ZPD-2, a Small Compound That Inhibits α-Synuclein Amyloid Aggregation and Its Seeded Polymerization.

α-Synuclein (α-Syn) forms toxic intracellular protein inclusions and transmissible amyloid structures in Parkinson's disease (PD). Preventing α-Syn self-assembly has become one of the most promising approaches in the search for disease-modifying treatments for this neurodegenerative disorder. Here, we describe the capacity of a small molecule (ZPD-2), identified after a high-throughput screening, to inhibit α-Syn aggregation.

Dysregulation of the splicing machinery is directly associated to aggressiveness of prostate cancer.

Background: Dysregulation of splicing variants (SVs) expression has recently emerged as a novel cancer hallmark. Although the generation of aberrant SVs (e.g.

Modulation of Biliary Cancer Chemo-Resistance Through MicroRNA-Mediated Rewiring of the Expansion of CD133+ Cells.

Background And Aims: Changes in single microRNA (miRNA) expression have been associated with chemo-resistance in biliary tract cancers (BTCs). However, a global assessment of the dynamic role of the microRNome has never been performed to identify potential therapeutic targets that are functionally relevant in the BTC cell response to chemotherapy.

Approach And Results: High-throughput screening (HTS) of 997 locked nucleic acid miRNA inhibitors was performed in six cholangiocarcinoma cell lines treated with cisplatin and gemcitabine (CG) seeking changes in cell viability.

C-mannosylation supports folding and enhances stability of thrombospondin repeats.

Previous studies demonstrated importance of C-mannosylation for efficient protein secretion. To study its impact on protein folding and stability, we analyzed both C-mannosylated and non-C-mannosylated thrombospondin type 1 repeats (TSRs) of netrin receptor UNC-5. In absence of C-mannosylation, UNC-5 TSRs could only be obtained at low temperature and a significant proportion displayed incorrect intermolecular disulfide bridging, which was hardly observed when C-mannosylated.

Immersive Versus Non-immersive Experience: Exploring the Feasibility of Memory Assessment Through 360° Technology.

Episodic memory is essential to effectively perform a number of daily activities, as it enables individuals to consciously recall experiences within their spatial and temporal environments. Virtual Reality (VR) serves as an efficacious instrument to assess cognitive functions like attention and memory. Previous studies have adopted computer-simulated VR to assess memory, which realized greater benefits compared to traditional procedures (paper and pencil).

The Provision of Education and Employment Support At the Outreach and Support in South London (OASIS) Service for People at Clinical High Risk for Psychosis.

Clinical services for the early detection of individuals at clinical high risk of psychosis, such as Outreach and Support in South-London (OASIS), have been successful in providing psychological intervention and psychosocial support to young people experiencing emerging signs of serious mental disorders. Despite this, several studies have repeatedly shown that vocational and functional recovery in the clinical high risk for psychosis population is still low. This study aimed at evaluating the presence and nature of educational and employment focused interventions within the OASIS service, in order to inform research and clinical interventions aimed at supporting young people with early signs of psychosis on their path to vocational recovery.

DisProt: intrinsic protein disorder annotation in 2020.

The Database of Protein Disorder (DisProt, URL: https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website.

Correction: Novel site-specific PEGylated L-asparaginase.

[This corrects the article DOI: 10.1371/journal.pone.

Distributed Selection of Continuous Features in Multilabel Classification Using Mutual Information.

Multilabel learning is a challenging task demanding scalable methods for large-scale data. Feature selection has shown to improve multilabel accuracy while defying the curse of dimensionality of high-dimensional scattered data. However, the increasing complexity of multilabel feature selection, especially on continuous features, requires new approaches to manage data effectively and efficiently in distributed computing environments.

Glycine-betaine-derived ionic liquids: Synthesis, characterization and ecotoxicological evaluation.

Ionic Liquids (ILs) are generically regarded as environmentally "harmless" and thus, assumed as "non-toxic". However, due to the endless design possibilities, their ecotoxicological profile is still poorly known. An accurate knowledge on the toxicity of a substance is required, under the scope of environmental regulation worldwide, before their application and commercialization.

A landscape of overlapping risks for wolf-human conflict in Wisconsin, USA.

Managing risk requires an adequate understanding of risk-factors that influence the likelihood of a particular event occurring in time and space. Risk maps can be valuable tools for natural resource managers, allowing them to better understand spatial characteristics of risk. Risk maps can also support risk-avoidance efforts by identifying which areas are relatively riskier than others.

CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction.

Background: The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation.

Dual Binding Mode of Metallacarborane Produces a Robust Shield on Proteins.

An inorganic sandwich molecule, Na[Co(C B H ) ], able to produce vesicles through self-assembly and known to produce strong dihydrogen-bond interactions with amine groups is capable of interacting with proteins. This dual non-bonding ability of Na[Co(C B H ) ] is what makes this molecule unique: it can be firmly anchored to a protein surface and is capable of extending over it. To prove this, the widely available bovine serum albumin (BSA), which has many pendant amino groups in its structure, has been taken as the model protein.

ABIN-2, of the TPL-2 Signaling Complex, Modulates Mammalian Inflammation.

Mammalian TPL-2 kinase (MAP3K8) mediates Toll-like receptor activation of ERK1/2 and p38α MAP kinases and is critical for regulating immune responses to pathogens. TPL-2 also has an important adaptor function, maintaining stability of associated ABIN-2 ubiquitin-binding protein. Consequently, phenotypes detected in Map3k8 mice can be caused by lack of TPL-2, ABIN-2, or both proteins.

Computational Assessment of Bacterial Protein Structures Indicates a Selection Against Aggregation.

The aggregation of proteins compromises cell fitness, either because it titrates functional proteins into non-productive inclusions or because it results in the formation of toxic assemblies. Accordingly, computational proteome-wide analyses suggest that prevention of aggregation upon misfolding plays a key role in sequence evolution. Most proteins spend their lifetimes in a folded state; therefore, it is conceivable that, in addition to sequences, protein structures would have also evolved to minimize the risk of aggregation in their natural environments.

Search for a heavy pseudoscalar boson decaying to a Z and a Higgs boson at .

A search is presented for a heavy pseudoscalar boson decaying to a Z  boson and a Higgs boson with mass of 125 . In the final state considered, the Higgs boson decays to a bottom quark and antiquark, and the Z  boson decays either into a pair of electrons, muons, or neutrinos. The analysis is performed using a data sample corresponding to an integrated luminosity of 35.

Putting Oneself in the Body of Others: A Pilot Study on the Efficacy of an Embodied Virtual Reality System to Generate Self-Compassion.

Compassion-based interventions (CBIs) have been shown to be effective for increasing empathy and compassion, and reducing stress, anxiety, and depression. CBIs are based on constructive meditations where imagery abilities are essential. One of the major difficulties that participants report during the training is the difficulty related to imagery abilities.

Temperature-responsive extraction of violacein using a tuneable anionic surfactant-based system.

A tuneable thermoresponsive system based on combinations of sodium dodecyl sulfate surfactant with tetrabutylammonium chloride salt is presented as an integrated process for the solid-liquid extraction of violacein from bio-engineered Yarrowia lipolytica yeast and its purification by cloud-point separation from contaminant proteins.

Computational re-design of protein structures to improve solubility.

: The rapid development of protein therapeutics is providing life-saving therapies for a wide range of human diseases. However, degradation reactions limit the quality and performance of these protein-based drugs. Among them, protein aggregation is the most common and one of the most challenging to prevent.

Prion soft amyloid core driven self-assembly of globular proteins into bioactive nanofibrils.

Amyloids have been exploited to build amazing bioactive materials. In most cases, short synthetic peptides constitute the functional components of such materials. The controlled assembly of globular proteins into active amyloid nanofibrils is still challenging, because the formation of amyloids implies a conformational conversion towards a β-sheet-rich structure, with a concomitant loss of the native fold and the inactivation of the protein.

Performing Multi-Target Regression via a Parameter Sharing-Based Deep Network.

Multi-target regression (MTR) comprises the prediction of multiple continuous target variables from a common set of input variables. There are two major challenges when addressing the MTR problem: the exploration of the inter-target dependencies and the modeling of complex input-output relationships. This paper proposes a neural network model that is able to simultaneously address these two challenges in a flexible way.

Efficient Extraction of Carotenoids from Using Aqueous Solutions of Tween 20.

The replacement of synthetic compounds by natural products witnesses an increasing demand from the pharmaceutical, cosmetic, food and nutraceutical industries. Included in the set of natural raw materials that are poorly explored are the macroalgae. Despite the detailed characterization and identification of most relevant biomolecules that are present in the main macroalgae species, there remains a lack of efficient and economically viable processes available to meet the needs of the markets.

Aggrescan3D (A3D) 2.0: prediction and engineering of protein solubility.

Protein aggregation is a hallmark of a growing number of human disorders and constitutes a major bottleneck in the manufacturing of therapeutic proteins. Therefore, there is a strong need of in-silico methods that can anticipate the aggregative properties of protein variants linked to disease and assist the engineering of soluble protein-based drugs. A few years ago, we developed a method for structure-based prediction of aggregation properties that takes into account the dynamic fluctuations of proteins.

Search for Dark Matter Particles Produced in Association with a Top Quark Pair at sqrt[s]=13 TeV.

A search is performed for dark matter particles produced in association with a top quark pair in proton-proton collisions at sqrt[s]=13  TeV. The data correspond to an integrated luminosity of 35.9  fb^{-1} recorded by the CMS detector at the LHC.