GABAergic Synapse Properties May Explain Genetic Variation in Hippocampal Network Oscillations in Mice

Cognitive ability and the properties of brain oscillation are highly heritable in humans. Genetic variation underlying oscillatory activity might give rise to differences in cognition and behavior. How genetic diversity translates into altered properties of oscillations and synchronization of neuronal activity is unknown. To address this issue, we investigated cellular and synaptic mechanisms of hippocampal fast network oscillations in eight genetically distinct inbred mouse strains. The frequency of carbachol-induced oscillations differed substantially between mouse strains. Since GABAergic inhibition sets oscillation frequency, we studied the properties of inhibitory synaptic inputs (IPSCs) received by CA3 and CA1 pyramidal cells of three mouse strains that showed the highest, lowest and intermediate frequencies of oscillations. In CA3 pyramidal cells, the frequency of rhythmic IPSC input showed the same strain differences as the frequency of field oscillations. Furthermore, IPSC decay times in both CA1 and CA3 pyramidal cells were faster in mouse strains with higher oscillation frequencies than in mouse strains with lower oscillation frequency, suggesting that differences in GABAA-receptor subunit composition exist between these strains. Indeed, gene expression of GABAA-receptor β2 (Gabrb2) and β3 (Gabrb2) subunits was higher in mouse strains with faster decay kinetics compared with mouse strains with slower decay kinetics. Hippocampal pyramidal neurons in mouse strains with higher oscillation frequencies and faster decay kinetics fired action potential at higher frequencies. These data indicate that differences in genetic background may result in different GABAA-receptor subunit expression, which affects the rhythm of pyramidal neuron firing and fast network activity through GABA synapse kinetics

Формування індивідуального стилю у творчості народних майстрів художньої обробки дерева (на прикладі різьбярських династій Шкрібляків та Корпанюків)

У статті розглянуто творчість видатних різьбярських династій Шкрібляків та Корпанюків з позиції формування власного стилю в кожного з майстрів та їхнього впливу на зародження Косівської школи художньої обробки дерева. Особливу увагу приділено тим технічним і технологічним новаціям, які застосовували у своїх творах різьбярі, та тим композиційним прийомам, які вирізняли їхні вироби з-поміж інших.В статье рассматривается творчество выдающихся династий резчиков Шкрибляков и Корпанюков с точки зрения формирования собственного стиля у каждого из мастеров и их влияния на зарождение Косовской школы художественной обработки дерева. Особое внимание уделяется тем техническим и технологическим новациям, которые использовали резчики в своих произведениях, и композиционным приёмам, выделяющим их изделия среди прочих.There is an observation of creative work of the illustrious Shkribliak and K orpaniuk houses of carvers from a position of formation of a master’s individual style and proceeding from each master’s impact on the K osiv artistic carving school’s origin. The author pays a specific attention to the technical and technological innovations which are put into practice by a carver as well as to the composition wethods which differ carver’s wares from the rest

Laboratory tests in uveitis - New developments in the analysis of local antibody production

Analysis of local intraocular antibody production is a valuable tool with which to confirm a suspected clinical diagnosis in uveitis. We have analysed paired serum and aqueous samples for the presence of specific antibodies against toxoplasma, cytomegalovirus, herpes simplex virus and varicella zoster virus. Of the patients retrospectively diagnosed as having toxoplasma chorioretinitis 75% had a positive antibody coefficient indicating specific antibody production in the eye. Local antibody production in the eye directed against CMV confirmed the suspected diagnosis of CMV retinitis in 50% of the AIDS patients investigated. So far we have not been able to demonstrate local antibody production against herpes simplex virus (26 samples tested). Two of three patients with acute retinal necrosis had a positive antibody coefficient against varicella zoster virus. Both of these patients had an even higher titer in the aqueous than in serum. Since the choice of therapy, in infectious uveitis, depends on the causative organisms, it is very important to confirm a suspected clinical diagnosis by means of aqueous humor analysi

The hibernation-derived compound SUL-138 shifts the mitochondrial proteome towards fatty acid metabolism and prevents cognitive decline and amyloid plaque formation in an Alzheimer’s disease mouse model

Background: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide and remains without effective cure. Increasing evidence is supporting the mitochondrial cascade hypothesis, proposing that loss of mitochondrial fitness and subsequent ROS and ATP imbalance are important contributors to AD pathophysiology. Methods: Here, we tested the effects of SUL-138, a small hibernation-derived molecule that supports mitochondrial bioenergetics via complex I/IV activation, on molecular, physiological, behavioral, and pathological outcomes in APP/PS1 and wildtype mice. Results: SUL-138 treatment rescued long-term potentiation and hippocampal memory impairments and decreased beta-amyloid plaque load in APP/PS1 mice. This was paralleled by a partial rescue of dysregulated protein expression in APP/PS1 mice as assessed by mass spectrometry-based proteomics. In-depth analysis of protein expression revealed a prominent effect of SUL-138 in APP/PS1 mice on mitochondrial protein expression. SUL-138 increased the levels of proteins involved in fatty acid metabolism in both wildtype and APP/PS1 mice. Additionally, in APP/PS1 mice only, SUL-138 increased the levels of proteins involved in glycolysis and amino acid metabolism pathways, indicating that SUL-138 rescues mitochondrial impairments that are typically observed in AD. Conclusion: Our study demonstrates a SUL-138-induced shift in metabolic input towards the electron transport chain in synaptic mitochondria, coinciding with increased synaptic plasticity and memory. In conclusion, targeting mitochondrial bioenergetics might provide a promising new way to treat cognitive impairments in AD and reduce disease progression

C<i>ampylobacter pinnipediorum</i> sp. nov., isolated from pinnipeds, comprising <i>Campylobacter pinnipediorum</i> subsp. <i>pinnipediorum</i> subsp. nov. and <i>Campylobacter pinnipediorum</i> subsp. <i>caledonicus</i> subsp. nov.

During independent diagnostic screenings of otariid seals in California (USA) and phocid seals in Scotland (UK), Campylobacter-like isolates, which differed from the established taxa of the genus Campylobacter, were cultured from abscesses and internal organs of different seal species. A polyphasic study was undertaken to determine the taxonomic position of these six isolates. The isolates were characterized by 16S rRNA gene and AtpA sequence analysis and by conventional phenotypic testing. The whole-genome sequences were determined for all isolates, and the average nucleotide identity (ANI) was determined. The isolates formed a separate phylogenetic clade, divergent from all other taxa of the genus Campylobacter and most closely related to Campylobactermucosalis. Although all isolates showed 100 % 16S rRNA gene sequence homology, AtpA and ANI analyses indicated divergence between the otariid isolates from California and the phocid isolates from Scotland, which warrants subspecies status for each clade. The two subspecies could also be distinguished phenotypically on the basis of catalase activity. This study shows clearly that the isolates obtained from pinnipeds represent a novel species within the genus Campylobacter, for which the name Campylobacter pinnipediorum sp. nov. is proposed. Within this novel species, the Californian isolates represent a separate subspecies, for which the name C. pinnipediorum subsp. pinnipediorum subsp. nov. is proposed. The type strain for both this novel species and subspecies is RM17260T (=LMG 29472T=CCUG 69570T). The Scottish isolates represent another subspecies, for which the name C. pinnipediorum subsp. caledonicus subsp. nov. is proposed. The type strain of this subspecies is M302/10/6T (=LMG 29473T=CCUG 68650T)

Within-Household Transmission and Bacterial Diversity of Staphylococcus pseudintermedius.

Staphylococcus pseudintermedius can be transmitted between dogs and their owners and can cause opportunistic infections in humans. Whole genome sequencing was applied to identify the relatedness between isolates from human infections and isolates from dogs in the same households. Genome SNP diversity and distribution of plasmids and antimicrobial resistance genes identified related and unrelated isolates in both households. Our study shows that within-host bacterial diversity is present in S. pseudintermedius, demonstrating that multiple isolates from each host should preferably be sequenced to study transmission dynamics

Identification of LukPQ, a novel, equid-adapted leukocidin of Staphylococcus aureus.

Bicomponent pore-forming leukocidins are a family of potent toxins secreted by Staphylococcus aureus, which target white blood cells preferentially and consist of an S- and an F-component. The S-component recognizes a receptor on the host cell, enabling high-affinity binding to the cell surface, after which the toxins form a pore that penetrates the cell lipid bilayer. Until now, six different leukocidins have been described, some of which are host and cell specific. Here, we identify and characterise a novel S. aureus leukocidin; LukPQ. LukPQ is encoded on a 45 kb prophage (ΦSaeq1) found in six different clonal lineages, almost exclusively in strains cultured from equids. We show that LukPQ is a potent and specific killer of equine neutrophils and identify equine-CXCRA and CXCR2 as its target receptors. Although the S-component (LukP) is highly similar to the S-component of LukED, the species specificity of LukPQ and LukED differs. By forming non-canonical toxin pairs, we identify that the F-component contributes to the observed host tropism of LukPQ, thereby challenging the current paradigm that leukocidin specificity is driven solely by the S-component

Whole genome-based phylogeny of reptile-associated Helicobacter indicates independent niche adaptation followed by diversification in a poikilothermic host

Reptiles have been shown to host a significant Helicobacter diversity. In order to survive, reptile-associated Helicobacter lineages need to be adapted to the thermally dynamic environment encountered in a poikilothermic host. The whole genomes of reptile-associated Helicobacter lineages can provide insights in Helicobacter host adaptation and coevolution. These aspects were explored by comparing the genomes of reptile-, bird-, and mammal-associated Helicobacter lineages. Based on average nucleotide identity, all reptile-associated Helicobacter lineages in this study could be considered distinct species. A whole genome-based phylogeny showed two distinct clades, one associated with chelonians and one associated with lizards. The phylogeny indicates initial adaptation to an anatomical niche, which is followed by an ancient host jump and subsequent diversification. Furthermore, the ability to grow at low temperatures, which might reflect thermal adaptation to a reptilian host, originated at least twice in Helicobacter evolution. A putative tricarballylate catabolism locus was specifically present in Campylobacter and Helicobacter isolates from reptiles. The phylogeny of reptile-associated Helicobacter parallels host association, indicating a high level of host specificity. The high diversity and deep branching within these clades supports long-term coevolution with, and extensive radiation within the respective reptilian host type.</p

Extended-Spectrum Beta-Lactamase and AmpC-producing Enterobacteriaceae in household dogs : a longitudinal study

A longitudinal study was performed (i) to investigate continuity of shedding of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae in dogs without clinical signs, (ii) to identify dominant plasmid-mediated ESBL genes and (iii) to quantify ESBL-producing Enterobacteriaceae in feces. Fecal samples of 38 dogs were collected monthly for 6 months. From 7 included dogs, additional samples were collected on a weekly basis for 6 weeks. CFU/g feces were determined for non-wild-type Enterobacteriaceae on MacConkey agar supplemented with 1 mg/L cefotaxime (MCC) and total number of Enterobacteriaceae on MacConkey agar. Cefotaxime-resistant isolates were screened by PCR and sequence analysis for presence of blaCTX-M, blaCMY, blaSHV, blaOXA and blaTEM gene families. Bacterial species were identified by MALDI-TOF MS analysis. PCR-negative isolates were tested by double disk synergy test for enhanced AmpC expression. 259 samples were screened, 126 samples were culture-positive on MCC, resulting in 352 isolates of which 327 isolates were Escherichia coli. Nine dogs were continuously positive during this study and 6 dogs were continuously negative. Monthly or weekly shifts in fecal shedding were observed in 23 dogs. Genotyping showed high variety of ESBL genes and gene combinations at single and multiple consecutive sampling moments. ESBL genes blaCTX-M-1, blaCTX-M-14, blaCTX-M-15, blaSHV-12 and blaCMY-2 were most frequently found. Mean cfu of non-wild-type Enterobacteriaceae was 6.11×10(8) cfu/g feces. This study showed an abundance of ESBL-producing Enterobacteriaceae in dogs in the Netherlands, mostly in high concentrations. Fecal shedding showed to be highly dynamic over time which is important to consider when studying ESBL epidemiology