The Locus of Innovation in Small and Medium-sized Firms: The Importance of Social Capital and Networking in Innovative Entrepreneurship

Social networks matter in the innovation processes of young and small firms, since ‘innovation does not exist in a vacuum (Van De Ven, 1986: 601).’ The contacts a firm has could both generate advantages for further innovation and growth, and disadvantages leading to inertia and stagnation. In the first case the existing social network or the new business contact provides opportunities furthering eventual success, in the second case, the existing network or the new business contacts turns out to have a constraining or even detrimental effect on performance. The search and use of social capital is driven by goal-specificity: it only includes those ties that help the actor in the attainment of particular goals. Most of the research so far has been deliberately or unwillingly one-sided, by for instance only looking at entrepreneurial firms in dynamic industries (or more specifically, start-ups in the high-tech industries). Or selective attention has been paid to either the internal sources or the external contacts to trigger inn

Advancing Qualitative Entrepreneurship Research: Leveraging Methodological Plurality for Achieving Scholarly Impact

This editorial aims to advance the use of qualitative research methods when studying entrepreneurship. First, it outlines four characteristics of the domain of entrepreneurship that qualitative research is uniquely placed to address. In studying these characteristics, we urge researchers to leverage the plurality of different qualitative approaches, including less conventional methods. Second, to help researchers develop high-level theoretical contributions, we point to multiple possible contributions, and highlight how such contributions can be developed through qualitative methods. Thus, we aim to broaden the types of contributions and forms that qualitative entrepreneurship research takes, in ways that move beyond prototypical inductive theory-building

Advancing Qualitative Entrepreneurship Research: Leveraging Methodological Plurality for Achieving Scholarly Impact

This editorial aims to advance the use of qualitative research methods when studying entrepreneurship. First, it outlines four characteristics of the domain of entrepreneurship that qualitative research is uniquely placed to address. In studying these characteristics, we urge researchers to leverage the plurality of different qualitative approaches, including less conventional methods. Second, to help researchers develop high-level theoretical contributions, we point to multiple possible contributions, and highlight how such contributions can be developed through qualitative methods. Thus, we aim to broaden the types of contributions and forms that qualitative entrepreneurship research takes, in ways that move beyond prototypical inductive theory-building

Advancing Qualitative Entrepreneurship Research: Leveraging Methodological Plurality for Achieving Scholarly Impact

This editorial aims to advance the use of qualitative research methods when studying entrepreneurship. First, it outlines four characteristics of the domain of entrepreneurship that qualitative research is uniquely placed to address. In studying these characteristics, we urge researchers to leverage the plurality of different qualitative approaches, including less conventional methods. Second, to help researchers develop high-level theoretical contributions, we point to multiple possible contributions, and highlight how such contributions can be developed through qualitative methods. Thus, we aim to broaden the types of contributions and forms that qualitative entrepreneurship research takes, in ways that move beyond prototypical inductive theory-building

Analysis of FUS, PFN2, TDP-43, and PLS3 as potential disease severity modifiers in spinal muscular atrophy

Objective To investigate mutations in genes that are potential modifiers of spinal muscular atrophy (SMA) severity. Methods We performed a hypothesis-based search into the presence of variants in fused in sarcoma (FUS), transactive response DNA-binding protein 43 (TDP-43), plastin 3 (PLS3), and profilin 2 (PFN2) in a cohort of 153 patients with SMA types 1-4, including 19 families. Variants were detected with targeted next-generation sequencing and confirmed with Sanger sequencing. Functional effects of the identified variants were analyzed in silico and for PLS3, by analyzing expression levels in peripheral blood. Results We identified 2 exonic variants in FUS exons 5 and 6 (p.R216C and p.S135N) in 2 unrelated patients, but clinical effects were not evident. We identified 8 intronic variants in PLS3 in 33 patients. Five PLS3 variants (c.1511+82T>C; c.748+130 G>A; c.367+182C>T; c.891-25T>C (rs145269469); c.1355+17A>G (rs150802596)) potentially alter exonic splice silencer or exonic splice enhancer sites. The variant c.367+182C>T, but not RNA expression levels, corresponded with a more severe phenotype in 1 family. However, this variant or level of PLS3 expression did not consistently correspond with a milder or more severe phenotype in other families or the overall cohort. We found 3 heterozygous, intronic variants in PFN2 and TDP-43 with no correlation with clinical phenotype or effects on splicing. Conclusions PLS3 and FUS sequence variants do not modify SMA severity at the population level. Specific variants in individual patients or families do not consistently correlate with disease severity

The interplay of agency, culture and networks in field evolution

We examine organizational field change instigated by activists. Contrary to existing views emphasizing incumbent resistance, we suggest that collaboration between incumbents and challenger movements may emerge when a movement's cultural and relational fabric becomes moderately structured, creating threats and market opportunities but remaining permeable to external influence. We also elucidate how lead incumbents' attempts at movement cooptation may be deflected through distributed brokerage. The resulting confluence of cultural and relational "structuration" between movement and field accelerates the pace but dilutes the radicalness of institutional innovation, ensuring ongoing, incremental field change. Overall, this article contributes to the emergent literature on field dynamics by uncovering the evolution and outcomes of collaborative work at the intersection of social movements and incumbent fields

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88

The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis

Motor effects of deep brain stimulation correlate with increased functional connectivity in Parkinson's disease: An MEG study

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established symptomatic treatment in Parkinson's disease, yet its mechanism of action is not fully understood. Locally in the STN, stimulation lowers beta band power, in parallel with symptom relief. Therefore, beta band oscillations are sometimes referred to as “anti-kinetic”. However, in recent studies functional interactions have been observed beyond the STN, which we hypothesized to reflect clinical effects of DBS. Resting-state, whole-brain magnetoencephalography (MEG) recordings and assessments on motor function were obtained in 18 Parkinson's disease patients with bilateral STN-DBS, on and off stimulation. For each brain region, we estimated source-space spectral power and functional connectivity with the rest of the brain. Stimulation led to an increase in average peak frequency and a suppression of absolute band power (delta to low-beta band) in the sensorimotor cortices. Significant changes (decreases and increases) in low-beta band functional connectivity were observed upon stimulation. Improvement in bradykinesia/rigidity was significantly related to increases in alpha2 and low-beta band functional connectivity (of sensorimotor regions, the cortex as a whole, and subcortical regions). By contrast, tremor improvement did not correlate with changes in functional connectivity. Our results highlight the distributed effects of DBS on the resting-state brain and suggest that DBS-related improvements in rigidity and bradykinesia, but not tremor, may be mediated by an increase in alpha2 and low-beta functional connectivity. Beyond the local effects of DBS in and around the STN, functional connectivity changes in these frequency bands might therefore be considered as “pro-kinetic”