Reflections on Collective Insecurity and Virtual Resistance in the times of COVID-19 in Malaysia

Environments of human insecurity are a widespread problem in our globalised world, particularly for migrant workers, one of the most vulnerable groups in society today. These experiences of insecurity have been heightened in the context of the COVID-19 pandemic. In this article, we examine the collective experience of insecurity among migrant workers in Malaysia. In our analysis, we outline collective insecurity at two levels: the micro level of migrant workers’ daily, subjective experiences of insecurity; and the macro level, in which insecurity is a consequence of structural forces, specifically the globalisation of labour. These two levels interact symbiotically, producing states of insecurity that are concretely experienced as anxiety and fear. Migrant workers in Malaysia also practice agency through small forms of resistance that they use to bolster one another and reduce their insecure experiences. Throughout the COVID-19 pandemic and subsequent Movement Control Order (MCO) in Malaysia, migrant workers have been further marginalised by the state, but they have also become connected to one another through acts of solidarity and resistance. However, the sustainability of these forms remains unclear

Results from screening over 9000 mutation-bearing mice for defects in the electroretinogram and appearance of the fundus

Random mutagenesis combined with phenotypic screening using carefully crafted functional tests has successfully led to the discovery of genes that are essential for a number of functions. This approach does not require prior knowledge of the identity of the genes that are involved and is a way to ascribe function to the nearly 6000 genes for which knowledge of the DNA sequence has been inadequate to determine the function of the gene product. In an effort to identify genes involved in the visual system via this approach, we have tested over 9000 first and third generation offspring of mice treated with the mutagen N-ethyl-N-nitrosourea (ENU) for visual defects, as evidenced by abnormalities in the electroretinogram and appearance of the fundus. We identified 61 putative mutations with this procedure and outline the steps needed to identify the affected genes

Argonaute High-Throughput Sequencing of RNAs Isolated by Cross-Linking Immunoprecipitation Reveals a Snapshot of miRNA Gene Regulation in the Mammalian Retina

[Image: see text] Mounting evidence points to roles for miRNA gene regulation in promoting development, function, and cell survival in the mammalian retina. However, little is known regarding which retinal genes are targets of miRNAs. Here, we employed a systematic, nonbiased, biochemical approach to identify targets of miRNA gene regulation in the bovine retina, a common model species for vision research. Using Argonaute high-throughput sequencing of RNAs isolated by cross-linking immunoprecipitation analysis, we identified 348 high-confidence miRNA target sites within 261 genes. This list was enriched in rod and cone photoreceptor genes and included 28 retinal disease genes, providing further evidence of a role of miRNAs in the pathology of blinding diseases

Generation, characterization, and molecular cloning of the Noerg-1 mutation of rhodopsin in the mouse

We performed genome-wide mutagenesis of C57BL/6J mice using the mutagen N-ethyl-N-nitrosourea (ENU) and screened the third generation (G3) offspring for visual system alterations using electroretinography and fundus photography. Several mice in one pedigree showed characteristics of retinal degeneration when tested at 12–14 weeks of age: no recordable electroretinogram (ERG), attenuation of retinal vessels, and speckled pigmentation of the fundus. Histological studies showed that the retinas undergo a photoreceptor degeneration with apoptotic loss of outer nuclear layer nuclei but visual acuity measured using the optomotor response under photopic conditions persists in spite of considerable photoreceptor loss. The Noerg-1 mutation showed an autosomal dominant pattern of inheritance in progeny. Studies in early postnatal mice showed degeneration to occur after formation of partially functional rods. The Noerg-1 mutation was mapped genetically to chromosome 6 by crossing C57BL/6J mutants with DBA/2J or BALB/cJ mice to produce an N2 generation and then determining the ERG phenotypes and the genotypes of the N2 offspring at multiple loci using SSLP and SNP markers. Fine mapping was accomplished with a set of closely spaced markers. A nonrecombinant region from 112.8 Mb to 115.1 Mb was identified, encompassing the rhodopsin (Rho) coding region. A single nucleotide transition from G to A was found in the Rho gene that is predicted to result in a substitution of Tyr for Cys at position 110, in an intradiscal loop. This mutation has been found in patients with autosomal dominant retinitis pigmentosa (RP) and results in misfolding of rhodopsin expressed in vitro. Thus, ENU mutagenesis is capable of replicating mutations that occur in human patients and is useful for generating de novo models of human inherited eye disease. Furthermore, the availability of the mouse genomic sequence and extensive DNA polymorphisms made the rapid identification of this gene possible, demonstrating that the use of ENU-induced mutations for functional gene identification is now practical for individual laboratories

A network comprising short and long noncoding RNAs and RNA helicase controls mouse retina architecture

Brain regions, such as the cortex and retina, are composed of layers of uniform thickness. The molecular mechanism that controls this uniformity is not well understood. Here we show that during mouse postnatal development the timed expression of Rncr4, a retina-specific long noncoding RNA, regulates the similarly timed processing of pri-miR-183/96/182, which is repressed at an earlier developmental stage by RNA helicase Ddx3x. Shifting the timing of mature miR-183/96/182 accumulation or interfering with Ddx3x expression leads to the disorganization of retinal architecture, with the photoreceptor layer being most affected. We identify Crb1, a component of the adhesion belt between glial and photoreceptor cells, as a link between Rncr4-regulated miRNA metabolism and uniform retina layering. Our results suggest that the precise timing of glia–neuron interaction controlled by noncoding RNAs and Ddx3x is important for the even distribution of cells across layers