The Spatial Distribution of Manufacturing in South Africa 1970-1996, its Determinants and Policy Implications

This paper researches the change in regional specialisation and industry concentration in South African (SA) manufacturing 1970-96, and evaluates possible determinants of industry location. No evident trend towards greater regional specialisation or despecialisation emerges over most of the period if we take the economic weight of the regions into account. However, between 1993 and 1996, the period of international reintegration, all provinces but one became more specialised. Industry concentration also does not show a clear trend if we account for industry size, although industries of the same rank were more concentrated in the early 1990s than the beginning of the 1970s and 1980s. Drawing on predictions from trade and economic geography models, we find that high plant-internal scale economies, intensity in the use of human capital and high industry-specific productivity gradients between locations are associated with greater geographical concentration of an industry. Scale economies are the most important pro-concentration force. A greater deviation of labour intensity of production from the mean, and strong in term linkages, are associated with low geographical concentration. The latter results can be explained within the economic geography framework. Linkages are the most important determinant of industry geography.Risk measures, expectations hypothesis, South Africa

Seasonal change in the temporal organization of wheel-running activity of the European hamster, Cricetus cricetus

In this paper we demonstrate that a dramatic annual change in the temporal organization of locomotor activity goes hand in hand with the seasonal cycle of reproduction. Activity levels increased when the animals entered reproductive conditions, which occurs naturally in spring and early summer. During the 2-3 months of reproduction, a well-defined activity rhythm was observed. During the rest of the year, the level of activity was dramatically reduced and almost no rhythmic organization was detected. The question arising from these observations is whether the loss of temporal organization reflects a weakening or arrhythmia of the underlying pacemaker or whether it is due to an uncoupling of the overt activity rhythm from the central clock

De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

New gain-of-function mutation shows CACNA1D as recurrently mutated gene in autism spectrum disorders and epilepsy

CACNA1D encodes the pore-forming alpha 1-subunit of Cav1.3, an L-type voltage-gated Ca2+-channel. Despite the recent discovery of two de novo missense gain-of-function mutations in Cav1.3 in two individuals with autism spectrum disorder (ASD) and intellectual disability CACNA1D has not been considered a prominent ASD-risk gene in large scale genetic analyses, since such studies primarily focus on likely-disruptive genetic variants. Here we report the discovery and characterization of a third de novo missense mutation in CACNA1D (V401L) in a patient with ASD and epilepsy. For the functional characterization we introduced mutation V401L into two major C-terminal long and short Cav1.3 splice variants, expressed wild-type or mutant channel complexes in tsA-201 cells and performed whole-cell patch-clamp recordings. Mutation V401L, localized within the channel's activation gate, significantly enhanced current densities, shifted voltage dependence of activation and inactivation to more negative voltages and reduced channel inactivation in both Cav1.3 splice variants. Altogether, these gating changes are expected to result in enhanced Ca2+-influx through the channel, thus representing a strong gain-of-function phenotype. Additionally, we also found that mutant channels retained full sensitivity towards the clinically available Ca2+-channel blocker isradipine. Our findings strengthen the evidence for CACNA1D as a novel candidate autism risk gene and encourage experimental therapy with available channel-blockers for this mutation. The additional presence of seizures and neurological abnormalities in our patient define a novel phenotype partially overlapping with symptoms in two individuals with PASNA (congenital primary aldosteronism, seizures and neurological abnormalities) caused by similar Cav1.3 gain-of-function mutations

Altmetrics for large, multidisciplinary research groups: Comparison of current tools

Most altmetric studies compare how often a publication has been cited or mentioned on the Web. Yet, a closer look at altmetric analyses reveals that the altmetric tools employed and the social media platforms considered may have a significant effect on the available information and ensuing interpretation. Therefore, it is indicated to investigate and compare the various tools currently available for altmetric analyses and the social media platforms they draw upon. This paper will present results from a comparative altmetric analysis conducted employing four well-established altmetric services based on a broad, multidisciplinary sample of scientific publications. Our study reveals that for several data sources the coverage of findable publications on social media platforms and metric counts (impact) can vary across altmetric data providers

Activating Somatic <em>FGFR2</em> Mutations in Breast Cancer

<div><p>It is known that <i>FGFR2</i> gene variations confer a risk for breast cancer. FGFR2 and FGF10, the main ligand of FGFR2, are both overexpressed in 5–10% of breast tumors. In our study, we sequenced the most important coding regions of <i>FGFR2</i> in somatic tumor tissue of 140 sporadic breast cancer patients and performed MLPA analysis to detect copy number variations in <i>FGFR2</i> and <i>FGF10</i>. We identified one somatic heterozygous missense mutation, p.K660N (c.1980G>C), within the tyrosine kinase domain of FGFR2 in tumor tissue of a sporadic breast cancer patient, which is likely mediated by the FGFR2-IIIb isoform. The presence of wild type and mutated alleles in equal quantities suggests that the mutation has driven clonal amplification of mutant cells. We have analyzed the tyrosine kinase activity of p.K660N and another recently described somatic breast cancer mutation in FGFR2, p.R203C, after expression in HEK293 cells and demonstrated that the intrinsic tyrosine kinase activity of both mutant proteins is strongly increased resulting in elevated phosphorylation and activity of downstream effectors. To our knowledge, this is the first report of functional analysis of somatic breast cancer mutations in FGFR2 providing evidence for the activating nature of FGFR2-mediated signalling in the pathogenesis of breast cancer.</p> </div

Identified <i>FGFR2</i> mutation in tumor tissue.

<p>The upper sequence chromatogram shows the heterozygous missense mutation in exon 14 in <i>FGFR2</i>, c.1980G>C (p.K660N), found in somatic tumor breast tissue of patient BC80. The middle and lower chromatograms illustrate the normal sequence in non-tumor breast tissue and blood-derived DNA of the same patient.</p

<i>FGFR2</i> mRNA isoform expression analysis in tumor tissue of three sporadic breast cancer patients. A) Representative electropherogram of GeneScan analysis.

<p>Isoforms FGFR2-IIIb and FGFR2-IIIc differ in exon 8, resulting in a variation of 3 bp in length of mature mRNA. A PCR fragment of 297 bp for <i>FGFR2</i>-IIIb or 294 bp for <i>FGFR2</i>-IIIc cDNA spanning exon 8 of both isoforms was amplified by PCR using a fluorescently-labeled primer pair located in exons 7 and 9, which are common in both isoforms. Fragment analysis showing a single sharp peak. <b>B) Representative sequence electropherogram showing the expression of IIIb isoform.</b></p