Miracle-dz/UniFAR-FTUs huggingface dataset:
An Edge-Fog Secure Self-Authenticable Data Transfer Protocol

Development of the Internet of Things (IoT) opens many new challenges. As IoT devices are getting smaller and smaller, the problems of so-called “constrained devices” arise. The traditional Internet protocols are not very well suited for constrained devices comprising localized network nodes with tens of devices primarily communicating with each other (e.g., various sensors in Body Area Network communicating with each other). These devices have very limited memory, processing, and power resources, so traditional security protocols and architectures also do not fit well. To address these challenges the Fog computing paradigm is used in which all constrained devices, or Edge nodes, primarily communicate only with less-constrained Fog node device, which collects all data, processes it and communicates with the outside world. We present a new lightweight secure self-authenticable transfer protocol (SSATP) for communications between Edge nodes and Fog nodes. The primary target of the proposed protocol is to use it as a secure transport for CoAP (Constrained Application Protocol) in place of UDP (User Datagram Protocol) and DTLS (Datagram Transport Layer Security), which are traditional choices in this scenario. SSATP uses modified header fields of standard UDP packets to transfer additional protocol handling and data flow management information as well as user data authentication information. The optional redundant data may be used to provide increased resistance to data losses when protocol is used in unreliable networks. The results of experiments presented in this paper show that SSATP is a better choice than UDP with DTLS in the cases, where the CoAP block transfer mode is used and/or in lossy networks.
Dynamic Expression and Regulation of Urotensin I and Corticotropin-Releasing Hormone Receptors in Ovary of Olive Flounder Paralichthys olivaceus

Urotensin I (UI), a fish corticotropin-releasing hormone (CRH) like peptide, has been found throughout vertebrate species that has great effects on adaptive physiology comprising stress-related responses, and osmotic regulation by binding with CRH type I receptor (CRHR1) and CRH type II receptor (CRHR2) in fish. Dynamic expression and regulation of UI and CRH receptors in the olive flounder ovarian follicle were studied so as to make further efforts to understand the role of UI in the development of teleost ovary. The results showed that stage-specific change in UI mRNA levels in ovarian follicles of olive flounder. UI and CRHR1 mRNA levels were higher in stage III follicles (300∼500 μm diameter) compared to stage II (90∼300 μm diameter) and IV (500∼800 μm diameter) follicles, however, the levels of CRHR2 mRNA were decreased in line with the ovarian development from stage II to stage IV. A strong signal of UI protein was observed in the follicular cells and oocyte in stage III and IV follicles by immunohistochemistry. In vitro treatment of olive flounder ovarian follicles with human chorionic gonadotropin (hCG) showed that the mRNA expression of UI increased significantly at low concentration and decreased at high concentration at 6 h, but the CRHR1 and CRHR2 mRNA did not change obviously. In addition, the results of incubation with 17α, 20β-dihydroxy-4-oregnen-3-one (DHP) show that UI and CRHR1 mRNA expression were elevated with increasing concentrations at 9 h. All above results indicated that UI and CRH receptors may have a vital effect on olive flounder ovarian development.
Synergistic Inhibition of Mycotoxigenic Fungi and Mycotoxin Production by Combination of Pomegranate Peel Extract and Azole Fungicide

Fungal plant pathogens cause considerable losses in yield and quality of field crops worldwide. In addition, under specific environmental conditions, many fungi, including such as some Fusarium and Aspergillus spp. , are further able to produce mycotoxins while colonizing their host, which accumulate in human and animal tissues, posing a serious threat to consumer health. Extensive use of azole fungicides in crop protection stimulated the emergence of acquired azole resistance in some plant and human fungal pathogens. Combination treatments, which become popular in clinical practice, offer an alternative strategy for managing potentially resistant toxigenic fungi and reducing the required dosage of specific drugs. In the current study we tested the effect of pomegranate peel extract (PPE) on the growth and toxin production of the mycotoxigenic fungi Aspergillus flavus and Fusarium proliferatum, both alone and in combination with the azole fungicide prochloraz (PRZ). Using time-lapse microscopy and quantitative image analysis we demonstrate significant delay of conidial germination and hyphal elongation rate in both fungi following PPE treatment in combination with PRZ. Moreover, PPE treatment reduced aflatoxin production by A. flavus up to 97%, while a combined treatment with sub-inhibitory doses of PPE and PRZ resulted in complete inhibition of toxin production over a 72 h treatment. These findings were supported by qRT-PCR analysis, showing down-regulation of key genes involved in the aflatoxin biosynthetic pathway under combined PPE/PRZ treatment al low concentrations. Our results provide first evidence for synergistic effects between the commercial drug PRZ and natural compound PPE. Future application of these findings may allow to reduce the required dosage of PRZ, and possibly additional azole drugs, to inhibit mycotoxigenic fungi, ultimately reducing potential concerns over exposure to high doses of these potentially harmful fungicides.
Genes and Mechanisms Involved in the Generation and Amplification of Basal Radial Glial Cells

The development of the cerebral cortex relies on different types of progenitor cell. Among them, the recently described basal radial glial cell (bRG) is suggested to be of critical importance for the development of the brain in gyrencephalic species. These cells are highly numerous in primate and ferret brains, compared to lissencephalic species such as the mouse in which they are few in number. Their somata are located in basal subventricular zones in gyrencephalic brains and they generally possess a basal process extending to the pial surface. They sometimes also have an apical process directed toward the ventricular surface, similar to apical radial glial cells (aRGs) from which they are derived, and whose somata are found more apically in the ventricular zone. bRGs share similarities with aRGs in terms of gene expression (SOX2, PAX6, and NESTIN), whilst also expressing a range of more specific genes (such as HOPX). In primate brains, bRGs can divide multiple times, self-renewing and/or generating intermediate progenitors and neurons. They display a highly specific cytokinesis behavior termed mitotic somal translocation. We focus here on recently identified molecular mechanisms associated with the generation and amplification of bRGs, including bRG-like cells in the rodent. These include signaling pathways such as the FGF-MAPK cascade, SHH, PTEN/AKT, PDGF pathways, and proteins such as INSM, GPSM2, ASPM, TRNP1, ARHGAP11B, PAX6, and HIF1α. A number of these proteins were identified through transcriptome comparisons in human aRGs vs. bRGs, and validated by modifying their activities or expression levels in the mouse. This latter experiment often revealed enhanced bRG-like cell production, even in some cases generating folds (gyri) on the surface of the mouse cortex. We compare the features of the identified cells and methods used to characterize them in each model. These important data converge to indicate pathways essential for the production and expansion of bRGs, which may help us understand cortical development in health and disease.
What We Have Learned From the Framework for Ocean Observing: Evolution of the Global Ocean Observing System

The Global Ocean Observing System (GOOS) and its partners have worked together over the past decade to break down barriers between open-ocean and coastal observing, between scientific disciplines, and between operational and research institutions. Here we discuss some GOOS successes and challenges from the past decade, and present ideas for moving forward, including highlights of the GOOS 2030 Strategy, published in 2019. The OceanObs' 09 meeting in Venice in 2009 resulted in a remarkable consensus on the need for a common set of guidelines for the global ocean observing community. Work following the meeting led to development of the Framework for Ocean Observing (FOO) published in 2012 and adopted by GOOS as a foundational document that same year. The FOO provides guidelines for the setting of requirements, assessing technology readiness, and assessing the usefulness of data and products for users. Here we evaluate successes and challenges in FOO implementation and consider ways to ensure broader use of the FOO principles. The proliferation of ocean observing activities around the world is extremely diverse and not managed, or even overseen by, any one entity. The lack of coherent governance has resulted in duplication and varying degrees of clarity, responsibility, coordination and data sharing. GOOS has had considerable success over the past decade in encouraging voluntary collaboration across much of this broad community, including increased use of the FOO guidelines and partly effective governance, but much remains to be done. Here we outline and discuss several approaches for GOOS to deliver more effective governance to achieve our collective vision of fully meeting society's needs. What would a more effective and well-structured governance arrangement look like? Can the existing system be modified? Do we need to rebuild it from scratch? We consider the case for evolution versus revolution. Community-wide consideration of these governance issues will be timely and important before, during and following the OceanObs' 19 meeting in September 2019.
Differential Hippocampal Expression of BDNF Isoforms and Their Receptors Under Diverse Configurations of the Serotonergic System in a Mice Model of Increased Neuronal Survival

Neurotrophic factors are relevant regulators of the neurogenic process at different levels. In particular, the brain-derived neurotrophic factor, BDNF, is highly expressed in the hippocampus (HC) of rodents and participates in the control of neuronal proliferation, and survival in the dentate gyrus (DG). Likewise, serotonin is also involved in the regulation of neurogenesis, though its role is apparently more complex. Indeed, both enhancement of serotonin neurotransmission as well as serotonin depletion, paradoxically increase neuronal survival in the HC of mice. In this study, we analyzed the protein expression of the BDNF isoforms, i.e., pro- and mature-BDNF, and their respective receptors p75 and TrkB, in the HC of mice chronically treated with para-chloro-phenyl-alanine (PCPA), an inhibitor of serotonin synthesis. The same analysis was conducted in hyposerotonergic mice with concomitant administration of the 5-HT1A receptor agonist, 8-Hydroxy-2-(di-n- propylamino) tetralin (8-OH-DPAT). Increased expression of p75 receptor with decreased expression of pro-BDNF was observed after chronic PCPA. Seven-day treatment with 8-OH-DPAT reestablished the expression of pro-BDNF modified by PCPA, and induced an increase in the expression of p75 receptor. It has been demonstrated that PCPA-treated mice have higher number of immature neurons in the HC. Given that immature neurons participate in the pattern separation process, the object pattern separation test was conducted. A better performance of hyposerotonergic mice was not confirmed in this assay. Altogether, our results show that molecules in the BDNF signaling pathway are differentially expressed under diverse configurations of the serotonergic system, allowing for fine-tuning of the neurogenic process.
Photography in the planning of health interventions for the elderly.

OBJECTIVE To analyze potentialities of the use of photo-elicitation technique as a tool of access to the real needs of the beneficiaries of the intervention of health professionals. For this purpose, the aspects of their quality of life that they considered more relevant were identified with an elderly group. METHOD It is a qualitative investigation in which the discourse of the elderly on the changes to their quality of life is encouraged through the use of photographic images. RESULTS Based on the data obtained, it was possible to identify the aspects of quality of life considered more relevant by the elderly, allowing, therefore, to sustain a later intervention adjusted to the needs and expectations of the elderly. FINAL CONSIDERATIONS The use of photo-elicitation allowed verifying its potentialities as a strategy to collect significant and relevant information for the planning of interventions in the Health area.
Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma Is Reversed by SIRT1

Sorafenib is a multi-kinase inhibitor and one of the few systemic treatment options for patients with advanced hepatocellular carcinomas (HCCs). Resistance to sorafenib develops frequently and could be mediated by the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin (SIRT)1. We aimed to test whether sorafenib efficacy is influenced by cellular NAD levels and NAD-dependent SIRT1 function. We analyzed sorafenib effects on apoptosis induction, NAD salvage, mitochondrial function, and related signaling pathways in HCC cell lines (HepG2, Hep3B, und HUH7) overexpressing SIRT1 or supplemented with the NAD metabolite nicotinamide mononucleotide (NMN) compared to controls. Treatment of HCC cell lines with sorafenib dose-dependently induced apoptosis and a significant decrease in cellular NAD concentrations. The SIRT1 protein was downregulated in HUH7 cells but not in Hep3B cells. After sorafenib treatment, mitochondrial respiration in permeabilized cells was lower, citrate synthase activity was attenuated, and cellular adenosine triphosphate (ATP) levels were decreased. Concomitant to increased phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), sorafenib treatment led to decreased activity of the mechanistic target of rapamycin (mTOR), indicative of energy deprivation. Transient overexpression of SIRT1, as well as NAD repletion by NMN, decreased sorafenib-induced apoptosis. We can, therefore, conclude that sorafenib influences the NAD/SIRT1/AMPK axis. Overexpression of SIRT1 could be an underlying mechanism of resistance to sorafenib treatment in HCC.
Retromer and TBC1D5 maintain late endosomal RAB7 domains to enable amino acid–induced mTORC1 signaling

Retromer is an evolutionarily conserved multiprotein complex that orchestrates the endocytic recycling of integral membrane proteins. Here, we demonstrate that retromer is also required to maintain lysosomal amino acid signaling through mTORC1 across species. Without retromer, amino acids no longer stimulate mTORC1 translocation to the lysosomal membrane, which leads to a loss of mTORC1 activity and increased induction of autophagy. Mechanistically, we show that its effect on mTORC1 activity is not linked to retromer's role in the recycling of transmembrane proteins. Instead, retromer cooperates with the RAB7-GAP TBC1D5 to restrict late endosomal RAB7 into microdomains that are spatially separated from the amino acid-sensing domains. Upon loss of retromer, RAB7 expands into the ragulator-decorated amino acid-sensing domains and interferes with RAG-GTPase and mTORC1 recruitment. Depletion of retromer in Caenorhabditis elegans reduces mTORC1 signaling and extends the lifespan of the worms, confirming an evolutionarily conserved and unexpected role for retromer in the regulation of mTORC1 activity and longevity.
How much is enough? An appraisal of high‐power short‐duration radiofrequency ablation for pulmonary vein isolation

Any strategy being developed for ablation in the left atrium should strive to accomplish transmural lesions with no collateral tissue damage. A variety of modalities have been evaluated over the years to achieve these goals: radiofrequency (RF), cryotherapy, electroporation, laser and microwave.1 Application of RF energy has itself incorporated many innovations like integration of 3-D electroanatomical mapping and imaging tools during ablation, use of contact-force sensing catheters, and development of algorithms like force-time integral (FTI), stability monitoring, ablation index (AI), lesion size index (LSI) to guide ablation. This article is protected by copyright. All rights reserved.
Expression of receptor interacting protein 3 and mixed lineage kinase domain-like protein-key proteins in necroptosis is upregulated in ulcerative colitis.

BACKGROUND Ulcerative colitis (UC) is a chronic inflammatory colonic disease strongly associated with intestinal epithelial cell (IEC) death. Necroptosis is characterized by a newly programmed cell death through a caspase-independent pathway. Receptor interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) are very important in the pathway of necroptosis. However, their expression in UC remains unelucidated. This study aimed to investigate the expression of RIP3 and MLKL in patients with UC, along with its correlation with disease activity. METHODS Colonic tissue samples were taken from 22 UC patients and 19 healthy controls. RIP3 and MLKL expression levels were evaluated by immunohistochemical staining and western blotting. RESULTS RIP3 and MLKL were upregulated in inflamed tissues of UC (P<0.01). No variations were observed in healthy control subjects and non-inflamed colons (P>0.05). RIP3 and MLKL were positively correlated with UC disease activity (P<0.01). CONCLUSIONS Our results suggest that necroptosis is strongly associated with intestinal inflammation in patients with UC. Further studies of necroptosis may be helpful in future treatments of UC.
miR526b and miR655 Induce Oxidative Stress in Breast Cancer

In eukaryotes, overproduction of reactive oxygen species (ROS) causes oxidative stress, which contributes to chronic inflammation and cancer. MicroRNAs (miRNAs) are small, endogenously produced RNAs that play a major role in cancer progression. We established that overexpression of miR526b/miR655 promotes aggressive breast cancer phenotypes. Here, we investigated the roles of miR526b/miR655 in oxidative stress in breast cancer using in vitro and in silico assays. miRNA-overexpression in MCF7 cells directly enhances ROS and superoxide (SO) production, detected with fluorescence assays. We found that cell-free conditioned media contain extracellular miR526b/miR655 and treatment with these miRNA-conditioned media causes overproduction of ROS/SO in MCF7 and primary cells (HUVECs). Thioredoxin Reductase 1 (TXNRD1) is an oxidoreductase that maintains ROS/SO concentration. Overexpression of TXNRD1 is associated with breast cancer progression. We observed that miR526b/miR655 overexpression upregulates TXNRD1 expression in MCF7 cells, and treatment with miRNA-conditioned media upregulates TXNRD1 in both MCF7 and HUVECs. Bioinformatic analysis identifies two negative regulators of TXNRD1, TCF21 and PBRM1, as direct targets of miR526b/miR655. We validated that TCF21 and PBRM1 were significantly downregulated with miRNA upregulation, establishing a link between miR526b/miR655 and TXNRD1. Finally, treatments with oxidative stress inducers such as H2O2 or miRNA-conditioned media showed an upregulation of miR526b/miR655 expression in MCF7 cells, indicating that oxidative stress also induces miRNA overexpression. This study establishes the dynamic functions of miR526b/miR655 in oxidative stress induction in breast cancer.
A cluster of melioidosis infections in hatchling saltwater crocodiles (Crocodylus porosus) resolved using genome-wide comparison of a common north Australian strain of Burkholderia pseudomallei

Burkholderia pseudomallei is a Gram-negative saprophytic bacillus and the aetiological agent of melioidosis, a disease of public-health importance throughout Southeast Asia and northern Australia. Infection can occur in humans and a wide array of animal species, though zoonotic transmission and case clusters are rare. Despite its highly plastic genome and extensive strain diversity, fine-scale investigations into the population structure of B. pseudomallei indicate there is limited geographical dispersal amongst sequence types (STs). In the ‘Top End’ of northern Australia, five STs comprise 90 % of the overall abundance, the most prevalent and widespread of which is ST-109. In May 2016, ST-109 was implicated in two fatal cases of melioidosis in juvenile saltwater crocodiles at a wildlife park near Darwin, Australia. To determine the probable source of infection, we sampled the crocodile enclosures and analysed the phylogenetic relatedness of crocodile and culture-positive ST-109 environmental park isolates against an additional 135 ST-109 B. pseudomallei isolates from the Top End. Collectively, our whole-genome sequencing (WGS) and pathology findings confirmed B. pseudomallei detected in the hatchling incubator as the likely source of infection, with zero SNPs identified between clinical and environmental isolates. Our results also demonstrate little variation across the ST-109 genome, with SNPs in recombinogenic regions and one suspected case of ST homoplasy accounting for nearly all observed diversity. Collectively, this study supports the use of WGS for outbreak source attribution in highly recombinogenic pathogens, and confirms the epidemiological and phylogenetic insights that can be gained from high-resolution sequencing platforms.
Upregulation of MAPK10, TUBB2B and RASL11B may contribute to the development of neuroblastoma

The present study aimed to investigate genes and transcription factors (TFs) that may contribute to neuroblastoma (NB) development. The GSE78061 dataset that included 25 human NB cell lines and four retinal pigment epithelial cell lines was used to analyze differentially expressed genes (DEGs) between groups. Functional enrichment analysis and protein-protein interaction (PPI) network analysis were performed for the identified DEGs. Additionally, submodule analysis and TF-target regulatory networks were conducted. The relative mRNA expression levels of mitogen-activated protein kinase 10 (MAPK10), tubulin β 2B class IIb (TUBB2B), RAS like family 11 member B (RASL11B) and integrin subunit α 2 (ITGA2) in the NB cell line SH-SY5Y were compared with retinal pigment epithelial cell lines. A set of 386 upregulated and 542 downregulated DEGs were obtained. Upregulated DEGs were significantly associated with the ‘neuron migration’ and ‘dopaminergic synapse signaling’ pathways, whereas, downregulated DEGs were primarily involved in ‘focal adhesion’ such as ITGA2 and ITGA3. In the PPI networks analyzed, MAPK10, dopa decarboxylase (DDC), G protein subunit γ 2 (GNG2), paired like homeobox 2B (PHOX2B), TUBB2B, RASL11B, and ITGA2 were hub genes with high connectivity degrees. Additionally, PHOX2B was predicted to be a TF regulating TUBB2B in the regulatory network. The expressions of MAPK10, TUBB2B, RASL11B and ITGA2 were detected by reverse transcription-quantitative polymerase chain reaction in the NB cell line SH-SY5Y, and were consistent with the present bioinformatics results, suggesting that MAPK10, DDC, GNG2, PHOX2B, TUBB2B, RASL11B, ITGA2 and ITGA3 may contribute to NB development. Additionally, the present study identified a novel significant association between the increased expression levels of MAPK10, TUBB2B and RASL11B, and NB cells.