Influence of Natural Asymmetric Embryonic Visual Afferentation on the Neuronal Activations in the Caudomedial Mesopallium during the Freezing Response in Altricial Nestlings.

The study was designed to investigate the role of asymmetric prenatal visual stimulation on the activation of caudomedial mesopallium (CMM) neurons in nine-day-old pied flycatcher nestlings during auditory-guided freezing. Four groups of nestlings were studied: groups 1 and 2 included nestlings with normal vision and visually deprived, respectively, that were incubated and hatched in normal light environment; groups 3 and 4, nestlings with normal vision and visually deprived, respectively, that were incubated and hatched in the dark. The eyes of visually deprived nestlings were covered with non-transparent cups 2 h before the experiment. C-Fos expression was studied. It was shown that densities of neurons activated during freezing response differed in right vs. left CMM only in the group of visually deprived nestlings incubated under light. This suggests that the presence or absence of the asymmetric embryonic visual afferentation may result in the development of different strategies of the visual system integration into defense behavior.

[Intussusception followed by intestinal obstruction in adults]. / Invaginatsionnaia kishechnaia neprokhodimost' u vzroslykh.

AIM: To evaluate the effectiveness of complex preoperative diagnostics and medication of intussusception followed by intestinal obstruction in adults with the choice of surgical repair and analysis of the outcomes depending on the causes of intussusception. MATERIAL AND METHODS: 15 intussusception patients aged 19 - 86 years were enrolled. Mean age was 52.7 years. Patients were hospitalized within 12 hours - 1-2 weeks after onset of the disease. Diagnosis was established on the basis of complaints, anamnesis, objective and additional survey. All patients underwent abdominal X-ray and ultrasound. Intestinal obstruction at admission was diagnosed in all patients, and only 1 (6.7%) of them had intussusception. RESULTS: Medication and additional survey contributed to detection of intussusception followed by intestinal obstruction in 13 (86.7%) out of 15 patients prior to surgery. All patients underwent urgent or delayed surgery. Small intestine resection was performed in 9 patients, 2 patients underwent resection of small intestine with submucosal tumor (1) and Meckel's diverticulum (1) after intussusception repair. Right-sided hemicolectomy was performed in 3 patients, sigmoid colon resection with lymph nodes dissection - in 1 patient. The cause of intussusception followed by intestinal obstruction were epithelial and stromal tumors (9), less often metastasis of melanoma (2), Meckel's diverticulum (1) and functional bowel disorders (1). Postoperative complications arose in high risk patients hospitalized after 24 hours from onset of the disease and present concomitant diseases and malignancies. 1 (6,7%) patient died.

Base changes in tumour DNA have the power to reveal the causes and evolution of cancer.

Next-generation sequencing (NGS) technology has demonstrated that the cancer genomes are peppered with mutations. Although most somatic tumour mutations are unlikely to have any role in the cancer process per se, the spectra of DNA sequence changes in tumour mutation catalogues have the potential to identify the mutagens, and to reveal the mutagenic processes responsible for human cancer. Very recently, a novel approach for data mining of the vast compilations of tumour NGS data succeeded in separating and precisely defining at least 30 distinct patterns of sequence change hidden in mutation databases. At least half of these mutational signatures can be readily assigned to known human carcinogenic exposures or endogenous mechanisms of mutagenesis. A quantum leap in our knowledge of mutagenesis in human cancers has resulted, stimulating a flurry of research activity. We trace here the major findings leading first to the hypothesis that carcinogenic insults leave characteristic imprints on the DNA sequence of tumours, and culminating in empirical evidence from NGS data that well-defined carcinogen mutational signatures are indeed present in tumour genomic DNA from a variety of cancer types. The notion that tumour DNAs can divulge environmental sources of mutation is now a well-accepted fact. This approach to cancer aetiology has also incriminated various endogenous, enzyme-driven processes that increase the somatic mutation load in sporadic cancers. The tasks now confronting the field of molecular epidemiology are to assign mutagenic processes to orphan and newly discovered tumour mutation patterns, and to determine whether avoidable cancer risk factors influence signatures produced by endogenous enzymatic mechanisms. Innovative research with experimental models and exploitation of the geographical heterogeneity in cancer incidence can address these challenges.

[Wulst Activation in Pied Flycatcher Nestlings in Feeding Behavior Induced by Patterned Visual Stimulus].

Immunohistochemical detection of c-Fos was used to study the transcriptional activation in two higher visual centers (Wulst area and Entopallium) of 12-day-old pied flycatcher (Ficedula hypoleuca) during the realization of feeding behavior guided by patterned visual stimulus, simulating the species-specific one. Activation was compared in 4 groups of nestlings. Control group was not subjected to any experimental influence. In binocular, right-field (deprivation of the left eye) and left-filed (deprivation of the right eye) groups the vision feeding responses were provoked, reinforced and evaluated. It was shown that the visual afferentation from the right eye was more significant for the organization of early feeding behavior guided by a moving patterned visual stimulus as compared with the afferentation from the left eye. Feeding behavior induced activation of c-Fos expression only in neurons of the higher center of thalamofugal system--Wulst area. The comparison of transcriptional activation in different groups revealed the significant increase of c-Fos induction related with feeding behavior only in the left hemisphere and only in binocular and right-field groups.

SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair.

Defining mechanisms that generate intratumour heterogeneity and branched evolution may inspire novel therapeutic approaches to limit tumour diversity and adaptation. SETD2 (Su(var), Enhancer of zeste, Trithorax-domain containing 2) trimethylates histone-3 lysine-36 (H3K36me3) at sites of active transcription and is mutated in diverse tumour types, including clear cell renal carcinomas (ccRCCs). Distinct SETD2 mutations have been identified in spatially separated regions in ccRCC, indicative of intratumour heterogeneity. In this study, we have addressed the consequences of SETD2 loss-of-function through an integrated bioinformatics and functional genomics approach. We find that bi-allelic SETD2 aberrations are not associated with microsatellite instability in ccRCC. SETD2 depletion in ccRCC cells revealed aberrant and reduced nucleosome compaction and chromatin association of the key replication proteins minichromosome maintenance complex component (MCM7) and DNA polymerase δ hindering replication fork progression, and failure to load lens epithelium-derived growth factor and the Rad51 homologous recombination repair factor at DNA breaks. Consistent with these data, we observe chromosomal breakpoint locations are biased away from H3K36me3 sites in SETD2 wild-type ccRCCs relative to tumours with bi-allelic SETD2 aberrations and that H3K36me3-negative ccRCCs display elevated DNA damage in vivo. These data suggest a role for SETD2 in maintaining genome integrity through nucleosome stabilization, suppression of replication stress and the coordination of DNA repair.

Involvement of Wulst neurons in hiding reaction of pied flycatcher nestlings with different visual afferentation.

We studied transcriptional activity in the higher avian center visual system (Wulst area) in acoustically guided defensive behavior in visually deprived and non-deprived nestlings to evaluate the effects of visual afferentation on functional involvement of visual structures in acoustically guided defensive behavior. Exclusion of visual afferentation from already formed defensive behavior did not significantly change immunoreactivity of Wulst neurons, which attests to substantial contribution of other, non-visual, activating influences. Limitation of visual afferentation during the formation of defensive behavior decreased immunoreactivity of Wulst neurons. Dendritic sprouting in Wulst neurons of visually deprived nestlings unable to promote the formation of complex interneuronic interactions.

Modelling the magnetic signature of neuronal tissue.

Neuronal communication in the brain involves electrochemical currents, which produce magnetic fields. Stimulus-evoked brain responses lead to changes in these fields and can be studied using magneto- and electro-encephalography (MEG/EEG). In this paper we model the spatiotemporal distribution of the magnetic field of a physiologically idealized but anatomically realistic neuron to assess the possibility of using magnetic resonance imaging (MRI) for directly mapping the neuronal currents in the human brain. Our results show that the magnetic field several centimeters from the centre of the neuron is well approximated by a dipole source, but the field close to the neuron is not, a finding particularly important for understanding the possible contrast mechanism underlying the use of MRI to detect and locate these currents. We discuss the importance of the spatiotemporal characteristics of the magnetic field in cortical tissue for evaluating and optimizing an experiment based on this mechanism and establish an upper bound for the expected MRI signal change due to stimulus-induced cortical response. Our simulations show that the expected change of the signal magnitude is 1.6% and its phase shift is 1 degrees . An unexpected finding of this work is that the cortical orientation with respect to the external magnetic field has little effect on the predicted MRI contrast. This encouraging result shows that magnetic resonance contrast directly based on the neuronal currents present in the cortex is theoretically a feasible imaging technique. MRI contrast generation based on neuronal currents depends on the dendritic architecture and we obtained high-resolution optical images of cortical tissue to discuss the spatial structure of the magnetic field in grey matter.

[Evaluation of transcutaneous bilirubin measurement and agreement with bilirubinemia]. / Evaluation de la mesure transcutanée de la bilirubine et concordance avec la mesure sur sang total et plasma.

Evaluation of the neonates for jaundice and kernicterus is indispensable when early hospital discharge has become standard practice. Transcutaneous bilirubin (TcB) measurement is an advantageous option because of its non-invasive nature and the possibility of its use near the patient. The point of care device BiliCheck has been compared in numerous instances to serum bilirubin. However, its clinical utility remains a subject of discussion. We have compared total blood bilirubin (TBB) concentrations to TcB values using the BiliCheck in newborns at 48 +/- 12 hours of life, at the time of discharge when they have lost weight. One hundred and ninety-six term neonates were initially included into the study. Transcutaneous bilirubin could be compared to whole blood bilirubin for 178 of them. Methods were compared by linear regression analysis and by the non-parametric Bland and Altman method. The correlation between BiliCheck and whole blood bilirubin was adequate (r(2): 0.7768). However, the Bland-Altman analysis revealed a 95% CI of -50.4 to 47.5 micromol/L. Transcutaneous bilirubin was also compared to a measure on plasma in a sub-group of 53 infants, the correlation was 0.7749 with a 95% CI of -35.8 to 46.5 micromol/L. Comparing total blood bilirubin with plasma bilirubin in 35 patients, we observed a similar results with a correlation of 0.7583 and a 95% CI of -34.6 to 40.7 micromol/L. Finally, the extent of weight loss observed in our group of patients had little influence and did not affect the agreement between the 2 approaches. We conclude that the BiliCheck may be used to monitor bilirubin in term neonates at 48 hours of life even with a weight loss. Clinicians have however to be conscious of the limit of the precision of the measures both for the BiliCheck and the laboratory methods.

Sensory information--the major factor of ontogeny.

On the basis of their own data authors postulate that the increase in sensory input during early ontogeny results in a delay in the development of the sensory systems formed earlier. In connection with this, the sensory basis of behavioral patterns becomes ineffective, causing their reorganization and the appearance of new forms of behavior. Limitation of sensory input during during the critical periods of development stimulates the accelerated manifestation of behavioral patterns. However, this acceleration also has long-lasting negative effects - alterations in the process of learning and memory in adult animals.

Changes of auditory-evoked potentials in response to behaviorally meaningful tones induced by acute ethanol intake in altricial nestlings at the stage of formation of natural behavior.

Acute ethanol's influence on field L auditory-evoked potentials (AEP) was studied in 4-7-days-old altricial nestlings of the pied flycatcher. Nestlings were presented with behaviorally meaningful tone pips (2.0 and 5.0 kHz) and control tone pips (3.0 kHz). Ethanol ingestion was found to reduce the N1 amplitude and maturity index (MI) of the AEP in response to "behavioral" but not to control frequencies. This effect was first observed on day 5, when the nestlings' behavior became more complex (their eyes opened and defence behavior appeared), and when previously formed feeding behavior was undergoing modifications. The MI increase during the early postembryonic ontogeny was probably due to the selective involvement of neurons with newly formed behavioral specializations into the subserving of new behavioral patterns, while the decrease of the MI under alcohol was due to the depression of activity in these neurons.