The Status of Coastal Benthic Ecosystems in the Mediterranean Sea: Evidence From Ecological Indicators

The Mediterranean Sea is subject to multiple human pressures increasingly threatening its unique biodiversity. Spatially explicit information on the ecological status of marine ecosystems is therefore key to an effective maritime spatial planning and management, and to help the achievement of environmental targets. Here, we summarized scientific data on the ecological status of a selection of marine ecosystems based on a set of ecological indicators in more than 700 sites of the Mediterranean Sea. For Posidonia oceanica seagrass beds, rocky intertidal fringe, and coastal soft bottoms, more than 70% of investigated sites exhibited good to high ecological conditions. In contrast, about two-thirds of sites for subtidal rocky reefs were classified to be in moderate to bad conditions, stressing the need for prioritizing conservation initiatives on these productive and diverse environments. Very little quantitative information was available for the southern Mediterranean Sea, thus monitoring programs and assessments in this area are essential for a representative assessment of the health of marine coastal ecosystems in the whole basin. This overview represents a first step to implement a baseline that, through georeferenced data on ecological status, could help identifying information gaps, directing future research priorities, and supporting improvements to spatial models of expected cumulative impacts on marine ecosystems

Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts.

Recent studies indicated that seeded fibril formation and toxicity of α-synuclein (α-syn) play a main role in the pathogenesis of certain diseases including Parkinson's disease (PD), multiple system atrophy, and dementia with Lewy bodies. Therefore, examination of compounds that abolish the process of seeding is considered a key step towards therapy of several synucleinopathies. Using biophysical, biochemical and cell-culture-based assays, assessment of eleven compounds, extracted from Chinese medicinal herbs, was performed in this study for their effect on α-syn fibril formation and toxicity caused by the seeding process. Salvianolic acid B and dihydromyricetin were the two compounds that strongly inhibited the fibril growth and neurotoxicity of α-syn. In an in-vitro cell model, these compounds decreased the insoluble phosphorylated α-syn and aggregation. Also, in primary neuronal cells, these compounds showed a reduction in α-syn aggregates. Both compounds inhibited the seeded fibril growth with dihydromyricetin having the ability to disaggregate preformed α-syn fibrils. In order to investigate the inhibitory mechanisms of these two compounds towards fibril formation, we demonstrated that salvianolic acid B binds predominantly to monomers, while dihydromyricetin binds to oligomeric species and to a lower extent to monomers. Remarkably, these two compounds stabilized the soluble non-toxic oligomers lacking β-sheet content after subjecting them to proteinase K digestion. Eleven compounds were tested but only two showed inhibition of α-syn aggregation, seeded fibril formation and toxicity in vitro. These findings highlight an essential beginning for development of new molecules in the field of synucleinopathies treatment.The work conducted by Dr. El-Agnaf laboratory was supported by Qatar Biomedical Research Institute under the Start-up Fund SF 2017–007. Funding for this work was provided in part by NIH/NIA grant R37AG019391 to D.E. This study was made possible by NPRP grant 4–1371–1-223 from the Qatar National Research Fund (a member of Qatar Foundation). The funding bodies provided financial support for this study; they had no role in the study design, performance, data collection and analysis, decision to publish and preparation/writing of the manuscript

Automatic Autism Spectrum Disorder Detection Using Artificial Intelligence Methods with MRI Neuroimaging: A Review

Autism spectrum disorder (ASD) is a brain condition characterized by diverse signs and symptoms that appear in early childhood. ASD is also associated with communication deficits and repetitive behavior in affected individuals. Various ASD detection methods have been developed, including neuroimaging modalities and psychological tests. Among these methods, magnetic resonance imaging (MRI) imaging modalities are of paramount importance to physicians. Clinicians rely on MRI modalities to diagnose ASD accurately. The MRI modalities are non-invasive methods that include functional (fMRI) and structural (sMRI) neuroimaging methods. However, the process of diagnosing ASD with fMRI and sMRI for specialists is often laborious and time-consuming; therefore, several computer-aided design systems (CADS) based on artificial intelligence (AI) have been developed to assist the specialist physicians. Conventional machine learning (ML) and deep learning (DL) are the most popular schemes of AI used for diagnosing ASD. This study aims to review the automated detection of ASD using AI. We review several CADS that have been developed using ML techniques for the automated diagnosis of ASD using MRI modalities. There has been very limited work on the use of DL techniques to develop automated diagnostic models for ASD. A summary of the studies developed using DL is provided in the appendix. Then, the challenges encountered during the automated diagnosis of ASD using MRI and AI techniques are described in detail. Additionally, a graphical comparison of studies using ML and DL to diagnose ASD automatically is discussed. We conclude by suggesting future approaches to detecting ASDs using AI techniques and MRI neuroimaging

Extra Virgin Olive Oil Contains a Phenolic Inhibitor of the Histone Demethylase LSD1/KDM1A

The lysine-specific histone demethylase 1A (LSD1) also known as lysine (K)-specific demethylase 1A (KDM1A) is a central epigenetic regulator of metabolic reprogramming in obesity-associated diseases, neurological disorders, and cancer. Here, we evaluated the ability of oleacein, a biophenol secoiridoid naturally present in extra virgin olive oil (EVOO), to target LSD1. Molecular docking and dynamic simulation approaches revealed that oleacein could target the binding site of the LSD1 cofactor flavin adenosine dinucleotide with high affinity and at low concentrations. At higher concentrations, oleacein was predicted to target the interaction of LSD1 with histone H3 and the LSD1 co-repressor (RCOR1/CoREST), likely disturbing the anchorage of LSD1 to chromatin. AlphaScreen-based in vitro assays confirmed the ability of oleacein to act as a direct inhibitor of recombinant LSD1, with an IC50 as low as 2.5 umol/L. Further, oleacein fully suppressed the expression of the transcription factor SOX2 (SEX determining Region Y-box 2) in cancer stem-like and induced pluripotent stem (iPS) cells, which specifically occurs under the control of an LSD1-targeted distal enhancer. Conversely, oleacein failed to modify ectopic SOX2 overexpression driven by a constitutive promoter. Overall, our findings provide the first evidence that EVOO contains a naturally occurring phenolic inhibitor of LSD1, and support the use of oleacein as a template to design new secoiridoid-based LSD1 inhibitors.Work in the Menendez laboratory is supported by the Spanish Ministry of Science and Innovation (Grant SAF2016-80639-P, Plan Nacional de l+D+I, founded by the European Regional Development Fund, Spain) and by an unrestricted research grant from the Fundació Oncolliga Girona (Lliga catalana d’ajuda al malalt de càncer, Girona). The Spanish Ministry of Economy and Competitiveness (MINECO, Project RTI2018-096724-B-C21) and the Generalitat Valenciana (PROMETEO/2016/006) supports work in the Encinar laborator

Identification of potential transcription factors that enhance human iPSC generation

Although many factors have been identified and used to enhance the iPSC reprogramming process, its efficiency remains quite low. In addition, reprogramming efficacy has been evidenced to be affected by disease mutations that are present in patient samples. In this study, using RNA-seq platform we have identified and validated the differential gene expression of five transcription factors (TFs) (GBX2, NANOGP8, SP8, PEG3, and ZIC1) that were associated with a remarkable increase in the number of iPSC colonies generated from a patient with Parkinson's disease. We have applied different bioinformatics tools (Gene ontology, protein–protein interaction, and signaling pathways analyses) to investigate the possible roles of these TFs in pluripotency and developmental process. Interestingly, GBX2, NANOGP8, SP8, PEG3, and ZIC1 were found to play a role in maintaining pluripotency, regulating self-renewal stages, and interacting with other factors that are involved in pluripotency regulation including OCT4, SOX2, NANOG, and KLF4. Therefore, the TFs identified in this study could be used as additional transcription factors that enhance reprogramming efficiency to boost iPSC generation technology.This study was supported by QBRI internal grant (QB16) and the Qatar University Student grant (QUST-2-CMED-2019-1)

Hyperosmotic Stress Induces a Specific Pattern for Stress Granule Formation in Human-Induced Pluripotent Stem Cells

Stress granules (SGs) are assemblies of selective messenger RNAs (mRNAs), translation factors, and RNA-binding proteins in small untranslated messenger ribonucleoprotein (mRNP) complexes in the cytoplasm. Evidence indicates that different types of cells have shown different mechanisms to respond to stress and the formation of SGs. In the present work, we investigated how human-induced pluripotent stem cells (hiPSCs/IMR90-1) overcome hyperosmotic stress compared to a cell line that does not harbor pluripotent characteristics (SH-SY5Y cell line). Gradient concentrations of NaCl showed a different pattern of SG formation between hiPSCs/IMR90-1 and the nonpluripotent cell line SH-SY5Y. Other pluripotent stem cell lines (hiPSCs/CRTD5 and hESCs/H9 (human embryonic stem cell line)) as well as nonpluripotent cell lines (BHK-21 and MCF-7) were used to confirm this phenomenon. Moreover, the formation of hyperosmotic SGs in hiPSCs/IMR90-1 was independent of eIF2α phosphorylation and was associated with low apoptosis levels. In addition, a comprehensive proteomics analysis was performed to identify proteins involved in regulating this specific pattern of hyperosmotic SG formation in hiPSCs/IMR90-1. We found possible implications of microtubule organization on the response to hyperosmotic stress in hiPSCs/IMR90-1. We have also unveiled a reduced expression of tubulin that may protect cells against hyperosmolarity stress while inhibiting SG formation without affecting stem cell self-renewal and pluripotency. Our observations may provide a possible cellular mechanism to better understand SG dynamics in pluripotent stem cells

Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity

Synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are characterized by pathological accumulation of α-synuclein (α-syn). Amongst the various approaches attempting to tackle the pathological features of synucleinopathies, antibody-based immunotherapy holds much promise. However, the large size of antibodies and corresponding difficulty in crossing the blood-brain barrier has limited development in this area. To overcome this issue, we engineered single-chain variable fragments (scFvs) against fibrillar α-syn, a putative disease-relevant form of α-syn. The purified scFvs showed specific activity towards α-syn fibrils and oligomers in comparison to monomers and recognized intracellular inclusions in human post-mortem brain tissue of Lewy body disease cases, but not aged controls. In vitro studies indicated scFvs inhibit the seeding of α-syn aggregation in a time-dependent manner, decreased α-syn seed-induced toxicity in a cell model of PD, and reduced the production of insoluble α-syn phosphorylated at Ser-129 (pS129-α-syn). These results suggest that our α-syn fibril-specific scFvs recognize α-syn pathology and can inhibit the aggregation of α-syn in vitro and prevent seeding-dependent toxicity. Therefore, the scFvs described here have considerable potential to be utilized towards immunotherapy in synucleinopathies and may also have applications in ante-mortem imaging modalities.Dr. El-Agnaf’s laboratory was funded by Qatar Biomedical Research Institute under the Start-up Fund SF 2017– 007. The Newcastle Brain Tissue Resource is funded in part by a grant from the UK Medical Research Council, by NIHR Newcastle Biomedical Research Centre awarded to the Newcastle upon Tyne NHS Foundation Trust and Newcastle University, and by a grant from the Alzheimer’s Society and Alzheimer’s Research UK as part of the Brains for Dementia Research Project

Can working with the private for-profit sector improve utilization of quality health services by the poor? A systematic review of the literature

BACKGROUND: There has been a growing interest in the role of the private for-profit sector in health service provision in low- and middle-income countries. The private sector represents an important source of care for all socioeconomic groups, including the poorest and substantial concerns have been raised about the quality of care it provides. Interventions have been developed to address these technical failures and simultaneously take advantage of the potential for involving private providers to achieve public health goals. Limited information is available on the extent to which these interventions have successfully expanded access to quality health services for poor and disadvantaged populations. This paper addresses this knowledge gap by presenting the results of a systematic literature review on the effectiveness of working with private for-profit providers to reach the poor. METHODS: The search topic of the systematic literature review was the effectiveness of interventions working with the private for-profit sector to improve utilization of quality health services by the poor. Interventions included social marketing, use of vouchers, pre-packaging of drugs, franchising, training, regulation, accreditation and contracting-out. The search for published literature used a series of electronic databases including PubMed, Popline, HMIC and CabHealth Global Health. The search for grey and unpublished literature used documents available on the World Wide Web. We focused on studies which evaluated the impact of interventions on utilization and/or quality of services and which provided information on the socioeconomic status of the beneficiary populations. RESULTS: A total of 2483 references were retrieved, of which 52 qualified as impact evaluations. Data were available on the average socioeconomic status of recipient communities for 5 interventions, and on the distribution of benefits across socioeconomic groups for 5 interventions. CONCLUSION: Few studies provided evidence on the impact of private sector interventions on quality and/or utilization of care by the poor. It was, however, evident that many interventions have worked successfully in poor communities and positive equity impacts can be inferred from interventions that work with types of providers predominantly used by poor people. Better evidence of the equity impact of interventions working with the private sector is needed for more robust conclusions to be drawn

Functional Analysis of the Cathepsin-Like Cysteine Protease Genes in Adult Brugia malayi Using RNA Interference

Filarial nematodes are an important group of human pathogens, causing lymphatic filariasis and onchocerciasis, and infecting around 150 million people throughout the tropics with more than 1.5 billion at risk of infection. Control of filariasis currently relies on mass drug administration (MDA) programs using drugs which principally target the microfilarial life-cycle stage. These control programs are facing major challenges, including the absence of a drug with macrofilaricidal or permanent sterilizing activity, and the possibility of the development of drug-resistance against the drugs available. Cysteine proteases are essential enzymes which play important roles in a wide range of cellular processes, and the cathepsin-like cysteine proteases have been identified as potential targets for drug or vaccine development in many parasites. Here we have studied the function of several of the cathepsin-like enzymes in the filarial nematode, B. malayi, and demonstrate that these cysteine proteases are involved in the development of embryos, show similar functions to their counterparts in C. elegans, and therefore, provide an important target for future drug development targeted to eliminate filariasis

Rapid transcriptional plasticity of duplicated gene clusters enables a clonally reproducing aphid to colonise diverse plant species

Background: The prevailing paradigm of host-parasite evolution is that arms races lead to increasing specialisation via genetic adaptation. Insect herbivores are no exception and the majority have evolved to colonise a small number of closely related host species. Remarkably, the green peach aphid, Myzus persicae, colonises plant species across 40 families and single M. persicae clonal lineages can colonise distantly related plants. This remarkable ability makes M. persicae a highly destructive pest of many important crop species. Results: To investigate the exceptional phenotypic plasticity of M. persicae, we sequenced the M. persicae genome and assessed how one clonal lineage responds to host plant species of different families. We show that genetically identical individuals are able to colonise distantly related host species through the differential regulation of genes belonging to aphid-expanded gene families. Multigene clusters collectively upregulate in single aphids within two days upon host switch. Furthermore, we demonstrate the functional significance of this rapid transcriptional change using RNA interference (RNAi)-mediated knock-down of genes belonging to the cathepsin B gene family. Knock-down of cathepsin B genes reduced aphid fitness, but only on the host that induced upregulation of these genes. Conclusions: Previous research has focused on the role of genetic adaptation of parasites to their hosts. Here we show that the generalist aphid pest M. persicae is able to colonise diverse host plant species in the absence of genetic specialisation. This is achieved through rapid transcriptional plasticity of genes that have duplicated during aphid evolution