Impact of the longitudinal and seasonal changes of the water quality on the benthic macroinvertebrate assemblages of the Andorran streams

The ecological quality of the Andorran streams was assessed in 1998-1999, based on the survey of the water chemistry and the benthic macroinvertebrate assemblages. Two types of modification of the water quality were observed in the Andorran rivers: (i) a progressive degradation along the longitudinal gradient with a chronic degradation in the lower water courses; (ii) a seasonal modification in the mid-elevation sites. Two responses of the benthic macroinvertebrate assemblages to these disturbances were observed: an extreme simplification of the composition and a change of the trophic structure of the assemblages in the more impacted sites.     

Determination of fuzzy logic membership functions using genetic algorithms: application to structure–odor modeling

Fuzzy logic has been used as a tool in structure–camphoraceous odor relationships. The data base studied included 99 molecules. The rules used to discriminate between camphor and non camphor molecules lead to 77% correct discrimination. Such rules account for the shape and the size of the molecule. Their adjustment by means of genetic algorithms led to 84% correct discrimination between camphor and non-camphor molecules.Figure Membership function for the chosen variables     

How morphological constraints affect axonal polarity in mouse neurons

Neuronal differentiation is under the tight control of both biochemical and physical information arising from neighboring cells and micro-environment. Here we wished to assay how external geometrical constraints applied to the cell body and/or the neurites of hippocampal neurons may modulate axonal polarization in vitro. Through the use of a panel of non-specific poly-L-lysine micropatterns, we manipulated the neuronal shape. By applying geometrical constraints on the cell body we provided evidence that centrosome location was not predictive of axonal polarization but rather follows axonal fate. When the geometrical constraints were applied to the neurites trajectories we demonstrated that axonal specification was inhibited by curved lines. Altogether these results indicated that intrinsic mechanical tensions occur during neuritic growth and that maximal tension was developed by the axon and expressed on straight trajectories. The strong inhibitory effect of curved lines on axon specification was further demonstrated by their ability to prevent formation of multiple axons normally induced by cytochalasin or taxol treatments. Finally we provided evidence that microtubules were involved in the tension-mediated axonal polarization, acting as curvature sensors during neuronal differentiation. Thus, biomechanics coupled to physical constraints might be the first level of regulation during neuronal development, primary to biochemical and guidance regulations.     

Generating bispecific human IgG1 and IgG2 antibodies from any antibody pair

Bispecific antibodies and antibody fragments are a new class of therapeutics increasingly utilized in the clinic for T cell recruitment (catumaxomab anti-EpCAM/CD3 and blinatumomab anti-CD19/CD3), increase in the selectivity of targeting, or simultaneous modulation of multiple cellular pathways. While the clinical potential for certain bispecific antibody formats is clear, progress has been hindered because they are often difficult to manufacture, may suffer from suboptimal pharmacokinetic properties, and may be limited due to potential immunogenicity issues. Current state-of-the-art human IgG-like bispecific technologies require co-expression of two heavy chains with a single light chain, use crossover domains to segregate light chains, or utilize scFv (single-chain fragment variable)-Fc fusion. We have engineered both human IgG1 and IgG2 subtypes, with minimal point mutations, to form full-length bispecific human antibodies with high efficiency and in high purity. In our system, the two antibodies of interest can be expressed and purified separately, mixed together under appropriate redox conditions, resulting in a formation of a stable bispecific antibody with high yields. With this approach, it is not necessary to generate new antibodies that share a common light chain, therefore allowing the immediate use of an existing antibody regardless of whether it has been generated via standard hybridoma or display methods. We demonstrate the generality of the approach and show that these bispecific antibodies have properties similar to those of wild-type IgGs, and we further demonstrate the utility of the technology with an example of a CD3/CD20 bispecific antibody that effectively depletes B cells in vitro and in vivo.     

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist

The efficient spread of SARS-CoV-2 resulted in a unique pandemic in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLR_S) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2⁺ Vero E6 cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. These data have been then confirmed using authentic SARS-CoV-2 virus and human respiratory cell lines. Thus, we described a mechanism potentiating viral spreading of infection.     

Ketamine alters cortical integration of GABAergic interneurons and induces long-term sex-dependent impairments in transgenic Gad67-GFP mice

Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, widely used as an anesthetic in neonatal pediatrics, is also an illicit drug named Super K or KitKat consumed by teens and young adults. In the immature brain, despite several studies indicating that NMDA antagonists are neuroprotective against excitotoxic injuries, there is more and more evidence indicating that these molecules exert a deleterious effect by suppressing a trophic function of glutamate. In the present study, we show using Gad67-GFP mice that prenatal exposure to ketamine during a time-window in which GABAergic precursors are migrating results in (i) strong apoptotic death in the ganglionic eminences and along the migratory routes of GABAergic interneurons; (ii) long-term deficits in interneuron density, dendrite numbers and spine morphology; (iii) a sex-dependent deregulation of γ-aminobutyric acid (GABA) levels and GABA transporter expression; (iv) sex-dependent changes in the response to glutamate-induced calcium mobilization; and (v) the long-term sex-dependent behavioral impairment of locomotor activity. In conclusion, using a preclinical approach, the present study shows that ketamine exposure during cortical maturation durably affects the integration of GABAergic interneurons by reducing their survival and differentiation. The resulting molecular, morphological and functional modifications are associated with sex-specific behavioral deficits in adults. In light of the present data, it appears that in humans, ketamine could be deleterious for the development of the brain of preterm neonates and fetuses of addicted pregnant women.Neonatal brain lesions, which affect both preterm and term infants, result in cerebral palsy and cognitive deficits.¹ The main risks associated with these lesions are prematurity, hypoxia-ischemia, hemorrhages, fetal-placental infections and exposure to toxins.^{1, 2} Although the underlying neurochemical processes are complex and only partially elucidated, the production of pro-inflammatory cytokines, free-radical stress induced by both reactive oxygen and nitrogen species, and the massive release of glutamate at both synaptic and extrasynaptic sites, leading to an excitotoxic cell death, have been described.^{3, 4} In particular, because of its high permeability to calcium, the N-methyl-D-aspartate (NMDA) receptor has been shown to have a key role in excitotoxicity, and several studies reported that NMDA receptor antagonists exert a protective effect in both adults and neonates.^{4, 5, 6} However, the innocuousness of NMDA antagonists in the developing brain is debatable. Indeed, several research groups have described a deleterious effect of molecules such as MK801 or memantine in the immature neocortex.^{4, 7, 8, 9} In particular, it has been shown that MK801 exerts a dual effect in cultured cortical slices from mouse neonates; although it reduces excitotoxic death in the deep cortical layers V and VI, it has a pro-apoptotic effect on immature GABAergic interneurons present in the superficial layers II–IV.⁷Because of its short onset of action, rapid clearance and low influence on respiratory and cardiac functions, ketamine is an anesthetic widely used in neonatal pediatrics.^{10, 11} However, similar to MK801, ketamine is a non-competitive NMDA-receptor blocker, and even though its effects are less long-lasting than those of MK801, recent studies point to neurotoxic effects of ketamine in the immature brain of rats and non-human primates.^{12, 13} These reports raise the possibility that ketamine could also have deleterious effects in the developing human brain.¹⁴ Moreover, ketamine is also listed as an illicit drug (named Special K, KitKat or Super K) in most countries and is increasingly used by teens and young adults at raves, with the associated risk of addiction and consumption during pregnancy.^{15, 16} It appears, therefore, that the clinical use of ketamine in pediatrics as well as drug-abuse practices lead to a risk of perinatal exposure during a time-window in which GABAergic interneurons are still differentiating.¹⁷Based on our recent demonstration that MK801 affects the survival of GABAergic interneurons, we hypothesized that ketamine would also interfere with the GABAergic system and result in long-term deficits. Here we tested this hypothesis by using Gad67-GFP transgenic mice to investigate ex vivo and in vivo the effects of prenatal exposure to ketamine on (i) the survival of GABAergic precursors, (ii) the molecular and morphometric characteristics of GABAergic interneuron differentiation, (iii) glutamate-induced neuronal activation and (iv) the long-term impairment of motor activity.     

The fish fauna of three North African lagoons: specific inventories,ecological status and production

This paper examines the ecological and biological status of fisheries in three coastal lagoons in the southern Mediterranean region: Merja Zerga in Morocco, Ghar El Melh in Tunisia and Lake Manzala in Egypt. Despite similarities in some ecological characteristics, the three lagoons’ respective fisheries show differences in specific composition, in population structure and in their production both in qualitative and quantitative aspects. Thus, in Merja Zerga and Ghar El Melh the fish fauna shows a marine affinity where grey mullet and eels dominate the fish production. In Lake Manzala the ichthyofauna displays a more freshwater affinity with tilapia the dominant group of species. Otherwise, overall fish production at the three sites is regulated by variations in fishing activities, local environments and seasonal conditions. A decrease in fish production was noted over recent years and this is attributed to deteriorating ecological conditions. A variety of factors are implicated including sea communication problems, reduction of the continental (fresh) water supply and increase of pollution causing eutrophication. In addition, over fishing with a continuing increase of fishing effort units, contributes to fisheries decline. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Guest editors: J. R. Thompson & R. J. Flower Hydro-ecological Monitoring and Modelling of North African Coastal Lagoons     

The fauna and associated artefacts from the Lower Pleistocene site of Mansourah (Constantine, Algeria)

The site of Mansourah (Constantine, Algeria) had yielded to the early authors, and more recently to the late G. Laplace, a lithic industry associated with a fauna of large Mammals, which looks contemporaneous with that of Aïn Hanech, although it is well-distinct ecologically, and might even be slightly older. The lithic assemblage is completely devoid of any bifacial artefact or cleaver and can only be referred to the Oldowan. Thus, the Mansourah site documents a very early human occupation of North Africa, and perhaps one of the earliest. To cite this article: Y. Chaid-Saoudi et al., C. R. Palevol 5 (2006).     

BENA435, a new cell-permeant photoactivated green fluorescent DNA probe

N′-(2,8-Dimethoxy-12-methyl-dibenzo [c,h] [1,5] naphthyridin-6-yl)-N,N-dimethyl-propane-1,3-diamine (BENA435) is a new cell-membrane permeant DNA dye with absorption/emission maxima in complex with DNA at 435 and 484 nm. This new reagent is unrelated to known DNA dyes, and shows a distinct preference to bind double-stranded DNA over RNA. Hydrodynamic studies suggest that BENA435 intercalates between the opposite DNA strands. BENA435 fluoresces much stronger when bound to dA/dT rather than dG/dC homopolymers. We evaluated 14 related dibenzonaphthyridine derivatives and found BENA435 to be superior in its in vivo DNA-binding properties. Molecular modelling was used to develop a model of BENA435 intercalation between base pairs of a DNA helix. BENA435 fluorescence in the nuclei of cells increases upon illumination, suggesting photoactivation. BENA435 represents thus the first known cell-permeant photoactivated DNA-binding dye.     

Female sex workers and the social context of workplace violence in Tijuana, Mexico

Gender-based violence in the workplace impacts the physical and emotional wellbeing of sex workers and may lead to other health problems, such as PTSD and depression, drug abuse, and a greater likelihood of sexually transmitted infections. This study examines the social context of workplace violence and risk avoidance in the context of legal regulations meant to reduce harms associated with the industry. Ethnographic research, including 18 months of extended field observations and interviews with 190 female sex workers, is used to illustrate how sex workers in Tijuana, Mexico, experience and manage workplace violence. Multiple subthemes emerge from this analysis, including deciding where to work, working with a third party, avoiding theft, and dealing with police. These findings support the idea that the risk of violence is part of a larger "hierarchy of risk" that can result in a "tradeoff" of harms.