Small intestinal development in suckling rats after enteral obestatin administration

This study investigated the effect of enteral administration of obestatin on the development of small intestine, as well as oxidative stress markers and trancriptomic profile of gastrointestinal genes. Suckling rats were assigned to 3 groups treated with: C-saline solution; OL-obestatin (125 nmol/kg BW); OH-obestatin (250 nmol/kg BW) administered twice daily, from the 14th to the 21st day of life. Enteral administration of obestatin in both studied doses had no effect neither on the body weight of animals nor the BMI calculated in the day of euthanasia. Compared to the control group (C), treatment with obestatin resulted in significant changes in the histometry of the small intestinal wall as well as intestinal epithelial cell remodeling. The observed changes and their possible implications for intestinal development were dependent on the dosage of peptide. The enteral administration of high dose (OH) of obestatin significantly decreased its expression in the stomach and increased markers of oxidative stress. The gene profile revealed MAPK3 (mitogen-activated protein kinase-3) as the key regulator gene for obestatin action in the gastrointestinal track. In conclusion, we have showed that enteral administration of obestatin influences the gut mucosa remodeling. It is also suggested that the administration of high dose (OH) has inhibitory effect on the intestinal maturation of suckling rats

Growth performance, carcass and meat quality of lambs supplemented different vegetable oils

Objective The purpose of this study was to evaluate the effect of rapeseed and linseed oil supplementations on performance and meat quality of lambs. Methods The experiment was conducted on 18 growing (100-day-old) lambs of 19.7±1.9 kg live weight, assigned to 3 groups of 6 animals each. Control lambs were fed meadow hay and concentrate alone. Experimental animals additionally received rapeseed or linseed oils at a dose of 50 g/d. The lambs were slaughtered at an average body weight of 35.7±0.5 kg. Results The dressing percentage was higher in lambs fed rapeseed oil. Total saturated fatty acids (SFA) and C15:0, C16:0, C17:0, C21:0, C24:0 were lower in longissimus dorsi muscle (MLD) in lambs fed linseed oil. Supplementation of diet with linseed oil decreased concentrations of total monounsaturated fatty acids and C16:1, C17:1, C18:1 cis-9 in MLD. The concentrations of n-3 polyunsaturated fatty acids (PUFA) and C18:3 n-3, C20:5 n-3 in MLD were higher in lambs fed linseed oil than in other groups. Oils supplementation to diets resulted in increased concentration of C22:6 n-3 in MLD. The inclusion of linseed oil into the diet increased the contents of total PUFA, n-3 PUFA and C18:3 n-3, C20:5 n-3, C22:6 n-3 in semitendinosus muscle in comparison to control. A tendency towards a lower n:6/n:3 ratio in MLD was observed when lambs were supplemented linseed oil. Conclusion The supplementation of linseed oil to diets seems to reduce the concentration of SFA and increase the concentration of n-3 PUFA. The n-6/n-3 ratio is an important nutritional factor, and its value has been favorably decreased below 2, thereby achieving an important target related to human health. Due to these changes carcass fatty acid profile was improved, and so enhanced lamb meat healthy properties

Natural and induced antibodies against phages in humans: induction kinetics and immunogenicity for structural proteins of PB1-related phages

Background: Bacteriophages may induce specific antibodies after natural exposure to phages or after phage therapy. As such, phage-specific antibodies might impact phage bioavailability in vivo, although limited non-neutralizing or insignificant effects have also been reported. Materials and Methods: Here, we report antibody induction against PB1-related phages (Pseudomonas viruses LMA2, F8, DP1) in mice over an 80-day period, for a healthy population of humans, and in patients undergoing phage therapy (oral and/or topical treatment). Results: All phages effectively induced specific immunoglobulin M and immunoglobulin G in mice. Phage-specific antibodies were observed in humans, whereas recombinant virion proteins (PB1 gp22, gp29) did not induce phage-neutralizing antibodies, either in mice or in humans. The healthy human population was differentiated for frequency of phage-neutralizing antibodies. Conclusions: These data can hold key considerations for phage therapy cocktail design, as highly similar phages can still be highly complementary in cases where specific immune response hinders therapeutic use of phages.This work was supported by the National Science Centre in Poland grant no. UMO-2012/05/E/NZ6/03314 (granted to K.D.). S.M.S. acknowledges the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 713640.info:eu-repo/semantics/publishedVersio

To be or not to be polar: the ferroelectric and antiferroelectric nematic phases.

We report two new series of compounds that show the ferroelectric nematic, NF, phase in which the terminal chain length is varied. The longer the terminal chain, the weaker the dipole–dipole interactions of the molecules are along the director and thus the lower the temperature at which the axially polar NF phase is formed. For homologues of intermediate chain lengths, between the non-polar and ferroelectric nematic phases, a wide temperature range nematic phase emerges with antiferroelectric character. The size of the antiparallel ferroelectric domains critically increases upon transition to the NF phase. In dielectric studies, both collective ("ferroelectric") and non-collective fluctuations are present, and the "ferroelectric" mode softens weakly at the N–NX phase transition because the polar order in this phase is weak. The transition to the NF phase is characterized by a much stronger lowering of the mode relaxation frequency and an increase in its strength, and a typical critical behavior is observed

Molecular mechanisms of tigecycline-resistance among Enterobacterales

The global emergence of antimicrobial resistance to multiple antibiotics has recently become a significant concern. Gram-negative bacteria, known for their ability to acquire mobile genetic elements such as plasmids, represent one of the most hazardous microorganisms. This phenomenon poses a serious threat to public health. Notably, the significance of tigecycline, a member of the antibiotic group glycylcyclines and derivative of tetracyclines has increased. Tigecycline is one of the last-resort antimicrobial drugs used to treat complicated infections caused by multidrug-resistant (MDR) bacteria, extensively drug-resistant (XDR) bacteria or even pan-drug-resistant (PDR) bacteria. The primary mechanisms of tigecycline resistance include efflux pumps’ overexpression, tet genes and outer membrane porins. Efflux pumps are crucial in conferring multi-drug resistance by expelling antibiotics (such as tigecycline by direct expelling) and decreasing their concentration to sub-toxic levels. This review discusses the problem of tigecycline resistance, and provides important information for understanding the existing molecular mechanisms of tigecycline resistance in Enterobacterales. The emergence and spread of pathogens resistant to last-resort therapeutic options stands as a major global healthcare concern, especially when microorganisms are already resistant to carbapenems and/or colistin

Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia

Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterised by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the Default Mode Network. Interactions within the Default Mode Network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the Default Mode Network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. 19 traumatic brain injury patients were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalised when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients in post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing

Immunogenic epitope scanning in bacteriolytic enzymes Pal and Cpl-1 and engineering Pal to escape antibody responses

Bacteriolytic enzymes are promising antibacterial agents, but they can cause a typical immune response in vivo. In this study, we used a targeted modification method for two antibacterial endolysins, Pal and Cpl-1. We identified the key immunogenic amino acids, and designed and tested new, bacteriolytic variants with altered immunogenicity. One new variant of Pal (257-259 MKS → TFG) demonstrated decreased immunogenicity while a similar mutant (257-259 MKS → TFK) demonstrated increased immunogenicity. A third variant (280-282 DKP → GGA) demonstrated significantly increased antibacterial activity and it was not cross-neutralized by antibodies induced by the wild-type enzyme. We propose this variant as a new engineered endolysin with increased antibacterial activity that is capable of escaping cross-neutralization by antibodies induced by wild-type Pal. We show that efficient antibacterial enzymes that avoid cross-neutralization by IgG can be developed by epitope scanning, in silico design, and substitutions of identified key amino acids with a high rate of success. Importantly, this universal approach can be applied to many proteins beyond endolysins and has the potential for design of numerous biological drugs

Segmentation of glioblastomas in early post-operative multi-modal MRI with deep neural networks

Extent of resection after surgery is one of the main prognostic factors for patients diagnosed with glioblastoma. To achieve this, accurate segmentation and classification of residual tumor from post-operative MR images is essential. The current standard method for estimating it is subject to high inter- and intra-rater variability, and an automated method for segmentation of residual tumor in early post-operative MRI could lead to a more accurate estimation of extent of resection. In this study, two state-of-the-art neural network architectures for pre-operative segmentation were trained for the task. The models were extensively validated on a multicenter dataset with nearly 1000 patients, from 12 hospitals in Europe and the United States. The best performance achieved was a 61\% Dice score, and the best classification performance was about 80\% balanced accuracy, with a demonstrated ability to generalize across hospitals. In addition, the segmentation performance of the best models was on par with human expert raters. The predicted segmentations can be used to accurately classify the patients into those with residual tumor, and those with gross total resection.Comment: 13 pages, 4 figures, 4 table