LET-381/FoxF and its target UNC-30/Pitx2 specify and maintain the molecular identity of C. elegans mesodermal glia that regulate motor behavior.

While most glial cell types in the central nervous system (CNS) arise from neuroectodermal progenitors, some, like microglia, are mesodermally derived. To understand mesodermal glia development and function, we investigated C. elegans GLR glia, which envelop the brain neuropil and separate it from the circulatory system cavity. Transcriptome analysis shows that GLR glia combine astrocytic and endothelial characteristics, which are relegated to separate cell types in vertebrates. Combined fate acquisition is orchestrated by LET-381/FoxF, a fate-specification/maintenance transcription factor also expressed in glia and endothelia of other animals. Among LET-381/FoxF targets, the UNC-30/Pitx2 transcription factor controls GLR glia morphology and represses alternative mesodermal fates. LET-381 and UNC-30 co-expression in naive cells is sufficient for GLR glia gene expression. GLR glia inactivation by ablation or let-381 mutation disrupts locomotory behavior and promotes salt-induced paralysis, suggesting brain-neuropil activity dysregulation. Our studies uncover mechanisms of mesodermal glia development and show that like neuronal differentiation, glia differentiation requires autoregulatory terminal selector genes that define and maintain the glial fate.

LET-381/FoxF and UNC-30/Pitx2 control the development of C. elegans mesodermal glia that regulate motor behavior.

While most CNS glia arise from neuroectodermal progenitors, some, like microglia, are mesodermally derived. To understand mesodermal glia development and function, we investigated C. elegans GLR glia, which ensheath the brain neuropil and separate it from the circulatory-system cavity. Transcriptome analysis suggests GLR glia merge astrocytic and endothelial characteristics relegated to separate cell types in vertebrates. Combined fate acquisition is orchestrated by LET-381/FoxF, a fate-specification/maintenance transcription factor expressed in glia and endothelia of other animals. Among LET-381/FoxF targets, UNC-30/Pitx2 transcription factor controls GLR glia morphology and represses alternative mesodermal fates. LET-381 and UNC-30 co-expression in naïve cells is sufficient for GLR glia gene expression. GLR glia inactivation by ablation or let-381 mutation disrupts locomotory behavior and induces salt hypersensitivity, suggesting brain-neuropil activity dysregulation. Our studies uncover mechanisms of mesodermal glia development and show that like neurons, glia differentiation requires autoregulatory terminal selector genes that define and maintain the glial fate.

Monitoring Health Parameters of Elders to Support Independent Living and Improve Their Quality of Life.

Improving the well-being and quality of life of the elderly population is closely related to assisting them to effectively manage age-related conditions such as chronic illnesses and anxiety, and to maintain their independence and self-sufficiency as much as possible. This paper presents the design, architecture and implementation structure of an adaptive system for monitoring the health and well-being of the elderly. The system was designed following best practices of the Human-Centred Design approach involving representative end-users from the early stages.

Analysis of spherical isotropic noise fields with an A-Format tetrahedral microphone.

Several applications in spatial audio signal processing benefit from the knowledge of the diffuseness of the sound field. In this paper, several experiments are performed to determine the response of a tetrahedral microphone array under a spherically isotropic sound field. The data were gathered with numerical simulations and real recordings using a spherical loudspeaker array. The signal analysis, performed in the microphone signal and spherical harmonic domains, reveals the characteristic coherence curves of spherical isotropic noise as a function of the frequency.

Efficient implementation of superdirective beamforming in a half-space environment.

In this paper, the case considered is a planar microphone array placed in front of a wall of the room so that the microphone array plane is perpendicular to that of the wall. For this arrangement, a so-called half-space propagation model has been recently proposed, which accounts for the joint contribution of the direct path and the earliest reflection introduced by the adjacent wall. Based on this propagation model, a numerical process to estimate a model of the diffuse noise spatial coherence, which accounts for the presence of the reflecting surface, is proposed. The suggested noise covariance model is used in order to extend the superdirective beamformer in half-space, achieving notable improvements in performance in comparison to a more typical implementation that involves the spherical isotropic coherence model.

Silencing of Repetitive DNA Is Controlled by a Member of an Unusual Caenorhabditis elegans Gene Family.

Repetitive DNA sequences are subject to gene silencing in various animal species. Under specific circumstances repetitive DNA sequences can escape such silencing. For example, exogenously added, extrachromosomal DNA sequences that are stably inherited in multicopy repetitive arrays in the nematode Caenorhabditis elegans are frequently silenced in the germline, whereas such silencing often does not occur in the soma. This indicates that somatic cells might utilize factors that prevent repetitive DNA silencing. Indeed, such "antisilencing" factors have been revealed through genetic screens that identified mutant loci in which repetitive transgenic arrays are aberrantly silenced in the soma. We describe here a novel locus, pals-22 (for protein containing ALS2CR12 signature), required to prevent silencing of repetitive transgenes in neurons and other somatic tissue types. pals-22 deficiency also severely impacts animal vigor and confers phenotypes reminiscent of accelerated aging. We find that pals-22 is a member of a large family of divergent genes (39 members), defined by homology to the ALS2CR12 protein family. While gene family members are highly divergent, they show striking patterns of chromosomal clustering. The family expansion appears C. elegans-specific and has not occurred to the same extent in other nematode species for which genome sequences are available. The transgene-silencing phenotype observed upon loss of PALS-22 protein depends on the biogenesis of small RNAs. We speculate that the pals gene family may be part of a species-specific cellular defense mechanism.

Regulatory Logic of Pan-Neuronal Gene Expression in C. elegans.

While neuronal cell types display an astounding degree of phenotypic diversity, most if not all neuron types share a core panel of terminal features. However, little is known about how pan-neuronal expression patterns are genetically programmed. Through an extensive analysis of the cis-regulatory control regions of a battery of pan-neuronal C. elegans genes, including genes involved in synaptic vesicle biology and neuropeptide signaling, we define a common organizational principle in the regulation of pan-neuronal genes in the form of a surprisingly complex array of seemingly redundant, parallel-acting cis-regulatory modules that direct expression to broad, overlapping domains throughout the nervous system. These parallel-acting cis-regulatory modules are responsive to a multitude of distinct trans-acting factors. Neuronal gene expression programs therefore fall into two fundamentally distinct classes. Neuron-type-specific genes are generally controlled by discrete and non-redundantly acting regulatory inputs, while pan-neuronal gene expression is controlled by diverse, coincident and seemingly redundant regulatory inputs.

The molecular and gene regulatory signature of a neuron.

Neuron-type specific gene batteries define the morphological and functional diversity of cell types in the nervous system. Here, we discuss the composition of neuron-type specific gene batteries and illustrate gene regulatory strategies which determine the unique gene expression profiles and molecular composition of individual neuronal cell types from C. elegans to higher vertebrates. Based on principles learned from prokaryotic gene regulation, we argue that neuronal terminal gene batteries are functionally grouped into parallel-acting 'regulons'. The theoretical concepts discussed here provide testable hypotheses for future experimental analysis of the exact gene-regulatory mechanisms employed in the generation of neuronal diversity and identity.

Evidence for association of the G1733A polymorphism of the androgen receptor gene with recurrent spontaneous abortions.

OBJECTIVE: To determine whether the G1733A polymorphism of the androgen receptor gene is associated with an increased risk for recurrent spontaneous abortion (RSA). DESIGN: Case-control study. SETTING: Division of Genetics and Biotechnology, Department of Biology, University of Athens. PATIENT(S): A total of 131 women with at least three unexplained spontaneous abortions before 20 weeks' gestation, with the same partner, composed the study group. INTERVENTION(S): Subjects were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. MAIN OUTCOME MEASURE(S): G1733A polymorphism genotypes and allele frequencies. RESULT(S): The observed frequencies of GG, GA, and AA genotypes of the G1733A polymorphism were 0.57, 0.27, and 0.16, respectively, for the patient group and 0.76, 0.15, and 0.09, respectively, for the control group. Allele frequencies were 0.70 and 0.84, respectively, for the patient and control groups for the G allele (wild type) and 0.30 and 0.16, respectively, for the patient and control groups for the A allele (mutant). Statistical analysis of these results indicated significant differences between the two groups. CONCLUSION(S): These results indicated for the first time that the androgen receptor G1733A polymorphism is strongly associated with increased risk for RSA.