Abstract: Disclosed herein are modified Clostridial Botulinum neurotoxin (BoNT) polypeptides with a modified receptor binding domain of Clostridial Botulinum serotype B, comprising one or more substitution mutations at positions corresponding 1248 or 1249 in serotype B, strain 1. Specific substitution mutations include I1248F, I1248Y, I1248H, I1248W, V1249W, V1249F, V1249Y, V1249H, I1248W/V1249F, I1248W/V1249Y, I1248W/V1249H, I1248F/V1249Y, I1248F/V1249H, I1248Y/V1249H, I1248F/V1249W, I1248Y/V1249W, I1248H/V1249W, I1248Y/V1249F, I1248H/V1249F, or I1248H/V1249Y. Other substitution mutations are also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical compositions, and methods of using the same are also disclosed.

Abstract: The instant disclosure provides methods and compositions related to discovery of MAP2K (MEK1) as a therapeutic target for treatment or prevention of arteriovenous malformations (AVMs). Therapeutic and/or prophylactic uses and compositions of known MEK1 inhibitors, including small molecules and nucleic acid agents, are described.

Abstract: Described herein are modified integrin ? and/or ? headpiece polypeptides, and crystallizable integrin polypeptide dimers comprising a modified integrin ? and/or ? headpiece polypeptide and a disulfide bond linking the two integrin headpiece polypeptide subunits. Methods for using the modified integrin ? and/or ? headpiece polypeptides and the integrin polypeptide dimers are also provided herein. For example, methods for characterizing integrin-ligand interaction and identifying integrin ligands are also provided herein. In some embodiments, the identified integrin ligands can be used as inhibitors of integrins.

Abstract: Methods and apparatuses relate to an implantable device for providing contractile assistance to an organ. The device may include an actuator and anchors located on either side of the actuator. The anchors engage with oppositely positioned tissue walls of an organ chamber, and provide contractile assistance to the organ, repeatedly, at appropriate times. For example, the device may be implanted within the right ventricle, anchored to the right ventricular free wall and the ventricular septum. The device may function to bring the opposing walls of the ventricle toward one another, synchronized with the pacing of the heart, resulting in an improved ejection fraction of blood from the chamber. In some embodiments, the actuator includes a bladder that is configured to contract upon receiving an inflow of pressurized fluid therein. When the fluid exits therefrom, the bladder relaxes back to an initial, extended state.

Abstract: Described herein are methods and compositions for treating a spinal injury. Aspects of the invention relate to administering to a subject an agent that upmodulates KCC2. Another aspect of the invention relates to administering to a subject an agent that that reduces excitability of inhibitory interneurons. Compositions comprising these agents are additionally described herein.

Abstract: Compositions and methods for treating cancer that include administering a therapeutically effective amount of a tumor suppressor mRNA complexed with a delivery vehicle as described herein, e.g., a nanoparticle.

Abstract: The present invention provides for methods of epigenetic analysis. In some cases, the methods may include obtaining a sample comprising a nucleic acid sequence. In some cases, the nucleic acid sequence may comprise one or more epigenetic marks. The methods may include performing a sequencing. The methods may include distinguishing a hydroxymethylated base from a methylated base.

Abstract: An apparatus for measuring a characteristic of a sample using a centrifuge and optical components is disclosed. The centrifuge may be a standard benchtop centrifuge. The optical components may be sized and dimensioned to fit, along with the sample, inside the centrifuge.

Abstract: A robotic system comprising a robotic catheter steerable by a motorized drive system, an imaging device positioned on a distal end of the robotic catheter, and a controller configured to: process one or more images captured by the imaging device to identify an anatomical feature, implanted device, or medical instrument; estimate a location of the imaging device in the body based on the identified anatomical feature, implanted device, or medical instrument; determine, based on the estimated location of the imaging device, a direction in which to steer the robotic catheter for advancement towards an interventional site; and monitor at least one of (i) a stream of images captured by the imaging device and (ii) a force or distance measurement captured by the imaging device or a sensor proximate the imaging device, to adjust the direction in which to steer the robotic catheter during advancement towards the interventional site.

Abstract: Provided herein are Toll-like receptor 2 (TLR2) agonists for use in enhancing human immune response and/or as adjuvants in vaccines. The TLR2 agonists include thiophenes, imidazoles, or phenyl-containing compounds, which may be compounds of Formulae (I), (II), (III), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. The compounds described herein are used as enhancers of an immune response (e.g., innate and/or adaptive immune response), and are useful in treating and/or preventing a disease, as adjuvants in a vaccine for the disease, (e.g., proliferative disease, inflammatory disease, autoimmune disease, infectious disease, or chronic disease). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.

Abstract: The present invention generally relates to particles such as nanoparticles and, in particular, to targeted nanoparticles. In some cases, the particles may have a targeting moiety that is inhibited from recognizing a target, for example, by being positioned within the particle at an internal location. The application of a stimulus, such as light, may allow the targeting moiety to interact externally of the particle. Accordingly, the particles may be targeted to specific locations using the application of a suitable stimulus. For instance, in one embodiment, particles containing cell-penetrating peptides attached via a first attachment and a second attachment containing a photocleavable entity may be administered to a subject, and light may be applied, e.g., to the eye, to cleave the photocleavable entity. However, despite the cleavage, the peptides remain associated with the particle via the first attachment, and thus, the particles may be able to penetrate cells within the eye due to peptides.

Abstract: Described herein are compositions (e.g. cells and transgenic animals) and methods relating to engineered Ig loci that permit expression of particular antibodies or antibody segments while still permitting recombination and/or maturation process for antibody optimization.

Abstract: Methods and devices for the repair of a ruptured ligament using a scaffold device are provided. Aspects of the invention, may include a scaffold attached by a suture to an anchor. In aspects of the invention, the anchor may be secured to a bone near or at the repair site.

Abstract: Methods and devices for the repair of a ruptured ligament using a scaffold device are provided. Aspects of the invention may include a scaffold attached by a suture to an anchor. In aspects of the invention, the anchor may be secured to a bone near or at the repair site.

Abstract: A robotic device comprising a support structure, a robotic arm coupled to the support structure and having a working channel extending from a proximal end to a distal end of the robotic arm, a drive system coupled to the support structure, and a tool module configured to detachably couple to the drive system, wherein the tool module comprises an elongate tool configured to be advanced through the working channel to a surgical site at the distal end of the robotic arm and subsequently removed from the robotic arm without having to withdraw the robotic arm from the surgical site, and a transmission configured to operatively connect the drive system and the elongate tool when the tool module is coupled with the drive system thereby providing for operation of the elongate tool by the drive system.

Abstract: The present invention provides for methods of epigenetic analysis. In some cases, the methods may include obtaining a sample comprising a nucleic acid sequence. In some cases, the nucleic acid sequence may comprise one or more epigenetic marks. The methods may include performing a sequencing. The methods may include distinguishing a hydroxymethylated base from a methylated base.

Abstract: The present invention provides for novel methods for regulating and detecting the cytosine methylation status of DNA. The invention is based upon identification of a novel and surprising catalytic activity for the family of TET proteins, namely TET1, TET2, TET3, and CXXC4. The novel activity is related to the enzymes being capable of converting the cytosine nucleotide 5-methylcytosine into 5-hydroxymethylcytosine by hydroxylation.

Abstract: Compositions comprising polymers comprising one or more ketal, monothioketal, and/or thioketal bonds are provided, as well as related methods and kits. In some embodiments, a polymer may comprise one or more repeat units comprising one or more ketal, monothioketal, and/or thioketal bonds and a precursor of a pharmaceutically active agent. The precursor of the pharmaceutically active agent may be located in the backbone or may be a pendant group. The polymer may degrade in certain environments (e.g., aqueous environments, acidic environments, in vivo, etc.) to produce the pharmaceutically active agent and other biocompatible degradation products, such as certain ketones, alcohols, and/or thiols. Regardless of the location of the precursor of the pharmaceutically active agent in the repeat unit(s), the polymer may have a prolonged degradation time and/or release of the pharmaceutically active agent in certain environments.

Abstract: Some aspects of this disclosure provide engineered exopolysaccharide-associated proteins, engineered bacteria expressing such proteins, and engineered biofilms comprising such proteins. Some aspects of this disclosure provide methods for engineering exopolysaccharide-associated proteins, and for the generation of engineered bacteria and biofilms expressing or comprising such proteins. Some aspects of this disclosure provide compositions and methods useful for the generation of vaccines and the vaccination of subjects, for delivering molecules of interest to a target site, for example, a surface, for purification of molecules of interest, for example, from bioreactors comprising engineered bacteria as provided herein, and for bioremediation applications, such as the cleanup of environmental pollutants.

Abstract: Nanoparticles as described herein are configured to bind to bacterial contaminants, such as Gram positive bacteria, Gram negative bacteria, and endotoxins. The nanoparticles include a core comprising a magnetic material; and a plurality of ligands attached to the core. The ligands include, for example, bis(dipicolylamine) (“DPA”) coordinated with a metal ion, e.g., Zn2+ or Cu2+, to form, e.g., bis-Zn-DPA or bis-Cu-DPA, which can bind to the bacterial contaminants. The nanoparticles can be included in compositions for use in methods and systems to separate bacterial contaminants from liquids, such as liquids, such as blood, e.g., whole or diluted blood, buffer solutions, albumin solutions, beverages for human and/or animal consumption, e.g., drinking water, liquid medications for humans and/or animals, or other liquids.