Opening the black box: Unpacking board involvement in innovation

Corporate governance research suggests that boards of directors play key roles in governing company strategy. Although qualitative research has examined board-management relationships to describe board involvement in strategy, we lack detailed insights into how directors engage with organizational members for governing a complex and long-term issue such as product innovation. Our multiple-case study of four listed pharmaceutical firms reveals a sequential process of board involvement: Directors with deep expertise govern scientific innovation, followed by the full board's involvement in its strategic aspects. The nature of director involvement varies across board levels in terms of the direction (proactive or reactive), timing (regular or spontaneous), and the extent of formality of exchanges between directors and organizational members. Our study contributes to corporate governance research by introducing the concept of board behavioral diversity and by theorizing about the multilevel, structural, and temporal dimensions of board behavior and its relational characteristics

Klimawandel und Ökolandbau – Anpassungsmaßnahmen für die Praxis (Workshop)

Die Landwirtschaft ist – ob konventionell oder bio – gleichermaßen vom Klimawandel betroffen. Dies gilt für Trockenstress oder das Auffangen der Böden von vermehrten Starkniederschlägen. Besondere Prob-leme des ökologischen Ackerbaus sind der vermehrte Unkraut-, Schädlings- und Krankheitsdruck, dem nicht durch konventionelle Methoden beizukommen ist. Probleme sind beispielsweise, dass vermehrter Unkrautdruck zu mehr notwendigen Arbeitsgängen führt. Durch Schädlinge geschwächte Leguminosen fixieren weniger Stickstoff. Welche Lösungsstrategien gibt es für diese drei Problemfelder? Wie können Grundbodenbearbeitung und Fruchtfolgen angepasst werden? Welche Sorten und Aussaatzeitpunkte empfehlen sich? Dieser Workshop richtet sich an Berater, Landwirte und Wissenschaftler gleichermaßen.Zunächst gibt es Kurzpräsentationen ausgewählter Einzelthemen aus Wissenschaft und Praxis. Der Workshop bietet die Möglichkeit, über bestehende Probleme in der Praxis zu diskutieren, Handlungsempfehlungen zu entwickeln und weiterführende Forschungsfragen abzuleiten

CAF-1 Is Essential for Heterochromatin Organization in Pluripotent Embryonic Cells

During mammalian development, chromatin dynamics and epigenetic marking are important for genome reprogramming. Recent data suggest an important role for the chromatin assembly machinery in this process. To analyze the role of chromatin assembly factor 1 (CAF-1) during pre-implantation development, we generated a mouse line carrying a targeted mutation in the gene encoding its large subunit, p150CAF-1. Loss of p150CAF-1 in homozygous mutants leads to developmental arrest at the 16-cell stage. Absence of p150CAF-1 in these embryos results in severe alterations in the nuclear organization of constitutive heterochromatin. We provide evidence that in wild-type embryos, heterochromatin domains are extensively reorganized between the two-cell and blastocyst stages. In p150CAF-1 mutant 16-cell stage embryos, the altered organization of heterochromatin displays similarities to the structure of heterochromatin in two- to four-cell stage wild-type embryos, suggesting that CAF-1 is required for the maturation of heterochromatin during preimplantation development. In embryonic stem cells, depletion of p150CAF-1 using RNA interference results in the mislocalization, loss of clustering, and decondensation of pericentric heterochromatin domains. Furthermore, loss of CAF-1 in these cells results in the alteration of epigenetic histone methylation marks at the level of pericentric heterochromatin. These alterations of heterochromatin are not found in p150CAF-1-depleted mouse embryonic fibroblasts, which are cells that are already lineage committed, suggesting that CAF-1 is specifically required for heterochromatin organization in pluripotent embryonic cells. Our findings underline the role of the chromatin assembly machinery in controlling the spatial organization and epigenetic marking of the genome in early embryos and embryonic stem cells

Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies

Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy, cap myopathy, core-rod myopathy, congenital fiber-type disproportion, distal arthrogryposes, and Escobar syndrome. We correlate the clinical picture of these diseases with novel (19) and previously reported (31) mutations of the TPM2 and TPM3 genes. Included are altogether 93 families: 53 with TPM2 mutations and 40 with TPM3 mutations. Thirty distinct pathogenic variants of TPM2 and 20 of TPM3 have been published or listed in the Leiden Open Variant Database (http://www.dmd.nl/). Most are heterozygous changes associated with autosomal-dominant disease. Patients with TPM2 mutations tended to present with milder symptoms than those with TPM3 mutations, DA being present only in the TPM2 group. Previous studies have shown that five of the mutations in TPM2 and one in TPM3 cause increased Ca2+ sensitivity resulting in a hypercontractile molecular phenotype. Patients with hypercontractile phenotype more often had contractures of the limb joints (18/19) and jaw (6/19) than those with nonhypercontractile ones (2/22 and 1/22), whereas patients with the non-hypercontractile molecular phenotype more often (19/22) had axial contractures than the hypercontractile group (7/19). Our in silico predictions show that most mutations affect tropomyosin–actin association or tropomyosin head-to-tail binding

Bioturbation effects on bioaccumulation of cadmium in the wetland plant Typha latifolia: A nature-based experiment

The development of efficient bioremediation techniques to reduce aquatic pollutant load in natural sediment is one of the current challenges in ecological engineering. A nature-based solution for metal bioremediation is proposed through a combination of bioturbation and phytoremediation processes in experimental indoor microcosms. The invertebrates Tubifex tubifex (Oligochaeta Tubificidae) was used as an active ecological engineer for bioturbation enhancement. The riparian plant species Typha latifolia was selected for its efficiency in phytoaccumulating pollutants from sediment. Phytoremediation efficiency was estimated by using cadmium as a conservative pollutant known to bioaccumulate in plants, and in itially introduced in the overlying water (20 μg Cd/L of cadmium nitrate – Cd(NO3)2· 4H2O). Biological sedim ent reworking by invertebrates' activity was quantified using luminophores(inert particulates). Our results showed that bioturbation caused by tubificid worms' activity followed the bio-conveying transport model with a downward vertical velocity (V) of luminophores ranging from 16.7 ± 4.5 to 18.5 ± 3.9 cm· year− 1. The biotransport changed the granulometric properties of the surface sediments, and this natural process was still efficient under cadmium contamination. The highest value of Cd enrichment coefficient for plant roots was observed in subsurface sediment layer (below 1 cm to 5 cm depth) with tubificids addition. We demonstrated that biotransport changed the distribution of cadmium across the sediment column as well as it enhanced the pumping of this metal from the surface to the anoxic sediment layers, thereby increasing the bioaccumulation of cadmium in the root system of Typha latifolia. This therefore highlights the potential of bioturbation as a tool to be considered in future as integrated bioremediation strategies of metallic polluted sediment in aquatic ecosystems

Mutation discovery in mice by whole exome sequencing

We report the development and optimization of reagents for in-solution, hybridization-based capture of the mouse exome. By validating this approach in a multiple inbred strains and in novel mutant strains, we show that whole exome sequencing is a robust approach for discovery of putative mutations, irrespective of strain background. We found strong candidate mutations for the majority of mutant exomes sequenced, including new models of orofacial clefting, urogenital dysmorphology, kyphosis and autoimmune hepatitis

Extending Epigenesis: From Phenotypic Plasticity to the Bio-Cultural Feedback

The paper aims at proposing an extended notion of epigenesis acknowledging an actual causal import to the phenotypic dimension for the evolutionary diversification of life forms. Section 1 offers introductory remarks on the issue of epigenesis contrasting it with ancient and modern preformationist views. In Section 2 we propose to intend epigenesis as a process of phenotypic formation and diversification a) dependent on environmental influences, b) independent of changes in the genomic nucleotide sequence, and c) occurring during the whole life span. Then, Section 3 focuses on phenotypic plasticity and offers an overview of basic properties (like robustness, modularity and degeneracy) that allows biological systems to be evolvable – i.e. to have the potentiality of producing phenotypic variation. Successively (Section 4), the emphasis is put on environmentally-induced modification in the regulation of gene expression giving rise to phenotypic variation and diversification. After some brief considerations on the debated issue of epigenetic inheritance (Section 5), the issue of culture (kept in the background of the preceding sections) is considered. The key point is that, in the case of humans and of the evolutionary history of the genus Homo at least, the environment is also, importantly, the cultural environment. Thus, Section 6 argues that a bio-cultural feedback should be acknowledged in the “epigenic” processes leading to phenotypic diversification and innovation in Homo evolution. Finally, Section 7 introduces the notion of “cultural neural reuse”, which refers to phenotypic/neural modifications induced by specific features of the cultural environment that are effective in human cultural evolution without involving genetic changes. Therefore, cultural neural reuse may be regarded as a key instance of the bio-cultural feedback and ultimately of the extended notion of epigenesis proposed in this work

Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study

Background Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites. Methods Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded. Findings Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19–2.25]), 26 months (1.20 [95% CI 0.48–1.91]), and 38 months (1.52 [95% CI 0.74–2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43–1.07]), 26 months (mean difference 0.65 [95% CI 0.27–1.03]), and 38 months (mean difference 0.72 [95% CI 0.25–1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34–43.38]), 26 months (mean difference 29.26 m [95% CI 14.87–43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32–54.09]). No new safety signals were identified. Interpretation Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA. Funding Financial support for the registry from Biogen, Novartis and Roche