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Nitric oxide is necessary for labilization of a consolidated context memory during reconsolidation in terrestrial snails

© 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. Nitric oxide (NO) is known to be involved in associative memory formation. We investigated the influence of blocking NO function on the reconsolidation of context memory in terrestrial snails (Helix lucorum L.). After a 10 day session of electric shocks in one context only, context memory in snails was observed in test sessions as the significant difference of amplitudes of withdrawal responses to tactile stimuli in two different contexts. After a 1 day rest, a session of 'reminding' was performed, preceded by injection in different groups of the snails with either vehicle or combination of the protein synthesis blocker anisomycin (ANI) with one of the following drugs: the NO scavenger carboxy-PTIO, the NO-synthase inhibitors N-omega-nitro-L-arginin, nitroindazole and NG-nitro-L-arginine methyl ester hydrochloride, or the NO donor S-nitroso-N-acetyl-DL-penicillamine. Testing the context memory at different time intervals after the reminder under ANI injection showed that the context memory was impaired at 24 h and later, whereas the reminder under combined injection of ANI and each of the NO-synthase inhibitors used or the NO scavenger showed no impairment of long-term context memory. Injection of the NO donor S-nitroso-N-acetyl-DL-penicillamine with or without reminder had no effect on context memory. The results obtained demonstrated that NO is necessary for labilization of a consolidated context memory. After a 10-day session of electric shocks in one context only, context memory in snails was observed in test sessions as the significant difference of amplitudes of withdrawal responses to tactile stimuli in two different contexts.A session of 'reminding', preceded by injection either with vehicle, or combination of a protein synthesis blocker anisomycin (ANI) with one of the NO-synthase inhibitors has shown that the context memory was impaired, while the reminder under combined injection of ANI and each of the NO-synthase inhibitors used or the NO scavenger showed no impairment of long-term context memory. Obtained results demonstrate that NO is necessary for labilization of a consolidated context memory

Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring

Abstract Background Engineered nanoparticles are smaller than 100 nm and designed to improve or creating even new physico-chemical properties. Consequently, toxicological properties of materials may change as size reaches the nm size-range. We examined outcomes related to the central nervous system in the offspring following maternal inhalation exposure to nanosized carbon black particles (Printex 90). Methods Time-mated mice (NMRI) were exposed by inhalation, for 45 min/day to 0, 4.6 or 37 mg/m3 aerosolized carbon black on gestation days 4–18, i.e. for a total of 15 days. Outcomes included maternal lung inflammation (differential cell count in bronchoalveolar lavage fluid and Saa3 mRNA expression in lung tissue), offspring neurohistopathology and behaviour in the open field test. Results Carbon black exposure did not cause lung inflammation in the exposed females, measured 11 or 28–29 days post-exposure. Glial fibrillary acidic protein (GFAP) expression levels were dose-dependently increased in astrocytes around blood vessels in the cerebral cortex and hippocampus in six weeks old offspring, indicative of reactive astrogliosis. Also enlarged lysosomal granules were observed in brain perivascular macrophages (PVMs) in the prenatally exposed offspring. The number of parvalbumin-positive interneurons and the expression levels of parvalbumin were decreased in the motor and prefrontal cortices at weaning and 120 days of age in the prenatally exposed offspring. In the open field test, behaviour was dose-dependently altered following maternal exposure to Printex 90, at 90 days of age. Prenatally exposed female offspring moved a longer total distance, and especially males spent significantly longer time in the central zone of the maze. In the offspring, the described effects were long-lasting as they were present at all time points investigated. Conclusion The present study reports for the first time that maternal inhalation exposure to Printex 90 carbon black induced dose-dependent denaturation of PVM and reactive astrocytes, similarly to the findings observed following maternal exposure to Printex 90 by airway instillation. Of note, some of the observed effects have striking similarities with those observed in mouse models of neurodevelopmental disorders

Identification of Novel High-Frequency DNA Methylation Changes in Breast Cancer

Recent data have revealed that epigenetic alterations, including DNA methylation and chromatin structure changes, are among the earliest molecular abnormalities to occur during tumorigenesis. The inherent thermodynamic stability of cytosine methylation and the apparent high specificity of the alterations for disease may accelerate the development of powerful molecular diagnostics for cancer. We report a genome-wide analysis of DNA methylation alterations in breast cancer. The approach efficiently identified a large collection of novel differentially DNA methylated loci (∼200), a subset of which was independently validated across a panel of over 230 clinical samples. The differential cytosine methylation events were independent of patient age, tumor stage, estrogen receptor status or family history of breast cancer. The power of the global approach for discovery is underscored by the identification of a single differentially methylated locus, associated with the GHSR gene, capable of distinguishing infiltrating ductal breast carcinoma from normal and benign breast tissues with a sensitivity and specificity of 90% and 96%, respectively. Notably, the frequency of these molecular abnormalities in breast tumors substantially exceeds the frequency of any other single genetic or epigenetic change reported to date. The discovery of over 50 novel DNA methylation-based biomarkers of breast cancer may provide new routes for development of DNA methylation-based diagnostics and prognostics, as well as reveal epigenetically regulated mechanism involved in breast tumorigenesis

Unusual congenital polydactyly in mini-pigs from the breeding group of the Institute of Cytology and Genetics (Novosibirsk, Russia)

The article describes a new phenomenon in the breeding group of mini-pigs at the Institute of Cytology and Genetics (ICG, Novosibirsk): polydactyly (extra digits), which is unusual because the additional digits are situated at the lateral surface of legs or at the lateral and medial ones. This anomaly was first found here in 2017 in adult animals intended for culling due to incorrect positioning of the legs caused by flexor tendon laxity and resulting in weight-bearing on the palmar surface of the proximal phalanges (“bear’s paw”). Therefore, the polydactyly of mini-pigs has a pronounced negative selection effect. A visual survey of the livestock was conducted, and a description of the detected anomaly was compiled. The polydactyly in mini-pigs is a stand-alone trait and is not part of any syndromes. Individuals with polydactyly may have extra digits either on pectoral or on pectoral and pelvic limbs. On thoracic limbs, there may be either one lateral digit or a lateral digit and a medially located rudimentary hooflet. On pelvic limbs, only lateral extra digits can occur. Anatomical and morphological analyses showed that the lateral extra digit is an anatomically complete (“mature”) structure, whereas the medial rudimentary digit consists of only a hooflet without other structures characteristic of normal digits. Cytological examination revealed no specific karyotypic features, except for Robertsonian translocation Rb 16;17 previously reported for the mini-pigs of the same livestock. Cytological findings indicated that the polydactyly and Robertsonian translocation are not linked genetically. Genealogical analysis and results of crosses are consistent with a working hypothesis of recessive inheritance of the trait. Overall, the study shows that this type of polydactyly is anatomically and morphologically unique and not typical of Sus scrofa. In this species, only polydactyly types with medial accessory toes have been described and are usually inherited as a dominant trait with incomplete penetrance. In our case, the results of test crosses indicate recessive inheritance of the trait with varying expression and incomplete penetrance, because of which poorly expressed phenotypes are not visually detectable

Systems-wide analysis of manganese deficiency-induced changes in gene activity of Arabidopsis roots

Manganese (Mn) is pivotal for plant growth and development, but little information is available regarding the strategies that evolved to improve Mn acquisition and cellular homeostasis of Mn. Using an integrated RNA-based transcriptomic and high-throughput shotgun proteomics approach, we generated a comprehensive inventory of transcripts and proteins that showed altered abundance in response to Mn deficiency in roots of the model plant Arabidopsis. A suite of 22,385 transcripts was consistently detected in three RNA-seq runs; LC-MS/MS-based iTRAQ proteomics allowed the unambiguous determination of 11,606 proteins. While high concordance between mRNA and protein expression (R = 0.87) was observed for transcript/protein pairs in which both gene products accumulated differentially upon Mn deficiency, only approximately 10% of the total alterations in the abundance of proteins could be attributed to transcription, indicating a large impact of protein-level regulation. Differentially expressed genes spanned a wide range of biological functions, including the maturation, translation, and transport of mRNAs, as well as primary and secondary metabolic processes. Metabolic analysis by UPLC-qTOF-MS revealed that the steady-state levels of several major glucosinolates were significantly altered upon Mn deficiency in both roots and leaves, possibly as a compensation for increased pathogen susceptibility under conditions of Mn deficiency

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Dissecting selective signatures and candidate genes in grandparent lines subject to high selection pressure for broiler production and in a local Russian chicken breed of Ushanka

Breeding improvements and quantitative trait genetics are essential to the advancement of broiler production. The impact of artificial selection on genomic architecture and the genetic markers sought remains a key area of research. Here, we used whole-genome resequencing data to analyze the genomic architecture, diversity, and selective sweeps in Cornish White (CRW) and Plymouth Rock White (PRW) transboundary breeds selected for meat production and, comparatively, in an aboriginal Russian breed of Ushanka (USH). Reads were aligned to the reference genome bGalGal1.mat.broiler.GRCg7b and filtered to remove PCR duplicates and low-quality reads using BWA-MEM2 and bcftools software; 12,563,892 SNPs were produced for subsequent analyses. Compared to CRW and PRW, USH had a lower diversity and a higher genetic distinctiveness. Selective sweep regions and corresponding candidate genes were examined based on ZFST, hapFLK, and ROH assessment procedures. Twenty-seven prioritized chicken genes and the functional projection from human homologs suggest their importance for selection signals in the studied breeds. These genes have a functional relationship with such trait categories as body weight, muscles, fat metabolism and deposition, reproduction, etc., mainly aligned with the QTLs in the sweep regions. This information is pivotal for further executing genomic selection to enhance phenotypic traits