A 90-Day Subchronic Toxicity Study of Consumption of GH-Transgenic Triploid Carp in Wistar Rats

Genetic modification (GM) offers an alternative strategy to conventional animal breeding. The present study was carried out to investigate the potential health effects of the consumption of growth hormone-transgenic triploid carp (GH-ttc) through a 90-day subchronic rodent feeding study. Wistar rats (n = 10/sex/group) were given formulated diets containing GH-ttc or non-GM carp at an incorporated rate of 2.5%, 5%, or 10% (w/w) for 90 days. An additional control group of rats (n = 10/sex/group) was fed a basic rodent diet. During the 90-day study, clinical observation, ophthalmic examination, body weight, and food intake were evaluated. At the end of the study, rats were killed, and the hematology, serum chemistry, urine test, necropsy, and histopathology were assessed. Compared with the non-GM carp and the basic control groups, no biologically significant differences were observed on clinical signs of toxicity, body weights, food intake, hematology, serum chemistry, urinalysis, organ weight, and histopathology on selected organs for the GH-ttc group. The results of this 90-day subchronic feeding study indicated that, at the dose level used in this study, consumption of GH-ttc showed no subchronic toxicity to Wistar rats.

Galleria mellonella as a Suitable Model of Bacterial Infection: Past, Present and Future

The increasing interest for Galleria mellonella larvae as an infection model is evidenced by the number of papers reporting its use, which increases exponentially since the early 2010s. This popularity was initially linked to limitation of conventional animal models due to financial, technical and ethical aspects. In comparison, alternative models (e.g. models using Caenorhabditis elegans, Drosophila melanogaster or G. mellonella) were cheap, simple to use and not limited by ethical regulation. Since then, similar results have been established with G. mellonella model comparatively to vertebrates, and it is more and more often used as a robust model per se, not only as an alternative to the murine model. This review attempts to summarize the current knowledge supporting the development of this model, both on immunological and microbiological aspects. For that, we focus on investigation of virulence and new therapies for the most important pathogenic bacteria. We also discuss points out directions for standardization, as well as recent advances and new perspectives for monitoring host-pathogen interactions.

Crop Residue Based Complete Feed for Enhancing Livestock Performance- A Review

The estimated projected data regarding demand and supply of feed and fodder shows13.20% and 18.43% deficit between demand and supply of dry and green fodder to livestock, respectively. Shortage of land for cultivation of fodders and increased human as well as livestock population has led to heavy competition for food grains that necessitates using the crop residues for the feeding of livestock. These crop residues are rich in fibre and low in other nutrients; they also have low palatability and digestibility. The best way to efficiently utilize the crop residues is to prepare complete feeds from pretreated crop residues + concentrates mixture. Pretreatment of crop residues increases digestibility by increasing rate of delignification, increasing enzymatic hydrolysis of cellulose, hemicelluloses and thus increasing the glucose yield. The complete feed is a quantitative mixture of all dietary ingredients to provide the specific nutrient requirement for various physiological functions of livestock. Crop residue-based complete feed could be prepared in mash, block and pellet (Expander and extruder) form. In this system, all feed ingredients including roughages are proportioned, processed and mixed into a uniform blend. Different researchers undertook feeding trials of complete animal feed and conventional animal feed and reported better performance in terms of weight gain, milk yield and reproductive performance on feeding complete feed pellets or complete feed blocks to ruminants as compared to conventional ration. In conclusion, crop residue based complete feed could improve ruminant performance and reduces cost of feeding per kg gain or yield and thereby improving livestock based rural economy in developing countries like India.

The zebrafish embryo as an in vivo model for screening nanoparticle-formulated lipophilic anti-tuberculosis compounds

With the increasing emergence of drug-resistant Mycobacterium tuberculosis strains, new and effective antibiotics against tuberculosis (TB) are urgently needed. However, the high frequency of poorly water-soluble compounds among hits in high-throughput drug screening (HTS) campaigns is a major obstacle in drug discovery. Moreover, in vivo testing using conventional animal TB models such as mice is time-consuming and costly, and represents a major bottleneck in lead compound discovery and development. Here, we report the use of the zebrafish embryo TB model, to evaluate the in vivo toxicity and efficacy of five poorly water-soluble nitronaphthofuran derivatives, which were recently identified to possess anti-tuberculosis activity in vitro. To aid solubilization compounds were formulated in biocompatible polymeric micelles (PM). Three of the five PM-formulated nitronaphthofuran derivatives showed low toxicity in vivo, significantly reduced bacterial burden and improved survival in infected zebrafish embryos. We propose the zebrafish embryo TB-model as a quick and sensitive tool for evaluating in vivo toxicity and efficacy of new anti-TB compounds during early stages of drug development. Thus, this model is well suited to pinpoint promising compounds for further development.

Cultured Meat Prospects for a Billion!

The dietary protein requirements of almost 9.8 billion people need to be fulfilled in a healthy and sustainable manner by 2050. Meat consumption contributes to 35% of the total protein requirement of the Indian population. Meat intake needs to be sustainable and economical without causing food security and production issues. Consumption of meat in India is projected to rise with an increase in consumer incomes. Hence, novel alternative proteins, including cultured meat (CM) and plant-based meat (PBM), are being developed to satisfy the demand for meat-derived proteins in the diet. This involves the creation of novel PBM/CM products with a similar taste and texture as conventional animal meat with tailor-made nutritional attributes. In this article, we provide critical insights into the technical and business aspects of relevance to production and sustainability encountered by the Indian CM industry at a series of stages that can be termed the CM value chain comprising upstream and downstream processes. We shed light on the need for regulatory authorities and a framework. Consumer concerns towards CM products can be alleviated through effective scientific communication strategies, including prior familiarity, narrative building and transparency, and labelling aspects of CM products.

The goldfish Carassius auratus: an emerging animal model for comparative cardiac research

The use of unconventional model organisms is significantly increasing in different fields of research, widely contributing to advance life sciences understanding. Among fishes, the cyprinid Carassius auratus (goldfish) is largely used for studies on comparative and evolutionary endocrinology, neurobiology, adaptive and conservation physiology, as well as for translational research aimed to explore mechanisms that may be useful in an applicative biomedical context. More recently, the research possibilities offered by the goldfish are further expanded to cardiac studies. A growing literature is available to illustrate the complex networks involved in the modulation of the goldfish cardiac performance, also in relation to the influence of environmental signals. However, an overview on the existing current knowledge is not yet available. By discussing the mechanisms that in C. auratus finely regulate the cardiac function under basal conditions and under environmental challenges, this review highlights the remarkable flexibility of the goldfish heart in relation not only to the basic morpho-functional design and complex neuro-humoral traits, but also to its extraordinary biochemical-metabolic plasticity and its adaptive potential. The purpose of this review is also to emphasize the power of the heart of C. auratus as an experimental tool useful to investigate mechanisms that could be difficult to explore using more conventional animal models and complex cardiac designs.

Pre-clinical Investigation of Rett Syndrome Using Human Stem Cell-Based Disease Models

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, mostly caused by mutations in MECP2. The disorder mainly affects girls and it is associated with severe cognitive and physical disabilities. Modeling RTT in neural and glial cell cultures and brain organoids derived from patient- or mutation-specific human induced pluripotent stem cells (iPSCs) has advanced our understanding of the pathogenesis of RTT, such as disease-causing mechanisms, disease progression, and cellular and molecular pathology enabling the identification of actionable therapeutic targets. Brain organoid models that recapitulate much of the tissue architecture and the complexity of cell types in the developing brain, offer further unprecedented opportunity for elucidating human neural development, without resorting to conventional animal models and the limited resource of human neural tissues. This review focuses on the new knowledge of RTT that has been gleaned from the iPSC-based models as well as limitations of the models and strategies to refine organoid technology in the quest for clinically relevant disease models for RTT and the broader spectrum of neurodevelopmental disorders.

Amazon rainforest rodents (Proechimys) are resistant to post-stroke epilepsy

There are no clinical interventions to prevent post-injury epilepsy, a common and devastating outcome after brain insults. Epileptogenic events that run from brain injury to epilepsy are poorly understood. Previous studies in our laboratory suggested Proechimys, an exotic Amazonian rodent, as resistant to acquired epilepsy development in post-status epilepticus models. The present comparative study was conducted to assess (1) stroke-related brain responses 24-h and 30 days after cortical photothrombosis and (2) post-stroke epilepsy between Proechimys rodents and Wistar rats, a traditional animal used for laboratory research. Proechimys group showed smaller volume of ischemic infarction and lesser glial activation than Wistar group. In contrast to Wistar rats, post-stroke decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators and growth factors were found in Proechimys. Electrophysiological signaling changes assessed by cortical spreading depression, in vitro and in vivo, showed that Wistar’s brain is most severely affected by stroke. Chronic electrocorticographic recordings showed that injury did not lead to epilepsy in Proechimys whereas 88% of the Wistar rats developed post-stroke epilepsy. Science gains insights from comparative studies on diverse species. Proechimys rodents proved to be a useful animal model to study antiepileptogenic mechanisms after brain insults and complement conventional animal models.

Motor dysfunction in Drosophila melanogaster as a biomarker for developmental neurotoxicity

Humans interact with numerous chemical compounds with direct health implications, with several able to induce developmental neurotoxicity (DNT), which bear developmental, behavioral, and cognitive consequences from a young age. Current guidelines for DNT testing are notably costly, time consuming, and unsuitable for testing large numbers of chemicals. Therefore, there is a need for adequate alternatives to conventional animal testing for neurotoxicity and DNT. Here we show that detailed kinematic analysis can provide a strong indicator for DNT, using known (chlorpyrifos, CPS) or putative (β–N–methylamino–L–alanine, BMAA) neurotoxic compounds. Here we Drosophila melanogaster exposed to these compounds during development and evaluated for common general toxicity – notably developmental survival and pupal positioning, together with the FlyWalker system, a detailed adult kinematics evaluation method. At concentrations that do not induce general toxicity, the solvent DMSO had a significant effect on kinematic parameters. Nonetheless, CPS not only induced developmental lethality but also significantly impaired coordination in comparison to DMSO, altering 16 motor parameters, validating the usefulness of our kinematic approach. Interestingly, BMAA, although not lethal during development, induced a dose–dependent motor decay, targeting most parameters in young adult animals, phenotypically resembling normally aged, non-exposed flies. This effect was subsequently attenuated during ageing, indicating an adaptive response. Furthermore, BMAA induced an abnormal terminal differentiation of leg motor neurons, without inducing degeneration, underpinning the observed altered mobility phenotype. Overall, our results support our kinematic approach as a novel, highly sensitive and reliable tool to assess potential DNT of chemical compounds.