The LARGE Principle of Cellular Reprogramming: Lost, Acquired and Retained Gene Expression in Foreskin and Amniotic Fluid-Derived Human iPS Cells

Human amniotic fluid cells (AFCs) are routinely obtained for prenatal diagnostics procedures. Recently, it has been illustrated that these cells may also serve as a valuable model system to study developmental processes and for application in regenerative therapies. Cellular reprogramming is a means of assigning greater value to primary AFCs by inducing self-renewal and pluripotency and, thus, bypassing senescence. Here, we report the generation and characterization of human amniotic fluid-derived induced pluripotent stem cells (AFiPSCs) and demonstrate their ability to differentiate into the trophoblast lineage after stimulation with BMP2/BMP4. We further carried out comparative transcriptome analyses of primary human AFCs, AFiPSCs, fibroblast-derived iPSCs (FiPSCs) and embryonic stem cells (ESCs). This revealed that the expression of key senescence-associated genes are down-regulated upon the induction of pluripotency in primary AFCs (AFiPSCs). By defining distinct and overlapping gene expression patterns and deriving the LARGE (Lost, Acquired and Retained Gene Expression) Principle of Cellular Reprogramming, we could further highlight that AFiPSCs, FiPSCs and ESCs share a core self-renewal gene regulatory network driven by OCT4, SOX2 and NANOG. Nevertheless, these cell types are marked by distinct gene expression signatures. For example, expression of the transcription factors, SIX6, EGR2, PKNOX2, HOXD4, HOXD10, DLX5 and RAXL1, known to regulate developmental processes, are retained in AFiPSCs and FiPSCs. Surprisingly, expression of the self-renewal-associated gene PRDM14 or the developmental processes-regulating genes WNT3A and GSC are restricted to ESCs. Implications of this, with respect to the stability of the undifferentiated state and long-term differentiation potential of iPSCs, warrant further studies

Polymeric ultrafiltration membranes and surfactants.

Surfactants have been extensively used in ultrafiltration processes such as membrane cleaning,removal of surfactants or other organic toxic compounds and metal ions from solutions and estimation of interactions at surfactant and membrane interface. The aim of this review is to present the possibilities that arise from the data reported in the literature on the field of ultrafiltration (UF) membranes and surfactants. This data is classified into five groups and a brief description of each article is given. Pretreatment of membranes with surfactant solutions can lead to performance increase of UF process. By Micellar-Enhanced Ultrafiltration the separation of low molecular weight toxic substances and heavy metals is possible, extending the applications of conventional UF (e.g. separation of proteins). Through estimation of the type of interactions on membrane surface with surfactants the prediction of retention and removal of small size substances, the prevention of fouling, the modification of surfactant-membrane system, the design of new surfactant-membrane system could be achieved. Finally economical aspects of UF-surfactant processes are given

Opsoclonus-myoclonus-ataxia syndrome with autoantibodies to glutamic acid decarboxylase

Opsoclonus-myoclonus-ataxia syndrome (OMS) is a rare neurological disorder of probably autoimmune origin. Most cases are associated with a remote neoplasm or a viral infection; however in some instances no underlying aetiology can be demonstrated. We report the presence of anti-glutamic acid decarboxylase antibodies (anti-GAD Abs) in the serum and CSF of a patient with idiopathic OMS. Treatment with intravenous immunoglobulin led to a remarkable clinical improvement with parallel reduction of anti-GAD titers. Anti-GAD Abs have been associated with several neurological syndromes. They could also be responsible for the clinical triad of OMS, by impairing GABAergic transmission in specific brainstem and cerebellar circuits. We propose that testing for anti-GAD Abs should be performed in OMS, especially when no other aetiological association can be demonstrated. © 2008 Elsevier B.V. All rights reserved

A Normalization Mechanism for Estimating Visual Motion across Speeds and Scales

Interacting with the natural environment leads to complex stimulations of our senses. Here we focus on the estimation of visual speed, a critical source of information for the survival of many animal species as they monitor moving prey or approaching dangers. In mammals, and in particular in primates, speed information is conceived to be represented by a set of channels sensitive to different spatial and temporal characteristics of the optic flow [1–5]. However, it is still largely unknown how the brain accurately infers the speed of complex natural scenes from this set of spatiotemporal channels [6–14]. As complex stimuli, we chose a set of well-controlled moving naturalistic textures called ‘‘compound motion clouds’’ (CMCs) [15, 16] that simultaneously activate multiple spatiotemporal channels. We found that CMC stimuli that have the same physical speed are perceived moving at different speeds depending on which channel combinations are activated. We developed a computational model demonstrating that the activity in a given channel is both boosted and weakened after a systematic pattern over neighboring channels. This pattern of interactions can be under- stood as a combination of two components oriented in speed (consistent with a slow-speed prior) and scale (sharpening of similar features). Interestingly, the interaction along scale implements a lateral inhibition mechanism, a canonical principle that hitherto was found to operate mainly in early sensory processing. Overall, the speed-scale normalization mechanism may reflect the natural tendency of the visual system to integrate complex inputs into one coherent percept