What we learned from Franklin's first expedition on CD

pp. 299-30

The Missing Piece in the Puzzle of Inflammation

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Kvalitativni i kvantitativni sastav zajednice bentosa u proceni kvaliteta vode reke Neretve na lokalitetima Višići i Žitomišlići

This paper is a result of the research of the river Neretva benthos at sites Zitomislici and Visici (downstream of Mostar) from 2005. to 2010. The sampling was done once a year, and 'kick-sampling' sampling was used for macrointervertebrates, while the samples for the analysis of the phytobenthos composition were scraped from the sediment with a scalpel or run-off from the sediment (standard EN 13946: 2003 Water quality – Guidance). Results of the analysis point to 62 algae taxa at site Zitomislici and 69 at site Visici. Macrointervertebrates benthos composition points on dominance of snails and sensible groups of larvae stages of the EPT insect groups. Saprobic values of both biological factors are relatively balanced and for the river Neretva, at site Zitomislici, point to oligo/betamesosaprobe level, while at site Visici they point to betamesosaprobe level of quality

Dietary (poly)phenols in traumatic brain injury

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Traumatic brain injury (TBI) remains one of the leading causes of death and disability in young adults worldwide. Despite growing evidence and advances in our knowledge regarding the multifaceted pathophysiology of TBI, the underlying mechanisms, though, are still to be fully elucidated. Whereas initial brain insult involves acute and irreversible primary damage to the brain, the processes of subsequent secondary brain injury progress gradually over months to years, providing a window of opportunity for therapeutic interventions. To date, extensive research has been focused on the identification of druggable targets involved in these processes. Despite several decades of successful pre-clinical studies and very promising results, when transferred to clinics, these drugs showed, at best, modest beneficial effects, but more often, an absence of effects or even very harsh side effects in TBI patients. This reality has highlighted the need for novel approaches that will be able to respond to the complexity of the TBI and tackle TBI pathological processes on multiple levels. Recent evidence strongly indicates that nutritional interventions may provide a unique opportunity to enhance the repair processes after TBI. Dietary (poly)phenols, a big class of compounds abundantly found in fruits and vegetables, have emerged in the past few years as promising agents to be used in TBI settings due to their proven pleiotropic effects. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by a state-of-the-art summary of the studies that have evaluated the efficacy of (poly)phenols administration to decrease TBI-associated damage in various animal TBI models and in a limited number of clinical trials. The current limitations on our knowledge concerning (poly)phenol effects in TBI in the pre-clinical studies are also discussed.This research was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement No 804229. iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is co-funded by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Ciência e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged (UIDB/04462/2020 and UIDP/04462/2020) as well LS4FUTURE Associated Laboratory (LA/P/0087/2020). The authors would like to acknowledge FCT for financial support: RC (PD/BD/135492/2018) DC (2020.04630.BD); IF (2022.00151.CEECIND).info:eu-repo/semantics/publishedVersio

Overview of beneficial effects of (Poly)phenol metabolites in the context of neurodegenerative diseases on model organisms

Funding Information: Funding: This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 804229. iNOVA4Health Research Unit (LISBOA—01–0145—FEDER—007344), which is cofunded by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Ciência e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged. Authors Aβ—Amyloid beta; CAT—catalase; NF–κB—Nuclear factor kappa–light–chain–enhancer of activated B cell; GSK— Glycogen synthase kinase; GSH—glutathione; APP—Amyloid precursor protein; ROS—Reactive Oxygen Species; TNF— Tumor necrosis factor; JNK—c–Jun N–terminal kinases; SOD—Superoxide Dismutase; Tg—transgenic; PPAR— Peroxisome proliferator–activated receptor alpha; LPS—lipopolysaccharide; MPTP—1—methyl–4—phenyl–1,2,3,6— tetrahydropyridine. 1 (Poly)phenol metabolites are named accordingly the recommendations recently published [32], however the name cited in the original publications where the effect is described is indicated in brackets. ↑—increased ↓— decreased. Funding Information: would like to acknowledge FCT for financial support of D.C (2020.04630.BD), R.M (CEEC/04567/CBIOS/2020) and S.F (UIDP/BD4/04567/2020). Funding Information: This work has received funding from the European Research Council (ERC) under the European Union?s Horizon 2020 research and innovation programme under grant agreement No 804229. iNOVA4Health Research Unit (LISBOA?01?0145?FEDER?007344), which is cofunded by Funda??o para a Ci?ncia e Tecnologia (FCT)/Minist?rio da Ci?ncia e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged. Authors would like to acknowledge FCT for financial support of D.C (2020.04630.BD), R.M (CEEC/04567/CBIOS/2020) and S.F (UIDP/BD4/04567/2020). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.The rise of neurodegenerative diseases in an aging population is an increasing problem of health, social and economic consequences. Epidemiological and intervention studies have demonstrated that diets rich in (poly)phenols can have potent health benefits on cognitive decline and neurodegenerative diseases. Meanwhile, the role of gut microbiota is ever more evident in modulating the catabolism of (poly)phenols to dozens of low molecular weight (poly)phenol metabolites that have been identified in plasma and urine. These metabolites can reach circulation in higher concentrations than parent (poly)phenols and persist for longer periods of time. However, studies addressing their potential brain effects are still lacking. In this review, we will discuss different model organisms that have been used to study how low molecular weight (poly)phenol metabolites affect neuronal related mechanisms gathering critical insight on their potential to tackle the major hallmarks of neurodegeneration.publishersversionpublishe

Automated detection of residual cells after sex-mismatched stem-cell transplantation – evidence for presence of disease-marker negative residual cells

<p>Abstract</p> <p>Background</p> <p>A new chimerism analysis based on automated interphase fluorescence in situ hybridization (FISH) evaluation was established to detect residual cells after allogene sex-mismatched bone marrow or blood stem-cell transplantation.</p> <p>Cells of 58 patients were characterized as disease-associated due to presence of a bcr/abl-gene-fusion or a trisomy 8 and/or a simultaneous hybridization of gonosome-specific centromeric probes. The automatic slide scanning platform Metafer with its module MetaCyte was used to analyse 3,000 cells per sample.</p> <p>Results</p> <p>Overall 454 assays of 58 patients were analyzed. 13 of 58 patients showed residual recipient cells at one stage of more than 4% and 12 of 58 showed residual recipient cells less than 4%, respectively. As to be expected, patients of the latter group were associated with a higher survival rate (48 vs. 34 month). In only two of seven patients with disease-marker positive residual cells between 0.1–1.3% a relapse was observed. Besides, disease-marker negative residual cells were found in two patients without relapse at a rate of 2.8% and 3.3%, respectively.</p> <p>Conclusion</p> <p>The definite origin and meaning of disease-marker negative residual cells is still unclear. Overall, with the presented automatic chimerism analysis of interphase FISH slides, a sensitive method for detection of disease-marker positive residual cells is on hand.</p

Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence

BACKGROUND: Defensins are important components of innate immunity to combat bacterial and viral infections, and can even elicit antitumor responses. Clusters of defensin (DEF) genes are located in a 2 Mb range of the human chromosome 8p23.1. This DEF locus, however, represents one of the regions in the euchromatic part of the final human genome sequence which contains segmental duplications, and recalcitrant gaps indicating high structural dynamics. RESULTS: We find that inter- and intraindividual genetic variations within this locus prevent a correct automatic assembly of the human reference genome (NCBI Build 34) which currently even contains misassemblies. Manual clone-by-clone alignment and gene annotation as well as repeat and SNP/haplotype analyses result in an alternative alignment significantly improving the DEF locus representation. Our assembly better reflects the experimentally verified variability of DEF gene and DEF cluster copy numbers. It contains an additional DEF cluster which we propose to reside between two already known clusters. Furthermore, manual annotation revealed a novel DEF gene and several pseudogenes expanding the hitherto known DEF repertoire. Analyses of BAC and working draft sequences of the chimpanzee indicates that its DEF region is also complex as in humans and DEF genes and a cluster are multiplied. Comparative analysis of human and chimpanzee DEF genes identified differences affecting the protein structure. Whether this might contribute to differences in disease susceptibility between man and ape remains to be solved. For the determination of individual DEF gene repertoires we provide a molecular approach based on DEF haplotypes. CONCLUSIONS: Complexity and variability seem to be essential genomic features of the human DEF locus at 8p23.1 and provides an ongoing challenge for the best possible representation in the human reference sequence. Dissection of paralogous sequence variations, duplicon SNPs ans multisite variations as well as haplotypes by sequencing based methods is the way for future studies of interindividual DEF locus variability and its disease association

Involvement of proteasome activation

Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by a progressive decline in a variety of cognitive and non-cognitive functions. The amyloid beta protein cascade hypothesis places the formation of amyloid beta protein aggregates on the first position in the complex pathological cascade leading to neurodegeneration, and therefore AD might be considered to be a protein-misfolding disease. The Ubiquitin Proteasome System (UPS), being the primary protein degradation mechanism with a fundamental role in the maintenance of proteostasis, has been identified as a putative therapeutic target to delay and/or to decelerate the progression of neurodegenerative disorders that are characterized by accumulated/aggregated proteins. The purpose of this study was to test if the activation of proteasome in vivo can alleviate AD pathology. Specifically by using two compounds with complementary modes of proteasome activation and documented antioxidant and redox regulating properties in the 5xFAD transgenic mice model of AD, we ameliorated a number of AD related deficits. Shortly after proteasome activation we detected significantly reduced amyloid-beta load correlated with improved motor functions, reduced anxiety and frailty level. Essentially, to our knowledge this is the first report to demonstrate a dual activation of the proteasome and its downstream effects. In conclusion, these findings open up new directions for future therapeutic potential of proteasome-mediated proteolysis enhancement.publishersversionpublishe

Sexual unfaithfulness can be judged with some accuracy from men's but not women's faces

Peer reviewedPublisher PD

Hemijski sastav jetri i bubrega svinja pet čistih rasa odgajanih u Vojvodini

In this paper the content of moisture, protein, total fat and total ash in the M. semimembranosus (SM) and M. longissimus thoracis et lumborum (LTL) from five purebred pigs: Large White (n=118), Landrace (n=116), Duroc (n=112), Hampshire (n=112) and Pietrain (n=121), reared in Vojvodina was determined. Components of proximate composition were determined by ISO methods. Overall, the average content (g/100g) of moisture, protein, total fat and total ash in all the SM and LTL (n=1158) was: 75.68, 21.73, 1.36 and 1.14, respectively. The Vojvodian pork showed same moisture, protein, total fat and total ash content compared with the values found in other countries.U ovom radu utvrđen je sadržaj vlage, proteina, ukupne masti i ukupnog pepela u jetrama i bubrezima svinja pet čistih rasa: Velika Bela (n=118), Landras (n=116), Durok (n=112), Hempšir (n=112) i Pietren (n=121), odgajanih u Vojvodini. Osnovni hemijski sastav određen je ISO metodama. Rasa svinja ne utiče značajno (P>0.05), dok vrsta iznutrice utiče značajno (P<0.05; P<0.001) na sadržaj vlage, proteina, ukupne masti i ukupnog pepela. Prosečan sadržaj (g/100g) vlage, proteina, ukupne masti i ukupnog pepela u svim ispitanim jetrama (n=579) je bio: 71.05, 21.34, 3.24 i 1.48, dok je u svim ispitanim bubrezima (n=579) bio: 79.43, 16.16, 3.13 i 1.20, respektivno