Bridging the great divide? Making sense of the human rights-CSR relationship in UK multinational companies

Human rights (HR) and corporate social responsibility (CSR) are both fields of knowledge and research that have been shaped by, and examine, the role of multi-national enterprises in society. Whilst scholars have highlighted the overlapping nature of CSR and HR, our understanding of this relationship within business practice remains vague and under-researched. To explore the interface between CSR and HR, this paper presents empirical data from a qualitative study involving 22 international businesses based in the UK. Through an analysis based on sensemaking, the paper examines how and where CSR and HR overlap, contrast and shape one another, and the role that companies’ international operations has on this relationship. The findings reveal a complex and multi-layered relationship between the two, and concludes that in contrast to management theory, companies have bridged the ‘great divide’ in varying degrees most notably in their implementation strategies

Comprehensive investigation of <i>CASK</i> mutations and other genetic etiologies in 41 patients with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH)

<div><p>The <i>CASK</i> gene (Xp11.4) is highly expressed in the mammalian nervous system and plays several roles in neural development and synaptic function. Loss-of-function mutations of <i>CASK</i> are associated with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH), especially in females. Here, we present a comprehensive investigation of 41 MICPCH patients, analyzed by mutational search of <i>CASK</i> and screening of candidate genes using an SNP array, targeted resequencing and whole-exome sequencing (WES). In total, we identified causative or candidate genomic aberrations in 37 of the 41 cases (90.2%). <i>CASK</i> aberrations including a rare mosaic mutation in a male patient, were found in 32 cases, and a mutation in <i>ITPR1</i>, another known gene in which mutations are causative for MICPCH, was found in one case. We also found aberrations involving genes other than <i>CASK</i>, such as <i>HDAC2</i>, <i>MARCKS</i>, and possibly <i>HS3ST5</i>, which may be associated with MICPCH. Moreover, the targeted resequencing screening detected heterozygous variants in <i>RELN</i> in two cases, of uncertain pathogenicity, and WES analysis suggested that concurrent mutations of both <i>DYNC1H1</i> and <i>DCTN1</i> in one case could lead to MICPCH. Our results not only identified the etiology of MICPCH in nearly all the investigated patients but also suggest that MICPCH is a genetically heterogeneous condition, in which <i>CASK</i> inactivating mutations appear to account for the majority of cases.</p></div

Candidate genes for the target resequencing.

<p>Candidate genes for the target resequencing.</p

Detailed analysis of the mosaicism of <i>CASK</i> in patient 23.

<p><b>A</b> Sequence chromatogram showing a heterozygous-like pattern in the latter part of exon 15 (arrow). <b>B</b> Scheme of the indel mutation. Compared with the reference allele (upper), the affected allele (lower) had a 21-bp deletion and a 2-bp insertion at the exon-intron junction of exon 15 and intron 15. <b>C</b> Results of the genomic PCR using WT-specific and indel-specific primer sets in the patient and a male control. The red box indicates a product amplified only in the patient with the indel-specific primer sets. M: marker; phiX174 RF DNA/Hae III Fragments, P: patient 23, C: control, N: negative control, no DNA added. <b>D</b> Real-time quantitative PCR of genomic DNA from patient 23 and male and female controls. While the relative copy number of the male control is naturally approximately half of that of the female control, those amplified with both WT-specific and deletion-specific primers in the patient are also approximately half of that of the male control.</p

Schemes of the point mutations and CNVs involving CASK.

<p>(A) Schematic representation of the structure of <i>CASK</i> domains (NCBI Reference Sequence: NP_003679.2) and the position of the point mutations in patients 1–23. CaMK: calmodulin-dependent kinase, L27: LIN-2 and LIN-7 interaction, PDZ: PSD-95-Dlg-ZO1, SH3: Src homologous 3, GK: guanylate kinase. (B) Mapping of the CNVs involving <i>CASK</i> identified in patients 24–32. Black horizontal bars indicate the deletions and gray bars indicate the duplications, respectively, and horizontal arrows indicate genes and their directions. Dashed lines enlarge around <i>CASK</i>. The regional information is from the UCSC built on February 2009 (GRCh37/hg19).</p

Genomic analysis of candidate genes other than <i>CASK</i>.

<p>(A) Result of the SNP array in patient 33 showing Heterozygous deletion at 6q21-q22.31 including <i>HDAC2</i> and <i>MARCKS</i>. This result is described as follows: arr 6q21q22.31(109,497,085–122,505,593)x1. The double-headed arrow indicates the deletion. (B) Mapping of the heterozygous deletion in patient 33. The red box denotes <i>HDAC2</i> and <i>MARCKS</i>. (C) Electropherograms depicting the mutations of <i>RELN</i> detected by targeted resequencing. Arrows indicate the mutated nucleotides. (upper) c.4918A>G (p.I1640V) in patient 34, (lower) c.7093G>A (p.V2365M) in patient 35. (D) Conservation of amino acids around each mutation of <i>RELN</i> in patient 34 (upper) and patient 35 (lower). The red box denotes the amino acid substituted by the mutation. (E) Electropherograms depicting the mutations detected by whole exome sequencing. Each arrow indicates the mutated nucleotide. (upper) c.1677dupG (p.R560Afs*20) of <i>CASK</i> in patient 11, (lower) c.7753A>C (p.T2585P) of <i>ITPR1</i> in patient 36. (F) Electropherograms depicting the mutations of <i>DYNC1H1</i> and <i>DCTN1</i> in patient 37 and her parents. Arrows indicate the mutated nucleotides. The left three panels indicating c.11824C>T (p.P3942S) of <i>DYNC1H1</i> show that the mutation is inherited from the mother, and the right three panels indicating c.497C>G (p.S166C) of <i>DCTN1</i> show the mutation is inherited from the father.</p

Additional file 9: Figure S3. of In vitro characterization of neurite extension using induced pluripotent stem cells derived from lissencephaly patients with TUBA1A missense mutations

Differentiating pPBCAG-TUBA1A-IRES-AcGFP-transfected human NPCs. Measurements of AcGFP-positive neurites from each cell (μm: mean ± SEM, n = 50, one-way ANOVA followed by Dunnett’s test, **p < 0.01). Overexpression of mutant TUBA1A (p.N329S) interfered with neurite extension in the human NSCs (scale bar = 200 μm). (TIF 19759 kb