Nanotubes Make Big Science

Tiny protrusions on the surface of cells might be a more common mechanism for cell communication than previously expecte

Segmentation of Fault Networks Determined from Spatial Clustering of Earthquakes

We present a new method of data clustering applied to earthquake catalogs, with the goal of reconstructing the seismically active part of fault networks. We first use an original method to separate clustered events from uncorrelated seismicity using the distribution of volumes of tetrahedra defined by closest neighbor events in the original and randomized seismic catalogs. The spatial disorder of the complex geometry of fault networks is then taken into account by defining faults as probabilistic anisotropic kernels, whose structures are motivated by properties of discontinuous tectonic deformation and previous empirical observations of the geometry of faults and of earthquake clusters at many spatial and temporal scales. Combining this a priori knowledge with information theoretical arguments, we propose the Gaussian mixture approach implemented in an Expectation-Maximization (EM) procedure. A cross-validation scheme is then used and allows the determination of the number of kernels that should be used to provide an optimal data clustering of the catalog. This three-steps approach is applied to a high quality relocated catalog of the seismicity following the 1986 Mount Lewis ($M_l=5.7$) event in California and reveals that events cluster along planar patches of about 2 km$^2$, i.e. comparable to the size of the main event. The finite thickness of those clusters (about 290 m) suggests that events do not occur on well-defined euclidean fault core surfaces, but rather that the damage zone surrounding faults may be seismically active at depth. Finally, we propose a connection between our methodology and multi-scale spatial analysis, based on the derivation of spatial fractal dimension of about 1.8 for the set of hypocenters in the Mnt Lewis area, consistent with recent observations on relocated catalogs

Coordinated control of Notch-Delta signalling and cell cycle progression drives lateral inhibition mediated tissue patterning

Coordinating cell differentiation with cell growth and division is crucial for the successful development, homeostasis and regeneration of multicellular tissues. Here, we use bristle patterning in the fly notum as a model system to explore the regulatory and functional coupling of cell cycle progression and cell fate decision-making. The pattern of bristles and intervening epithelial cells (ECs) becomes established through Notch-mediated lateral inhibition during G2 phase of the cell cycle, as neighbouring cells physically interact with each other via lateral contacts and/or basal protrusions. Since Notch signalling controls cell division timing downstream of Cdc25, ECs in lateral contact with a Delta-expressing cell experience higher levels of Notch signalling and divide first, followed by more distant neighbours, and lastly Delta-expressing cells. Conversely, mitotic entry and cell division makes ECs refractory to lateral inhibition signalling, fixing their fate. Using a combination of experiments and computational modelling, we show that this reciprocal relationship between Notch signalling and cell cycle progression acts like a developmental clock, providing a delimited window of time during which cells decide their fate, ensuring efficient and orderly bristle patterning

Two Notch Ligands, Dll1 and Jag1, Are Differently Restricted in Their Range of Action to Control Neurogenesis in the Mammalian Spinal Cord

Notch signalling regulates neuronal differentiation in the vertebrate nervous system. In addition to a widespread function in maintaining neural progenitors, Notch signalling has also been involved in specific neuronal fate decisions. These functions are likely mediated by distinct Notch ligands, which show restricted expression patterns in the developing nervous system. Two ligands, in particular, are expressed in non-overlapping complementary domains of the embryonic spinal cord, with Jag1 being restricted to the V1 and dI6 progenitor domains, while Dll1 is expressed in the remaining domains. However, the specific contribution of different ligands to regulate neurogenesis in vertebrate embryos is still poorly understood.In this work, we investigated the role of Jag1 and Dll1 during spinal cord neurogenesis, using conditional knockout mice where the two genes are deleted in the neuroepithelium, singly or in combination. Our analysis showed that Jag1 deletion leads to a modest increase in V1 interneurons, while dI6 neurogenesis was unaltered. This mild Jag1 phenotype contrasts with the strong neurogenic phenotype detected in Dll1 mutants and led us to hypothesize that neighbouring Dll1-expressing cells signal to V1 and dI6 progenitors and restore neurogenesis in the absence of Jag1. Analysis of double Dll1;Jag1 mutant embryos revealed a stronger increase in V1-derived interneurons and overproduction of dI6 interneurons. In the presence of a functional Dll1 allele, V1 neurogenesis is restored to the levels detected in single Jag1 mutants, while dI6 neurogenesis returns to normal, thereby confirming that Dll1-mediated signalling compensates for Jag1 deletion in V1 and dI6 domains.Our results reveal that Dll1 and Jag1 are functionally equivalent in controlling the rate of neurogenesis within their expression domains. However, Jag1 can only activate Notch signalling within the V1 and dI6 domains, whereas Dll1 can signal to neural progenitors both inside and outside its domains of expression

An apicobasal gradient of Rac activity determines protrusion form and position

Each cell within a polarised epithelial sheet must align and correctly position a wide range of subcellular structures, including actin-based dynamic protrusions. Using in vivo inducible transgenes that can sense or modify Rac activity, we demonstrate an apicobasal gradient of Rac activity that is required to correctly form and position distinct classes of dynamic protrusion along the apicobasal axis of the cell. We show that we can modify the Rac activity gradient in genetic mutants for specific polarity proteins, with consequent changes in protrusion form and position and additionally show, using photoactivatable Rac transgenes, that it is the level of Rac activity that determines protrusion form. Thus, we demonstrate a mechanism by which polarity proteins can spatially regulate Rac activity and the actin cytoskeleton to ensure correct epithelial cell shape and prevent epithelial-to-mesenchymal transitions

Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex–Specific Prkar1a Knockout Mice

Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 α-regulatory subunit (R1α) of the cAMP–dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1α loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1α loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1α is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD

The MYST-Containing Protein Chameau Is Required for Proper Sensory Organ Specification during Drosophila Thorax Morphogenesis

The adult thorax of Drosophila melanogaster is covered by a stereotyped pattern of mechanosensory bristles called macrochaetes. Here, we report that the MYST containing protein Chameau (Chm) contributes to the establishment of this pattern in the most dorsal part of the thorax. Chm mutant pupae present extra-dorsocentral (DC) and scutellar (SC) macrochaetes, but a normal number of the other macrochaetes. We provide evidences that chm restricts the singling out of sensory organ precursors from proneural clusters and genetically interacts with transcriptional regulators involved in the regulation of achaete and scute in the DC and SC proneural cluster. This function of chm likely relies on chromatin structure regulation since a protein with a mutation in the conserved catalytic site fails to rescue the formation of supernumerary DC and SC bristles in chm mutant flies. This is further supported by the finding that mutations in genes encoding chromatin modifiers and remodeling factors, including Polycomb group (PcG) and Trithorax group (TrxG) members, dominantly modulate the penetrance of chm extra bristle phenotype. These data support a critical role for chromatin structure modulation in the establishment of the stereotyped sensory bristle pattern in the fly thorax

Drosophila

The Drosophila adult posterior midgut has been identified as a powerful system in which to study mechanisms that control intestinal maintenance, in normal conditions as well as during injury or infection. Early work on this system has established a model of tissue turnover based on the asymmetric division of intestinal stem cells. From the quantitative analysis of clonal fate data, we show that tissue turnover involves the neutral competition of symmetrically dividing stem cells. This competition leads to stem-cell loss and replacement, resulting in neutral drift dynamics of the clonal population. As well as providing new insight into the mechanisms regulating tissue self-renewal, these findings establish intriguing parallels with the mammalian system, and confirm Drosophila as a useful model for studying adult intestinal maintenance

Obstacles when facing ISO 14001 EMS implementation for organizations in developing countries : A case study about Stora Enso’s agro-forestry project in Lao Peoples’ Democratic Republic

Today many global dilemmas are stemming from organizations’ business activities. In addition, many corporations’ have realized the importance to aspire a green-public image in combination with cutting possible liability costs. Therefore, many companies are interested to participate in the attempts of reducing the impacts related to their business activities. However, at the same time organizations are facing many constraints in the transformation towards environmentally aware and responsible organizations. Therefore, companies often strive to implement an Environmental Management System (EMS) in order to achieve organizational guidance when establishing, developing and reviewing their business practices towards both corporate and environmental goals. The theories discussed in this master thesis discloses that the implementation process of an EMS often requires a cultural revolution in organizations, which can be a challenge especially for companies present in developing countries, where environmental issues often are marginalized due to low levels of environmental awareness and weak institutions. The purpose of this master thesis identifies potential obstacles in facing ISO 14001 EMS for Stora Enso’s agro-forestry project in Lao People’s Democratic Republic and the efforts that would stimulate the adoption facing ISO 14001 EMS. This was analyzed through a combination of a qualitative text analysis of scientific papers and a case study with eight semi-structured interviews with managers from Stora Enso Lao Co., Ltd. This study points out limited availability of support and resources, unclear policies, constrained participation and communication, inadequate knowledge about environmental management and ISO 14001 EMS as the potential obstacles for Stora Enso Lao Co., Ltd to tackle. Therefore, in order to stimulate the adoption of ISO 14001 EMS the potential efforts suggested in this master thesis are more money in order to promote environmental training and organizational changes in terms of increased participation of employees and communication between internal and external stakeholders