bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast tumor cells promotes the horizontal propagation of EMT, stemness, and metastasis by transferring the MAP17 protein between subsets of neoplastic cells
Authors: García-Heredia José Manuel , Otero-Albiol Daniel , Pérez Marco , Pérez-Castejón Elena , Muñoz-Galván Sandra , Carnero Amancio
Published: October 2020

MAP17 (PDZK1IP1) is a small protein regulating inflammation and tumor progression, upregulated in a broad range of carcinomas. MAP17 levels increase during tumor progression in a large percentage of advanced tumors. In the present work, we explored the role of this protein shaping tumor evolution. Here we show that in breast cancer, cells increased MAP17 levels in tumors by demethylation induced multiple changes in gene expression through specific miRNAs downregulation. These miRNA changes are dependent on Notch pathway activation. As a consequence, epithelial mesenchymal transition (EMT) and stemness are induced promoting the metastatic potential of these cells both in vitro and in vivo. Furthermore, MAP17 increased the exosomes in tumor cells, where MAP17 was released as cargo, and this horizontal propagation also increased the EMT in the recipient cells. Importantly, an antibody against MAP17 in the media reduces the EMT and stemness alterations promoted by the conditioned media from MAP17-expressing cells. Therefore, MAP17 expression promotes the horizontal propagation of EMT and metastasis by transferring the MAP17 protein between subsets of neoplastic cells. Thus, MAP17 can be used to describe a new mechanism for cell malignity at distance, without the involvement of genetic or epigenetic modifications. MAP17 can also be taken in consideration as new target for metastatic high-grade breast tumors.
Genome-wide association studies of antidepressant class response and treatment-resistant depression
Authors: Li Qingqin S. , Tian Chao , Hinds David ,   23andMe Research Team, Agee Michelle , Alipanahi Babak , Auton Adam , Bell Robert K. , Bryc Katarzyna , Elson Sarah L. , Fontanillas Pierre , Furlotte Nicholas A. , Huber Karen E. , Kleinman Aaron , Litterman Nadia K. , McIntyre Matthew H. , Mountain Joanna L. , Noblin Elizabeth S. , Northover Carrie A. M. , Pitts Steven J. , Sathirapongsasuti J. Fah , Sazonova Olga V. , Shelton Janie F. , Shringarpure Suyash , Tung Joyce Y. , Vacic Vladimir , Wilson Catherine H. , Zare Amir S.
Published: October 2020

The “antidepressant efficacy” survey (AES) was deployed to > 50,000 23andMe, Inc. research participants to investigate the genetic basis of treatment-resistant depression (TRD) and non-treatment-resistant depression (NTRD). Genome-wide association studies (GWAS) were performed, including TRD vs. NTRD, selective serotonin reuptake inhibitor (SSRI) responders vs. non-responders, serotonin-norepinephrine reuptake inhibitor (SNRI) responders vs. non-responders, and norepinephrine-dopamine reuptake inhibitor responders vs. non-responders. Only the SSRI association reached the genome-wide significance threshold (p < 5 × 10−8): one genomic region in RNF219-AS1 (SNP rs4884091, p = 2.42 × 10−8, OR = 1.21); this association was also observed in the meta-analysis (13,130 responders vs. 6,610 non-responders) of AES and an earlier “antidepressant efficacy and side effects” survey (AESES) cohort. Meta-analysis for SNRI response phenotype derived from AES and AESES (4030 responders vs. 3049 non-responders) identified another genomic region (lead SNP rs4955665, p = 1.62 × 10−9, OR = 1.25) in an intronic region of MECOM passing the genome-wide significance threshold. Meta-analysis for the TRD phenotype (31,068 NTRD vs 5,714 TRD) identified one additional genomic region (lead SNP rs150245813, p = 8.07 × 10−9, OR = 0.80) in 10p11.1 passing the genome-wide significance threshold. A stronger association for rs150245813 was observed in current study (p = 7.35 × 10−7, OR = 0.79) than the previous study (p = 1.40 × 10−3, OR = 0.81), and for rs4955665, a stronger association in previous study (p = 1.21 × 10−6, OR = 1.27) than the current study (p = 2.64 × 10−4, OR = 1.21). In total, three novel loci associated with SSRI or SNRI (responders vs. non-responders), and NTRD vs TRD were identified; gene level association and gene set enrichment analyses implicate enrichment of genes involved in immune process.
T cell-intrinsic role for Nod2 in protection against Th17-mediated uveitis
Authors: Napier Ruth J. , Lee Ellen J. , Davey Michael P. , Vance Emily E. , Furtado João M. , Snow Paige E. , Samson Kimberly A. , Lashley Sydney J. , Brown Brieanna R. , Horai Reiko , Mattapallil Mary J. , Xu Biying , Callegan Michelle C. , Uebelhoer Luke S. , Lancioni Christina L. , Vehe Richard K. , Binstadt Bryce A. , Smith Justine R. , Caspi Rachel R. , Rosenzweig Holly L.
Published: October 2020

Mutations in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) cause Blau syndrome, an inflammatory disorder characterized by uveitis. The antimicrobial functions of Nod2 are well-established, yet the cellular mechanisms by which dysregulated Nod2 causes uveitis remain unknown. Here, we report a non-conventional, T cell-intrinsic function for Nod2 in suppression of Th17 immunity and experimental uveitis. Reconstitution of lymphopenic hosts with Nod2−/−CD4+T cells or retina-specific autoreactive CD4+T cells lacking Nod2 reveals a T cell-autonomous, Rip2-independent mechanism for Nod2 in uveitis. In naive animals, Nod2 operates downstream of TCR ligation to suppress activation of memory CD4+T cells that associate with an autoreactive-like profile involving IL-17 and Ccr7. Interestingly, CD4+T cells from two Blau syndrome patients show elevated IL-17 and increased CCR7. Our data define Nod2 as a T cell-intrinsic rheostat of Th17 immunity, and open new avenues for T cell-based therapies for Nod2-associated disorders such as Blau syndrome.
Over-activation of primate subgenual cingulate cortex enhances the cardiovascular, behavioral and neural responses to threat
Authors: Alexander Laith , Wood Christian M. , Gaskin Philip L. R. , Sawiak Stephen J. , Fryer Tim D. , Hong Young T. , McIver Lauren , Clarke Hannah F. , Roberts Angela C.
Published: October 2020

Stress-related disorders such as depression and anxiety are characterized by enhanced negative emotion and physiological dysfunction. Whilst elevated activity within area 25 of the subgenual anterior cingulate cortex (sgACC/25) has been implicated in these illnesses, it is unknown whether this over-activity is causal. By combining targeted intracerebral microinfusions with cardiovascular and behavioral monitoring in marmosets, we show that over-activation of sgACC/25 reduces vagal tone and heart rate variability, alters cortisol dynamics during stress and heightens reactivity to proximal and distal threat.18F-FDG PET imaging shows these changes are accompanied by altered activity within a network of brain regions including the amygdala, hypothalamus and dorsolateral prefrontal cortex. Ketamine, shown to have rapid antidepressant effects, fails to reverse elevated arousal to distal threat contrary to the beneficial effects we have previously demonstrated on over-activation induced reward blunting, illustrating the symptom-specificity of its actions.
Presence of low virulence chytrid fungi could protect European amphibians from more deadly strains
Authors: Greener Mark S. , Verbrugghe Elin , Kelly Moira , Blooi Mark , Beukema Wouter , Canessa Stefano , Carranza Salvador , Croubels Siska , De Troyer Niels , Fernandez-Giberteau Daniel , Goethals Peter , Lens Luc , Li Zhimin , Stegen Gwij , Strubbe Diederik , van Leeuwenberg Robby , Van Praet Sarah , Vila-Escale Mireia , Vervaeke Muriel , Pasmans Frank , Martel An
Published: October 2020

Wildlife diseases are contributing to the current Earth’s sixth mass extinction; one disease, chytridiomycosis, has caused mass amphibian die-offs. While global spread of a hypervirulent lineage of the fungusBatrachochytrium dendrobatidis(BdGPL) causes unprecedented loss of vertebrate diversity by decimating amphibian populations, its impact on amphibian communities is highly variable across regions. Here, we combine field data with in vitro and in vivo trials that demonstrate the presence of a markedly diverse variety of low virulence isolates ofBdGPL in northern European amphibian communities. Pre-exposure to some of these low virulence isolates protects against disease following subsequent exposure to highly virulentBdGPL in midwife toads (Alytes obstetricans) and alters infection dynamics of its sister speciesB. salamandrivoransin newts (Triturus marmoratus), but not in salamanders (Salamandra salamandra). The key role of pathogen virulence in the complex host-pathogen-environment interaction supports efforts to limit pathogen pollution in a globalized world.
Structure of Epstein-Barr virus tegument protein complex BBRF2-BSRF1 reveals its potential role in viral envelopment
Authors: He Hui-Ping , Luo Meng , Cao Yu-Lu , Lin Yu-Xin , Zhang Hua , Zhang Xiao , Ou Jun-Ying , Yu Bing , Chen Xiaoxue , Xu Miao , Feng Lin , Zeng Mu-Sheng , Zeng Yi-Xin , Gao Song
Published: October 2020

Epstein-Barr virus (EBV) is a γ-herpesvirus associated with the occurrence of several human malignancies. BBRF2 and BSRF1 are two EBV tegument proteins that have been suggested to form a hetero-complex and mediate viral envelopment, but the molecular basis of their interaction and the functional mechanism of this complex remains unknown. Here, we present crystal structures of BBRF2 alone and in complex with BSRF1. BBRF2 has a compact globular architecture featuring a central β-sheet that is surrounded by 10 helices, it represents a novel fold distinct from other known protein structures. The central portion of BSRF1 folds into two tightly associated antiparallel α-helices, forming a composite four-helix bundle with two α-helices from BBRF2 via a massive hydrophobic network. In vitro, a BSRF1-derived peptide binds to BBRF2 and reduces the number of viral genome copies in EBV-positive cells. Exogenous BBRF2 and BSRF1 co-localize at the Golgi apparatus. Furthermore, BBRF2 binds capsid and capsid-associated proteins, whereas BSRF1 associates with glycoproteins. These findings indicate that the BBRF2-BSRF1 complex tethers EBV nucleocapsids to the glycoprotein-enriched Golgi membrane, facilitating secondary envelopment.
Insights into the use of mesenchymal stem cells in COVID-19 mediated acute respiratory failure
Authors: Durand Nisha , Mallea Jorge , Zubair Abba C.
Published: October 2020

The emergence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) at the end of 2019 in Hubei province China, is now the cause of a global pandemic present in over 150 countries. COVID-19 is a respiratory illness with most subjects presenting with fever, cough and shortness of breath. In a subset of patients, COVID-19 progresses to hypoxic respiratory failure and acute respiratory distress syndrome (ARDS), both of which are mediated by widespread inflammation and a dysregulated immune response. Mesenchymal stem cells (MSCs), multipotent stromal cells that mediate immunomodulation and regeneration, could be of potential benefit to a subset of COVID-19 subjects with acute respiratory failure. In this review, we discuss key features of the current COVID-19 outbreak, and the rationale for MSC-based therapy in this setting, as well as the limitations associated with this therapeutic approach.
Phenolic profiles and antioxidant activities in selected drought-tolerant leafy vegetable amaranth
Authors: Sarker Umakanta , Oba Shinya
Published: October 2020

Four selected advance lines of drought-tolerant leafy vegetable amaranth were characterized for phenolic profiles, vitamins, and antioxidant activities. The selected advance lines exhibited differences in terms of genotypes with remarkable phenols, vitamins, flavonoids content, and potential radical quenching capacity. We identified twenty-five phenolic and flavonoid compounds including protocatechuic acid, salicylic acid, gentisic acid, gallic acid, β-resorcylic acid, vanillic acid, p-hydroxybenzoic acid, chlorogenic acid, ellagic acid, syringic acid, ferulic acid, kaempferol, m-coumaric acid, trans-cinnamic acid, quercetin, p-coumaric acid, apigenin, caffeic acid, rutin, sinapic acid, isoquercetin, naringenin, myricetin, catechin, and hyperoside. The selected advance lines VA14 and VA16 had abundant phenols, vitamins, flavonoids, and antioxidants potentiality. The selected drought-tolerant leafy vegetable amaranth showed high antioxidant potentiality as phenols, vitamins, flavonoids of these lines had a significant positive correlation with antioxidant capacities equivalent to Trolox using 2,2-diphenyl-1-picrylhydrazyl and ABTS+. Therefore, drought-tolerant leafy vegetable amaranth VA14 and VA16 can be grown in semi-arid and drought-prone areas in the world to attaining vitamins and antioxidant sufficiency. The phenolic and flavonoids compounds identified in drought-tolerant leafy vegetable amaranth demand a comprehensive pharmacological study. The baseline data on phenolic and flavonoids compounds obtained in the present study will contribute to the scientist forum for the scientific evaluation of these compounds in vegetable amaranth.
The endosomal protein sorting nexin 4 is a synaptic protein
Authors: Vazquez-Sanchez Sonia , Gonzalez-Lozano Miguel A. , Walfenzao Alexarae , Li Ka Wan , van Weering Jan R. T.
Published: October 2020

Sorting nexin 4 (SNX4) is an evolutionary conserved protein that mediates recycling from endosomes back to the plasma membrane in yeast and mammalian cells. SNX4 is expressed in the brain. Altered protein levels are associated with Alzheimer’s disease, but the neuronal localization and function of SNX4 have not been addressed. Using a new antibody, endogenous neuronal SNX4 co-localized with both early and recycling endosome markers, similar to the reported localization of SNX4 in non-neuronal cells. Neuronal SNX4 accumulated specifically in synaptic areas, with a predominant localization to presynaptic terminals. Acute depletion of neuronal SNX4 using independent short hairpin RNAs did not affect the levels of the transferrin receptor, a canonical SNX4 cargo. Quantitative mass spectrometry revealed that upon SNX4 knockdown the class of proteins involved in neurotransmission was the most dysregulated. This included integral membrane proteins at both the presynaptic and postsynaptic side of the synapse that participate in diverse synaptic processes such as synapse assembly, neurotransmission and the synaptic vesicle cycle. These data suggest that SNX4 is implicated in a variety of synaptic processes.
Disruption of Tip60 HAT mediated neural histone acetylation homeostasis is an early common event in neurodegenerative diseases
Authors: Beaver Mariah , Bhatnagar Akanksha , Panikker Priyalakshmi , Zhang Haolin , Snook Renee , Parmar Visha , Vijayakumar Gayathri , Betini Niteesha , Akhter Sunya , Elefant Felice
Published: October 2020

Epigenetic dysregulation is a common mechanism shared by molecularly and clinically heterogenous neurodegenerative diseases (NDs). Histone acetylation homeostasis, maintained by the antagonistic activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs), is necessary for appropriate gene expression and neuronal function. Disruption of neural acetylation homeostasis has been implicated in multiple types of NDs including Alzheimer’s disease (AD), yet mechanisms underlying alterations remain unclear. We show that like AD, disruption of Tip60 HAT/HDAC2 balance with concomitant epigenetic repression of common Tip60 target neuroplasticity genes occurs early in multiple types of Drosophila ND models such as Parkinson’s Disease (PD), Huntington’s Disease (HD) and Amyotrophic Lateral Sclerosis (ALS). Repressed neuroplasticity genes show reduced enrichment of Tip60 and epigentic acetylation signatures at all gene loci examined with certain genes showing inappropriate HDAC2 repressor enrichment. Functional neuronal consequences for these disease conditions are reminiscent of human pathology and include locomotion, synapse morphology, and short-term memory deficits. Increasing Tip60 HAT levels specifically in the mushroom body learning and memory center in the Drosophila brain protects against locomotion and short-term memory function deficits in multiple NDs. Together, our results support a model by which Tip60 protects against neurological impairments in different NDs via similar modes of action.
Differential immune gene expression associated with contemporary range expansion in two invasive rodents in Senegal
Authors: Charbonnel Nathalie , Galan Maxime , Tatard Caroline , Loiseau Anne , Diagne Christophe , Dalecky Ambroise , Parrinello Hugues , Rialle Stephanie , Severac Dany , Brouat Carine
Published: October 2020

Biological invasions are major anthropogenic changes associated with threats to biodiversity and health. However, what determines the successful establishment and spread of introduced populations remains unclear. Here, we explore several hypotheses linking invasion success and immune phenotype traits, including those based on the evolution of increased competitive ability concept. We compared gene expression profiles between anciently and recently established populations of two major invading species, the house mouse Mus musculus domesticus and the black rat Rattus rattus, in Senegal (West Africa). Transcriptome analyses identified differential expression between anciently and recently established populations for 364 mouse genes and 83 rat genes. All immune-related genes displaying differential expression along the mouse invasion route were overexpressed at three of the four recently invaded sites studied. Complement activation pathway genes were overrepresented among these genes. By contrast, no particular immunological process was found to be overrepresented among the differentially expressed genes of black rat. Changes in transcriptome profiles were thus observed along invasion routes, but with different specific patterns between the two invasive species. These changes may be driven by increases in infection risks at sites recently invaded by the house mouse, and by stochastic events associated with colonization history for the black rat. These results constitute a first step toward the identification of immune eco-evolutionary processes potentially involved in the invasion success of these two rodent species.
Particle size effect on sorting with optical lattice
Authors: Madadi Ebrahim , Biagooi Morad , Mohammadjafari Farhad , Nedaaee Oskoee SeyedEhsan
Published: October 2020

Transport of mesoscale particles due to driving flow fields or external forces on a periodic surface appears in many areas. Geometrical and physical characteristics of particles affect the velocities of the particles in these periodic landscapes. In this paper, we present a numerical simulation based on solving the Langevin equation for the meso-size particles subjected to the thermal fluctuations in a periodic array of optical traps. We consider the real-size particles which cause the partial trapping of particles in the optical traps. The particles are sorted for the size-dependency of particles’ trajectories. Our results are in good agreement with experiments.
Growth promotion and protection from drought in Eucalyptus grandis seedlings inoculated with beneficial bacteria embedded in a superabsorbent polymer
Authors: Chaín José María , Tubert Esteban , Graciano Corina , Castagno Luis Nazareno , Recchi Marina , Pieckenstain Fernando Luis , Estrella María Julia , Gudesblat Gustavo , Amodeo Gabriela , Baroli Irene
Published: October 2020

Eucalyptus grandis is a globally important tree crop. Greenhouse-grown tree seedlings often face water deficit after outplanting to the field, which can affect their survival and establishment severely. This can be alleviated by the application of superabsorbent hydrophilic polymers (SAPs). Growth promoting bacteria can also improve crop abiotic stress tolerance; however, their use in trees is limited, partly due to difficulties in the application and viability loss. In this work, we evaluated the improvement of drought tolerance of E. grandis seedlings by inoculating with two Pseudomonas strains (named M25 and N33), carried by an acrylic-hydrocellulosic SAP. We observed significant bacterial survival in the seedling rhizosphere 50 days after inoculation. Under gradual water deficit conditions, we observed a considerable increase in the water content and wall elasticity of M25-inoculated plants and a trend towards growth promotion with both bacteria. Under rapid water deficit conditions, which caused partial defoliation, both strains significantly enhanced the formation of new leaves, while inoculation with M25 reduced the transpiration rate. Co-inoculation with M25 and N33 substantially increased growth and photosynthetic capacity. We conclude that the selected bacteria can benefit E. grandis early growth and can be easily inoculated at transplant by using an acrylic-hydrocellulosic SAP.
Impaired contraction of blood clots precedes and predicts postoperative venous thromboembolism
Authors: Evtugina Natalia G. , Peshkova Alina D. , Pichugin Arseniy A. , Weisel John W. , Litvinov Rustem I.
Published: October 2020

Deep vein thrombosis (DVT) is a common but unpredictable complication of surgical interventions. To reveal an association between the blood clot contraction (retraction) and the incidence of postoperative venous thrombosis, 78 patients with brain tumors that were operated on were studied, of which 23 (29%) were diagnosed with postoperative DVT. A clot contraction assay, along with other hemostatic and hematologic tests, was performed 1–3 days before the surgery and on the 1st day and 5–7th days after the surgery. On the 1st postoperative day, clot contraction was significantly suppressed in patients who subsequently developed DVT, compared to the patients without DVT. Importantly, this difference was observed at least 5 days before DVT had developed. The weakening of contraction on the 1st postoperative day was more pronounced in the DVT patients with malignant versus benign brain tumors, atherosclerosis, hypertension, as well as in patients receiving steroids before and during the operation. These results indicate that impaired clot contraction in the postoperative period is associated with imminent DVT, suggesting that it is a prothrombotic risk factor and promotional mechanism. The clot contraction assay has a predictive value in assessing the threat of postoperative thrombosis in patients with benign and malignant brain tumors.
A large deletion on CFA28 omitting ACSL5 gene is associated with intestinal lipid malabsorption in the Australian Kelpie dog breed
Authors: O’Brien Mitchell J. , Beijerink Niek J. , Sansom Mandy , Thornton Sarah W. , Chew Tracy , Wade Claire M.
Published: October 2020

Inborn errors of metabolism are genetic conditions that can disrupt intermediary metabolic pathways and cause defective absorption and metabolism of dietary nutrients. In an Australian Kelpie breeding population, 17 puppies presented with intestinal lipid malabsorption. Juvenile dogs exhibited stunted postnatal growth, steatorrhea, abdominal distension and a wiry coat. Using genome-wide association analysis, an associated locus on CFA28 (Praw = 2.87E−06) was discovered and validated in a closely related population (Praw = 1.75E−45). A 103.3 kb deletion NC_006610.3CFA28:g.23380074_23483377del, containing genes Acyl-CoA Synthetase Long Chain Family Member 5 (ACSL5) and Zinc Finger DHHC-Type Containing 6 (ZDHHC6), was characterised using whole transcriptomic data. Whole transcriptomic sequencing revealed no expression of ACSL5 and disrupted splicing of ZDHHC6 in jejunal tissue of affected Kelpies. The ACSL5 gene plays a key role in long chain fatty acid absorption, a phenotype similar to that of our affected Kelpies has been observed in a knockout mouse model. A PCR-based diagnostic test was developed and confirmed fully penetrant autosomal recessive mode of inheritance. We conclude the structural variant causing a deletion of the ACSL5 gene is the most likely cause for intestinal lipid malabsorption in the Australian Kelpie.
Title: Cytokine release syndrome is not usually caused by secondary hemophagocytic lymphohistiocytosis in a cohort of 19 critically ill COVID-19 patients
Authors: Lorenz Georg , Moog Philipp , Bachmann Quirin , La Rosée Paul , Schneider Heike , Schlegl Michaela , Spinner Christoph , Heemann Uwe , Schmid Roland M. , Algül Hana , Lahmer Tobias , Huber Wolfgang , Schmaderer Christoph
Published: October 2020

Severe COVID-19 associated respiratory failure, poses the one challenge of our days. Assessment and treatment of COVID-19 associated hyperinflammation may be key to improve outcomes. It was speculated that in subgroups of patients secondary hemophagocytic lymphohistiocytosis (sHLH) or cytokine release syndrome (CRS) with features of macrophage activation syndrome might drive severe disease trajectories. If confirmed, profound immunosuppressive therapy would be a rationale treatment approach. Over a median observation period of 11 (IQR: 8; 16) days, 19 consecutive confirmed severe COVID-19-patients admitted to our intensive-care-unit were tested for presence of sHLH by two independent experts. HScores and 2004-HLH diagnostic criteria were assessed. Patients were grouped according to short-term clinical courses: discharge from ICU versus ongoing ARDS or death at time of analysis. The median HScore at admission was 157 (IQR: 98;180), without the key clinical triad of HLH, i.e. progressive cytopenia, persistent fever and organomegaly. Independent expert chart review revealed the absence of sHLH in all cases. No patient reached more than 3/6 of modified HLH 2004 criteria. Nevertheless, patients presented hyperinflammation with peripheral neutrophilic signatures (neutrophil/lymphocyte-ratio > 3.5). The latter best paralleled their short-term clinical courses, with declining relative neutrophil numbers prior to extubation (4.4, [IQR: 2.5;6.3]; n = 8) versus those with unfavourable courses (7.6, [IQR: 5.2;31], n = 9). Our study rules out virus induced sHLH as the leading cause of most severe-COVID-19 trajectories. Instead, an associated innate neutrophilic hyperinflammatory response or virus-associated-CRS appears dominant in patients with an unfavourable clinical course. Therapeutic implications are discussed.
Prognostic impact of malignant diseases in idiopathic pulmonary fibrosis
Authors: Lee Hong Yeul , Cho Jaeyoung , Kwak Nakwon , Lee Jinwoo , Park Young Sik , Lee Chang-Hoon , Lee Sang-Min , Yoo Chul-Gyu , Kim Young Whan , Choi Sun Mi
Published: October 2020

No studies on idiopathic pulmonary fibrosis (IPF) have investigated the prognostic impact of extrapulmonary cancers in patients with IPF. We aimed to determine the prognostic impact of malignancies in patients with IPF. We retrospectively reviewed the medical records of patients diagnosed with IPF between 2001 and 2015. Patients were divided into three groups: IPF without cancer (n = 440), IPF with lung cancer (n = 69), and IPF with extrapulmonary cancer (n = 70). Of the 579 patients with IPF, 139 (24%) had cancer; the three most common types were lung (11.9%), gastric (2.4%), and colorectal (1.9%). Survival was significantly worse in patients with lung cancer than in those without cancer (hazard ratio [HR] = 1.83, 95% confidence interval [CI], 1.35–2.48) or those with extrapulmonary cancer (HR = 1.70, 95% CI, 1.14–2.54). The rate of hospitalisation for cancer-related complications was significantly higher in IPF patients with lung cancer than in those with extrapulmonary cancer. The annual rates of decline in percent predicted forced vital capacity and diffusion capacity for carbon monoxide did not differ among the groups. Physicians should pay attention to the development and progression of cancer and its prognostic impact in patients with IPF.
Human amniotic membrane plug to promote failed macular hole closure
Authors: Caporossi Tomaso , Pacini Bianca , Bacherini Daniela , Barca Francesco , Faraldi Francesco , Rizzo Stanislao
Published: October 2020

The failed macular hole is a full-thickness defect involving the fovea that fails to close despite 1 or more surgeries. While many surgical options have been proposed to manage it, none of these guarantee complete anatomical success and satisfactory visual recovery. We report postoperative outcomes on 36 patients affected by failed macular hole, treated with a human amniotic membrane plug transplant. Follow-ups were performed with a standard ophthalmological examination and with advanced multimodal diagnostic imaging. Anatomical closure was achieved at 3 months in all patients. Mean best-corrected visual acuity improved statistically significantly at 6 months (p < 0.05). Through microperimetric tests, we assessed a partial recovery of the macular sensitivity on the edges of the plug. Analyzing SD-OCT images, we reported a tissutal ingrowth above the plug, and its segmentation into layers, mimicking normal retinal architecture. OCT-Angiography images non invasively analysed the retinal parafoveal capillary microvasculature; the elaboration of Adaptive Optics images showed the presence of photoreceptors at the edges of the plug. This work demonstrates not only the complete anatomical success of our technique, but also remarkable functional results, and opens the door to a greater understanding of modifications induced by the presence of a human amniotic membrane plug.
Visualization and quantification of dynamic intercellular coupling in human embryonic stem cells using single cell sonoporation
Authors: Fan Zhenzhen , Xue Xufeng , Fu Jianping , Deng Cheri X.
Published: October 2020

Gap junctions (GJs), which are proteinaceous channels, couple adjacent cells by permitting direct exchange of intracellular molecules with low molecular weights. GJ intercellular communication (GJIC) plays a critical role in regulating behaviors of human embryonic stem cells (hESCs), affecting their proliferation and differentiation. Here we report a novel use of sonoporation that enables single cell intracellular dye loading and dynamic visualization/quantification of GJIC in hESC colonies. By applying a short ultrasound pulse to excite single microbubbles tethered to cell membranes, a transient pore on the cell membrane (sonoporation) is generated which allows intracellular loading of dye molecules and influx of Ca2+ into single hESCs. We employ live imaging for continuous visualization of intercellular dye transfer and Ca2+ diffusion in hESC colonies. We quantify cell–cell permeability based on dye diffusion using mass transport models. Our results reveal heterogeneous intercellular connectivity and a variety of spatiotemporal characteristics of intercellular Ca2+ waves in hESC colonies induced by sonoporation of single cells.
Morphological and physiological responses of two willow species from different habitats to salt stress
Authors: Feng Shuang , Ren Lulu , Sun Hongwei , Qiao Kun , Liu Shenkui , Zhou Aimin
Published: October 2020

Plant salt tolerance is a complex mechanism, and different plant species have different strategies for surviving salt stress. In the present study, we analyzed and compared the morphological and physiological responses of two willow species (Salix linearistipularis and Salix matsudana) from different habitats to salt stress. S. linearistipularis exhibited higher seed germination rates and seedling root Na+ efflux than S. matsudana under salt stress. After salt treatment, S. linearistipularis leaves exhibited less Na+ accumulation, loss of water and chlorophyll, reduction in photosynthetic capacity, and damage to leaf cell structure than leaves of S. matsudana. Scanning electron microscopy combined with gas chromatography mass spectrometry showed that S. linearistipularis leaves had higher cuticular wax loads than S. matsudana leaves. Overall, our results showed that S. linearistipularis had higher salt tolerance than S. matsudana, which was associated with different morphological and physiological responses to salt stress. Furthermore, our study suggested that S. linearistipularis could be a promising tree species for saline-alkali land greening and improvement.
E-TUBE: dielectric waveguide cable for high-speed communication
Authors: Song Ha Il , Lee Joon-Yeong , Won Hyosup , Kim Chang-Ahn , Jin Huxian , Eu Jake , Park Jinho , Bae Hyeon-Min
Published: October 2020

The demand for advanced interconnects to satisfy market requirements on bandwidth, cost, and power is ever increasing with the expansion of data centers. An interconnect called E-TUBE is presented as a cost-and-power-efficient all-electrical-domain wideband waveguide solution for high-speed high-volume short-reach communication links. The E-TUBE achieves an unprecedented level of throughput-distance product, bending radius, and channel density without requiring complex manufacturing process. The E-TUBE link demonstrates nearly 25 GHz bandwidth at a carrier frequency of 70 GHz and exhibits a frequency-independent insertion loss of 5 dB/m with a frequency-independent group delay of 4 ns/m. Such loss and delay characteristics independent of frequency enabled broadband data transmission over extended reach compared to conventional waveguide links. The E-TUBE link transmits 25 Gbps NRZ data over 3 m distance using a 70 GHz RF CMOS transceiver IC, which is the state-of-the-art throughput-reach product. This new interconnect is expected to overcome the limitations of existing electrical and optical interconnects and to replace them in high throughput links, including but not limited to, 100/400 Gbps board-to-board communications.
Spatio-temporal distribution and acoustic characterization of haddock (Melanogrammus aeglefinus, Gadidae) calls in the Arctic fjord Kongsfjorden (Svalbard Islands)
Authors: Buscaino G. , Picciulin M. , Canale D. E. , Papale E. , Ceraulo M. , Grammauta R. , Mazzola S.
Published: October 2020

In this study we analysed the acoustic properties and presence of haddock calls in the Arctic fjord Kongsfjorden (79° N–12° E, Svalbard Islands, Norway) in one year. Data were collected with three autonomous acoustic recorders located in the inner, middle, and outer parts of the fjord. The fjord is characterized by a gradient of oceanographic conditions from the inner to the outer part, reflecting changes from Arctic to Atlantic waters. Haddock sounds were more abundant in the outer fjord than in the middle fjord, whereas they were absent at the inner site. Mainly at the open-water site, the call abundance exhibited strong periodicity and a correlation with the cycles of neap tide (15 days) in August, with a clear diel cycle (24 h) in September and October. This result suggests that in this extreme environment with 24 h of light during summer, haddock regulate their acoustic activity according to the main available oscillating external physical driver, such as tide during the polar summer, while when the alternation of light/dark starts, they shift the periodicity of their calls to a diel cycle. Calls were recorded outside the spawning period (from July to October), and their characteristics indicated non-reproductive communicative contests. By using a detailed sound analysis based on previous laboratory studies for the first time, we suggest that the monitored population contains mainly juveniles (44% compared to 41% females and only approximately 15% mature males), showing the predominance of females in the middle fjord and juveniles at the open-water site.
Cerebrospinal fluid neopterin as a biomarker of neuroinflammatory diseases
Authors: Molero-Luis Marta , Casas-Alba Didac , Orellana Gabriela , Ormazabal Aida , Sierra Cristina , Oliva Clara , Valls Anna , Velasco Jesus , Launes Cristian , Cuadras Daniel , Pérez-Dueñas Belén , Jordan Iolanda , Cambra Francisco J. , Ortigoza-Escobar Juan D. , Muñoz-Almagro Carmen , Garcia-Cazorla Angels , Armangué Thais , Artuch Rafael
Published: October 2020

The elevation of neopterin in cerebrospinal fluid (CSF) has been reported in several neuroinflammatory disorders. However, it is not expected that neopterin alone can discriminate among different neuroinflammatory etiologies. We conducted an observational retrospective and case–control study to analyze the CSF biomarkers neopterin, total proteins, and leukocytes in a large cohort of pediatric patients with neuroinflammatory disorders. CSF samples from 277 subjects were included and classified into four groups: Viral meningoencephalitis, bacterial meningitis, acquired immune-mediated disorders, and patients with no-immune diseases (control group). CSF neopterin was analyzed with high-performance liquid chromatography. Microbiological diagnosis included bacterial CSF cultures and several specific real-time polymerase chain reactions. Molecular testing for multiple respiratory pathogens was also included. Antibodies against neuronal and glial proteins were tested. Canonical discriminant analysis of the three biomarkers was conducted to establish the best discriminant functions for the classification of the different clinical groups. Model validation was done by biomarker analyses in a new cohort of 95 pediatric patients. CSF neopterin displayed the highest values in the viral and bacterial infection groups. By applying canonical discriminant analysis, it was possible to classify the patients into the different groups. Validation analyses displayed good results for neuropediatric patients with no-immune diseases and for viral meningitis patients, followed by the other groups. This study provides initial evidence of a more efficient approach to promote the timely classification of patients with viral and bacterial infections and acquired autoimmune disorders. Through canonical equations, we have validated a new tool that aids in the early and differential diagnosis of these neuroinflammatory conditions.
Affinity enrichment of extracellular vesicles from plasma reveals mRNA changes associated with acute ischemic stroke
Authors: Wijerathne Harshani , Witek Malgorzata A. , Jackson Joshua M. , Brown Virginia , Hupert Mateusz L. , Herrera Kristina , Kramer Cameron , Davidow Abigail E. , Li Yan , Baird Alison E. , Murphy Michael C. , Soper Steven A.
Published: October 2020

Currently there is no in vitro diagnostic test for acute ischemic stroke (AIS), yet rapid diagnosis is crucial for effective thrombolytic treatment. We previously demonstrated the utility of CD8(+) T-cells’ mRNA expression for AIS detection; however extracellular vesicles (EVs) were not evaluated as a source of mRNA for AIS testing. We now report a microfluidic device for the rapid and efficient affinity-enrichment of CD8(+) EVs and subsequent EV’s mRNA analysis using droplet digital PCR (ddPCR). The microfluidic device contains a dense array of micropillars modified with anti-CD8α monoclonal antibodies that enriched 158 ± 10 nm sized EVs at 4.3 ± 2.1 × 109 particles/100 µL of plasma. Analysis of mRNA from CD8(+) EVs and their parental T-cells revealed correlation in the expression for AIS-specific genes in both cell lines and healthy donors. In a blinded study, 80% test positivity for AIS patients and controls was revealed with a total analysis time of 3.7 h.
Solid-state Nanopore Confinement for Single Molecule Detection
Authors: Lin Yao , Li Qiao , Liu Shao-Chuang , Lu Si-Min , Ying Yi-Lun , Long Yi-Tao
Published: October 2020

This chapter focuses on the electrochemical confinement effect of nanopores fabricated from inorganic materials for single molecule sensing by electrochemical and optical readouts. The fabrication methods are summarized with examples such as focused ion beam, high-power electron beam and controlled dielectric breakdown approaches. The DNA molecule unzipping process and DNA-based target protein detection using solid-state nanopores are demonstrated. Moreover, the nanopore can efficiently capture a single molecule within its electrochemically confined space for real-time monitoring the transient intermediate states. Based on this strategy, the dynamics of an individual DNA–protein complex within solid-state nanopores is discussed.
Biomaterials-based approaches to model embryogenesis
Authors: Spiteri Chantelle , Caprettini Valeria , Chiappini Ciro
Published: October 2020

Biomaterials are emerging as invaluable tools to investigate key mechanisms of human development using advancein vitromodels. Nanomaterials can contribute to further refine these models.
Ab initio insights into the stabilization and binding mechanisms of MoS2 nanoflakes supported on graphene
Authors: Caturello Naidel A. M. S. , F. R. V. Silveira Julian , Da Silva Juarez L. F.
Published: October 2020

The MoS2–graphene interactions do not play a role in the relative stability of large (MoS2)n nanoflakes supported on graphene, n > 6.
Selective hydrogenation of fluorinated arenes using rhodium nanoparticles on molecularly modified silica
Authors: Kacem Souha , Emondts Meike , Bordet Alexis , Leitner Walter
Published: October 2020

Rh nanoparticles prepared on hydrophobic molecularly modified silica act as effective catalysts for the hydrogenation of fluoroarenes to fluorocyclohexane derivatives.
Evaluating aqueous flow battery electrolytes: a coordinated approach
Authors: Robb Brian H. , Waters Scott E. , Marshak Michael P.
Published: October 2020

Here, we outline some basic pitfalls in the electrochemical investigation of aqueous metal complexes, advocate for the use of bulk electrolysis in redox flow cells for electrolyte analysis, and demonstrate methods of operation and performance of a lab scale redox flow battery.
A catalytic study of water dispersed gold nanoparticles for the hydrolytic oxidation of diorganosilanes – en route formation of a Pickering catalyst and synthesis of tetraorganodisiloxane-1,3-diols
Authors: Shankar Ravi , Mahavar Nidhi
Published: October 2020

This study unfolds the formation of a AuNP-stabilized Pickering catalyst (PIC) en route to the hydrolytic oxidation of diorganosilanes. The method offers a viable route for the synthesis of disiloxane-1,3-diols.
Immobilizing cobalt phthalocyanine into a porous carbonized wood membrane as a self-supported heterogenous electrode for selective and stable CO2 electroreduction in water
Authors: Zhang Haidong , Min Shixiong , Wang Fang , Zhang Zhengguo
Published: October 2020

Immobilizing CoPc into a porous carbonized wood membrane (CoPc/CWM) leads to a self-supported heterogenous electrode for efficient CO2 electroreduction in water.
Nitrite denitrification using biomass acclimatized with methanol as complementary carbon source: long-term performance and kinetics study
Authors: Badia Ahmed , Kim Mingu , Dagnew Martha
Published: October 2020

The objective of this study was to investigate the dynamic specific denitrification rates (SDNRs) from nitrite at various COD/N ratios in a system that used methanol as a complementary carbon source.
Digestibility, bioactivity and prebiotic potential of phenolics released from whole gold kiwifruit and pomace byin vitrogastrointestinal digestion and colonic fermentation
Authors: Xie Xing , Chen Chun , Huang Qiang , Fu Xiong
Published: October 2020

The aim of this study was to evaluate the release of phenolics, biological activity variation and prebiotic potential of whole gold kiwifruit and pomace byin vitrodigestion and colonic fermentation.
Monolayer hydrophilic MoS2 with strong charge trapping for atomically thin neuromorphic vision systems
Authors: Hu Yunxia , Dai Mingjin , Feng Wei , Zhang Xin , Zhang Shichao , Tan Biying , Shang Huiming , Fu Yong Qing , Hu PingAn
Published: October 2020

Through covalently introducing hydroxyl groups, monolayer hydrophilic MoS2 is synthesized with strong charge trapping and can be applied to an atomically thin neuromorphic visual system with image sensing, image memorization, and color discrimination.
Engineering the photoresponse of liquid-exfoliated 2D materials by size selection and controlled mixing for an ultrasensitive and ultraresponsive photodetector
Authors: Alzakia Fuad Indra , Tang Baoshan , Pennycook Stephen John , Tan Swee Ching
Published: October 2020

The photoresponse dynamics of a TMD network can be controlled via the careful selection of nanosheet sizes and controlled mixing with graphene nanosheets.
Reliable organic memristors for neuromorphic computing by predefining a localized ion-migration path in crosslinkable polymer
Authors: Park Hea-Lim , Kim Min-Hwi , Kim Min-Hoi , Lee Sin-Hyung
Published: October 2020

A novel concept for confining filament growth in an organic memristor is demonstrated by exploiting the functionality of crosslinkable polymers.
Rapid access to 3-acyl indoles using ethyl acetate/triflic acid couple as the acylium donor and Cu(OAc)2 catalysed aerial oxidation of indole benzoins
Authors: Talukdar Ranadeep
Published: October 2020

R′ = 1° and 2° alkyls, benzyl, allyl, cyanomethyl, carboxymethyl, phenyl; Ar = C6H5, 4-F-C6H4, 4-MeO–C6H4; X = N, O, S; Y = H, Me; Z = H, Br.
In situsurface modification of bulk or nano materials by cytochrome-cfor active hydrogen evolution catalysis
Authors: Thakur Pallavi , Mannuthodikayil Jamsad , Kalita Golap , Mandal Kalyaneswar , Narayanan Tharangattu N.
Published: October 2020

Protein assisted electrochemical hydrogen evolution catalyst development has been proposed here.
Visible-light-induced selectivity controllable synthesis of diamine or imidazoline derivatives by multicomponent decarboxylative radical coupling reactions
Authors: Pan Shulei , Jiang Min , Zhong Guofu , Dai Linlong , Zhou Yu , Wei Kaihang , Zeng Xiaofei
Published: October 2020

A visible-light-induced and photoredox-catalyzed three-component selectivity controllable synthesis of vicinal diamines and imidazoles from readily available starting materials under mild reaction conditions has been realized.
Nitriles as radical acceptors in radical cascade reactions
Authors: Sun Kai , Lv Qi-Yan , Lin Ying-Wu , Yu Bing , He Wei-Min
Published: October 2020

The application of the cyano group as a radical acceptor in the cascade reactions for the construction of various important heterocycles and carbocycles was summarized.
Metal-free synthesis of 3-chalcogenyl chromones from alkynyl aryl ketones and diorganyl diselenides/disulfides mediated by PIFA
Authors: Ai Zhenkang , Xiao Jiaxi , Li Yadong , Guo Boying , Du Yunfei , Zhao Kang
Published: October 2020

3-Selenyl/sulfenyl chromones/thiochromones were conveniently synthesized from the PIFA-mediated reactions between alkynyl aryl ketones bearing an ortho-methoxy/methylthio group and diorganyl diselenides/disulfides.
A novel lamellar structural biomaterial and its effect on bone regeneration
Authors: Cheng Guoping , Guo Shujuan , Wang Ningxin , Xiao Shimeng , Jiang Bo , Ding Yi
Published: October 2020

To evaluate a novel lamellar structural biomaterial for guided bone regeneration, we describe the preparation of a collagen membrane with high mechanical strength and anti-enzyme degradation ability using Ctenopharyngodon idella scales.
Investigation of the process stability of different anammox configurations and assessment of the simulation validity of various anammox-based kinetic models
Authors: Wang Chunyan , Wu Hanyang , Zhu Bin , Song Jianyang , Lu Tingjie , Li Yu-You , Niu Qigui
Published: October 2020

Over the last 30 years, the successful implementation of the anammox process has attracted research interest from all over the world.
A single amino acid Gly-tag enables metal-free protein purification
Authors: Purushottam Landa , V. B. Unnikrishnan , Rawale Dattatraya Gautam , Gujrati Mansi , Mishra Surya Dev , T. K. Sajeev , Reddy Neelesh C. , Adusumalli Srinivasa Rao , Mishra Ram Kumar , Rai Vishal
Published: October 2020

Gly-tag resin precisely captures and releases a protein with one glycine at the N-terminus. The user-friendly protocol delivers analytically pure protein free of metal contaminants.
A cyclopentadienyl functionalized silylene – a flexible ligand for Si- and C-coordination
Authors: Kaufmann Sebastian , Krätschmer Frederic , Köppe Ralf , Schon Thorben , Schoo Christoph , Roesky Peter W.
Published: October 2020

A cyclopentadienyl functionalized silylene or its derivatives can be coordinated in all three forms: silylene (A), anion (B), and sila fulvene (C).