Methylation-directed regulatory networks determine enhancing and silencing of mutation disease driver genes and explain inter-patient expression variation.

Background: Common diseases manifest differentially between patients, but the genetic origin of this variation remains unclear. To explore possible involvement of gene transcriptional-variation, we produce a DNA methylation-oriented, driver-gene-wide dataset of regulatory elements in human glioblastomas and study their effect on inter-patient gene expression variation.

Results: In 175 of 177 analyzed gene regulatory domains, transcriptional enhancers and silencers are intermixed.

Micropatterned topographies reveal measurable differences between cancer and benign cells.

During metastasis, cancer cells migrate away from the primary tumor-site, encountering different microenvironment topographies that may facilitate or inhibit cancer cell adherence and growth; those relate to sites of invasion and seeding. To evaluate topography effects, poly-lactic-poly-glycolic (PLGA) gels are generated as flat substrates, porous, or with rectangular microchannels of varying widths (5-100 µm) and depths (10/20 µm). The topography effect on time-dependent adherence, proliferation, morphology, alignment and long-term structural development of metastatic breast-cancer and benign cells are evaluated; adherence at short time-scales (3 h) is compared to developed morphologies and multicellular structures (>2 days) indicating function.

Non-damaging stretching combined with sodium pyruvate supplement accelerate migration of fibroblasts and myoblasts during gap closure.

Background: Sustained, low- and mid-level (3-6%), radial stretching combined with varying concentrations of sodium pyruvate (NaPy) supplement increase the migration rate during microscale gap closure following an in vitro injury; NaPy is a physiological supplement often used in cell-culture media. Recently we showed that low-level tensile strains accelerate in vitro kinematics during en masse cell migration; topically applied mechanical deformations also accelerate in vivo healing in larger wounds. The constituents and nutrients at injury sites change.

Spontaneous Activity Characteristics of 3D "Optonets".

Sporadic spontaneous network activity emerges during early central nervous system (CNS) development and, as the number of neuronal connections rises, the maturing network displays diverse and complex activity, including various types of synchronized patterns. These activity patterns have major implications on both basic research and the study of neurological disorders, and their interplay with network morphology tightly correlates with developmental events such as neuronal differentiation, migration and establishment of neurotransmitter phenotypes. Although 2D neural cultures models have provided important insights into network activity patterns, these cultures fail to mimic the complex 3D architecture of natural CNS neural networks and its consequences on connectivity and activity.

Microfluidic Chip for Site-Specific Neuropharmacological Treatment and Activity Probing of 3D Neuronal "Optonet" Cultures.

The study introduces a "brain-on-a-chip" microfluidic platform that hosts brain-like 3D cultures ("optonets") whose activity and responses to flowing drugs are recorded optically. Optonets are viable, optically accessible 3D neural networks whose characteristics approximate cortical networks. The results demonstrate the ability to monitor complex 3D activity patterns during extended site-specific, reversible neuropharmacogical exposure, suggesting an interesting potential in drug screening.

The timing and spatiotemporal patterning of Neanderthal disappearance.

The timing of Neanderthal disappearance and the extent to which they overlapped with the earliest incoming anatomically modern humans (AMHs) in Eurasia are key questions in palaeoanthropology. Determining the spatiotemporal relationship between the two populations is crucial if we are to understand the processes, timing and reasons leading to the disappearance of Neanderthals and the likelihood of cultural and genetic exchange. Serious technical challenges, however, have hindered reliable dating of the period, as the radiocarbon method reaches its limit at ∼50,000 years ago.

Hybrid multiphoton volumetric functional imaging of large-scale bioengineered neuronal networks.

Planar neural networks and interfaces serve as versatile in vitro models of central nervous system physiology, but adaptations of related methods to three dimensions (3D) have met with limited success. Here, we demonstrate for the first time volumetric functional imaging in a bioengineered neural tissue growing in a transparent hydrogel with cortical cellular and synaptic densities, by introducing complementary new developments in nonlinear microscopy and neural tissue engineering. Our system uses a novel hybrid multiphoton microscope design combining a 3D scanning-line temporal-focusing subsystem and a conventional laser-scanning multiphoton microscope to provide functional and structural volumetric imaging capabilities: dense microscopic 3D sampling at tens of volumes per second of structures with mm-scale dimensions containing a network of over 1,000 developing cells with complex spontaneous activity patterns.

Holographically patterned activation using photo-absorber induced neural-thermal stimulation.

Objective: Patterned photo-stimulation offers a promising path towards the effective control of distributed neuronal circuits. Here, we demonstrate the feasibility and governing principles of spatiotemporally patterned microscopic photo-absorber induced neural-thermal stimulation (PAINTS) based on light absorption by exogenous extracellular photo-absorbers.

Approach: We projected holographic light patterns from a green continuous-wave (CW) or an IR femtosecond laser onto exogenous photo-absorbing particles dispersed in the vicinity of cultured rat cortical cells.

Single amino acid radiocarbon dating of Upper Paleolithic modern humans.

Archaeological bones are usually dated by radiocarbon measurement of extracted collagen. However, low collagen content, contamination from the burial environment, or museum conservation work, such as addition of glues, preservatives, and fumigants to "protect" archaeological materials, have previously led to inaccurate dates. These inaccuracies in turn frustrate the development of archaeological chronologies and, in the Paleolithic, blur the dating of such key events as the dispersal of anatomically modern humans.

Amelioration of brain pathology and behavioral dysfunction in mice with lupus following treatment with a tolerogenic peptide.

Objective: Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is manifested by neurologic deficits and psychiatric disorders. The aim of this study was to examine SLE-associated CNS pathology in lupus-prone (NZBxNZW)F1 (NZB/NZW) mice, and to evaluate the ameliorating effects of treatment with a tolerogenic peptide, hCDR1 (human first complementarity-determining region), on these manifestations.

Methods: Histopathologic analyses of brains from lupus-prone NZB/NZW mice treated with vehicle, hCDR1, or a control scrambled peptide were performed.