Casting Light Upon The Great Endarkenment

While the Enlightenment promoted thinking for oneself independent of religious authority, the ‘Endarkenment’ (Millgram 2015) concerns deference to a new authority: the specialist, a hyperspecializer. Non-specialists need to defer to such authorities as they are unable to understand their reasoning. Millgram describes how humans are capable of being serial hyperspecializers, able to move from one specialism to another. We support the basic thrust of Millgram’s position, and seek to articulate how the core idea is deployed in very different ways in relation to extremely different philosophical areas. We attend to the issue of the degree of isolation of different specialists and we urge greater emphasis on parallel hyperspecialization, which describes how different specialisms can be embodied in one person at one time

Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients

CDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and a novel frameshift variant (c.1041dup, p.Ser348Glnfs*2) in the gene CDC14A, respectively. To evaluate the pathogenicity of both loss-of-function variants, we analyzed the effects of both variants on the RNA-level. The splice variant was characterized using a minigene assay. Altered expression levels due to the c.1041dup variant were assessed using RT-qPCR. In summary, cDNA analysis confirmed that the c.1421+2T>C variant activates a cryptic splice site, resulting in a truncated transcript (c.1414_1421del, p.Val472Leufs*20) and the c.1041dup variant results in a defective transcript that is likely degraded by nonsense-mediated mRNA decay. The present study functionally characterizes two variants and provides further confirmatory evidence that CDC14A is associated with a rare form of hereditary hearing loss

Enteric Species F Human Adenoviruses use Laminin-Binding Integrins as Co-Receptors for Infection of Ht-29 Cells

The enteric species F human adenovirus types 40 and 41 (HAdV-40 and -41) are the third most common cause of infantile gastroenteritis in the world. Knowledge about HAdV-40 and -41 cellular infection is assumed to be fundamentally different from that of other HAdVs since HAdV-40 and -41 penton bases lack the aV-integrin-interacting RGD motif. This motif is used by other HAdVs mainly for internalization and endosomal escape. We hypothesised that the penton bases of HAdV-40 and -41 interact with integrins independently of the RGD motif. HAdV-41 transduction of a library of rodent cells expressing specific human integrin subunits pointed to the use of laminin-binding alpha 2-, alpha 3- and alpha 6- containing integrins as well as other integrins as candidate co-receptors. Specific laminins prevented internalisation and infection, and recombinant, soluble HAdV-41 penton base proteins prevented infection of human intestinal HT-29 cells. Surface plasmon resonance analysis demonstrated that HAdV-40 and -41 penton base proteins bind to alpha 6-containing integrins with an affinity similar to that of previously characterised penton base:integrin interactions. With these results, we propose that laminin-binding integrins are co-receptors for HAdV-40 and -41

The Anthropocene monument:on relating geological and human time

In the Parthenon frieze, the time of mortals and the time of gods seem to merge. Dipesh Chakrabarty has argued that with the advent of the Anthropocene the times of human history and of the Earth are similarly coming together. Are humans entering the ‘monumental time’ of the Earth, to stand alongside the Olympian gods of the other geological forces? In this paper I first look at the cultural shifts leading to the modern idea of separate human and Earth histories. I examine the changing use of monuments to mediate between human and other temporalities. I explore the use of ‘stratigraphic sections’ as natural monuments to mark transitions between the major time units of Earth history, and the erection of intentional monuments nearby. I suggest that the Anthropocene, as a geological epoch-in-the-making, may challenge the whole system of monumental semiotics used to stabilise our way of thinking about deep time

Nonparametric Simulation of Signal Transduction Networks with Semi-Synchronized Update

Simulating signal transduction in cellular signaling networks provides predictions of network dynamics by quantifying the changes in concentration and activity-level of the individual proteins. Since numerical values of kinetic parameters might be difficult to obtain, it is imperative to develop non-parametric approaches that combine the connectivity of a network with the response of individual proteins to signals which travel through the network. The activity levels of signaling proteins computed through existing non-parametric modeling tools do not show significant correlations with the observed values in experimental results. In this work we developed a non-parametric computational framework to describe the profile of the evolving process and the time course of the proportion of active form of molecules in the signal transduction networks. The model is also capable of incorporating perturbations. The model was validated on four signaling networks showing that it can effectively uncover the activity levels and trends of response during signal transduction process