A system is provided comprising a plurality of C. elegans cultures, where each culture comprises a transgenic C. elegans strain that models a mammalian disease or condition. Methods of using a system, e.g., for characterizing microbial strains of a mammalian microbiome and determining whether such microbial strains affect a mammalian disease or disorder.

The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA, Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications.

Provided herein, are compositions and methods of treatment for neurodegenerative diseases, such as neurodegenerative diseases associated with aging and methods for increasing longevity by inhibiting the expression of the protein exportin-1 (XPO1, CRM-1 or karyopherin) or a fragment thereof.

A support element for storing crates, wherein the support element is an elongate element having a cross section that is substantially formed in an U-shape, comprising a bottom section and two opposite side walls extending from the bottom section. The side walls each comprise a top portion, forming two elongate supporting areas, whereby the elongate supporting areas are configured to support a crate or a column of stacked crates, The inner side sections of the side walls each comprise a step symmetrically protruding to the inside of the U-shape forming two elongate running surfaces, whereby the elongate running surfaces are configured to support a conveyor system for transporting the crate. The invention further refers to a support system, a storage system and to a rearing unit.

Provided herein are screening methods that utilize transgenic nematodes exposed to heat shock conditions, such as agents that increase stability of F-actin. The transgenic nematodes used can be in a wild-type background, functionally deleted for OSG-1, or express human ARHGEF10 in an OSG-1 background. Such transgenic nematodes also express a fluorescent protein, such as GFP. Such methods are in some examples high throughput and automated. Also provided are recombinant nematodes and kits that can be used with such methods.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

The present disclosure provides methods and systems for performing, observing, and/or recording defecation motor program (DMP) events using microfluidic devices. The methods may be performed wherein the nematodes ingest fluorescent or color material and are then loaded in a microfluidic chip and stimulated to feed and defecate. DMP events are observed with use of a fluorescent microscope. In other methods, a microfluidic device with two or more electrodes is used to record electrical events of the DMP.

The present disclosure provides a microfluidic device and system for measuring a composite electropharyngeogram (EPG) signal from a pool of multiple nematodes, wherein the composite EPG signal is measured from the pool of nematodes present in a single recording channel connected to two or more integrated electrodes. The microfluidic device includes an inlet port and outlet port directly connected to a single recording channel and two or more electrodes directly connected to the recording channel. The recording channel is configured to hold 10 to 10,000 nematodes.

Described herein are nucleic acid molecules and complexes useful as i-switch pH reporters that have increased sensitivities as a pH reporter and have alternate pH reporting capacity ranges. Aspects of the disclosure relate to a method for determining pH comprising providing a nucleic acid complex comprising: a first single-stranded nucleic acid molecule comprising the sequence C.sub.nXC.sub.nYC.sub.nZC.sub.n (SEQ ID NO. 6) wherein C is cytosine; X, Y and Z are each one or more of adenine, thymine, guanine, or combinations thereof; and n is greater than or equal to 2; and wherein at least 2 cytosine residues of the first single-stranded nucleic acid molecule are modified; and a second single-stranded nucleic acid molecule that is partially or fully complementary to the first single-stranded molecule, wherein a first label is conjugated to the first single-stranded nucleic acid molecule or the second single-stranded nucleic acid molecule; and wherein the first label is capable of producing a signal, wherein the intensity of the signal varies as a function of the conformation of the nucleic acid complex; and measuring the intensity of the signal and determining the pH from the measured signal.

The present disclosure provides a method for genetic analysis of gene variants as well as a system for implementing such analysis.