Abstract: In a first aspect, the present invention features methods for differentiating DNA species originating from different individuals in a biological sample. These methods may be used to differentiate or detect fetal DNA in a maternal sample or to differentiate DNA of an organ donor from DNA of an organ recipient. In preferred embodiments, the DNA species are differentiated by observing epigenetic differences in the DNA species such as differences in DNA methylation. In a second aspect, the present invention features methods of detecting genetic abnormalities in a fetus by detecting fetal DNA in a biological sample obtained from a mother. In a third aspect, the present invention features methods for differentiating DNA species originating from an organ donor from those of an organ recipient. In a fourth aspect, the present invention features kits for differentiating DNA species originating from different individuals in a biological sample.

Abstract: The present invention is directed to engineered enzymatically active bacteriophages that are both capable of killing the bacteria by lysis and dispersing the bacterial biofilm because they have been also engineered to express biofilm-degrading enzymes, particularly dispersin B (DspB), an enzyme that hydrolyzes ?-1,6-N-acetyl-D-glucosamine, a crucial adhesion molecule needed for biofilm formation and integrity in Staphylococcus and E. coli, including E. coli K-12, as well as clinical isolates.

Abstract: The invention pertains to nucleic acids encoding a mutT domain-containing polypeptide, including fragments and biologically functional variants thereof. The invention also pertains to therapeutics and diagnostics involving the foregoing polypeptide and nucleic acids and agents that bind the foregoing polypeptide and nucleic acids. The invention also pertains to the identification of a novel mutT domain in human TrpC7, a polypeptide previously described as a putative calcium ion channel. Accordingly, the invention also pertains to methods and compositions for identifying agents useful modulating mutT domain-mediated calcium or other ion transport in cells expressing a polypeptide comprising a mutT domain and a calcium or other ion channel.

Abstract: Disclosed herein, in certain embodiments, is an HC•HA complex comprising hyaluronan and a heavy chain of I?I, wherein the transfer of the heavy chain of I?I is catalyzed by TSG-6. Further disclosed herein, in certain embodiments, is an HC•HA complex comprising hyaluronan and a heavy chain of I?I, wherein the transfer of the heavy chain of I?I is catalyzed by the TSG-6 like protein.

Abstract: Various methods for the production of cellulase are disclosed. In one embodiment the method for producing cellulase includes contacting a culture comprising a sophorolipid producer and a cellulase producer with a substrate that is consumed by the sophorolipid producer. In addition, a microorganism culture made from a sophorolipid producer and a cellulase producer is disclosed.

Abstract: Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Abstract: The invention provides a novel system for the tunable expression of nucleic acids encoding e.g., polypeptides such as recombinant proteins in prokaryotic systems. The system is based on the ability of T7 lysozyme (T7Lys) to inhibit the activity of T7RNAP. Expression of T7Lys can be continuously adjusted as its expression is under the control of a promoter whose activity can be titrated. The invention provides a host cell capable of expressing T7 RNA polymerase, the host cell comprising a first nucleic acid having a T7 lysozyme gene or a T7 lysozyme variant gene and a tunable promoter for controlling the expression of the T7 lysozyme gene. It also provides a host cell further comprising a second nucleic acid having a T7 promoter operably linked to a nucleic acid sequence encoding a target polypeptide, whereby expression of the target polypeptide is tuned via controlling the expression of the T7 lysozyme gene.

Abstract: This application generally relates to an isoform Nell-1 peptide, compositions thereof, and methods of using the same.

Abstract: Lower eukaryotic cells such as Pichia pastoris that normally cannot use galactose as a carbon source but which have been genetically engineered according to the methods herein to use galactose as a sole source of carbon are described. The cells are genetically engineered to express several of the enzymes comprising the Leloir pathway. In particular, the cells are genetically engineered to express a galactokinase, a UDP-galactose-C4-epimerase, and a galactose-1-phosphate uridyltransferase, and optionally a galactose permease. In addition, a method is provided for improving the yield of glycoproteins that have galactose-terminated or -containing N-glycans in cells that have been genetically engineered to produce glycoproteins with N-glycans having galactose residues but which normally lack the enzymes comprising the Leloir pathway comprising transforming the cells with one or more nucleic acid molecules encoding a galactokinase, a UDP-galactose-C4-epimerase, and a galactose-1-phosphate uridyltransferase.

Abstract: The instant invention provides a method of treating an animal suffering a disease characterized by excessive apoptosis by administering a therapeutically effective amount of at least one serine protease inhibitor and thereafter monitoring a decrease in apoptosis. The inhibitor of the invention includes ?1-antitrypsin or an ?1-antitrypsin-like agent, including, but not limited to oxidation-resistant variants of ?1-antitrypsin, and peptoids with antitrypsin activity. The diseases treatable by the invention include cancer, autoimmune disease, sepsis neurodegenerative disease, myocardial infarction, stroke, ischemia-reperfusion injury, toxin induced liver injury and AIDS. The method of the invention is also suitable for the prevention or amelioration of diseases characterized by excessive apoptosis.

Abstract: The present invention relates to a polypeptide which has a novel specific arabinose transporter function as well as to nucleic acids coding therefore. The invention further relates to host cells, in particular modified yeast strains which contain the coding nucleic acids and express the polypeptide and functionally integrate it into the plasma membrane and are thus able to absorb L-arabinose. When using modified host cells which express additional proteins of the arabinose metabolic pathway, arabinose can be fermented by these cells, in particular into ethanol. The present invention is therefore relevant, inter alia, in connection with the production of biochemicals from biomass, such as bioethanol for example.

Abstract: An intracellular selection system allows screening for peptide bioactivity and stability. Randomized recombinant peptides are screened for bioactivity in a tightly regulated expression system, preferably derived from the wild-type lac operon. Bioactive peptides thus identified are inherently protease- and peptidase-resistant. Also provided are bioactive peptides stabilized by a stabilizing group at the N-terminus, the C-terminus, or both. The stabilizing group can be a small stable protein, such as the Rop protein, glutathione sulfotransferase, thioredoxin, maltose binding protein, or glutathione reductase, an ?-helical moiety, or one or more proline residues.

Abstract: This invention is in the field of medical devices. Specifically, the present invention provides portable medical devices that allow real-time detection of analytes from a biological fluid. The methods and devices are particularly useful for providing point-of-care testing for a variety of medical applications. In particular, the medical device reduces interference with an optical signal which is indicative of the presence of an analyte in a bodily sample.

Abstract: Disclosed are methods and compositions for the identification of inhibitors of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21ras. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme.

Abstract: The present invention pertains in general to Bromelain and particularly to the active compounds contained in this complex mixture of proteins. The present invention provides recombinant expressed Bromelain inhibitor precursor and Bromelain inhibitors, which are found in Bromelain. It has been found that the recombinant expressed inhibitors have superior effects in terms of treatment of disorders and conditions than Bromelain or its protein fractions from plant extracts.

Abstract: Streptomyces and Bacillus host cells comprising a recombinant nucleic acid encoding a fusion protein containing a signal sequence and a Streptomyces subtilisin inhibitor (SSI) protein are provided, as well as methods of producing SSI protein using those cells. In certain embodiments, the host cell is a Streptomyces host cell and the signal to sequence is a celA signal sequence. In other embodiments, the host cell is a Bacillus host cell has a genome that contains inactivated protease genes.

Abstract: A novel metalloproteinase inhibitor, analogs thereof, polynucleotides encoding the same, and methods of production, are disclosed. Pharmaceutical compositions and methods of treating disorders caused by excessive amounts of metalloproteinase are also disclosed.

Abstract: The invention provides a method of evaluating metabolism-based drug interactions. The method involves selecting time points for the determination of the inactivation rate constant of a time-dependent enzyme inhibitor based on the results of a multi-time point IC50 test. Advantageously, with the subject invention, the determination and use of the multi-time point IC50 test provides an indication of the inactivation rate of a test compound and eliminates trial and error tests associated with the selection of appropriate assay conditions for the second assay conducted to determine the inactivation rate constant of the test compound.

Abstract: The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) ?-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising ?-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) ?-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising ?-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4.

Abstract: This invention features novel proteins that are homologous to the first Kunitz domain (K1) of lipoprotein-associated coagulation inhibitor (LACI), and are capable of inhibiting plasmin and nucleic acids encoding these proteins. The invention also features the use of such proteins in therapeutic, diagnostic, and clinical methods.

Abstract: Activation of the immune response by NF-kB inducers, induction of an anergic response by NF-kB inhibitors and the inhibition and activation of immune response by the administration of an activator or inhibitor of NF-kB is disclosed. Examples of NF-kB inhibitors include IkB?, PSI, a nucleotide sequence encoding IkB? anti-sense nucleic acid encoding an NF-kB sequence, such as Rel B, and anti-NF-kB antibodies. Examples of NF-kB inducers include NIK, MEKK, IKK2, TFRRF2, and Rel B. Also disclosed are vectors encoding inducers and inhibitors of NF-kB, for example adenoviral vectors.

Abstract: The present invention relates to a method for activation of TRPV2 (transient receptor potential vanilloid 2) using probenecid, more precisely a method for selecting a candidate for TRPV2 blocker using probenecid. Probenecid of the present invention works on TRPV2 specifically so that it facilitates the isolation of sensory neurons expressing TRPV2. Therefore, probenecid of the invention can be effectively used for the studies on TRPV2 mechanisms and the development of a TRPV2 based anodyne.

Abstract: A recombinant filamentous fungal cell (e.g. Aspergillus) having one or more inactivated chromosomal genes is provided. The chromosomal genes in some embodiments correspond to derA, derB, htmA, mnn9, mnn10, ochA, dpp4, dpp5, pepAa, pepAb, pepAc, pepAd, pepF and combinations thereof. The recombinant fungal cells may include further inactivated chromosomal genes which correspond to pepA, pepB, pepC and pepD. The recombinant filamentous fungal cells may include a heterologous nucleic acid encoding a protein of interest. Also provided are methods of producing a protein of interest in said recombinant filamentous fungal cell.

Abstract: In certain aspects, the invention relates to methods for identifying compounds which modulate Akt activity mediated by the rictor-mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activity.

Abstract: This invention provides a method of preventing or treating in a subject contact dermatitis which comprises administering to the subject an amount of a compound capable of inhibiting the stem cell factor signaling pathway effective to prevent or treat contact dermatitis so as to thereby prevent or treat contact dermatitis in the subject.

Abstract: Isoform-binding molecules that specifically bind to one or more isoforms expressed and/or associated with oncogenic phenotypes in a hyperproliferative cell (e.g., a cancerous or tumor cell) are disclosed. The isoform-binding molecules can be used to treat, prevent and/or diagnose cancerous conditions and/or disorders. Methods of using the isoform-binding molecules to selectively detect oncogenic isoforms, to reduce the activity and/or induce the killing of a hyperproliferative cell expressing an oncogenic isoform in vitro, ex vivo or in vivo are also disclosed. Diagnostic and/or screening methods and kits for evaluating the function or expression of an oncogenic isoform are also disclosed.

Abstract: Methods for characterizing a biochemical reaction and analysis of reaction products by establishing continuously variable concentration gradients of one or more reagents of the biochemical reaction are provided. Methods for determining mechanism of inhibition or activation, potency of inhibition or activation, or both of an enzyme inhibitor or activator, respectively, are also provided. The continuously variable concentration gradients can be established in a microfluidic chip.

Abstract: In order to obtain a novel binding protein against a chosen target, DNA molecules, each encoding a protein comprising one of a family of similar potential binding domains and a structural signal calling for the display of the protein on the outer surface of a chosen bacterial cell, bacterial spore or phage (genetic package) are introduced into a genetic package. The protein is expressed and the potential binding domain is displayed on the outer surface of the package. The cells or viruses bearing the binding domains which recognize the target molecule are isolated and amplified. The successful binding domains are then characterized. One or more of these successful binding domains is used as a model for the design of a new family of potential binding domains, and the process is repeated until a novel binding domain having a desired affinity for the target molecule is obtained.

Abstract: Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways.

Abstract: Nucleic acid compositions encoding mammalian DGAT2? polypeptide products with diglyceride acyltransferase activity, as well as the mammalian DGAT2? polypeptide products encoded thereby and methods for producing the same, are provided. The subject DGAT2? polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications, as well as in treatment therapies and in the production of triacylglycerols.

Abstract: JNK-interacting protein 1 (JIP-1), an inhibitor of the JNK1 protein, and methods of treating a pathological condition or of preventing the occurrence of a pathological condition in a patient by the administration of a therapeutically effective amount of JIP-1 polypeptides, peptides, peptide mimetics, or nucleic acids are described.

Abstract: The present invention relates to methods of inducing ovulation in a female host comprising the administration of a non-polypeptide cyclic adenosine monophosphate (cAMP) level modulator to the female host. In another aspect, the invention provides for specific administration of the phosphodiesterase inhibitor prior to the luteal phase of the host's ovulatory cycle. Preferred non-polypeptide cAMP level modulators include phosphodiesterase inhibitors, particularly inhibitors of phosphodiesterase 4 isoforms.

Abstract: Disclosed are compositions and methods related to the isolation and identification of the primate T-lymphotropic viruses, HTLV-3 and HTLV-4. The diversity of HTLVs was investigated among central Africans reporting contact with NHP blood and body fluids through hunting, butchering, and keeping primate pets. Herein it is shown that this population is infected with a variety of HTLVs, including two retroviruses; HTLV-4 is the first member of a novel phylogenetic lineage that is distinct from all known HTLVs and STLVs; HTLV-3 falls within the genetic diversity of STLV-3, a group that has not previously been seen in humans. The present disclosure also relates to vectors and vaccines for use in humans against infection and disease. The disclosure further relates to a variety of bioassays and kits for the detection and diagnosis of infection with and diseases caused by HTLV-3 and HTLV-4 and related viruses.

Abstract: The invention relates to methylated proteins that control protein phosphorylation, particularly phosphoesterases, such as PP2A. It relates to screening methods for determining agents that affect methylation of these proteins and thus also modulate the level of phosphorylation of phosphoproteins. It relates as well to the agents and to compositions comprising the agents. In a particular aspect in this regard the invention relates to agents that alter PP2A methylation and that thereby affect phosphorylation of phosphoproteins that play an important role in health or disease, such as the tau protein which is implicated in the etiology of Alzheimer's Disease. The invention further relates to diagnostic methods based on protein methylation levels, to compositions comprising agents for affecting methylation of proteins and for controlling the phosphate complement of phosphoproteins.

Abstract: Methods and materials for inducing anti-tumor responses in melanoma patients are disclosed. These methods and materials involve gp100-derived polypeptides that contain both a helper T-cell epitope and a cytotoxic T-cell epitope.

Abstract: The present invention provides long half life genetically modified TFPI sequences (LTFPI) for anticoagulation. On the genetically modified TFPI sequence, the lysine at the carboxy-terminal sites 241, 254, 260 and 261 are replaced by alanin and the amino acid asparagine at glycosylation sites 117, 167, 228 and the amino acids serine and threonine at glycosylation sites 174 and 175 are substitutionally mutated. The present invention also provides methods of making the LTFPI through high efficient LTFPI expression from yeast production system.

Abstract: The present invention relates to an assay system for specific inhibitors of protein kinase C-related kinases (PRKs) relating to one or more of the reactions wherein said protein kinase C-related kinases are involved under physiological conditions. The invention also relates to a process for identifying specific inhibitors for protein kinase C-related kinases.

Abstract: LSD1, a homolog of nuclear amine oxidases, functions as a histone demethylase and transcriptional co-repressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. Lysine demethylation occurs via an oxidation reaction that generates formaldehyde. Importantly, RNAi inhibition of LSD1 causes an increase in H3 lysine 4 methylation and concomitant de-repression of target genes, suggesting that LSD1 represses transcription via histone demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.

Abstract: The present invention provides novel physiological substrates of mammalian glutaminyl cyclase (QC, EC 2.3.2.5), new effectors of QC, methods for screening for such effectors, and the use of such effectors and pharmaceutical compositions comprising such effectors for the treatment of conditions that can be treated by modulation of QC-activity. Preferred compositions additionally comprise inhibitors of DP IV or DP IV-like enzymes for the treatment or alleviation of conditions that can be treated by modulation of QC- and DP IV-activity.

Abstract: A protein includes or is formed by: (i) SEQ ID NO: 1; (ii) any sequence that is derived from sequence SEQ ID NO: 1, for example, by the substitution, removal or addition of one or more amino acids, on the condition that the derivative sequence binds to the phosphate; (iii) any sequence that is homologous to sequence SEQ ID NO: 1, preferably having a homology of at least approximately 80% with sequence SEQ ID NO: 1, on the condition that the homologous sequence binds to the phosphate; or (iv) any fragment of one of the aforementioned sequences on the condition that the fragment binds to the phosphate, such as any fragment comprising at least approximately 20 contiguous amino acids in sequence SEQ ID NO: 1.

Abstract: Disclosed is a pO157 plasmid-specified polypeptide found in E. coli EDL933 and other E. coli that binds to and cleaves C1-esterase inhibitor, and antibodies specific for the polypeptide. Also disclosed are methods employing the polypeptide for diagnosing enterohemorrhagic E. coli infection, identifying potential inhibitors of its activity, and reducing viscosity of material containing glycosylated polypeptides.

Abstract: A method is described for the expression of heterologous polypeptides in rodent cells. The method comprises the oriP/EBNA-1 episomal replication and maintenance system of the Epstein-Barr-Virus (EBV). With the stable integration of an EBNA-1-protein expression cassette under the control of a promoter into the genome of a rodent cell an EBNA-1-protein expression in the cells was obtained. The heterologous protein is expressed from an episome comprising an EBV origin of replication and a functional expression cassette of said heterologous protein. The invention further comprises transformed rodent cell lines, a method for the production of a heterologous protein in said cell lines and a kit for the construction of said cell lines.

Abstract: A method for production of artificial skin by administering matrix metalloproteinase inhibitor or matrix metalloproteinase inhibitor and matrix protein production promoting agent. The matrix metalloproteinase inhibitor is N-hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](3-picolyl)amino]-3-methylbutanamide hydrochloride.

Abstract: An improved process for the production of streptokinase using a genetically engineered strain of Escherichia coli which overproduces streptokinase intracellularly and more particularly, the overall process disclosed herein, concerns with an improvement in the fermentative production of streptokinase using an optimized growth medium mainly comprised of simple salts and trace-elements; thus, in principal, the present process constitutes an improved and more economical means for the production of streptokinase which may be useful in thrombolytic therapy.

Abstract: The current invention describes a nucleic acid comprising in a 5? to 3? direction a) a first nucleic acid encoding a heterologous polypeptide without an in frame stop codon, b) a second nucleic acid beginning with a 5? splice donor site and terminated by a 3? splice acceptor site comprising an in frame translational stop codon and a polyadenylation signal, and c) a nucleic acid encoding i) at least a fragment of a transmembrane domain, or ii) a signal peptide for a GPI-anchor.

Abstract: A Rapid And Sensitive Radiometric Assay For Assessing The Activity Of Cytochrome P-450 (CYP) 2C9 And The Potential Of An Analyte To Inhibit CYP2C9 Activity Or Induce CYP2C9 Expression is described. All the steps of the assay, including incubations, product separation, and radioactivity counting are preferably performed in a multiwell format, which can be automated.

Abstract: The invention provides for isolated peptides having phospholipase inhibitory activity, polypeptides comprising phospholipase inhibitory activity and lipases capable of being inhibited by the isolated peptides and/or polypeptides comprising phospholipase inhibitory activity. The invention also relates to nucleic acid constructs, recombinant expression vectors, and recombinant host cells comprising the polynucleotides as well as methods for producing and using the peptides and the polypeptides having lipase inhibitory activity.

Abstract: The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating polypeptides capable of anchoring heterologous polypeptides to a bacterial inner membrane. In the technique, libraries of candidate anchor polypeptides are expressed as fusions with a heterologous polypeptide that is capable of being detected when bound to the inner membrane. In bacteria expressing a functional anchor sequence, the heterologous polypeptide becomes bound to outer face of the inner membrane. Bacteria with the functional anchor sequence can be identified by removing the outer membrane to remove non-anchored heterologous polypeptide followed by detection of anchored heterologous polypeptide. Such bacteria may be detected in numerous ways, including use of direct fluorescence or secondary antibodies that are fluorescently labeled, allowing use of efficient techniques such as fluorescence activated cell sorting (FACS).

Abstract: The present invention relates to the recombinant method used for the production of soluble form of human tissue plasminogen activator variant. In this variant the threonine at position 103 of the endogenous tissue plasminogen activator is replaced by an asparagine leading to a new glycosylation site. At position 117 of the endogenous tissue plasminogen activator asparagine has been replaced by glutamine, leading to the removal of an N linked glycosylation site. At position 296-299 the amino acids lysine, histidine, arginine, and arginine have been replaced by four alanine amino acids. The invention further relates to the de novo synthesis of the nucleic acid sequence encoding tissue plasminogen activator, transformation of the constructed nucleic acid sequences into competent bacteria and sub-cloning of the same into mammalian expression vectors for the expression of the desired protein. DNA constructs comprising the control elements associated with the gene of interest have been disclosed.

Abstract: Described herein are protease inhibitors, variants thereof and methods for their production.