Abstract: The present invention belongs to the field of functional proteomics and more particularly to the field of protein aggregation. The invention discloses a method for interfering with the function of a target protein and uses a non-naturally, user-designed molecule, designated as interferor, that has a specificity for a target protein and which induces aggregation upon contact with said target protein. The present invention also discloses such interferor molecules and their use in agrobiotech applications.

Abstract: The present invention provides genetically engineered strains of Pichia capable of producing proteins with reduced glycosylation. In particular, the genetically engineered strains of the present invention are capable of expressing either or both of an ?-1,2-mannosidase and glucosidase II. The genetically engineered strains of the present invention can be further modified such that the OCH1 gene is disrupted. Methods of producing glycoproteins with reduced glycosylation using such genetically engineered stains of Pichia are also provided.

Abstract: A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. Therefore the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2+/? mice was studied. Haplodeficiency of PHD2 did not affect tumor vessel density or lumen size, but normalized the endothelial lining and vessel maturation. This resulted in improved tumor perfusion and oxygenation, and inhibited tumor cell invasion, intravasation and metastasis. Haplodeficiency of PHD2 redirected the specification of endothelial tip cells to a more quiescent phenotype of a filopodia-lacking “phalanx” cell type. Without being bound to a particular mechanism, this transition could at least in part be explained by upregulation of (soluble) VEGFR-1 and VE-cadherin.

Abstract: The present application relates to the field of motor neuron diseases, most particularly to amyotrophic lateral sclerosis and spinomuscular atrophy. Provided herein are strategies to improve symptoms and increase survival in patients with these axonopathies by inhibiting signaling mediated by the EphA4 ephrin receptor.

Abstract: The present invention relates to the field of plant molecular biology and concerns methods for enhancing the abiotic stress tolerance in plants by modulating the expression of a gene involved in the ethylene signal transduction pathway during the period of abiotic stress. The present invention also provides chimeric constructs useful in the methods in the invention. In addition, the invention provides transgenic plants having an enhanced abiotic stress resistance.

Abstract: It has now been found that the p53 pathway is inactivated in ocular cancers such as retinoblastoma. As such, the present invention is a method for inducing ocular cancer cell death using a p53 activator. In particular embodiments, the p53 activator blocks the interaction between DM2 or DMX and p53. As the p53 activator induces ocular cancer cell death, a method for preventing or treating ocular cancer is also provided.

Abstract: Tuberculosis (TB) is a major health problem and currently, the only licensed TB vaccine is Mycobacterium bovis Bacille Calmette-Guerin (M. bovis BCG). In the present invention, mutation of mycobacterial components reportedly involved in phagosome maturation inhibition was evaluated for vaccine purposes, as such mutations should result in better vaccine antigen processing and presentation. Thus, BCG mutants in genes coding for ManLAM capping ?-1,2-mannosyltransferases and the PI3P phosphatase SapM were evaluated as TB vaccines in a stringent mouse model. Vaccination with both ManLAM capping mutants and the SapM mutant resulted in significantly longer survival as compared to non-vaccinated mice, whereas vaccination with the parental BCG did not. Moreover, mice vaccinated with the SapM mutant survived significantly longer than mice vaccinated with the parental BCG.

Abstract: The present invention belongs to the field of functional proteomics and more particularly to the field of protein aggregation. The invention discloses a method for interfering with the function of a target protein and uses a non-naturally, user-designed molecule, designated as interferor, that has a specificity for a target protein and which induces aggregation upon contact with said target protein. The present invention also discloses such interferor molecules and their use in agrobiotech applications.

Abstract: The present invention provides genetically engineered strains of Pichia capable of producing proteins with reduced glycosylation. In particular, the genetically engineered strains of the present invention are capable of expressing either or both of an ?-1,2-mannosidase and glucosidase II. The genetically engineered strains of the present invention can be further modified such that the OCH1 gene is disrupted. Methods of producing glycoproteins with reduced glycosylation using such genetically engineered stains of Pichia are also provided.

Abstract: Described are MMP8 inactivating antigen binding proteins, such as antigen binding proteins comprising an amino acid sequence that comprises 4 framework regions and 3 complementary determining regions; further described is the use of such antigen binding proteins to treat inflammation, such as, but not limited to, systemic inflammatory response syndrome, sepsis, LPS induced inflammation, renal ischemia/reperfusion injury, ventilation induced lung injury, periodontal inflammation, rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, Lyme arthritis and osteoarthritis.

Abstract: The disclosure relates to a cytoplasmic protein complex comprising: (a) a first recombinant fusion protein comprising a kinase, fused to a first interaction polypeptide; and (b) a second recombinant fusion protein comprising a domain comprising a reporter phosphorylation site, whereby the domain is fused to a second interaction polypeptide. The disclosure relates further to a method to detect compound-compound-interaction using the cytoplasmic protein complex, and to cells comprising such cytoplasmic protein complex.

Abstract: This document relates to methods and materials for detecting mutations that can be linked to dementia. For example, methods and materials for detecting one or more mutations within PGRN nucleic acid are provided. This document also provides methods and materials for detecting the level of progranulin expression. In addition, this document relates to methods and materials for treating mammals having a neurodegenerative disorder (e.g., dementia). For example, methods and materials for increasing PGRN polypeptide levels in mammals are provided, as are methods and materials for identifying agents that can be used to increase PGRN polypeptide levels in mammals.

Abstract: It has now been found that the p53 pathway is inactivated in ocular cancers such as retinoblastoma. As such, the present invention is a method for inducing ocular cancer cell death using a p53 activator. In particular embodiments, the p53 activator blocks the interaction between DM2 or DMX and p53. As the p53 activator induces ocular cancer cell death, a method for preventing or treating ocular cancer is also provided.

Abstract: The present disclosure relates to the field of oncology, more particularly to the field of melanoma. Provided are methods of treating melanoma, particularly advanced cutaneous melanoma, with a combination of pharmaceutical agents comprising MDM4-specific antagonists (such as an inhibitor of the MDM4-p53 interaction or a molecule that decreases MDM4 protein stability) or MDM4-MDM2 dual inhibitors (i.e., molecules that disrupt the interactions between p53 and MDM2 and p53 and MDM4) and one or more chemotherapeutic agents such as for example alkylating agents (i.e., Dacarbazine (DITC) or melphalan), alkylating-like agents (i.e., cisplatin or carboplatin) or mitotic inhibitors (taxanes docetaxel or paclitaxel) and PI3K-AKT, B-RAF and MEK inhibitors. Further provided are pharmaceutical formulations of MDM4-specific antagonists (be it an inhibitor of the MDM4-p53 interaction or a molecule that decreases MDM4 protein stability) or MDM4-MDM2 dual inhibitors (i.e.

Abstract: Described herein are methods and genetically engineered cells useful for producing an altered N-glycosylation form of a target molecule. Also described are methods and molecules with altered N-glycosylation useful for treating a variety of disorders such as metabolic disorders.

Abstract: Described is a vaccine against Respiratory Syncytial Virus (RSV). More specifically, described is a recombinant subunit vaccine comprising the ectodomain of the RSV-encoded Small Hydrophobic (SH) protein. The ectodomain of SH is referred to as SHe. The ectodomain is typically presented as an oligomer, or a pentamer. Further described are antibodies, raised against the ectodomain or specific for the ectodomain, and their use for protecting a subject against RSV infection and/or for treatment of an infected subject.

Abstract: The present disclosure provides a device for analyzing target molecules. The device comprises a substrate retention device for holding a substrate having a functionalized surface provided thereon. This functionalized surface is adapted for capturing a plurality of target molecules. The device also comprises a light source for illuminating the functionalized surface and an image sensor for recording interference patterns of magnetic particles present on the functionalized surface. The device further comprises a first magnetic field generator configured to generate a magnetic field to attract magnetic particles linked to the target molecules to the functionalized surface. The disclosure further relates to a method for analyzing target molecules.

Abstract: The invention relates to the field of disorders of the peripheral or central nervous system, in particular, Alzheimer's disease, and the prevention and/or treatment thereof. In particular, the invention relates to the screening of compounds that modulate GPR3 activity and/or beta-arrestin signaling in a mammalian cell and, in particular, compounds that reduce the formation of amyloid beta peptides. The invention also relates to inhibiting agents targeting beta-arrestin signaling and pharmaceutical compositions thereof, and their use in therapeutic applications of those disorders.

Abstract: Described are single domain antibodies with a specificity for BACE1. More specifically, described are single variable-domain antibodies derived from camelids that bind to BACE1 and are capable of inhibiting the activity of BACE1. The antibodies can be used for research and medical applications. Specific applications include the use of BACE1-specific antibodies for the treatment of Alzheimer's disease.

Abstract: The present application relates to the field of cancer, particularly to mismatch repair (MMR?) deficient tumors. New markers are presented herein that have a high sensitivity to detect whether a tumor is mismatch repair deficient or not. The markers are particularly mutations in microsatellite regions. Accordingly, methods are provided for diagnosing microsatellite instability of a tumor, comprising determining the presence of these markers. Further, kits are provided to detect the presence of these markers (or subsets thereof) in a sample.