Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (<1 hr) P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors

Tumor necrosis factor alpha and epidermal growth factor act additively to inhibit matrix gene expression by chondrocyte

The failure of chondrocytes to replace the lost extracellular matrix contributes to the progression of degenerative disorders of cartilage. Inflammatory mediators present in the joint regulate the breakdown of the established matrix and the synthesis of new extracellular matrix molecules. In the present study, we investigated the effects of tumor necrosis factor alpha (TNF-α) and epidermal growth factor (EGF) on chondrocyte morphology and matrix gene expression. Chondrocytes were isolated from distal femoral condyles of neonatal rats. Cells in primary culture displayed a cobblestone appearance. EGF, but not TNF-α, increased the number of cells exhibiting an elongated morphology. TNF-α potentiated the effect of EGF on chondrocyte morphology. Individually, TNF-α and EGF diminished levels of aggrecan and type II collagen mRNA. In combination, the effects of TNF-α and EGF were additive, indicating the involvement of discrete signaling pathways. Cell viability was not compromised by TNF-α or by EGF, alone or in combination. EGF alone did not activate NF-κB or alter NF-κB activation by TNF-α. Pharmacologic studies indicated that the effects of TNF-α and EGF alone or in combination were independent of protein kinase C signaling, but were dependent on MEK1/2 activity. Finally, we analyzed the involvement of Sox-9 using a reporter construct of the 48 base pair minimal enhancer of type II collagen. TNF-α attenuated enhancer activity as expected; in contrast, EGF did not alter either the effect of TNF-α or basal activity. TNF-α and EGF, acting through distinct signaling pathways, thus have additive adverse effects on chondrocyte function. These findings provide critical insights into the control of chondrocytes through the integration of multiple extracellular signals

DARIS : a low-frequency distributed aperture array for radio astronomy in space

The frequency band below 30 MHz is one of the last unexplored bands in radio astronomy. This band is well suited for studying the early cosmos at high hydrogen redshifts, the so-called dark ages, extragalactic surveys, (extra) solar planetary bursts, and high energy particle physics. In addition, space research such as space weather tomography, are also areas of scientific interest. \ud \ud Due to ionospheric scintillation (below 30MHz) and its opaqueness (below 15MHz), earth-bound radio astronomy observations in these bands are either severely limited in sensitivity and spatial resolution or entirely impossible. A radio telescope in space obviously would not be hampered by the Earth's ionosphere. In the past, several (limited) studies have been conducted to explore possibilities for such an array in space. These studies considered aperture synthesis arrays in space, at the back-side of the Moon, or a satellite constellation operating in a coherent mode. \u

Design of a ring resonator-based optical beam forming network for phased array receive antennas

A novel squint-free ring resonator-based optical beam forming network (OBFN) for phased array antennas (PAA) is proposed. It is intended to provide broadband connectivity to airborne platforms via geostationary satellites. In this paper, we present the design of the OBFN and its control system. Our goal is to deliver large bandwidth Ku-band connectivity between antennas, mount conformal to the airplane fuselage and on a geostationary satellite, respectively.This way it would be possible to bring live DVB-S television to airplane passengers. In this paper, we present recent research conducted on a 4 × 1 ring resonator-based OBFN test set-up. This OBFN has four optical input ports and one optical output port. It is tuned to provide the desired signal combination with optimal constructive interference between the modulated input signals from the PAA. Therefore, combining circuitry and delay elements are required. The OBFN is tuned by electrically heating tunable true time delay (TTD) elements. These are built using optical ring resonators (ORRs). By cascading multiple ORRs with different resonance frequencies, it is possible to create a TTD with a large bandwidth. Optical beam forming is used because it provides advantages over traditional beam forming methods. These advantages are: large bandwidth, EMI resistance, and, when integrated onto a single chip, compactness and low costs. The OBFN is created using planar optical waveguide technology and consists of the following building blocks: waveguides, Mach-Zehnder interferometers, (MZIs) couplers and ORRs. The tuning of the OBFN is done by an electronic control system using a microcontroller. Communication with a PC is possible using USB. To our knowledge, this is the first integrated ORR-based OBFN circuit for PAA satellite reception

Saltatory Conduction along Myelinated Axons Involves a Periaxonal Nanocircuit

The propagation of electrical impulses along axons is highly accelerated by the myelin sheath and pro- duces saltating or ‘‘jumping’’ action potentials across internodes, from one node of Ranvier to the next. The underlying electrical circuit, as well as the existence and role of submyelin conduction in salta- tory conduction remain, however, elusive. Here, we made patch-clamp and high-speed voltage-cali- brated optical recordings of potentials across the nodal and internodal axolemma of myelinated neocortical pyramidal axons combined with electron microscopy and experimentally constrained cable modeling. Our results reveal a nanoscale yet conduc- tive periaxonal space, incompletely sealed at the paranodes, which separates the potentials across the low-capacitance myelin sheath and internodal axolemma. The emerging double-cable model repro- duces the recorded evolution of voltage waveforms across nodes and internodes, including rapid nodal potentials traveling in advance of attenuated waves in the internodal axolemma, revealing a mechanism for saltation across time and space

Targeting and activation of Rac1 are mediated by the exchange factor β-Pix

Rho guanosine triphosphatases (GTPases) are critical regulators of cytoskeletal dynamics and control complex functions such as cell adhesion, spreading, migration, and cell division. It is generally accepted that localized GTPase activation is required for the proper initiation of downstream signaling events, although the molecular mechanisms that control targeting of Rho GTPases are unknown. In this study, we show that the Rho GTPase Rac1, via a proline stretch in its COOH terminus, binds directly to the SH3 domain of the Cdc42/Rac activator β-Pix (p21-activated kinase [Pak]–interacting exchange factor). The interaction with β-Pix is nucleotide independent and is necessary and sufficient for Rac1 recruitment to membrane ruffles and to focal adhesions. In addition, the Rac1–β-Pix interaction is required for Rac1 activation by β-Pix as well as for Rac1-mediated spreading. Finally, using cells deficient for the β-Pix–binding kinase Pak1, we show that Pak1 regulates the Rac1–β-Pix interaction and controls cell spreading and adhesion-induced Rac1 activation. These data provide a model for the intracellular targeting and localized activation of Rac1 through its exchange factor β-Pix