A Novel Implantable Glaucoma Valve Using Ferrofluid

Purpose

To present a novel design of an implantable glaucoma valve based on ferrofluidic nanoparticles and to compare it with a well-established FDA approved valve.

Setting

Massachusetts Eye & Ear Infirmary, Boston, USA.

Methods

A glaucoma valve was designed using soft lithography techniques utilizing a water-immiscible magnetic fluid (ferrofluid) as a pressure-sensitive barrier to aqueous flow. Two rare earth micro magnets were used to calibrate the opening and closing pressure. In-vitro flow measurements were performed to characterize the valve and to compare it to Ahmed™ glaucoma valve. The reliability and predictability of the new valve was verified by pressure/flow measurements over a period of three months and X-ray diffraction (XRD) analysis over a period of eight weeks. In vivo assessment was performed in three rabbits.

Results

In the in vitro experiments, the opening and closing pressures of the valve were 10 and 7 mmHg, respectively. The measured flow/pressure response was linearly proportional and reproducible over a period of three months (1.8 µl/min at 12 mmHg; 4.3 µl/min at 16 mmHg; 7.6 µl/min at 21 mmHg). X-ray diffraction analysis did not show oxidization of the ferrofluid when exposed to water or air. Preliminary in vivo results suggest that the valve is biocompatible and can control the intraocular pressure in rabbits.

Conclusions

The proposed valve utilizes ferrofluid as passive, tunable constriction element to provide highly predictable opening and closing pressures while maintaining ocular tone. The ferrofluid maintained its magnetic properties in the aqueous environment and provided linear flow to pressure response. Our in-vitro tests showed reliable and reproducible results over a study period of three months. Preliminary in-vivo results were very promising and currently more thorough investigation of this device is underway.     

CXCL12-Mediated Murine Neural Progenitor Cell Movement Requires PI3Kβ Activation

The migratory route of neural progenitor/precursor cells (NPC) has a central role in central nervous system development. Although the role of the chemokine CXCL12 in NPC migration has been described, the intracellular signaling cascade involved remains largely unclear. Here we studied the molecular mechanisms that promote murine NPC migration in response to CXCL12, in vitro and ex vivo. Migration was highly dependent on signaling by the CXCL12 receptor, CXCR4. Although the JAK/STAT pathway was activated following CXCL12 stimulation of NPC, JAK activity was not necessary for NPC migration in vitro. Whereas CXCL12 activated the PI3K catalytic subunits p110α and p110β in NPC, only p110β participated in CXCL12-mediated NPC migration. Ex vivo experiments using organotypic slice cultures showed that p110β blockade impaired NPC exit from the medial ganglionic eminence. In vivo experiments using in utero electroporation nonetheless showed that p110β is dispensable for radial migration of pyramidal neurons. We conclude that PI3K p110β is activated in NPC in response to CXCL12, and its activity is necessary for immature interneuron migration to the cerebral cortex.     

Macrohistone Variants Preserve Cell Identity by Preventing the Gain of H3K4me2 during Reprogramming to Pluripotency

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Highlights? Macrohistone variants are regulated during reprogramming and differentiation ? The levels of macrohistone variants modulate the efficiency of reprogramming ? MacroH2A.1 occupies pluripotency and differentiation genes in keratinocytes ? MacroH2A.1 occupancy prevents the gain of H3K4me2 during reprogramming     

Assessing the Fecal Microbiota: An Optimized Ion Torrent 16S rRNA Gene-Based Analysis Protocol

Assessing the distribution of 16S rRNA gene sequences within a biological sample represents the current state-of-the-art for determination of human gut microbiota composition. Advances in dissecting the microbial biodiversity of this ecosystem have very much been dependent on the development of novel high-throughput DNA sequencing technologies, like the Ion Torrent. However, the precise representation of this bacterial community may be affected by the protocols used for DNA extraction as well as by the PCR primers employed in the amplification reaction. Here, we describe an optimized protocol for 16S rRNA gene-based profiling of the fecal microbiota.     

SETD7 Regulates the Differentiation of Human Embryonic Stem Cells

The successful use of specialized cells in regenerative medicine requires an optimization in the differentiation protocols that are currently used. Understanding the molecular events that take place during the differentiation of human pluripotent cells is essential for the improvement of these protocols and the generation of high quality differentiated cells. In an effort to understand the molecular mechanisms that govern differentiation we identify the methyltransferase SETD7 as highly induced during the differentiation of human embryonic stem cells and differentially expressed between induced pluripotent cells and somatic cells. Knock-down of SETD7 causes differentiation defects in human embryonic stem cell including delay in both the silencing of pluripotency-related genes and the induction of differentiation genes. We show that SETD7 methylates linker histone H1 in vitro causing conformational changes in H1. These effects correlate with a decrease in the recruitment of H1 to the pluripotency genes OCT4 and NANOG during differentiation in the SETD7 knock down that might affect the proper silencing of these genes during differentiation.     

In the Pursuit of the Predatory Behavior of Borophagines (Mammalia,Carnivora, Canidae): Inferences from Forelimb Morphology

Here, we perform an ecomorphological study on the major bones (humerus, radius, and ulna) of the carnivoran forelimb using three-dimensional geometric morphometrics. More specifically, we test the association between forelimb morphology and predatory behavior. Our results suggest that the main morphological adaptions of carnivorans to different predatory behaviors relate to: (i) the capacity to perform long and efficient runs as in pounce/pursuit and pursuit predators; (ii) the ability to maneuver as in occasional predators; and (iii) the capacity to exert and resist large loads as in ambushing predators. We used borophagine canids as a case study, given the controversy on the predatory behavior of this extinct subfamily. Our results indicate that borophagines displayed a limited set of adaptions towards efficient running, including reduced joint mobility in both the elbow and the wrist, aspects in which they resemble the living canids. Furthermore, they had forelimbs as powerful as those of the extant ambushing carnivorans (i.e., most felids). This combination of traits suggests that the predatory behavior of borophagines was unique among carnivorans, as it was not fully equivalent to any of the living species.