Developmental trajectory of Caenorhabditis elegans nervous system governs its structural organization

A central problem of neuroscience involves uncovering the principles governing the organization of nervous systems which ensure robustness in brain development. The nematode Caenorhabditis elegans provides us with a model organism for studying this question. In this paper, we focus on the invariant connection structure and spatial arrangement of the neurons comprising the somatic neuronal network of this organism to understand the key developmental constraints underlying its design. We observe that neurons with certain shared characteristics - such as, neural process lengths, birth time cohort, lineage and bilateral symmetry - exhibit a preference for connecting to each other. Recognizing the existence of such homophily helps in connecting the physical location and morphology of neurons with the topological organization of the network. Further, the functional identities of neurons appear to dictate the temporal hierarchy of their appearance during the course of development. Providing crucial insights into principles that may be common across many organisms, our study shows how the trajectory in the developmental landscape constrains the eventual spatial and network topological organization of a nervous system.Comment: 25 pages, 8 figures + 24 pages supplementary materia

Nanosafety: an evolving concept to bring the safest possible nanomaterials to society and environment

The use of nanomaterials has been increasing in recent times, and they are widely used in industries such as cosmetics, drugs, food, water treatment, and agriculture. The rapid development of new nanomaterials demands a set of approaches to evaluate the potential toxicity and risks related to them. In this regard, nanosafety has been using and adapting already existing methods (toxicological approach), but the unique characteristics of nanomaterials demand new approaches (nanotoxicology) to fully understand the potential toxicity, immunotoxicity, and (epi)genotoxicity. In addition, new technologies, such as organs-on-chips and sophisticated sensors, are under development and/or adaptation. All the information generated is used to develop new in silico approaches trying to predict the potential effects of newly developed materials. The overall evaluation of nanomaterials from their production to their final disposal chain is completed using the life cycle assessment (LCA), which is becoming an important element of nanosafety considering sustainability and environmental impact. In this review, we give an overview of all these elements of nanosafety.European Union’s H2020 project Sinfonia (N.857253). SbDToolBox, with reference NORTE-01-0145-FEDER-000047, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fun

Mesoscopic organization reveals the constraints governing C. elegans nervous system

One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations, such as optimizing for resource constraints (viz., total wiring cost) and communication efficiency (i.e., network path length). Comparison with other complex networks designed for efficient transport (of signals or resources) implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis, we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including its key functional role as a processor of information.Comment: Published version, Minor modifications, 16 pages, 9 figure

Synthetic Studies on Fused N-/O-Based Heterocycles and Sugar Containing Heterocyclic Molecules of Biological Importance

Chapter I. This chapter is sub-divided into 4 parts. Part A contains a brief review of the metal mediated coupling reactions for the synthesis of N-/O-rich heterocycles mainly by Sonogashira cyclization reactions. The recent modifications of Sonogashira cyclization reactions are also included in this part. Part B. In this section green approach for the regio- & stereo-selective syntheses of Z)-3-methyleneisoindoline-1-ones in aqueous medium has been described. The introduction to the work, results and discussion, experimental procedures, conclusion, spectroscopic data and related references are also included. The work has been published in Tetrahedron Lett. 2013, 54, 3748-3751. Part C contains the synthesis of 3-alkyl/aryl-3-(pyrrole-2-yl)-2-phenyl-2,3-dihydroisoindolinones and 3-alkyl/aryl-3-(indole-3-yl)-2-phenyl-2,3-dihydro-isoindolinones using nanodomain cubic cuprous oxide as reusable catalyst in aqueous medium under one-pot condition. The introduction to the work, results and discussion, experimental procedures, conclusion, spectroscopic data and related references are included. The work has been published in RSC Adv., 2014, 4, 7024-7029. Part D deals with regio- and stereo- selective syntheses of (Z)-3-methyleneisoindoline- 1-ones and furo[3,2-h]quinolines using reusable palladium nanoparticles in onepot domino Sonogashira-cyclization in aqueous medium. The introduction, results and discussion, experimental procedures, conclusion, spectroscopic data and related references are included. The work has been communicated to Tetrahedron Lett. Chapter II. This chapter is sub-divided into three parts. Part A. This part contains a brief review of the syntheses of 1,2,3-triazole linked glycoconjugates and fused heterocycles. The syntheses of some important biologically active compounds along with related references reported in the literature are also incorporated. Part B. Application of nanodomain cubic cuprous oxide as reusable catalyst for the synthesis of triazole-fused tetracyclic glycosides and heterocycles in aqueous medium is described in this chapter. The introduction to the work, results and discussion, experimental procedures, conclusion, spectroscopic data and related references are included. The work has been published in Tetrahedron Lett. 2015, 56, 3886-3889. Part C deals with the syntheses of triazolo benzoxazines, triazolo quinoxalines, triazolo benzodiazepines, triazolo benzoxazepines and triazolo benzthiazines via a simple and convenient protocol using basic alumina as solid support. The introduction to the work, results and discussion, experimental procedures, conclusion, spectroscopic data and related references are included in this part. The work has been published in Tetrahedron Lett. 2014, 55, 2261-2265

The role of the NG2 proteoglycan in migration and characterization of the interaction with the intracellular binding partner, Syntenin

NG2 is a transmembrane proteoglycan with two N-terminal LNS domains and a C-terminal PDZ-binding motif. It is expressed in the developing and adult CNS by oligodendroglial precursor cells and subpopulations of perisynaptic glia and elsewhere by many immature cell types. In order to elucidate the functions of the protein and the heterogenous cell population which expresses it, we undertook to identify and characterise interaction partners of the molecule. The presence of the C-terminal PDZ recognition site in NG2 suggested PDZ-domain proteins as intracellular binding partners. In this work, interaction between the PDZ protein Syntenin and NG2 has been characterised. Syntenin is known to be involved in plasma membrane dynamics, metastasis and adhesion. Syntenin may thus link NG2 to the cytoskeleton, mediating migration of developing oligodendrocytes to axonal tracts prior to myelination, as well as process movement of NG2+ perisynaptic glia. NG2 is involved in cell spreading and polyclonal antibodies against NG2 inhibit the migration of immature glia and cell lines expressing the molecule. In this work we have characterised the segments of the extracellular portion of NG2 that are involved in migration. We found that the extracellular region immediately preceding the transmembrane segment is most important for cell motility. As part of this thesis, biochemical approaches to identify a trans-binding ligand interacting with the extracellular part of NG2 was also explored.NG2 ist ein transmembranes Proteoglykan mit zwei N-terminalen LNS Domänen und einer C-terminalen PDZ-Bindungsmotif. Es wird im sich entwicklenden und adulten ZNS in Oligodendrozyten Vorläufer Zellen (OVZ) exprimiert und kommt in der Subpopulation von perisynaptischen Gliazellen und ausserdem bei Vorläufer Zell typen vor. Um die Funktion des Proteins und der heterogen NG2+ Zellpopulation zu eklären, habe ich die Interaktionpartner des Moleküls identifiziert und charakterisiert. Die Anwesenheit des C-terminalen PDZ-Bindungsmotif in NG2 lässt vermuten, dass PDZ-Domänen Proteine als intrazelluläre Bindungspartner fungieren. In dieser Arbeit wird die Interaktion zwischen dem PDZ Protein Syntenin und NG2 charakterisiert. Syntenin ist an Plasmamembran-Vorgängen, Bildung von Metastasen und Adhäsion beteiligt. Syntenin könnte NG2 mit dem Zytoskelett verbinden, um vor der Myelinisierung, die Migration von in Vorläufer oligodendrozyten zu Axonen zu vermitteln. Weiterhin, könnte die Bewegung der Vorsätze der perisynaptischen Gliazellen reguliert werden. NG2 ist an der Zell-ausbreitung beteiligt. Polyklonale Antikörper gegen NG2 verhindern die Ausbreitung von OVZ und Zell linien, die dieses Molekül exprimieren. In meiner Arbeit habe ich die Segmente des extrazellulären Teils von NG2 charakterisiert, die an der Migration beteiligt sind. Dabei habe ich herausgefunden, dass die extrazelluläre Region, die sich direkt vor dem Transmembran-Segment befindet, am wichtigsten für die Zellbewegung ist. Als ein Teil dieser Arbeit wurde biochemisch versucht einen in trans-bindenden Liganden zu identifizieren, der mit einem extrazellulären Teil von NG2 interagiert

In Vitro Cell Transformation Assays: A Valuable Approach for Carcinogenic Potentiality Assessment of Nanomaterials

This review explores the application of in vitro cell transformation assays (CTAs) as a screening platform to assess the carcinogenic potential of nanomaterials (NMs) resulting from continuously growing industrial production and use. The widespread application of NMs in various fields has raised concerns about their potential adverse effects, necessitating safety evaluations, particularly in long-term continuous exposure scenarios. CTAs present a realistic screening platform for known and emerging NMs by examining their resemblance to the hallmark of malignancy, including high proliferation rates, loss of contact inhibition, the gain of anchorage-independent growth, cellular invasion, dysregulation of the cell cycle, apoptosis resistance, and ability to form tumors in experimental animals. Through the deliberate transformation of cells via chronic NM exposure, researchers can investigate the tumorigenic properties of NMs and the underlying mechanisms of cancer development. This article examines NM-induced cell transformation studies, focusing on identifying existing knowledge gaps. Specifically, it explores the physicochemical properties of NMs, experimental models, assays, dose and time requirements for cell transformation, and the underlying mechanisms of malignancy. Our review aims to advance understanding in this field and identify areas for further investigation

Isolation and identification of Profenofos degrading bacteria

An enrichment culture technique was used to isolate bacterial strains responsible for the biodegradation of profenofos in a soil from Hubei province of central China. Two pure bacterial cultures, named W and Y, were isolated and subsequently characterized by sequencing of 16S rRNA genes and biochemical tests. Isolate W showed 96% similarity to the 16S rRNA gene of a Pseudomonas putida unlike Y which showed 99% similarity to the 16S rRNA gene of Burkholderia gladioli. Both strains grew well at pH 5.5-7.2 with a broad temperature profile ranging from 28º to 36 ºC. Bioremediation of profenofos-contaminated soil was examined using soil treated with 200 ug g-1; profenofos resulted in a higher degradation rate than control soils without inoculation. In a mineral salt medium (FTW) reduction in profenofos concentration was 90% within 96 hours of incubation. A literature survey revealed that no data is available regarding the role of Burkholderia gladioli on pesticide biodegradation as well as on profenofos