0.62, p < 0.001). On the other hand, there was a correlation between BMI and the risk of BD, with the “moderately obese (30–35 kg/m2)” group having an aOR of 1.24 (95% CI 1.12–1.38, p < 0.001). BD patients were also twice more likely to be associated with PsA (aOR = 2.19, 95% CI 1.42–3.38, p < 0.001). However, in contrast to the case of psoriatic disease itself, females were exposed to a greater risk of developing BD compared to the male PsA cohort (aOR = 2.02, 95% CI 1.88–2.16, p < 0.001). As with PSO, older BD patients were exposed to a significantly higher risk of developing PsA (aOR = 3.13, 95% CI 2.90–3.40, p < 0.001). Behçet disease may place an individual at a significantly increased risk of psoriasis, and still greater hazard of being affected with psoriatic arthritis. This added risk was pronounced in the male cohort, and tended to impact senile population, and this phenomenon may be related with the relatively poor prognosis of BD in males and PSO in older patients.
iPSC-derived cardiomyocytes from patients with myotonic dystrophy type 1 have abnormal ion channel functions and slower conduction velocities
Authors: Poulin Hugo , Mercier Aurélie , Djemai Mohammed , Pouliot Valérie , Deschenes Isabelle , Boutjdir Mohamed , Puymirat Jack , Chahine Mohamed
Published: January 2021

Cardiac complications such as electrical abnormalities including conduction delays and arrhythmias are the main cause of death in individuals with Myotonic Dystrophy type 1 (DM1). We developed a disease model using iPSC-derived cardiomyocytes (iPSC-CMs) from a healthy individual and two DM1 patients with different CTG repeats lengths and clinical history (DM1-1300 and DM1-300). We confirmed the presence of toxic RNA foci and mis-spliced MBNL1/2 transcripts in DM1 iPSC-CMs. In DM1-1300, we identified a switch in the cardiac sodium channel SCN5A from the adult to the neonatal isoform. The down-regulation of adult SCN5A isoforms is consistent with a shift in the sodium current activation to depolarized potentials observed in DM1-1300. L-type calcium current density was higher in iPSC-CMs from DM1-1300, which is correlated with the overexpression of the CaV1.2 transcript and proteins. Importantly, INa and ICaL dysfunctions resulted in prolonged action potentials duration, slower velocities, and decreased overshoots. Optical mapping analysis revealed a slower conduction velocity in DM1-1300 iPSC-CM monolayers. In conclusion, our data revealed two distinct ions channels perturbations in DM1 iPSC-CM from the patient with cardiac dysfunction, one affecting Na+ channels and one affecting Ca2+ channels. Both have an impact on cardiac APs and ultimately on heart conduction.
In-depth quantitative proteomic characterization of organotypic hippocampal slice culture reveals sex-specific differences in biochemical pathways
Authors: Weis Simone Nardin , Souza Jaques Miranda F. , Hoppe Juliana Bender , Firmino Marina , Auer Manfred , Ataii Nassim N. , da Silva Leonardo Assis , Gaelzer Mariana Maier , Klein Caroline Peres , Mól Alan R. , de Lima Consuelo M. R. , Souza Diogo Onofre , Salbego Christianne G. , Ricart Carlos André O. , Fontes Wagner , de Sousa Marcelo Valle
Published: January 2021

Sex differences in the brain of mammals range from neuroarchitecture through cognition to cellular metabolism. The hippocampus, a structure mostly associated with learning and memory, presents high vulnerability to neurodegeneration and aging. Therefore, we explored basal sex-related differences in the proteome of organotypic hippocampal slice culture, a major in vitro model for studying the cellular and molecular mechanisms related to neurodegenerative disorders. Results suggest a greater prevalence of astrocytic metabolism in females and significant neuronal metabolism in males. The preference for glucose use in glycolysis, pentose phosphate pathway and glycogen metabolism in females and high abundance of mitochondrial respiration subunits in males support this idea. An overall upregulation of lipid metabolism was observed in females. Upregulation of proteins responsible for neuronal glutamate and GABA synthesis, along with synaptic associated proteins, were observed in males. In general, the significant spectrum of pathways known to predominate in neurons or astrocytes, together with the well-known neuronal and glial markers observed, revealed sex-specific metabolic differences in the hippocampus. TEM qualitative analysis might indicate a greater presence of mitochondria at CA1 synapses in females. These findings are crucial to a better understanding of how sex chromosomes can influence the physiology of cultured hippocampal slices and allow us to gain insights into distinct responses of males and females on neurological diseases that present a sex-biased incidence.
Observation of positive–negative sub-wavelength interference without intensity correlation calculation
Authors: Dou Ling-Yu , Cao De-Zhong , Xu De-Qin , Zhang An-Ning , Song Xin-Bing
Published: January 2021

We report an experimental demonstration of positive–negative sub-wavelength interference without correlation. Typically, people can achieve sub-wavelength effects with correlation measurement no matter by using bi-photon or thermal light sources. In this paper, we adopt a thermal light source, and we count the realizations in which the intensities of the definite symmetric points are above or below a certain threshold. The distribution of numbers of these realizations which meet the restriction will show a sub-wavelength effect. With proper constrictions, positive and negative interference patterns are demonstrated.
OAM light propagation through tissue
Authors: Biton Netanel , Kupferman Judy , Arnon Shlomi
Published: January 2021

A major challenge in use of the optical spectrum for communication and imaging applications is the scattering of light as it passes through diffuse media. Recent studies indicate that light beams with orbital angular momentum (OAM) can penetrate deeper through diffuse media than simple Gaussian beams. To the best knowledge of the authors, in this paper we describe for the first time an experiment examining transmission of OAM beams through biological tissue with thickness of up to a few centimeters, and for OAM modes reaching up to 20. Our results indicate that OAM beams do indeed show a higher transmittance relative to Gaussian beams, and that the greater the OAM, the higher the transmittance also up to 20, Our results extend measured results to highly multi scattering media and indicate that at 2.6 cm tissue thickness for OAM of order 20, we measure nearly 30% more power in comparison to a Gaussian beam. In addition, we develop a mathematical model describing the improved permeability. This work shows that OAM beams can be a valuable contribution to optical wireless communication (OWC) for medical implants, optical biological imaging, as well as recent innovative applications of medical diagnosis.
Protective effect of thymoquinone against lung intoxication induced by malathion inhalation
Authors: Abdo Walied , Elmadawy Mostafa A. , Abdelhiee Ehab Yahya , Abdel-Kareem Mona A. , Farag Amira , Aboubakr Mohamed , Ghazy Emad , Fadl Sabreen E.
Published: January 2021

Malathion is considered one of the vastest pesticides use all over the world. Malathion-inhalation toxicity commonly occurred in many occupational farmers. Therefore, this study aimed to ameliorate the possible malathion-induced pulmonary toxicity through thymoquinone administration. Forty animals were used to conduct our study, divided into five groups; G1 control group, G2 thymoquinone (50 mg/kg) group, G3 malathion group (animals inhaled 100 mg/ml/m3 for 15 min for 5 days/week for three weeks), G4 and G5 were subjected to the same malathion inhalation protocol beside oral thymoquinone administration at doses of 25 and 50 (mg/kg), respectively. Malathion-inhalation induced marked systemic toxicity as hepatotoxicity and nephrotoxicity associated with increased serum hepatic and renal enzymes, and hypersensitivity accompanied with increased total IgE serum level. The lung showed severe interstitial pneumonia associated with severe vascular damage and marked eosinophil infiltration. Moreover, the lung showed a marked decrease in the pulmonary surfactant protein, especially SP-D gene expression. While, thymoquinone treatment to malathion-inhaled animals decremented the following; hepatic enzymes and renal function tests, total IgE as well as pneumonia and hypersensitivity pathological features, and augmented the expression of SP-D. In conclusion, thymoquinone could be potentially used in pest control workers to ameliorate the systemic and pulmonary intoxication caused by one of the most field-used pesticides.
18F-fluorodeoxyglucose positron emission tomography–computed tomography for assessing organ distribution of stressed red blood cells in mice
Authors: Yin Wen-yu , Yuan Jiao , Zhang Zhi-min , Mei Cheng , Xu Wei , Tang Yong-xiang , Peng Fang , Li Ning
Published: January 2021

Red blood cells (RBCs) stressed by high temperature are similar to senescent or damaged RBCs in pathological conditions. RBCs can be efficiently labelled with18F-fluorodeoxyglucose (FDG). The aim of this study was to assess stressed RBCs erythrophagocytosis and organ distribution in vivo with the application of18F-FDG PET/CT. RBCs were induced under high temperature (48 °C) to prepare stressed RBCs. Fluorescence-activated cell sorting (FACS) was used to analyse reactive oxygen species (ROS) generation, intracellular Ca2+concentration and membrane phosphatidylserine (PS) externalization of RBCs.18F-FDG was used to label RBCs and assess the erythrophagocytosis. Finally,18F-FDG PET/CT was applied to reveal and measure the organ distribution of stressed RBCs in mice. Compared with untreated RBCs, stressed RBCs decreased in cell volume and increased in ROS level, intracellular Ca2+concentration, and PS exposure. RBCs could be labelled by18F-FDG. Stressed RBCs tended to be phagocytosed by macrophages via assessment of FACS and radioactivity.18F-FDG PET/CT imaging showed that stressed RBCs were mainly trapped in spleen, while untreated RBCs remained in circulation system. Thus, stressed RBCs can be effectively labelled by18F-FDG and tend to be trapped in spleen of mice as assessed by PET/CT.
On the physical mechanisms underlying single molecule dynamics in simple liquids
Authors: Keanini Russell G. , Dahlberg Jerry , Tkacik Peter T.
Published: January 2021

Physical arguments and comparisons with published experimental data suggest that in simple liquids: (i) single-molecule-scale viscous forces are produced by temperature-dependent London dispersion forces, (ii) viscosity decay with increasing temperature reflects electron cloud compression and attendant suppression of electron screening, produced by increased nuclear agitation, and (iii) temperature-dependent self-diffusion is driven by a narrow band of phonon frequencies lying at the low-frequency end of the solid-state-like phonon spectrum. The results suggest that collision-induced electron cloud distortion plays a decisive role in single molecule dynamics: (i) electron cloud compression produces short-lived repulsive states and single molecule, self-diffusive hops, while (ii) shear-induced distortion generates viscosity and single-molecule-scale viscous drag. The results provide new insight into nonequilibrium molecular dynamics in nonpolar, nonmetallic liquids.
Identification of triptonide as a therapeutic agent for triple negative breast cancer treatment
Authors: Gao Bowen , Chen Jiongyu , Han Bingchen , Zhang Xinfeng , Hao Jijun , Giuliano Armando E. , Cui Yukun , Cui Xiaojiang
Published: January 2021

Triple-negative breast cancer (TNBC) is associated with a high rate of early recurrence and distant metastasis, frequent development of therapeutic resistance, and a poor prognosis. There is a lack of targeted therapies for this aggressive subtype of breast cancer. Identifying novel effective treatment modalities for TNBC remains an urgent and unmet clinical need. In this study, we investigated the anti-cancer effect of triptonide, a natural compound derived from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F, in TNBC. We found that triptonide inhibits human TNBC cell growth in vitro and growth of TNBC xenograft mammary tumors. It induces apoptosis and suppresses stem-like properties as indicated by reduced mammosphere formation and aldehyde dehydrogenase activity in TNBC cells. We show that triptonide downregulates multiple cancer stem cell-associated genes but upregulates SNAI1 gene expression. In support of SNAI1 induction as a negative feedback response to triptonide treatment, in vitro-derived triptonide-resistant HCC1806 cells display a markedly higher expression of SNAI1 compared with parental cells. Mechanistically, the increase of SNAI1 expression is mediated by the activation of JNK signaling, but not by ERK and AKT, two well-established SNAI1 regulators. Furthermore, knockdown of SNAI1 in the triptonide-resistant HCC1806 cells increases sensitivity to triptonide and reduces mammosphere formation. These results indicate that triptonide holds promise as a novel anti-tumor agent for TNBC treatment. Our study also reveals a SNAI1-associated feedback mechanism which may lead to acquired resistance to triptonide.
Predicting the new carbon nanocages, fullerynes: a DFT study
Authors: Qasemnazhand Mohammad , Khoeini Farhad , Marsusi Farah
Published: January 2021

In this study, based on density functional theory, we propose a new branch of pseudo-fullerenes which contain triple bonds with sp hybridization. We call these new nanostructures fullerynes, according to IUPAC. We present four samples with the chemical formula of C4nHn, and the structures derived from fulleranes. We compare the structural and electronic properties of these structures with those of two common fullerenes and fulleranes systems. The calculated electron affinities of the sampled fullerynes are negative, and much smaller than those of fullerenes, so they should be chemically more stable than fullerenes. Although fulleranes also exhibit higher chemical stability than fullerynes, but pentagon or hexagon of the fullerane structures cannot pass ions and molecules. Applications of fullerynes can be included in the storage of ions and gases at the nanoscale. On the other hand, they can also be used as cathode/anode electrodes in lithium-ion batteries.
Mononucleotide repeat expansions with non-natural polymerase substrates
Authors: Chudinov Alexander V. , Vasiliskov Vadim A. , Kuznetsova Viktoriya E. , Lapa Sergey A. , Kolganova Natalia A. , Timofeev Edward N.
Published: January 2021

Replicative strand slippage is a biological phenomenon, ubiquitous among different organisms. However, slippage events are also relevant to non-natural replication models utilizing synthetic polymerase substrates. Strand slippage may notably affect the outcome of the primer extension reaction with repetitive templates in the presence of non-natural nucleoside triphosphates. In the current paper, we studied the ability of Taq, Vent (exo-), and Deep Vent (exo-) polymerases to produce truncated, full size, or expanded modified strands utilizing non-natural 2′-deoxyuridine nucleotide analogues and different variants of the homopolymer template. Our data suggest that the slippage of the primer strand is dependent on the duplex fluttering, incorporation efficiency for a particular polymerase-dNTP pair, rate of non-templated base addition, and presence of competing nucleotides.
Modified sensory feedback enhances the sense of agency during continuous body movements in virtual reality
Authors: Aoyagi Kei , Wen Wen , An Qi , Hamasaki Shunsuke , Yamakawa Hiroshi , Tamura Yusuke , Yamashita Atsushi , Asama Hajime
Published: January 2021

The sense of agency refers to the feeling of control over one’s own actions, and through them, the external events. This study examined the effect of modified visual feedback on the sense of agency over one’s body movements using virtual reality in healthy individuals whose motor control was disturbed. Participants moved a virtual object using their right hand to trace a trajectory (Experiment 1) or a leading target (Experiment 2). Their motor control was disturbed by a delay in visual feedback (Experiment 1) or a 1-kg weight attached to their wrist (Experiment 2). In the offset conditions, the virtual object was presented at the median point between the desired position and the participants’ actual hand position. In both experiments, participants reported improved sense of agency in the offset condition compared to the aligned condition where the visual feedback reflected their actual body movements, despite their motion being less precise in the offset condition. The results show that sense of agency can be enhanced by modifying feedback to motor tasks according to the goal of the task, even when visual feedback is discrepant from the actual body movements. The present study sheds light on the possibility of artificially enhancing body agency to improve voluntary motor control.