AAV- partially corrects motor deficits and ALS/FTLD-related pathology in mice.

Loss of function of progranulin (PGRN), encoded by the () gene, is implicated in several neurodegenerative diseases. Several therapeutics to boost PGRN levels are currently in clinical trials. However, it is difficult to test the efficacy of PGRN-enhancing drugs in mouse models due to the mild phenotypes of mice.

methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor.

Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires and is referred to as 'B12-mechanism-I'.

LF4/MOK and a CDK-related kinase regulate the number and length of cilia in Tetrahymena.

The length of cilia is controlled by a poorly understood mechanism that involves members of the conserved RCK kinase group, and among them, the LF4/MOK kinases. The multiciliated protist model, Tetrahymena, carries two types of cilia (oral and locomotory) and the length of the locomotory cilia is dependent on their position with the cell. In Tetrahymena, loss of an LF4/MOK ortholog, LF4A, lengthened the locomotory cilia, but also reduced their number.

A Zinc Finger Transcription Factor, , Required for the Specification of a Dopamine Neuron-Producing Lineage.

Invertebrate and vertebrate nervous systems generate different types of dopaminergic neurons in distinct parts of the brain. We have taken a genetic approach to understand how the four functionally related, but lineally unrelated, classes of dopaminergic neurons of the nematode , located in distinct parts of its nervous system, are specified. We have identified several genes involved in the generation of a specific dopaminergic neuron type that is generated from the so-called postdeirid lineage, called PDE.

The Hippo Pathway Maintains the Equatorial Division Plane in the Ciliate .

The mechanisms that govern pattern formation within the cell are poorly understood. Ciliates carry on their surface an elaborate pattern of cortical organelles that are arranged along the anteroposterior and circumferential axes by largely unknown mechanisms. Ciliates divide by tandem duplication: the cortex of the predivision cell is remodeled into two similarly sized and complete daughters.

PHYTOCHROME C is an essential light receptor for photoperiodic flowering in the temperate grass, Brachypodium distachyon.

We show that in the temperate grass, Brachypodium distachyon, PHYTOCHROME C (PHYC), is necessary for photoperiodic flowering. In loss-of-function phyC mutants, flowering is extremely delayed in inductive photoperiods. PHYC was identified as the causative locus by utilizing a mapping by sequencing pipeline (Cloudmap) optimized for identification of induced mutations in Brachypodium.

TargetOrtho: a phylogenetic footprinting tool to identify transcription factor targets.

The identification of the regulatory targets of transcription factors is central to our understanding of how transcription factors fulfill their many key roles in development and homeostasis. DNA-binding sites have been uncovered for many transcription factors through a number of experimental approaches, but it has proven difficult to use this binding site information to reliably predict transcription factor target genes in genomic sequence space. Using the nematode Caenorhabditis elegans and other related nematode species as a starting point, we describe here a bioinformatic pipeline that identifies potential transcription factor target genes from genomic sequences.

CloudMap: a cloud-based pipeline for analysis of mutant genome sequences.

Whole genome sequencing (WGS) allows researchers to pinpoint genetic differences between individuals and significantly shortcuts the costly and time-consuming part of forward genetic analysis in model organism systems. Currently, the most effort-intensive part of WGS is the bioinformatic analysis of the relatively short reads generated by second generation sequencing platforms. We describe here a novel, easily accessible and cloud-based pipeline, called CloudMap, which greatly simplifies the analysis of mutant genome sequences.

Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans.

Induced expression of the Flock House virus in the soma of C. elegans results in the RNAi-dependent production of virus-derived, small-interfering RNAs (viRNAs), which in turn silence the viral genome. We show here that the viRNA-mediated viral silencing effect is transmitted in a non-Mendelian manner to many ensuing generations.

HLA associations reveal genetic heterogeneity in psoriatic arthritis and in the psoriasis phenotype.

Objective: Rigorously ascertained cases of psoriatic arthritis in subjects presenting to a rheumatology unit were compared with cases of psoriasis in subjects presenting to a dermatology unit, where subjects with musculoskeletal features were excluded, to address 1) the extent to which the contribution of the major histocompatibility complex (MHC) to psoriatic arthritis susceptibility resembles that in psoriasis, and 2) whether MHC genes determine quantitative traits within the psoriatic arthritis phenotype.

Methods: Separate discovery and validation subcohorts of patients recruited from a relatively homogeneous population were studied by sequence-based HLA typing, in which frequencies of the HLA-B and HLA-C alleles and haplotypes were compared.

Results: In patients with psoriatic arthritis, the frequency of C*06:02 was lower than that in patients with psoriasis (28.

Natural killer cell responses to HIV-1 peptides are associated with more activating KIR genes and HLA-C genes of the C1 allotype.

Background: What characterizes individuals whose natural killer (NK) cells are able to respond to HIV-1 peptides is not known.

Methods: The association between NK cell responses and KIR gene profiles and HLA-B and HLA-C alleles was investigated among 76 HIV-1-infected women in South Africa previously categorized as responders (n = 39) or nonresponders (n = 37) to HIV-1 peptide pools in a whole blood intracellular cytokine assay. Viral load was significantly lower and CD4 T-cell counts higher among responders compared with nonresponders (P = 0.

KIR-HLA and maternal-infant HIV-1 transmission in sub-Saharan Africa.

Numerous studies have suggested a role for natural killer (NK) cells in attenuation of HIV-1 disease progression via recognition by killer-cell immunoglobulin-like receptors (KIRs) of specific HLA class I molecules. The role of KIR and HLA class I has not been addressed in the context of maternal-infant HIV-1 transmission. KIR and HLA class I B and C genes from 224 HIV-1-infected mothers and 222 infants (72 infected and 150 uninfected) from South Africa were characterized.