High-Speed Time-Domain Diffuse Optical Tomography with a Sensitivity Equation-based Neural Network.

Steady progress in time-domain diffuse optical tomography (TD-DOT) technology is allowing for the first time the design of low-cost, compact, and high-performance systems, thus promising more widespread clinical TD-DOT use, such as for recording brain tissue hemodynamics. TD-DOT is known to provide more accurate values of optical properties and physiological parameters compared to its frequency-domain or steady-state counterparts. However, achieving high temporal resolution is still difficult, as solving the inverse problem is computationally demanding, leading to relatively long reconstruction times.

Unrolled-DOT: an interpretable deep network for diffuse optical tomography.

Significance: Imaging through scattering media is critical in many biomedical imaging applications, such as breast tumor detection and functional neuroimaging. Time-of-flight diffuse optical tomography (ToF-DOT) is one of the most promising methods for high-resolution imaging through scattering media. ToF-DOT and many traditional DOT methods require an image reconstruction algorithm.

Optical scattering as an early marker of apoptosis during chemotherapy and antiangiogenic therapy in murine models of prostate and breast cancer.

Monitoring of the in vivo tumor state to track therapeutic response in real time may help to evaluate new drug candidates, maximize treatment efficacy, and reduce the burden of overtreatment. Current preclinical tumor imaging methods have largely focused on anatomic imaging (e.g.

RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues.

In situ analysis of biomarkers is highly desirable in molecular pathology because it allows the examination of biomarker status within the histopathological context of clinical specimens. Immunohistochemistry and DNA in situ hybridization (ISH) are widely used in clinical settings to assess protein and DNA biomarkers, respectively, but clinical use of in situ RNA analysis is rare. This disparity is especially notable when considering the abundance of RNA biomarkers discovered through whole-genome expression profiling.

Specific regulation of NRG1 isoform expression by neuronal activity.

Neuregulin 1 (NRG1) is a trophic factor that has been implicated in neural development, neurotransmission, and synaptic plasticity. NRG1 has multiple isoforms that are generated by usage of different promoters and alternative splicing of a single gene. However, little is known about NRG1 isoform composition profile, whether it changes during development, or the underlying mechanisms.

Drosophila E-cadherin and its binding partner Armadillo/ beta-catenin are required for axonal pathway choices in the developing larval brain.

The fly brain is formed by approximately hundred paired lineages of neurons, each lineage derived from one neuroblast. Embryonic neuroblasts undergo a small number of divisions and produce the primary neurons that form the functioning larval brain. In the larva, neuroblasts produce the secondary lineages that make up the bulk of the adult brain.

The steady-state level of the nervous-system-specific microRNA-124a is regulated by dFMR1 in Drosophila.

Fragile X syndrome is the most common form of inherited mental retardation caused by loss of the fragile X mental retardation protein 1 (FMRP). The detailed molecular pathways underlying the pathogenesis of this disorder remain incompletely understood. Here, we show that miR-124a, a nervous-system-specific miRNA, is associated with the Drosophila homolog of FMRP (dFMR1) in vivo.

The Drosophila homologue of the Angelman syndrome ubiquitin ligase regulates the formation of terminal dendritic branches.

Angelman syndrome is a severe neurodevelopmental disorder mostly caused by loss-of-function mutations in the maternal allele of UBE3A, a gene that encodes an E3 ubiquitin ligase. Drosophila UBE3A (dUBE3A) is highly homologous to human UBE3A (hUBE3A) at the amino acid sequence level, suggesting their functional conservation. We generated dUBE3A-null mutant fly lines and found that dUBE3A is not essential for viability.

Expression profile of the cadherin family in the developing Drosophila brain.

The Drosophila genome encodes 17 members of the cadherin family of adhesion molecules, which in vertebrates has been implicated in patterning the nervous system through cell and axon sorting. With only a few exceptions all cadherins show widespread expression in the larval brain. What expression patterns have in common is that 1) they are global, in the sense that all lineages of the central brain or optic lobe, or both, show expression; and 2) expression is stage-specific: some cadherins are expressed only in primary neurons (located closest to the neuropile), others in early secondary neurons (near the brain surface), or primaries plus late secondaries.

MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila.

MicroRNAs (miRNAs) have been implicated in regulating various aspects of animal development, but their functions in neurogenesis are largely unknown. Here we report that loss of miR-9a function in the Drosophila peripheral nervous system leads to ectopic production of sensory organ precursors (SOPs), whereas overexpression of miR-9a results in a severe loss of SOPs. We further demonstrate a strong genetic interaction between miR-9a and senseless (sens) in controlling the formation of SOPs in the adult wing imaginal disc.

Regulation of cell adhesion in the Drosophila embryo by phosphorylation of the cadherin-catenin-complex.

Cell-culture studies indicate that tyrosine phosphorylation of the cadherin-catenin-complex (CCC) is one of the post-translational mechanism regulating E-cadherin-mediated cell adhesion. In this investigation, controlled application of a tyrosine phosphatase inhibitor (orthovanadate) and tyrosine kinase inhibitor (tyrphostin) to early Drosophila embryos, followed by biochemical assays and phenotypic analysis, has been utilized to address the mechanism by which tyrosine phosphorylation regulates E-cadherin-mediated cell adhesion in vivo. Our data suggest that, in the Drosophila embryo, beta-catenin (Drosophila homolog Armadillo) is the primary tyrosine-phosphorylated protein in the CCC.

BTB/POZ-zinc finger protein abrupt suppresses dendritic branching in a neuronal subtype-specific and dosage-dependent manner.

How dendrites of different neuronal subtypes exhibit distinct branching patterns during development remains largely unknown. Here we report the mapping and identification of loss-of-function mutations in the abrupt (ab) gene that increased the number of dendritic branches of multiple dendritic (MD) sensory neurons in Drosophila embryos. Ab encodes an evolutionarily conserved transcription factor that contains a BTB/POZ domain and C2H2 zinc finger motifs.

The role of DE-cadherin during cellularization, germ layer formation and early neurogenesis in the Drosophila embryo.

The Drosophila E-cadherin homolog, DE-cadherin, is expressed and required in all epithelial tissues throughout embryogenesis. Due to a strong maternal component of DE-cadherin, its early function during embryogenesis has remained elusive. The expression of a dominant negative DE-cadherin construct (UAS-DE-cad(ex)) using maternally active driver lines allowed us to analyze the requirements for DE-cadherin during this early phase of development.

APC-independent activation of NK cells by the Toll-like receptor 3 agonist double-stranded RNA.

Toll-like receptors (TLRs) play a fundamental role in the recognition of bacteria and viruses. TLR3 is activated by viral dsRNA and polyinosinic-polycytidylic acid (poly(I:C)), a synthetic mimetic of viral RNA. We show that NK cells, known for their capacity to eliminate virally infected cells, express TLR3 and up-regulate TLR3 mRNA upon poly(I:C) stimulation.

Stanniocalcin 1 is an autocrine modulator of endothelial angiogenic responses to hepatocyte growth factor.

Stanniocalcin 1 (STC1) is a secreted glycoprotein originally described as a hormone involved in calcium and phosphate homeostasis in bony fishes. We recently identified the mammalian homolog of this molecule to be highly up-regulated in an in vitro model of angiogenesis, as well as focally and intensely expressed at sites of pathological angiogenesis (e.g.

Role of DE-cadherin in neuroblast proliferation, neural morphogenesis, and axon tract formation in Drosophila larval brain development.

In the wild-type brain, the Drosophila classic cadherin DE-cadherin is expressed globally by postembryonic neuroblasts and their lineages ("secondary lineages"), as well as glial cells. To address the role of DE-cadherin in the larval brain, we took advantage of the dominant-negative DE-cad(ex) construct, the expression of which was directed to neurons, glial cells, or both. Global expression of DE-cad(ex) driven by a heat pulse during the early second instar resulted in a severe phenotype that included deficits in neural proliferation.

Early development of the Drosophila brain: V. Pattern of postembryonic neuronal lineages expressing DE-cadherin.

The Drosophila E-cadherin homolog, DE-cadherin, is expressed postembryonically by brain neuroblasts and their lineages of neurons ("secondary lineages"). DE-cadherin appears in neuroblasts as soon as they can be identified by their increase in size and then remains expressed uninterruptedly throughout larval life. DE-cadherin remains transiently expressed in the cell bodies and axons of neurons produced by neuroblast proliferation.

Time course of skeletal muscle repair and gene expression following acute hind limb ischemia in mice.

DNA microarrays were used to measure the time course of gene expression during skeletal muscle damage and regeneration in mice following femoral artery ligation (FAL). We found 1,289 known sequences were differentially expressed between the FAL and control groups. Gene expression peaked on day 3, and the functional cluster "inflammation" contained the greatest number of genes.

Interaction between EGFR signaling and DE-cadherin during nervous system morphogenesis.

Dynamically regulated cell adhesion plays an important role during animal morphogenesis. Here we use the formation of the visual system in Drosophila embryos as a model system to investigate the function of the Drosophila classic cadherin, DE-cadherin, which is encoded by the shotgun (shg) gene. The visual system is derived from the optic placode which normally invaginates from the surface ectoderm of the embryo and gives rise to two separate structures, the larval eye (Bolwig's organ) and the optic lobe.