Clay Types Modulate the Toxicity of Low Concentrated Copper Oxide Nanoparticles Toward Springtails in Artificial Test Soils.

Copper oxide nanoparticles (CuO-NPs) can be applied as an efficient alternative to conventional Cu in agriculture. Negative effects of CuO-NPs on soil organisms were found, but only in clay-rich loamy soils. It is hypothesized that clay-NP interactions are the origin of the observed toxic effects. In the present study, artificial Organisation for Economic Co-operation and Development soils containing 30% of kaolin or montmorillonite as clay type were spiked with 1-32 mg Cu/kg of uncoated CuO-NPs or CuCl2 . We performed 28-day reproduction tests with springtails of the species Folsomia candida and recorded the survival, reproduction, dry weight, and Cu content of adults. In a second experiment, molting frequency and the Cu content of exuviae, as well as the biochemical endpoints metallothionein and catalase (CAT) in springtails, were investigated. In the reproduction assay, negative effects on all endpoints were observed, but only in soils containing montmorillonite and mostly for CuO-NPs. For the biochemical endpoints and Cu content of exuviae, effects were clearly distinct between Cu forms in montmorillonite soil, but a significant reduction compared to the control was only found for CAT activity. Therefore, the reduced CAT activity in CuO-NP-montmorillonite soil might be responsible for the observed toxicity, potentially resulting from reactive oxygen species formation overloading the antioxidant system. This process seems to be highly concentration-dependent, because all endpoints investigated in reproduction and biochemical assays of CuO-NP-montmorillonite treatments showed a nonlinear dose-response relationship and were constantly reduced by approximately 40% at a field-realistic concentration of 3 mg/kg, but not at 32 mg/kg. The results underline that clay-CuO-NP interactions are crucial for their toxic behavior, especially at low, field-realistic concentrations, which should be considered for risk assessment of CuO-NPs. Environ Toxicol Chem 2022;41:2454-2465. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Tau exon 2 responsive elements deregulated in myotonic dystrophy type I are proximal to exon 2 and synergistically regulated by MBNL1 and MBNL2.

The splicing of the microtubule-associated protein Tau is regulated during development and is found to be deregulated in a growing number of pathological conditions such as myotonic dystrophy type I (DM1), in which a reduced number of isoforms is expressed in the adult brain. DM1 is caused by a dynamic and unstable CTG repeat expansion in the DMPK gene, resulting in an RNA bearing long CUG repeats (n>50) that accumulates in nuclear foci and sequesters CUG-binding splicing factors of the muscle blind-like (MBNL) family, involved in the splicing of Tau pre-mRNA among others. However, the precise mechanism leading to Tau mis-splicing and the role of MBNL splicing factors in this process are poorly understood. We therefore used new Tau minigenes that we developed for this purpose to determine how MBNL1 and MBNL2 interact to regulate Tau exon 2 splicing. We demonstrate that an intronic region 250 nucleotides downstream of Tau exon 2 contains cis-regulatory splicing enhancers that are sensitive to MBNL and that bind directly to MBNL1. Both MBNL1 and MBNL2 act as enhancers of Tau exon 2 inclusion. Intriguingly, the interaction of MBNL1 and MBNL2 is required to fully reverse the mis-splicing of Tau exon 2 induced by the trans-dominant effect of long CUG repeats, similar to the DM1 condition. In conclusion, both MBNL1 and MBNL2 are involved in the regulation of Tau exon 2 splicing and the mis-splicing of Tau in DM1 is due to the combined inactivation of both.

Overexpression of MBNL1 fetal isoforms and modified splicing of Tau in the DM1 brain: two individual consequences of CUG trinucleotide repeats.

Neurofibrillary degeneration is often observed in the brain of patients with type 1 myotonic dystrophy (DM1). It consists principally of the aggregation of Tau isoforms that lack exon 2/3 encoded sequences, and is the consequence of the modified splicing of Tau pre-mRNA. In experimental models of DM1, the splicing of several transcripts is modified due to the loss of Muscleblind-like 1 (MBNL1) function. In the present study, we demonstrate that the MBNL1 protein is also present in the human brain, and consists of several isoforms, as shown by RT-PCR and sequencing. In comparison with controls, we show that the adult DM1 brain exhibits modifications in the splicing of MBNL1, with the preferential expression of long MBNL1 isoforms--a splicing pattern similar to that seen in the fetal human brain. In cultured HeLa cells, the presence of long CUG repeats, such as those found in the DM1 mutation, leads to similar changes in the splicing pattern of MBNL1, and the localization of MBNL1 in nuclear RNA foci. Long CUG repeats also reproduce the repression of Tau exon 2/3 inclusion, as in the human disease, suggesting that their effect on MBNL1 expression may lead to changes in Tau splicing. However, while an overall reduction in the expression of MBNL1 mimics the effect of the DM1 mutation, none of the MBNL1 isoforms tested so far modulates the endogenous splicing of Tau. The modified splicing of Tau thus results from a possibly CUG-mediated loss of function of MBNL1, but not from changes in the MBNL1 expression pattern.

Antibodies: an alternative for antibiotics?

In 1967, the success of vaccination programs, combined with the seemingly unstoppable triumph of antibiotics, prompted the US Surgeon General to declare that "it was time to close the books on infectious diseases." We now know that the prediction was overly optimistic and that the fight against infectious diseases is here to stay. During the last 20 yr, infectious diseases have indeed made a staggering comeback for a variety of reasons, including resistance against existing antibiotics. As a consequence, several alternatives to antibiotics are currently being considered or reconsidered. Passive immunization (i.e., the administration of more or less pathogen-specific antibodies to the patient) prior to or after exposure to the disease-causing agent is one of those alternative strategies that was almost entirely abandoned with the introduction of chemical antibiotics but that is now gaining interest again. This review will discuss the early successes and limitations of passive immunization, formerly referred to as "serum therapy," the current use of antibody administration for prophylaxis or treatment of infectious diseases in agriculture, and, finally, recent developments in the field of antibody engineering and "molecular farming" of antibodies in various expression systems. Especially the potential of producing therapeutic antibodies in crops that are routine dietary components of farm animals, such as corn and soy beans, seems to hold promise for future application in the fight against infectious diseases.

Economic sustainability of small ruminants production in semi-arid areas of Lebanon.

Small ruminant production in the near east region is facing serious constraint of feed availability. A study was conducted in marginal areas of Lebanon, using a cost-benefit analysis technique (CBA), to assess the feasibility of four small ruminant production systems ranging from semi-nomadic to settled. When the owned labor cost was included as an opportunity cost in the economic analysis, CBA revealed negative returns in all four systems. Only the settled system was profitable according to the financial analysis excluding labor cost. Moreover, feed expenses if coupled with grazing costs represented a major constraint to profitability. To remedy to the feed deficit problem, the potential of using agro-industrial by-products as feed block supplements was investigated. Simulated feed block diets, using the most available by-products, provided a better nutritive value per unit cost than hand-fed diets used in the systems studied. Preliminary analysis showed that the use of feed block diets could improve the economic sustainability of small ruminant production systems.

Humoral and cell-mediated immunopotentiation in vaccinated chicken layers by thymic hormones and zinc.

The humoral and cell-mediated immunities to a trivalent killed vaccine, administered subcutaneously to white leghorn-chicken layers at 29 and 31 weeks of age, and containing antigens of infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), and Newcastle disease virus (NDV), were quantitated in five vaccinated and one unvaccinated-control group. Four out of the five vaccinated groups were immunopotentiated by various combinations of zinc and thymic hormones administered intraperitoneally in a volume of 0.1 ml per bird at an interval of three days for a period of three weeks, starting at 29 weeks of age. At each time interval, each bird of the first group received thymulin (10 ng) and ZnCl2 (1 microM), while each bird of the second group received thymopoietin (25 ng) and ZnCl2 (1 microM); in the third group, each bird received thymulin (10 ng), thymopoietin (25 ng), and ZnCl2 (1 microM), while each bird of the fourth group received only ZnCl2 (1 microM). Birds of the fifth group were only vaccinated and the control birds in the sixth group were left without vaccination or other immunopotentiation. Among all combinations, the thymulin-ZnCl2 resulted in birds with the highest humoral immunopotentiation to IBV, IBDV, and NDV antigens with respective percent increase in the mean titer at 33 weeks of age, compared with initial titer at 29 weeks of age, equivalent to 199%, 671.7%, and 86.4%. The highest cell-mediated delayed hypersensitivity reaction, measured at 48 h following an intradermal administration of the trivalent vaccine in the wattles at 33 weeks of age, was obtained in chickens immunopotentiated by the thymulin-thymopoietin-ZnCl2 combination.