Biased M1 muscarinic receptor mutant mice show accelerated progression of prion neurodegenerative disease

There are currently no treatments that can slow the progression of neurodegenerative diseases, such as Alzheimer’s disease (AD). There is, however, a growing body of evidence that activation of the M1 muscarinic acetylcholine receptor (M1-receptor) can not only restore memory loss in AD patients but in preclinical animal models can also slow neurodegenerative disease progression. The generation of an effective medicine targeting the M1-receptor has however been severely hampered by associated cholinergic adverse responses. By using genetically engineered mouse models that express a G protein–biased M1-receptor, we recently established that M1-receptor mediated adverse responses can be minimized by ensuring activating ligands maintain receptor phosphorylation/arrestin-dependent signaling. Here, we use these same genetic models in concert with murine prion disease, a terminal neurodegenerative disease showing key hallmarks of AD, to establish that phosphorylation/arrestin-dependent signaling delivers neuroprotection that both extends normal animal behavior and prolongs the life span of prion-diseased mice. Our data point to an important neuroprotective property inherent to the M1-receptor and indicate that next generation M1-receptor ligands designed to drive receptor phosphorylation/arrestin-dependent signaling would potentially show low adverse responses while delivering neuroprotection that will slow disease progression.

A Spatiotemporal Characterisation of Redox Molecules in Planarians, with a Focus on the Role of Glutathione during Regeneration

A strict coordination between pro- and antioxidative molecules is needed for normal animal physiology, although their exact function and dynamics during regeneration and development remains largely unknown. Via in vivo imaging, we were able to locate and discriminate between reactive oxygen species (ROS) in real-time during different physiological stages of the highly regenerative planarian Schmidtea mediterranea. All ROS signals were strong enough to overcome the detected autofluorescence. Combined with an in situ characterisation and quantification of the transcription of several antioxidant genes, our data showed that the planarian gut and epidermis have a well-equipped redox system. Pharmacological inhibition or RNA interference of either side of the redox balance resulted in alterations in the regeneration process, characterised by decreased blastema sizes and delayed neurodevelopment, thereby affecting tails more than heads. Focusing on glutathione, a central component in the redox balance, we found that it is highly present in planarians and that a significant reduction in glutathione content led to regenerative failure with tissue lesions, characterised by underlying stem cell alterations. This exploratory study indicates that ROS and antioxidants are tightly intertwined and should be studied as a whole to fully comprehend the function of the redox balance in animal physiology.

CircRNA—Protein Interactions in Muscle Development and Diseases

Circular RNA (circRNA) is a kind of novel endogenous noncoding RNA formed through back-splicing of mRNA precursor. The biogenesis, degradation, nucleus–cytoplasm transport, location, and even translation of circRNA are controlled by RNA-binding proteins (RBPs). Therefore, circRNAs and the chaperoned RBPs play critical roles in biological functions that significantly contribute to normal animal development and disease. In this review, we systematically characterize the possible molecular mechanism of circRNA–protein interactions, summarize the latest research on circRNA–protein interactions in muscle development and myocardial disease, and discuss the future application of circRNA in treating muscle diseases. Finally, we provide several valid prediction methods and experimental verification approaches. Our review reveals the significance of circRNAs and their protein chaperones and provides a reference for further study in this field.

On the specificity of the tuberculin reaction

The classic studies of R. Koch'a showed for the first time that an organism infected with tbc reacts in a completely different way to the introduction of tbc cultures and various cultures derived from them. drugs than a normal animal that has not yet had a chance to get acquainted with the tbc antigen. Koch's main experiments boil down to the following: if you inject a healthy guinea pig with a pure culture of tbc rods, then, as a rule, the wound at the site of the injection heals up and seems to heal in the first days: however, then, within 10-14 days, a solid a nodule that soon opens and forms a place ulcerating until the death of the animal; at the same time, swelling of the nearest lymph glands develops, and later the generalization of the process occurs.

Standardisation of electrocardiographic examination in corn snakes (Pantherophis guttatus)

IntroductionCorn snakes are a very common pet reptile species, yet there is an absence of evidence-based literature standardising collection of ECG or detailing ECG deflection morphology in the normal animal. The authors describe a well-tolerated, reproducible technique and detail the cardiac cycle in terms of lead 2 equivalent waveforms and intervals.Animals29 adult corn snakes.Materials and methodsThis prospective study evaluated, under species-appropriate, standardised conditions, a technique for producing standard six-lead ECG tracings. Lead 2 equivalent cardiac cycles were described in detail and statistically analysed for sex, weight, length, heart rate and mean electrical axis.ResultsHigh-quality tracings demonstrated common ECG characteristics for this species, including no Q, S or SV waves, prolonged PR and RT intervals, rhythmic oscillation of the baseline, short TP segments, and a right displaced mean electrical axis. An influence of sex, weight or length on heart rate and mean electrical axis was not identified.ConclusionsTo the authors’ knowledge, this is the first study to describe a standardised technique for recording ECG in significant numbers of normal corn snakes. Ranges have been provided that may be of diagnostic value or form the basis for future development of reference intervals for this species.

‘We shouldn’t classify pet obesity as a disease’

Robin Hargreaves argues that the chronic weight gain that leads to obesity in pets is a normal animal behaviour and physiological mechanism, and so should not be regarded as a disease process.

Mikania Micrantha Improved Memory Perform on Dementia Model

BACKGROUND: The purpose of this research is to explore the existing natural resources in Jambi province which has potential as anti-dementia agent. So that will be many natural resources that can be a potential product in reducing the unwanted effects of dementia as a degenerative disorder that is currently an inevitable elderly disease. by investigating with various plants in Jambi that have activities as anti-dementia is expected more and more natural resources that can be used as neuron-protection and or neuron-curative. AIM: The purpose of this study is to find plants and / or compounds that are useful as neuroprotection METHODS: Dementia model is formed by diabetic test animals. The test group consisted of extract group, three fractions (hexane, ethyl acetate and butanol fraction at dose 500 mg/Kg BB p.o) and one group of antidiabetic drugs glibenclamide, and the group of normal animal test animals was tested with Radial arm maze (RAM) for seven days before alloxan induced to obtain dementia model. RESULTS: The results showed that extract and ethyl acetate fraction at dose 500 mg/Kg BW gave a positive effect on memory improvement based on animal performance on RAM tool during a testing time (P < 0, 05) with LSD statistical analysis. CONCLUSION: The extract and ethyl acetate fraction of Mikania micrantha showed good potential for improving the performance of animal memory in RAM devices representing dementia models.

Photo-movement in the sea anemone Aiptasia influenced by light quality and symbiotic association

The relationship between cnidarians and their micro-algal symbionts is crucial for normal animal function and the formation of coral reefs. We used the sea anemone Exaiptasia pallida (Aiptasia) as a model cnidarian–dinoflagellate system to determine the effects of white, blue and red light on photo-movement. In white light, phototropism and phototaxis of Aiptasia were dependent on the presence of symbionts; anemones with symbionts bent and moved toward the light, whereas aposymbiotic anemones (lacking algal symbionts) moved, but without strong directionality. Phototaxis and phototropism also occurred in blue light, but to a lesser extent than in white light, with no apparent response to red light. Phototactic behavior was also sensitive to the specific anemone–symbiont pairing. The ability to sense and move in response to light would presumably allow for selection of favorable habitats. Overall, this study demonstrates that the algal symbiont is required for photo-movement of the host and that the extent of movement is influenced by the different anemone–symbiont associations.

The Effect of Apple Cider Vinegar on the Lipid Profile and Electrolytes of Wistar Rats

Aim: This study was to investigate the effects of apple cider vinegar with “the mother” on lipid profile and electrolytes of Wistar rats. Materials and Methods: Twelve female albino rats with mean weight of 150±20 were grouped into four groups. The first group was the control. The control was given distilled water and allowed access to normal animal feed ad libitum but was not administered apple cider vinegar. The second group was the group to be sacrificed after the first week of experiment. The group was given distilled water, allowed access to normal animal feed ad libitum and administered 1ml apple cider vinegar solution twice daily. The third group was the group to be sacrificed after the second week of experiment. The group had same treatment as the second group above. The fourth group was the group to be sacrificed after the third week which was the final week of experiment. The group had same treatment like the second and third groups. Results: After oral administration of the apple cider vinegar on rats for 7 days up to 21 days, the results revealed that the significant reductions in a time dependent manner with the highest reductions obtained on the last week of experiment (p<0.05). After 21 days, triglycerides reduced from 3.37 ± 0.14 to 2.73 ± 0.13 mmol/l, total cholesterol from 4.04 ± 0.98 to 3.62 ± 0.33, low density lipoprotein cholesterol from 8.24 ± 1.31 to 7.02 ± 0.30, very low density lipoprotein cholesterol from 1.55 ± 0.07 to 1.42 ± 0.04mmol/l in the blood of rats. It also revealed a significant decrease (p< 0.05) in calcium electrolyte concentration from 11.54 ± 0.21 to 7.09 ± 0.20 mmol/l. It also revealed significant decrease (p<0.05) in the sodium and elevation in potassium electrolytes concentrations from 153.63 ±0.24 to 120.30 ± 1.31 and 3.61 ± 0.30 to 4.92± 0.46 mmol/l respectively. Conclusion: The results suggested that the apple cider vinegar reduced triglycerides and cholesterol levels in the blood of Wistar rats. The results also suggested that apple cider vinegar reduced calcium and sodium electrolyte levels in the blood but increased potassium levels in the blood of Wistar rats based on the 1ml administration for 21 days.