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Mutations in superoxide dismutase 1 (SOD1) account for ~ 10% of familial amyotrophic lateral sclerosis (fALS) cases. Most SOD1 ALS cases show a 2–5 year clinical course, but a subset of patients exhibit a slowly progressing illness lasting 10–20 years. Substantial evidence indicates that disease-causing mutations in SOD1 promote misfolding and aggregation. Spinal tissue homogenates from paralyzed transgenic mice containing misfolded mutant SOD1 accelerate paralysis when injected into the spine or sciatic nerve of young mutant SOD1 transgenic mice. Using this prion-like seeding model in G85R-SOD1:YFP transgenic mice to initiate the disease process, we show that human SOD1 variants associated with rapidly progressing ALS produce SOD1-ALS strains that cause paralysis earlier than mutations associated with slowly progressing disease. Our findings suggest that the heterogeneous clinical presentations of different SOD1 mutations in ALS could be linked to prion-like strain attributes that govern the templating and propagation kinetics of misfolded SOD1.

Long-term fish oil (FO) supplementation is able to improve Alzheimer’s disease (AD) pathology. We aimed to determine the impact of short-term fish oil (FO) intake on phospholipids composition and plaque pathology in 5xFAD mice, a widely used animal model of AD. A 3-week-long FO supplementation administered at 3 months of age decreased the number of dense core plaques in the 5xFAD cortex and changed phospholipids in the livers and brains of wild-type (Wt) and 5xFAD mice. Livers of both genotypes responded by increase of n-3 and reciprocal decrease of n-6 fatty acids. In Wt brains, FO supplementation induced elevation of n-3 fatty acids and subsequent enhancement of n-6/n-3 ratio. However, in 5xFAD brains the improved n-6/n-3 ratio was mainly due to FO-induced decrease in arachidonic and adrenic n-6 fatty acids. Also, brain and liver abundance of n-3 fatty acids were strongly correlated in Wts, oppositely to 5xFADs where significant brain-liver correlation exists only for n-6 fatty acids. Expression of omega-3 transporter Mfs2a remained unchanged after FO supplementation. We have demonstrated that even a short-term FO intake improves the phospholipid composition and has a significant effect on plaque burden in 5xFAD brains when applied in early stages of AD pathology.

Linking biochemistry and genetics of tolerance to osmotic stress is of interest for understanding plant adaptations to unfavorable conditions. The aims of this study were to investigate the variability in responses of panel of elite maize inbred lines to water withholding for stress-related traits through association study and to identify pathways linked to detected associations for better understanding of maize stress responses. Densely genotyped public and expired Plant Variety Protection Certificate (ex-PVP) inbred lines were planted in controlled conditions (16-h/8-h day/night, 25°C, 50% RH) in control (CO) and exposed to 10-day water withholding (WW). Traits analyzed were guaiacol peroxidase activity (GPOD), total protein content (PROT), lipid peroxidation (TBARS), hydrogen peroxide accumulation (H 2 O 2 ), proline accumulation (proline), and current water content (CWC). Proline accumulation was found to be influenced by H 2 O 2 and TBARS signaling pathways acting as an accumulation-switching mechanism. Most of the associations detected were for proline (29.4%) and TBARS (44.1%). Gene ontology (GO) enrichment analysis showed significant enrichment in regulation of integral membrane parts and peroxisomes along with regulation of transcription and polysaccharide catabolism. Dynamic studies involving inbreds with extreme phenotypes are needed to elucidate the role of this signaling mechanism in regulation of response to water deficit.

Bacillus anthracis is a well-known zoonotic pathogen that can cause disease in both animals and humans. Moreover, it has a high bioterrorism potential as its lethal spores are resistant to inactivation, are easy to produce in large quantities, and are easily spread over large areas. Anthrax cases occur in different parts of the world, including most European countries. Specific areas of Croatia are long known as anthrax districts, but with sporadically reported cases over the years. Here, we present a major outbreak of animal and human anthrax in the region of Lonjsko Polje in Croatia, a region not known to have anthrax cases in the past. The outbreak started in July 2022 and lasted several months, but most human and animal cases were reported in the first month. During the outbreak, there were 17 reported human cases of cutaneous anthrax and 29 laboratory-confirmed animal cases. However, due to issues in reporting in animals and the late finding of the carcasses, which made laboratory diagnostics challenging, the actual number of animal cases was probably significantly higher.

Dietary restriction (DR) exerts significant beneficial effects in terms of aging and age-related diseases in many organisms including humans. The present study aimed to examine the influence of long-term DR on the BDNF system at the transcriptional and translational levels in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month-old) male Wistar rats. The obtained results revealed that the DR upregulated the expression of exon-specific BDNF transcripts in both regions, followed by elevated levels of mBDNF only in the cortex in middle-aged animals. In aged animals, DR modulated BDNF protein levels by increasing proBDNF and by declining mBDNF levels. Additionally, elevated levels of the full-length TrkB accompanied by a decreased level of the less-glycosylated TrkB protein were observed in middle-aged rats following DR, while in aged rats, DR amplified only the expression of the less-glycosylated form of TrkB. The levels of phosphorylated TrkB Y816 were stable during aging regardless of feeding. Reduced levels of p75 NTR were detected in both regions of middle-aged DR-fed animals, while a significant increase was measured in the cortex of aged DR-fed rats. These findings shed additional light on DR as a modulator of BDNF system revealing its disparate effects in middle-aged and aged animals. Given the importance of the proBDNF/BDNF circuit-level expression in different brain functions and various aspects of behavior, it is necessary to further elucidate the optimal duration of the applied dietary regimen with regard to the animal age in order to achieve its most favorable effects.

One of the complications aneurysms subarachnoid hemorrhage is the development of vasospasm, which is the leading cause of disability and death from ruptured cerebral aneurysm. To evaluate the significance of previous comorbidities on early outcome of patients with subarachnoid hemorrhage caused by rupture of a cerebral aneurysm in the prevention of vasospasm. The study had prospective character in which included 50 patients, whose diagnosed with SAH caused by the rupture of a brain aneurysm in the period from 2011to 2013. Two groups of patients were formed. Group I: patients in addition to the standard initial treatment and \"3H therapy\" administered nimodipine at a dose of 15-30 mg / kg bw / h (3-10 ml) for the duration of the initial treatment. Group II: patients in addition to the standard initial treatment and \"3H therapy\" administered with MgSO4 at a dose of 12 grams in 500 ml of 0.9% NaCl / 24 h during the initial treatment. Two-thirds of the patients (68%) from both groups had a good outcome measured with values according to GOS scales, GOS IV and V. The poorer outcome, GOS III had 20% patients, the GOS II was at 2% and GOS I within 10% of patients. If we analyze the impact of comorbidity on the outcome, it shows that there is a significant relationship between the presence of comorbidity and outcomes. The patients without comorbidity (83.30%) had a good outcome (GOS IV and V), the same outcome was observed (59.4%) with comorbidities, which has a statistically significant difference (p = 0.04). Patients without diabetes (32%) had a good outcome (GOS IV and V), while the percentage of patients with diabetes less frequent (2%) with a good outcome, a statistically significant difference (p = 0.009). The outcome of treatment 30 days after the subarachnoid hemorrhage analyzed values WFNS and GOS, is not dependent on the method of prevention and treatment of vasospasm. Most concomitant diseases in patients with SAH which, requiring additional treatment measures are arterial hypertension and diabetes mellitus. The best predictors in the initial treatment of patients with subarachnoid hemorrhage caused by rupture of a cerebral aneurysm has the presence of comorbidity, which has statistical significance.