Life & Health Sciences

The search for the Adamic language and the emergence of transcultural aspiration in the aftermath of the European maritime discoveries


ABSTRACT

The main hypothesis of this project is connected to the notion of pre-cultural origins of the humanity, situated in the paradisaical reality, not only before the fall, but also before the invention of the human language (Adam naming the animals created by God). The myth of the pre-lapsarian unity of the human kind became crucial to the development of the European relationship with other peoples in the aftermath of the maritime discoveries in the 16th c. The examination of this topic is an important element of the projected transcultural humanities, searching to establish a comprehensive outlook of the cultural inscription and limitations of the human thought.


Self-DNA release and STING-dependent sensing drives inflammation to cigarette smoke in mice


ABSTRACT

Cigarette smoke exposure is a leading cause of chronic obstructive pulmonary disease (COPD), a major health issue characterized by airway inflammation with fibrosis and emphysema. Here we demonstrate that acute exposure to cigarette smoke causes respiratory barrier damage with the release of self-dsDNA in mice. This triggers the DNA sensor cGAS (cyclic GMP-AMP synthase) and stimulator of interferon genes (STING), driving type I interferon (IFN I) dependent lung inflammation, which are attenuated in cGAS, STING or type I interferon receptor (IFNAR) deficient mice. Therefore, we demonstrate a critical role of self-dsDNA release and of the cGAS-STING-type I interferon pathway upon cigarette smoke-induced damage, which may lead to therapeutic targets in COPD.


Ultrasound Image Improvement by Code Bit Elongation


ABSTRACT

This paper analyses the influence of the transducer bandwidth on the compression and the axial resolution of an ultrasound image. The distortion of an electrical signal visible in the final image is a major problem in ultrasonography. To solve this problem, the bit length in Golay-complementary sequences was elongated, narrowing the fractional bandwidth of the coded sequences. Therefore, more energy of the burst signal could be transferred through the ultrasound transducer. The experimental results obtained for transmission of the complementary Golay-coded sequences with two different bit lengths – one-cycle and two-cycles – have been compared, and the efficiency of the pulse compression and its influence on the axial resolution for two fractional bandwidths have been discussed. The results are presented for two transducers having a fractional bandwidth of 25% and 80% and operating at a 6-MHz frequency. The results obtained show that the elongation of the Golay single bit length (doubled in our case) compensate for the limited transducer bandwidth. 2D ultrasound images of a tissue-mimicking phantom are presented and demonstrate the benefits of the use of two-cycle bit length.


Transcriptomics supports local sensory regulation in the antenna of the kissing bug


ABSTRACT

Rhodnius prolixus has become a model for revealing the molecular bases of insect sensory biology due to the publication of its genome, its well characterized behavioural repertoire and the advent of NGS technologies. Gene expression modulation underlies behaviour-triggering processes at peripheral and central levels. Still, the regulation of sensory-related gene transcription in sensory organs is poorlyunderstood. Here we study the genetic bases of plasticity in antennal sensory function, using R. prolixus as
an insect model. Antennal expression of neuromodulatory genes such as those coding for neuropeptides, neurohormones and their receptors was characterized by means of RNA-Seq. New nuclear receptor and takeout gene sequences were identified for this species, as well as those of enzymes involved in the biosynthesis and processing of neuropeptides and biogenic amines. We report a broad repertoire of neuromodulatory and endocrine genes expressed in antennae and suggest that they modulate sensory
neuron function locally. Diverse neuropeptide-coding genes showed consistent expression in the antennae of all stages studied. Future studies should characterize the contribution of these modulatory components acting over antennal sensory processes to assess the relative contribution of peripheral and central regulatory systems on the plastic expression of insect behaviour.


Surgical Anatomy of the insula


ABSTRACT

The insula was for a long time considered as one of the most challenging areas of the brain. This is mainly related to its location, deep and medial to the frontoparietal, temporal, and fronto-orbital opercula. Another difficulty is the content of the lateral fossa, located between the insula and the opercula, which contains the trunks, stem, arteries, and cortical branches of the insular (M2) and opercular (M3) segments of the middle cerebral artery (MCA). Finally, the insula is surrounded by several white matter tracts and cortical structures having important functional roles, especially for language in the dominant hemisphere; the insula is indeed located between a dorsal phonological stream, centered by the arcuate fasciculus and lateral to the posterior insula, and a ventral semantic system, medial to the ventral aspect of the insula and centered by the inferior fronto-occipital fasciculus (IFOF). This chapter reviews some of these surgically relevant anatomical relationships.


The Debated Toxic Role of Aggregated TDP-43 in Amyotrophic Lateral Sclerosis: A Resolution in Sight?


ABSTRACT

Transactive Response DNA-Binding Protein-43 (TDP-43) is an RNA/DNA binding protein that forms phosphorylated and ubiquitinated aggregates in the cytoplasm of motor neurons in Amyotrophic Lateral Sclerosis (ALS), which is a hallmark of this disease. ALS is a neurodegenerative condition affecting the upper and lower motor neurons. Even though the aggregative property of TDP-43 is considered a cornerstone of ALS, there has been major controversy regarding the functional link between TDP-43 aggregates and cell death. In this review, we attempt to reconcile the current literature surrounding this debate by discussing the results and limitations of the published data relating TDP-43 aggregates to cytotoxicity, as well as therapeutic perspectives of TDP-43 aggregate clearance. We point out key data suggesting that the formation of TDP-43 aggregates and the capacity to self-template and propagate among cells as a “prion-like” protein, another pathological property of TDP-43 aggregates, are a significant cause of motor neuronal death. We discuss the disparities among the various studies, particularly with respect to the type of models and the different forms of TDP-43 utilized to evaluate cellular toxicity. We also examine how these disparities can interfere with the interpretation of the results pertaining to a direct toxic effect of TDP-43 aggregates. Furthermore, we present perspectives for improving models in order to better uncover the toxic role of aggregated TDP-43. Finally, we review the recent studies on the enhancement of the cellular clearance mechanisms of autophagy, the ubiquitin proteasome system, and endocytosis in an attempt to counteract TDP-43 aggregation-induced toxicity. Altogether, the data available so far encourage us to suggest that the cytoplasmic aggregation of TDP-43 is key for the neurodegeneration observed in motor neurons in ALS patients. The corresponding findings provide novel avenues toward early therapeutic interventions and clinical outcomes for ALS management.


Green Bio-Assisted Synthesis, Characterization and Biological Evaluation of Biocompatible ZnO NPs Synthesized from Different Tissues of Milk Thistle (Silybum marianum)


ABSTRACT

The purpose of the current study was green synthesis of ZnO-nanoparticles (NPs) from different tissues of Silybum marianum (L.) Gaernt. (i.e., seeds, wild plant, in vitro derived plantlets and callus cultures) followed by extensive characterization and evaluation of their biological potency. ZnO-NPs thus synthesized were subjected to characterization using standard techniques
such as XRD, FTIR and SEM. Thermal stability of synthesized NPs was also evaluated using thermo-gravimetric analysis. Highly stable crystalline NPs with size ranging between 30.8 and 46.0 nm were obtained from different tissues of S. marianum. These NPs have revealed a wide range of biological applications showing antioxidant, moderate α-amylase inhibitor, antibacterial and cytotoxicpotencies. The highest antibacterial activity (20 0.98 mm) was shown by seed extract-mediated ZnO NPs against Staphylococcus aureus (ATCC-6538). Seed extract-mediated ZnO NPs also showed the most potent antioxidant activity (27.7 .9 gAAE/mg, 23.8 0.7 gAAE/mg and 12.7 1.9% total antioxidant capacity (TAC), total reducing power (TRP) and DPPH-free radical scavenging assay (FRSA), respectively). All of the synthesized ZnO NPs also showed cytotoxic activity against
the hepato-cellular carcinoma (HepG2) human cells. Interestingly, these ZnO NPs were also highly biocompatible, as evidenced by the brine shrimp lethality and human red blood cells hemolytic assays. Among all of the NPs synthesized and used, the effect of seed extract-mediated NPs was found to be most promising for future applications.


Pre-conception maternal helminth infection transfers via nursing long-lasting cellular immunity against helminths to offspring


ABSTRACT

Maternal immune transfer is the most significant source of protection from early-life infection, but whether maternal transfer of immunity by nursing permanently alters offspring immunity is poorly understood. Here, we identify maternal immune imprinting of offspring nursed by mothers who had a pre-conception helminth infection.
Nursing of pups by helminth-exposed mothers transferred protective cellular immunity to these offspring against helminth infection. Enhanced control of infection was not dependent on maternal antibody. Protection associated with systemic development of protective type 2 immunity in T helper 2 (TH2) impaired IL-4R−/− offspring.
This maternally acquired immunity was maintained into maturity and required transfer (via nursing) to the offspring of maternally derived TH2-competent CD4 T cells. Our data therefore reveal that maternal exposure to a globally prevalent source of infection before pregnancy provides long-term nursing-acquired immune benefits to offspring mediated by maternally derived pathogen-experienced lymphocytes.


New crystallization strategies to fast-feed structure-guided pharmacological development – Applications to large biological assemblies involved in RNA metabolism


ABSTRACT

The elucidation of three-dimensional structures of molecular machines that control cellular physiology is necessary for the understanding of the mechanisms of life and for the development of rational screening tests for pharmaceutical applications. Due to the large size of these biological entities and the high resolution which is sought, X-ray crystallographic structure determination is the method of choice. Obtaining crystals of biological complexes however remains difficult and is the bottleneck to this method. In this project, we have applied sophisticated crystallization strategies to a hitherto intractable problem: crystallising a molecular motor, namely the bacterial transcription termination factor Rho from Mycobacterium tuberculosis. Rho is a ring-shaped hexameric helicase targeting transcriptional complexes and R-loops, and regulating RNA metabolism in a variety of ways. The first crystals of M.tub. Rho have been obtained, which however should now be optimised to reach an X-ray diffraction resolution sufficient for full three-dimensional structure determination. In addition, we have developed a theoretical model describing the varying usefulness of ions at different positions in the Hofmeister series, according to thermodynamic properties of the crystallizing protein.


The role of glycosylation in the functional activity and pathological consequences of serpin proteins


ABSTRACT

This project focus on the molecular basis of a peculiar class of conformational diseases, called Serpinopathies, with a special emphasis to glycosylation, an important post-translational modification which rules the functional and pathological behaviour of the proteins responsible for the diseases. The authors exploited their expertise on protein biophysics and glyco-biochemistry to set up a long-term program for the studies on the role of glycosylation in the functional activity and pathological consequences of serpin proteins. An experimental work was accomplished to start the expression and production of two serpins, neuroserpin and C1-inhibitor, in a novel eukaryotic expression model. Further, the program was given a wider scope by consolidating a European network of researchers working on closely related issues.