The invention relates to the field of obesity and related metabolic diseases. More specifically, the invention relates to methods of reducing aggrecanase activity or antigen in mammals in order to enhance brown adipose tissue (BAT) development, to promote conversion of white adipose tissue (WAT) into BAT in vivo, and to limit triglyceride accumulation and steatosis in the liver. The invention also relates to a strategy of neutralization or depletion of ADAMTS5 as a strategy to inhibit adipogenesis and more specifically, the invention relates to a method of reducing aggracanase-2 (ADAMTS5, A Disintegrin and Metalloproteinase with Thrombospondin motif 1; member 5) antigen and/or activity in mammals in order to impair differentiation of precursor cells into mature adipocytes (i.e., adipogenesis).

The present invention provides a method for detecting and assaying Clostridium neurotoxins and identification of serotypes of botulinum neurotoxins in various food matrices and clinical samples. This method is also used for detection of BoNT inside the neuronal and epithelial cells. The method comprises detecting and assaying the presence of a Clostridium neurotoxin in a sample by: exposing the sample containing a Clostridium neurotoxin to a sample comprising a novel SNAMPXIN/SNAMP universal recombinant substrate fusion protein capable of producing a detectable FRET, following cleavage; detecting and assaying the presence of the Clostridium neurotoxin by measuring a change in the energy transfer or the luminescence signal; and detecting and assaying an electrophoretic mobility pattern of one or more cleaved protein bands or a degraded protein, using a high throughput automated system to identify the different serotypes of the Clostridium neurotoxin. SNAMPXIN/SNAMP is formed from parts of BoNT substrates SNAP-25 and VAMP.

Provided is a means capable of predicting a formation of thrombus or a risk thereof in a medical device performing blood circulation by a pump, by a simple and minimally invasive method. A method for predicting a formation of thrombus or a risk thereof in a medical device performing blood circulation by a pump, wherein it is predicted that thrombus is formed or there is a risk thereof in the medical device when a concentration or expression amount of ADAM28 in a body fluid sample collected from a subject wearing the medical device is elevated compared with a reference value.

Provided is a means capable of determining the development of myocarditis or the risk thereof by a simple and minimally invasive method. A method of determining the development of myocarditis or risk thereof, wherein it is determined that myocarditis is developed or there is a risk thereof when a concentration or expression amount of ADAM28 in a body fluid sample collected from a subject is reduced compared with a reference value.

An unprecedented mechanism of ubiquitination that is independent of E1 and E2 enzymes, instead relying on activation of ubiquitin by ADP-ribosylation, and which is mediated by members of the SidE effector family encoded by the bacterial pathogen Legionella pneumophila is disclosed. The herein disclosed method demonstrates a method in which ubiquitination can be carried out by a single enzyme. In addition, the present disclosure also provides compositions that may be used in ubiquitination assays and/or methods of screening active substance that may inhibit the ubiquitination process.

The invention relates to recombinant nucleic acid and polypeptides encoding collagenase I and collagenase II, methods for the preparation thereof and methods for the use thereof. The invention also encompasses methods related to releasing a composition comprising collagenase prior to therapeutic administration.

A method of diagnosing breast cancer is disclosed. The method comprises lysing extracellular vesicles of a subject to generate a composition comprising components of extracellular vesicles; measuring the amount of MEK1 in the composition; and diagnosing the subject with breast cancer when a level of said MEK1 in said composition is above a predetermined threshold. Kits for breast cancer diagnosis are also disclosed.

Compositions and methods are provided that reduce the time required for detection of botulinum neurotoxins in cell-based assays. In one aspect an isoquinolynyl compound can be used for this purpose. In such cell-based assays the cell can include an enzyme that facilitates degradation of the reporter significantly faster after the cleavage than before the cleavage, and presence of the Botulinum toxin correlates with reduction of the signal from a baseline signal. The cell can advantageously express both the construct that includes the reporter, and an enzyme that facilitates the degradation.

The present invention refers to an In vitro method for screening for subjects at risk of developing thoracic aortic aneurysm (TAA) or a disease causing TAA comprising: (a) measuring the expression pattern or level of at least A Disintegrin And Metalloproteinase with Thrombospondin Motifs 1 (ADAMTS1) obtained from an isolated biological sample of the subjects to be screened; and (b) comparing said expression pattern or level of at least ADAMTS1 of the subjects to be screened with an already established expression pattern or level, wherein reduced expression of at least ADAMTS1 is indicative of a thoracic aortic aneurysm (TAA).

The present disclosure relates to a metalloprotein binder that specifically binds to a N-terminally modified peptide. Also provided herein is a method and related kits for treating or analyzing a peptide using the metalloprotein binder and/or modified cleavase. In some embodiments, the method provided herein comprises binding metalloprotein binder-coding tag conjugates to a modified N-terminal amino acid residue of an immobilized peptide associated with a recording tag, transferring identifying information from the coding tag to the recording tag using a ligation or primer extension, and cleaving the modified N-terminal amino acid residue. The method and metalloprotein binders provided herein are useful for de novo peptide identification or sequencing.