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Undercutting anchors are structural elements used in construction and geotechnics to stabilize both structures and soils. Their main applications include stabilizing slopes and embankments, reinforcing foundations, and providing support during tunnel construction and other underground works. The authors propose the use of these anchors in rock mass detachment technology. This article presents a comprehensive analysis of the mechanism behind rock mass detachment using an undercutting anchor. Particular attention is given to the influence of parameters such as the fracture energy of the medium and the coefficient of friction between the medium and the anchor head on the detachment process of rock elements during anchor expansion in the drilled hole. Numerical FEM analysis was employed to model the effect of changes in the shape and size of failure cones under varying simulation conditions. The discussed problem is crucial for evaluating the effectiveness of this anchor design under non-standard conditions, particularly in the unconventional destruction of rock media.

Purpose: To evaluate and compare the visual outcomes of an enhanced monofocal intraocular lens (IOL) with two different monofocal IOLs., Setting: Eye Clinic, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy., Design: Prospective, single-center, single-masked, randomized controlled clinical study., Methods: The study included patients undergoing phacoemulsification and IOL implantation. Patients were consecutively randomized by block randomization and assigned in a 1:1:1 allocation ratio to three study arms to bilaterally receive Tecnis Eyhance™ (model ICB00) or Tecnis ® monofocal 1-piece (model PCB00) or Clareon ® monofocal (model CNA0T0), respectively. Monocular and binocular (both corrected and uncorrected) visual acuities for far, intermediate and near were registered and compared among groups at 3 months. To track changes in patient quality of life, the Catquest-9SF questionnaire was administered to each patient before and after cataract extraction., Results: Ninety patients (30 for each group) were enrolled. At 3 months follow-up, statistically significant differences for intermediate visual acuities were found between the three groups. Nonstatistically significant differences were observed for distance visual acuities and the changes in Catquest-9SF scores., Conclusion: Tecnis Eyhance™ provided better results in intermediate visual outcomes without adverse effects on patients' quality of life., (© 2024. The Author(s).)

Oxidative post-translational modifications of protein thiols are well recognized as a readily occurring alteration of proteins, which can modify their function and thus control cellular processes. The development of techniques enabling the site-specific assessment of protein thiol oxidation on a proteome-wide scale significantly expanded the number of known oxidation-sensitive protein thiols. However, lacking behind are large-scale data on the redox state of proteins during ageing, a physiological process accompanied by increased levels of endogenous oxidants. Here, we present the landscape of protein thiol oxidation in chronologically aged wild-type Saccharomyces cerevisiae in a time-dependent manner. Our data determine early-oxidation targets in key biological processes governing the de novo production of proteins, protein folding, and degradation, and indicate a hierarchy of cellular responses affected by a reversible redox modification. Comparison with existing datasets in yeast, nematode, fruit fly, and mouse reveals the evolutionary conservation of these oxidation targets. To facilitate accessibility, we integrated the cross-species comparison into the newly developed OxiAge Database., (© 2024 Jonak et al.)

Genome haploidization at meiosis depends on two consecutive nuclear divisions, which are controlled by an oscillatory system consisting of Cdk1-cyclin B and the APC/C bound to the Cdc20 activator. How the oscillator generates exactly two divisions has been unclear. We have studied this question in yeast where exit from meiosis involves accumulation of the APC/C activator Ama1 at meiosis II. We show that inactivation of the meiosis I-specific protein Spo13/MEIKIN results in a single-division meiosis due to premature activation of APC/C Ama1 . In the wild type, Spo13 bound to the polo-like kinase Cdc5 prevents Ama1 synthesis at meiosis I by stabilizing the translational repressor Rim4. In addition, Cdc5-Spo13 inhibits the activity of Ama1 by converting the B-type cyclin Clb1 from a substrate to an inhibitor of Ama1. Cdc20-dependent degradation of Spo13 at anaphase I unleashes a feedback loop that increases Ama1's synthesis and activity, leading to irreversible exit from meiosis at the second division. Thus, by repressing the exit machinery at meiosis I, Cdc5-Spo13 ensures that cells undergo two divisions to produce haploid gametes., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Prefoldin is an evolutionarily conserved co-chaperone of the tailless complex polypeptide 1 ring complex (TRiC)/chaperonin containing tailless complex 1 (CCT). The prefoldin complex consists of six subunits that are known to transfer newly produced cytoskeletal proteins to TRiC/CCT for folding polypeptides. Prefoldin function was recently linked to the maintenance of protein homeostasis, suggesting a more general function of the co-chaperone during cellular stress conditions. Prefoldin acts in an adenosine triphosphate (ATP)-independent manner, making it a suitable candidate to operate during stress conditions, such as mitochondrial dysfunction. Mitochondrial function depends on the production of mitochondrial proteins in the cytosol. Mechanisms that sustain cytosolic protein homeostasis are vital for the quality control of proteins destined for the organelle and such mechanisms among others include chaperones., Results: We analyzed consequences of the loss of prefoldin subunits on the cell proliferation and survival of Saccharomyces cerevisiae upon exposure to various cellular stress conditions. We found that prefoldin subunits support cell growth under heat stress. Moreover, prefoldin facilitates the growth of cells under respiratory growth conditions. We showed that mitochondrial morphology and abundance of some respiratory chain complexes was supported by the prefoldin 2 (Pfd2/Gim4) subunit. We also found that Pfd2 interacts with Tom70, a receptor of mitochondrial precursor proteins that are targeted into mitochondria., Conclusions: Our findings link the cytosolic prefoldin complex to mitochondrial function. Loss of the prefoldin complex subunit Pfd2 results in adaptive cellular responses on the proteome level under physiological conditions suggesting a continuous need of Pfd2 for maintenance of cellular homeostasis. Within this framework, Pfd2 might support mitochondrial function directly as part of the cytosolic quality control system of mitochondrial proteins or indirectly as a component of the protein homeostasis network., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Since the beginning of SESN protein development, they have attracted highly progressive attention due to their regulatory role in multiple signalling pathways. Through their antioxidant activity and autophagy regulation implication, they can function as powerful antioxidants to reduce oxidative stress in cells. SESN proteins received special attention in the field of regulation of reactive oxygen species level in the cell and its interplay with signalling pathways determining energy and nutrient homeostasis. Since perturbations in these pathways are implicated in cancer onset and development, SESNs might constitute potential novel therapeutic targets of broad interest. In this review, we discuss the impact of SESN proteins on anti-cancer therapy based on naturally occurring compounds and conventionally used drugs that influence oxidative stress and autophagy-induced cellular signalling pathways. The significant changes in reactive oxygen species level and nutrient status in cancer cells generate subsequent biological effect through the regulation of SESN-dependent pathways. Thus, SESN may serve as the key molecule for regulating anti-cancer drugs' induced cellular response., (© 2023. The Author(s).)

(1) Background: Myopia is one of the most common refractive errors in the world. The aim of this study was to evaluate the transverse dimensions of selected masticatory muscles (temporalis muscle and masseter muscle) versus the transverse dimensions of selected extraocular muscles (superior rectus, inferior rectus, medial rectus and lateral rectus) in emmetropic and high myopic subjects. (2) Methods: Twenty-seven individuals were included in the analysis, resulting in 24 eyeballs of patients with high myopia and 30 eyeballs of emmetropic subjects. A 7 Tesla resonance was used to analyze the described muscles. (3) Results: Statistical analysis showed differences in all analyzed extraocular muscles and all analyzed masticatory muscles between emmetropic subjects and high myopic subjects. In the high myopic subject group, statistical analysis showed four correlations. The three negative correlations were between the lateral rectus muscle and an axial length eyeball, refractive error and an axial length eyeball, and the inferior rectus muscle and visual acuity. The positive correlation was between the lateral rectus muscle and the medial rectus muscle. (4) Conclusions: The high myopic subjects are characterized by a larger cross-sectional area of extraocular muscles and masticatory muscles compared to the emmetropic subjects. Correlations were observed between the thickness of the extraocular muscles and the masticatory muscles. The lateral rectus muscle was related to the length of the eyeball. The phenomenon requires further study.

Modern computational solutions used in the reconstruction of the global neuronal network arrangement seem to be particularly valuable for research on neuronal disconnection in schizophrenia. However, the vast number of algorithms used in these analyses may be an uncontrolled source of result inconsistency. Our study aimed to verify to what extent the characteristics of the global network organization in schizophrenia depend on the inclusion of a given type of functional connectivity measure. Resting-state EEG recordings from schizophrenia patients and healthy controls were collected. Based on these data, two identical procedures of graph-theory-based network arrangements were computed twice using two different functional connectivity measures (phase lag index, PLI , and phase locking value, PLV ). Two series of between-group comparisons regarding global network parameters calculated on the basis of PLI or PLV gave contradictory results. In many cases, the values of a given network index based on PLI were higher in the patients, and the results based on PLV were lower in the patients than in the controls. Additionally, selected network measures were significantly different within the patient group when calculated from PLI or PLV . Our analysis shows that the selection of FC measures significantly affects the parameters of graph-theory-based neuronal network organization and might be an important source of disagreement in network studies on schizophrenia.

When performing cognitively demanding tasks, people tend to experience momentary distractions or personal associations that intercept their stream of consciousness. This phenomenon is known as Mind Wandering (MW) and it has become a subject of neuroscientific investigations. Off-task thoughts can be analyzed during task performance, but currently, MW is also understood as a dimension of individual differences in cognitive processing. We wanted to recognize the intrinsically-organized functional networks that could be considered the neuronal basis for MW dispositional variability. To achieve this goal we recruited a group of normal adults, and eventually divided the group in half, based on participants' scores on the scale measuring dispositional MW. Next, these groups were compared regarding the arrangement of preselected intrinsic functional networks, which were reconstructed based on multi-channel signal-source resting-state EEG. It appeared that subjects who tend to mind wander often exhibited decreased synchronization within the default mode network, and, simultaneously, strengthened connectivity between 'on-task' networks of diverse functional specificity. Such within- and between networks integrity patterns might suggest that greater Mind Wanderers present an atypical organization of resting-state brain activity, which may translate into attenuated resources needed to maintain attentional control in task-related conditions., (© 2022. The Author(s).)

To investigate associations and predictive factors between macular neovascularization (MNV) lesion variants and drusen types in patients with treatment-naïve neovascular age-related macular degeneration (AMD). Methods: Multimodal imaging was retrospectively reviewed for druse type (soft drusen, subretinal drusenoid deposits (SDDs) or mixed) and MNV type (MNV 1, MNV 2, MNV 1/2 or MNV 3). The Consensus on Neovascular AMD Nomenclature (CONAN) classification was used for characterizing MNV at baseline. Results: One eye of each eligible patient was included (n = 191). Patients with predominant SDDs had an increased adjusted odds ratio (aOR) for MNV 2 (23.4453, p = 0.0025) and any type of MNV 3 (8.7374, p < 0.0001). Patients with MNV 1/2 had an aOR for predominant SDDs (0.3284, p = 0.0084). Patients with MNV1 showed an aOR for SDDs (0.0357, p < 0.0001). Eyes with SDDs only without other drusen types showed an aOR for MNV 2 (9.2945, p < 0.0001). Conclusions: SDDs represent a common phenotypic characteristic in AMD eyes with treatment-naïve MNV. The aOR for eyes with predominant SDDs to develop MNV 2 and MNV 3 was much higher, possibly due to their location in the subretinal space. The predominant druse type may help to predict which type of MNV will develop during the course of AMD.

Aim: To examine the effect of subthreshold micropulse yellow laser (SMYL) on best-corrected visual acuity (BCVA), central macular thickness (CMT), and optical coherence tomography angiography (OCT-A) changes in eyes with persistent diabetic macular edema (DME) after pars plana vitrectomy (PPV) for tractional DME (TDME). Patients and Methods: In a comparative study, 95 eyes of 95 consecutive patients with persistent DME were prospectively enrolled. The SMYL group (54 eyes) was treated with SMYL 6 months after PPV, while the control group (41 eyes) was followed up without treatment. BCVA and CMT by OCT were analyzed at baseline and 3 and 6 months. Additionally, parameters such as the vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), respectively, and the area of the foveal avascular zone (FAZ) were also evaluated on OCT-A. Results: There were no significant differences between both groups in demographic data. In the SMYL group, mean BCVA was significantly increased [F(2,106) = 17.25; p < 0.001; η p 2 = 0.246] from 51.54 ± 13.81 ETDRS letters at baseline to 57.81 ± 12.82 ETDRS letters at 3 months ( p < 0.001) and 57.83 ± 13.95 EDTRS letters at 6 months ( p < 0.001), respectively. In comparison to the control group, BCVA values were statistically significantly higher in the SMYL group at 3 and 6 months, respectively. Mean CMT significantly decreased [F(2,106) = 30.98; p < 0.001; η p 2 = 0.368] from the baseline value 410.59 ± 129.91 μm to 323.50 ± 89.66 μm at 3 months ( p < 0.001) and to 283.39 ± 73.45 μm at 6 months ( p < 0.001). CMT values were significantly lower in the SMYL group ( p < 0.001), especially at 6 months follow-up time ( p < 0.001) compared with the control group. Parafoveal VD in the SCP and DCP was significantly higher in the SMYL group in comparison to the control group, respectively, at 3-month (SCP p < 0.001; DCP p < 0.001) and 6-month follow-up (SCP p < 0.001; DCP p < 0.001). FAZ area was also significantly smaller in the SMYL group at 6-month follow-up ( p = 0.001). There were no adverse SMYL treatment effects. Conclusion: SMYL therapy may be a safe and effective treatment option in eyes with persistent macular edema following PPV for TDME., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bonfiglio, Rejdak, Nowomiejska, Zweifel, Justus Wiest, Romano, Bucolo, Gozzo, Castellino, Patane, Pizzo, Reibaldi, Russo, Longo, Fallico, Macchi, Vadalà, Avitabile, Costagliola, Jonak and Toro.)

Sexual reproduction requires genome haploidization by the two divisions of meiosis and a differentiation program to generate gametes. Here, we have investigated how sporulation, the yeast equivalent of gamete differentiation, is coordinated with progression through meiosis. Spore differentiation is initiated at metaphase II when a membrane-nucleating structure, called the meiotic plaque, is assembled at the centrosome. While all components of this structure accumulate already at entry into meiosis I, they cannot assemble because centrosomes are occupied by Spc72, the receptor of the γ-tubulin complex. Spc72 is removed from centrosomes by a pathway that depends on the polo-like kinase Cdc5 and the meiosis-specific kinase Ime2, which is unleashed by the degradation of Spo13/Meikin upon activation of the anaphase-promoting complex at anaphase I. Meiotic plaques are finally assembled upon reactivation of Cdk1 at entry into metaphase II. This unblocking-activation mechanism ensures that only single-copy genomes are packaged into spores and might serve as a paradigm for the regulation of other meiosis II-specific processes., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

In this study, we focused on the verification of suitable aggregation operators enabling accurate differentiation of selected neurophysiological features extracted from resting-state electroencephalographic recordings of patients who were diagnosed with schizophrenia (SZ) or healthy controls (HC). We built the Choquet integral-based operators using traditional classification results as an input to the procedure of establishing the fuzzy measure densities. The dataset applied in the study was a collection of variables characterizing the organization of the neural networks computed using the minimum spanning tree (MST) algorithms obtained from signal-spaced functional connectivity indicators and calculated separately for predefined frequency bands using classical linear Granger causality (GC) measure. In the series of numerical experiments, we reported the results of classification obtained using numerous generalizations of the Choquet integral and other aggregation functions, which were tested to find the most appropriate ones. The obtained results demonstrate that the classification accuracy can be increased by 1.81% using the extended versions of the Choquet integral called in the literature, namely, generalized Choquet integral or pre-aggregation operators., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Plechawska-Wójcik, Karczmarek, Krukow, Kaczorowska, Tokovarov and Jonak.)

Supporting the development of a child with autism is a multi-profile therapeutic work on disturbed areas, especially understanding and linguistic expression used in social communication and development of social contacts. Previous studies show that it is possible to perform some therapy using a robot. This article is a synthesis review of the literature on research with the use of robots in the therapy of children with the diagnosis of early childhood autism. The review includes scientific journals from 2005-2021. Using descriptors: ASD (Autism Spectrum Disorders), Social robots, and Robot-based interventions, an analysis of available research in PubMed, Scopus and Web of Science was done. The results showed that a robot seems to be a great tool that encourages contact and involvement in joint activities. The review of the literature indicates the potential value of the use of robots in the therapy of people with autism as a facilitator in social contacts. Robot-Assisted Autism Therapy (RAAT) can encourage child to talk or do exercises. In the second aspect (prompting during a conversation), a robot encourages eye contact and suggests possible answers, e.g., during free conversation with a peer. In the third aspect (teaching, entertainment), the robot could play with autistic children in games supporting the development of joint attention. These types of games stimulate the development of motor skills and orientation in the body schema. In future work, a validation test would be desirable to check whether children with ASD are able to do the same with a real person by learning distrust and cheating the robot.

Genome haploidization involves sequential loss of cohesin from chromosome arms and centromeres during two meiotic divisions. At centromeres, cohesin's Rec8 subunit is protected from separase cleavage at meiosis I and then deprotected to allow its cleavage at meiosis II. Protection of centromeric cohesin by shugoshin-PP2A seems evolutionarily conserved. However, deprotection has been proposed to rely on spindle forces separating the Rec8 protector from cohesin at metaphase II in mammalian oocytes and on APC/C-dependent destruction of the protector at anaphase II in yeast. Here, we have activated APC/C in the absence of sister kinetochore biorientation at meiosis II in yeast and mouse oocytes, and find that bipolar spindle forces are dispensable for sister centromere separation in both systems. Furthermore, we show that at least in yeast, protection of Rec8 by shugoshin and inhibition of separase by securin are both required for the stability of centromeric cohesin at metaphase II. Our data imply that related mechanisms preserve the integrity of dyad chromosomes during the short metaphase II of yeast and the prolonged metaphase II arrest of mammalian oocytes., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Examining individuals with Leber's hereditary optic neuropathy (LHON) provides a rare opportunity to understand how changes in mitochondrial DNA and loss of vision can be related to changes in organization of the whole-brain structural network architecture. In comparison with the previous neuroimaging studies with LHON participants, which were focused mainly on analyzing changes which occur in different areas of the patient's brain, network analysis not only makes it possible to observe single white matter fibers' aberrations but also the whole-brain nature of these changes. The purpose of our study was to better understand whole-brain neural network changes in LHON participants and see the correlation between the clinical data and the changes. To achieve this, we examined fifteen LHON patients and seventeen age-matched healthy subjects with the usage of ultra-high filed 7T magnetic resonance imaging (MRI). Basing on the analysis on MRI diffusion tensor imaging (DTI) data, whole-brain structural neural networks were reconstructed with the use of the minimum spanning tree algorithm (MST) for every participant. Our results revealed that the structural network in LHON participants was altered at both the local and the global level. The global network structures of LHON subjects were less centralized with path-like organization and there was an imbalance in the main hub centrality. Moreover, the inspection of nodes and hubs in terms of their anatomical placement revealed that in the LHON participants the prominent hubs were located within the basal ganglia (i.e. bilateral caudate, left pallidum), which differed them from healthy controls. An analysis of the relationships between the global MST metrics and LHON participants' clinical characteristics revealed significant correlations between the global network metrics and the duration of illness. Furthermore, the nodal parameters of the optic chiasm were significantly correlated with the duration of illness and the averaged thickness of the right retinal nerve fiber layer (RNFL). These findings clearly showed that the progression of the disease is accompanied by alterations within the brain network structure and its efficiency., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of this study was to assess the volumetry of the hippocampus in the Leber's hereditary optic neuropathy (LHON) of blind patients., Methods: A total of 25 patients with LHON were randomly included into the study from the national health database. A total of 15 patients were selected according to the inclusion criteria. The submillimeter segmentation of the hippocampus was based on three-dimensional spoiled gradient recalled acquisition in steady state (3D-SPGR) BRAVO 7T magnetic resonance imaging (MRI) protocol., Results: Statistical analysis revealed that compared to healthy controls (HC), LHON subjects had multiple significant differences only in the right hippocampus, including a significantly higher volume of hippocampal tail ( p = 0.009), subiculum body ( p = 0.018), CA1 body ( p = 0.002), hippocampal fissure ( p = 0.046), molecular layer hippocampus (HP) body ( p = 0.014), CA3 body ( p = 0.006), Granule Cell (GC) and Molecular Layer (ML) of the Dentate Gyrus (DG)-GC ML DG body ( p = 0.003), CA4 body ( p = 0.001), whole hippocampal body ( p = 0.018), and the whole hippocampus volume ( p = 0.023)., Discussion: The ultra-high-field magnetic resonance imaging allowed hippocampus quality visualization and analysis, serving as a powerful in vivo diagnostic tool in the diagnostic process and LHON disease course assessment. The study confirmed previous reports regarding volumetry of hippocampus in blind individuals.

The purpose of the study was to test the usefulness of deep learning artificial neural networks and statistical modeling in predicting the strength of bone cements with defects. The defects are related to the introduction of admixtures, such as blood or saline, as contaminants into the cement at the preparation stage. Due to the wide range of applications of deep learning, among others in speech recognition, bioinformation processing, and medication design, the extent was checked to which it is possible to obtain information related to the prediction of the compressive strength of bone cements. Development and improvement of deep learning network (DLN) algorithms and statistical modeling in the analysis of changes in the mechanical parameters of the tested materials will enable determining an acceptable margin of error during surgery or cement preparation in relation to the expected strength of the material used to fill bone cavities. The use of the abovementioned computer methods may, therefore, play a significant role in the initial qualitative assessment of the effects of procedures and, thus, mitigation of errors resulting in failure to maintain the required mechanical parameters and patient dissatisfaction., Competing Interests: The authors declare no conflict of interest.

This study employs the numerical analysis and experimental testing to analyze the fracturing mechanics and the size of rock cones formed in the pull-out of a system of three undercut anchors. The research sets out to broaden the knowledge regarding: (a) the potential of the undercut anchor pull-out process in mining of the rock mass, and (b) estimating the load-carrying capacity of anchors embedded in the rock mass (which is distinctly different from the anchorage to concrete). Undercut anchors are most commonly applied as fasteners of steel components in concrete structures. The new application for undercut anchors postulated in this paper is their use in rock mining in exceptional conditions, such as during mining rescue operations, which for safety considerations may exclude mechanical mining techniques, mining machines, or explosives. The remaining solution is manual rock fracture, whose effectiveness is hard to assess. The key issue in the analyzed aspect is the rock fracture mechanics, which requires in-depth consideration that could provide the assistance in predicting the breakout prism dimensions and the load-displacement behavior of specific anchorage systems, embedment depth, and rock strength parameters. The volume of rock breakout prisms is an interesting factor to study as it is critical to energy consumption and, ultimately, the efficiency of the process. Our investigations are supported by the FEM (Finite Element Method) analysis, and the developed models have been validated by the results from experimental testing performed in a sandstone mine. The findings presented here illuminate the discrepancies between the current technology, test results, and standards that favor anchorage to concrete, particularly in the light of a distinct lack of scientific and industry documentation describing the anchorage systems' interaction with rock materials, which exhibit high heterogeneity of the internal structure or bedding. The Concrete Capacity Design (CCD) method approximates that the maximum projected radius of the breakout cone on the free surface of concrete corresponds to the length of at the most three embedment depths ( h ef ). In rock, the dimensions of the breakout prism are found to exceed the CCD recommendations by 20-33%. The numerical computations have demonstrated that, for the nominal breakout prism angle of approx. 35% (CCD), the critical spacing for which the anchor group effect occurs is ~4.5 (a cross-section through two anchor axes). On average, the observed spacing values were in the range of 3.6-4.0.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited genetic disorder leading to severe and bilateral loss of central vision, with a young male predilection. In recent years, multiple studies examined structural abnormalities in visual white matter tracts such as the optic tract and optic radiation. However, it is still unclear if the disease alters only some parts of the white matter architecture or whether the changes also affect grey matter parts of the visual pathway. This study aimed at improving our understanding of morphometric changes in the lateral (LGN) and medial (MGN) geniculate nuclei and their associations with the clinical picture in LHON by the application of a submillimeter surface-based analysis approach to the ultra-high-field 7T magnetic resonance imaging data. To meet these goals, fifteen LHON patients and fifteen age-matched healthy subjects were examined. A quantitative analysis of the LGN and MGN volume was performed for all individuals. Additionally, morphometric results of LGN and MGN were correlated with variables covering selected aspects of the clinical picture of LHON. In comparison with healthy controls (HC), LHON participants showed a significantly decreased volume of the right LGN and the right MGN. Nevertheless, the volume of the right LGN was strongly correlated with the averaged thickness value of the right retinal nerve fiber layer (RNFL). The abnormalities in the volume of the LHON patients' thalamic nuclei indicate that the disease can cause changes not only in the white matter areas constituting visual tracts but also in the grey matter structures. Furthermore, the correlation between the changes in the LGN volume and the RNFL, as well as the right optic nerve surface area located proximally to the eyeball, suggest some associations between the atrophy of these structures. However, to fully confirm this observation, longitudinal studies should be conducted.

Leber's hereditary optic neuropathy (LHON) is a rare, maternally inherited genetic disease caused by a mutation of mitochondrial DNA. Classical descriptions have highlighted structural abnormalities in various parts of patients' optic tracts; however, current studies have proved that changes also affect many cortical and subcortical structures, not only these belonging to the visual system. This study aimed at improving our understanding of neurophysiological impairments in LHON. First of all, we wanted to know if there were any differences between the health control and LHON subjects in the whole-brain source electroencephalography (EEG) analysis. Second, we wanted to investigate the associations between the observed results and some selected aspects of Leber's disease's clinical picture. To meet these goals, 20 LHON patients and 20 age-matched healthy control (HC) subjects were examined. To investigate the electrophysiological differences between the HC and LHON groups, a quantitative analysis of the whole-brain current source density was performed. The signal analysis method was based on scalp EEG data and an inverse solution method called low-resolution brain electromagnetic tomography (eLORETA). In comparison with the healthy subjects, LHON participants showed significantly decreased neuronal activity in the alpha and gamma bands; more specifically, in the alpha band, the decrease was mainly found in the occipital lobes and secondary visual cortex, whereas, in the gamma band, the reduced activity occurred in multiple cortical areas. Additionally, a correlation was found between the alpha band activity of the right secondary visual cortex and the averaged thickness of the right retinal nerve fiber layer in the LHON participants. Our study suggests that LHON is associated with widespread cortical de-activation, rather than simply abnormalities of structures constituting the visual system.

Among multiple cognitive impairments present in schizophrenia, a decline in fast information processing is one of the most severe neuropsychological deficit. Reduced ability to efficiently launch a coherent cognitive activity might be a significant factor contributing to poor results in time-limited tasks obtained by schizophrenia patients. The aim of this study was to identify neurophysiological predictors of expected cognitive initiation failures in a group of first-episode schizophrenia individuals (SZ). To evaluate the effectiveness of initiation, a dynamic analysis of design fluency test was applied, assessing to what extent the productivity was focused within the first interval of the performance, what is a typical way healthy subjects execute this task. Resting-state EEG recordings were obtained from SZ patients (n = 34) and controls (n = 30) to examine functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for six conventionally analyzed frequencies. The nonparametric randomization approach was used to identify hypo- and hyper-connections, i.e. synchronizations significantly differentiating the studied samples in terms of connectivity strength. Generally, SZ patients obtained poor outcomes in fluency test and dynamic analysis of performance confirmed the presence of initiation deficit in clinical sample, which was a single factor explaining the intergroup difference regarding the entire task. In the majority of frequencies, the arrangement of synchronizations in SZ group was dominated by hypo-connections, except for the theta band, in which the strength of synchronizations between posterior cingulate cortex, cuneus and precuneus was significantly higher for SZ group. These theta-band hyper-connections turned out to be significant predictors of cognitive initiation failure in the clinical sample. Additionally, theta hyper-connections correlated negatively with the total number of unique designs generated by patients, however, the strength of this correlation was weaker than regarding initiation index. The results of this study suggest that baseline hyperconnectivity within the posterior hub of the Default Mode Network, containing posterior cingulate gyrus and precuneus, might disturb effective cognitive outcome, not only by interfering with task-positive functional networks but also by delaying the starting phase of performance, which might be specifically deleterious for the execution of time-limited tests., Competing Interests: Declaration of Competing Interest We declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

First of all, I would like to thank the reader for their interest and taking the time to analyze our work [...].

Schizophrenia has been considered a disorder linked with faulty lipid homeostasis, and the proposed tool for assessment of these disruptions is the niacin skin flush test. The aims of the study were: 1. Create a new tool to analyze results of the niacin skin flush test more precisely and objectively. 2. Verify the utility of a self-created tool for differentiating between schizophrenia (SZ; n = 56), bipolar disorder (BD; n = 29) and healthy control (HC; n = 45) individuals. The proposed developed method, based on the Skin Reaction Measurement Computer System (SKINREMS), allows one to evaluate the response to the niacin skin flush test quickly and objectively. SKINREMS showed good accuracy in discriminating SZ from BD (with sensitivity 91% and specificity 72%), and SZ from HC (71% and 66%, respectively), and sufficient but not excellent accuracy in discriminating BD from HC (55% and 54%, respectively). The pathophysiological pathways and features shared by schizophrenia and bipolar disorder may be the reason for difficulties in fully discriminating between these two mental disorders using the niacin challenge test. The management of disruptions in the phospholipid metabolism and the inflammatory process could potentially become an individualized form of therapy in a subgroup of psychiatric patients.

Leber's hereditary optic neuropathy (LHON) is one of the mitochondrial diseases that causes loss of central vision, progressive impairment and subsequent degeneration of retinal ganglion cells (RGCs). In recent years, diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts, such as the optic tract, and optic radiation. However, it is still unclear if the disease alters only some parts of the white matter architecture or whether the changes also affect other subcortical areas of the brain. This study aimed to improve our understanding of morphometric changes in subcortical brain areas and their associations with the clinical picture in LHON by the application of a submillimeter surface-based analysis approach to the ultra-high-field 7T magnetic resonance imaging data. To meet these goals, fifteen LHON patients and fifteen age-matched healthy subjects were examined. For all individuals, quantitative analysis of the morphometric results was performed. Furthermore, morphometric characteristics which differentiated the groups were correlated with variables covering selected aspects of the LHON clinical picture. Compared to healthy controls (HC), LHON carriers showed significantly lower volume of both palladiums (left p = 0.023; right p = 0.018), the right accumbens area ( p = 0.007) and the optic chiasm ( p = 0.014). Additionally, LHON patients have significantly higher volume of both lateral ventricles (left p = 0.034; right p = 0.02), both temporal horns of the lateral ventricles (left p = 0.016; right p = 0.034), 3rd ventricle ( p = 0.012) and 4th ventricle ( p = 0.002). Correlation between volumetric results and clinical data showed that volume of both right and left lateral ventricles significantly and positively correlated with the duration of the illness (left R = 0.841, p = 0.002; right R = 0.755, p = 0.001) and the age of the LHON participants (left R = 0.656, p = 0.007; right R = 0.691, p = 0.004). The abnormalities in volume of the LHON patients' subcortical structures indicate that the disease can cause changes not only in the white matter areas constituting visual tracts, but also in the other subcortical brain structures. Furthermore, the correlation between those results and the illness duration suggests that the disease might have a neurodegenerative nature; however, to fully confirm this observation, longitudinal studies should be conducted.

Since the beginning of the discovery of microRNAs (miRs), these molecules have attracted highly progressive attention due to their powerful regulatory roles in a broad spectrum of biological processes, including proliferation, differentiation, apoptosis and carcinogenesis. With regard to carcinogenesis, the miRs regulatory potency has been associated with cancer onset, progression, metastasis, diagnosis and therapeutic response. In this review we discuss the impact of miR-200 family on drug resistance development during anti-cancer therapy. Developing resistance to chemotherapeutic drugs as well as radiotherapy are major clinical obstacles in the successful therapeutic strategies to cancer treatment. Acquired cancer chemoresistance is a multifactorial phenomenon involving such factors as tumor type, tumor stage, cellular reactive oxygen species (ROS) level or ROS-responsive miRs profile. ROS level could influence the miRs expression level, which changes the cellular profile of the content of miRs. Such significant changes in the cellular miRs profile generate subsequent biological effects through the regulation of their target genes. This review outlines the interactions between ROS and miR-200 family in different kinds of cancers in response to chemotherapy., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Magnetic Resonance Imaging (MRI) of the Optic Nerve is difficult due to the fine extended nature of the structure, strong local magnetic field distortions induced by anatomy, and large motion artefacts associated with eye movement. To address these problems we used a Zero Echo Time (ZTE) MRI sequence with an Adiabatic SPectral Inversion Recovery (ASPIR) fat suppression pulse which also imbues the images with Magnetisation Transfer contrast. We investigated an application of the sequence for imaging the optic nerve in subjects with Leber's hereditary optic neuropathy (LHON). Of particular note is the sequence's near-silent operation, which can enhance image quality of the optic nerve by reducing the occurrence of involuntary saccades induced during Magnetic Resonance (MR) scanning., Competing Interests: G.J.B. receives honoraria for teaching from GE Healthcare.

Metformin (MET), 1,1-dimethylbiguanide hydrochloride, is a biguanide drug used as the first-line medication in the treatment of type 2 diabetes. The recent years have brought many observations showing metformin in its new role. The drug, commonly used in the therapy of diabetes, may also find application in the therapy of a vast variety of tumors. Its effectiveness has been demonstrated in colon, breast, prostate, pancreatic cancer, leukemia, melanoma, lung and endometrial carcinoma, as well as in gliomas. This is especially important in light of the poor options offered to patients in the case of high-grade gliomas, which include glioblastoma (GBM). A thorough understanding of the mechanism of action of metformin can make it possible to discover new drugs that could be used in neoplasm therapy.

Time-of-flight angiography (ToF) was presented for the first time by Suryan and used by Hinshaw et al. This protocol allows to visualize blood flow within the vessels in vivo without the contrast administration, which is possible due to the large magnitude of magnetization, received from the moving spins and small magnitude of magnetization received from the stationary spins. Fourteen participants (male:female = 7:7) were analyzed, who have never been diagnosed with any central nervous system disease as well as any cardiovascular, metabolic disease and have never had any trauma. Although, the gold standard of cerebral vessel analysis is still DSA, ultra high-field 3D ToF-MRA shows clearer picture of all LSAs and the branches of LSAs in comparison to poor in contrast DSA imaging. Ultra high-field time-of-flight MRA is a valuable method in visualizing small perforating arteries, which can be used in the future as a diagnostic tool for clinical practice. The diversity of LSAs morphometry is vast and may alter during aging, thus the clinical anatomy of those vessels should be further investigated in vivo., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introducing the Minimum Spanning Tree (MST) algorithms to neural networks science eliminated the problem of arbitrary setting of the threshold for connectivity strength. Despite these advantages, MST has been rarely used to study network abnormalities in schizophrenia. An MST graph mapping a network structure is its simplification, therefore, it is important to verify whether the reconfigured network is significantly related to the behavioural dimensions of the clinical picture of schizophrenia. 35 first-episode schizophrenia patients and 35 matched healthy controls underwent an assessment of information processing speed, cognitive inter-trial variability modelled with ex-Gaussian distributional analysis of reaction times and resting-state EEG recordings to obtain frequency-specific functional connectivity matrices from which MST graphs were computed. The patients' network had a more random structure and star-like arrangement with overloaded hubs positioned more posteriorly than it was in the case of the control group. Deficient processing speed in the group of patients was predicted by increased maximal betweenness centrality in beta and gamma bands, while decreased consistency in cognitive processing was predicted by the betweenness centrality of posterior nodes in the gamma band, together with duration of illness. The betweenness centrality of posterior nodes in the gamma band was also significantly correlated with positive psychotic symptoms in the clinical group.

The aim of this study was to compare neural network topology of 30 patients with first episode schizophrenia (FES) and 30 multiepisode schizophrenia (mean number of psychotic relapses =4 years, duration of illness >5 years) patients, who were assessed with graph theory methods. This comparison was designed to identify network differences, which might be assigned to the burden of a mental disease. To estimate functional connectivity, we applied the phase lag index algorithm and the minimum spanning tree (MST) for the characterization of network topology. Group comparison revealed significant between-group differences of maximal betweenness centrality and tree hierarchy in the beta-band and hierarchy in the gamma-band. MST results showed that in the beta-band the network of patients with longer duration of illness (LDI) was characterized by more centralized network, while subjects with short duration of illness (FES) showed more decentralized topology. Furthermore, in the gamma-band, our results suggest that illness duration can disturb the balance between overload prevention and large-scale integration in the brain network. A qualitative analysis proved that the topological displacement of hubs also differentiated the FES and LDI groups. Our findings suggest that the duration of illness significantly affects the topology of resting-state functional network, supporting the "disconnectivity hypothesis' in schizophrenia.

Trace elements play a crucial role in many biochemical processes, mainly as components of vitamins and enzymes. Although small amounts of metal ions have protective properties, excess metal levels result in oxidative injury, which is why metal ion homeostasis is crucial for the proper functioning of the brain. The changes of their level in the brain have been proven to be a risk factor for Alzheimer's, Parkinson's, and Huntington's diseases, as well as amyotrophic lateral sclerosis. Therefore, it is currently an important application of various analytical methods. This review covers the most important of them: inductively coupled ground mass spectrometry (ICP-MS), flame-induced atomic absorption spectrometry (FAAS), electrothermal atomic absorption spectrometry (GFAAS), optical emission spectrometry with excitation in inductively coupled plasma (ICP-OES), X-ray fluorescence spectrometry (XRF), and neutron activation analysis (NAA). Additionally, we present a summary of concentration values found by different research groups.

The study aimed at identifying the cognitive and clinical determinants of impaired design fluency in bipolar patients, with special reference to processing speed and performance strategy. A sample of bipolar disorder patients (BD, n = 45) and matched healthy controls (HC, n = 42) underwent the assessment of figural fluency, cognitive and manual speed, cognitive effort and affective state. An electronic version of design fluency test was applied, enabling assessment of performance speed, execution strategy and spontaneous fluctuations in production efficiency. Additional clinical variables were also controlled. BD patients produced significantly less unique designs, performed slower, utilized less effective strategy, their ability to concentrate designs production in the initial phase of performance was significantly reduced compared with HC. Regression analysis revealed that in BD patients design fluency main outcome was significantly predicted by slowed creation of designs and the number of hospitalizations, while in the HC group, the main fluency result was predicted only by the executive strategy indicators. Our study showed that non-verbal fluency in BD group was determined by essentially different neuropsychological functions than in healthy controls. Obtained findings confirm that cognitive slowdown should be an important goal of cognitive remediation and pharmacological interventions in bipolar disorder., (Copyright © 2018. Published by Elsevier B.V.)

This study aimed at identifying abnormal cortico-cortical functional connectivity patterns that could predict cognitive slowing in patients with schizophrenia. A group of thirty-two patients with the first-episode schizophrenia and comparable healthy controls underwent resting-state qEEG and cognitive assessment. Phase Lag Index (PLI) was applied as a connectivity index and the synchronizations were analyzed in six frequencies. Pairs of electrodes were grouped to separately cover frontal, temporal, central, parietal and occipital regions. PLI was calculated for intra-regional connectivity and between-regions connectivity. Computer version processing speed tests were applied to control for possible fluctuations in cognitive efficiency during the performance of the tasks. In the group of patients, in comparison to healthy controls, significantly higher PLI values were recorded in theta frequency, especially in the posterior areas and decreased PLI in low-alpha frequency within the frontal regions. Mean PLI in gamma frequency was also lower in the patients group. Regression analysis showed that lower intra-regional PLI for left frontal cortex and higher PLI within somatosensory cortex in theta band, together with the duration of untreated psychosis, proved to be significant predictors of impaired processing speed in first-episode patients. Our investigation confirmed that disrupted cortico-cortical synchronization contributes to cognitive slowing in schizophrenia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

There is an increasing amount of evidence which links the pathogenesis of irritable bowel syndrome (IBS) with food IgG hyperreactivity. Some authors have suggested that food IgG hyperreactivity could be also involved in the pathophysiology of major depressive disorder (MDD). The aim of this study was to compare levels of serum IgG against 39 selected food antigens between three groups of participants: patients with MDD (MDD group), patients with IBS (IBS group) and healthy controls (HC group). The study included 65 participants (22 in the MDD group, 22 in the IBS group and 21 in the HC group). Serum IgG levels were examined using enzyme-linked immunosorbent assay (ELISA). Medical records, clinical data and laboratory results were collected for the analysis. IgG food hyperreactivity (interpreted as an average of levels of IgG antibodies above 7.5 &micro;g/mL) was detected in 28 (43%) participants, including 14 (64%) from the MDD group, ten (46%) from the IBS group and four (19%) from the HC group. We found differences between extreme IgG levels in MDD versus HC groups and in IBS versus HC groups. Patients with MDD had significantly higher serum levels of total IgG antibodies and IgG against celery, garlic and gluten compared with healthy controls. The MDD group also had higher serum IgG levels against gluten compared with the IBS group. Our results suggest dissimilarity in immune responses against food proteins between the examined groups, with the highest immunoreactivity in the MDD group. Further studies are needed to repeat and confirm these results in bigger cohorts and also examine clinical utility of IgG-based elimination diet in patients with MDD and IBS.

Aims: Patients with schizophrenia (SCH) show impaired verbal and non-verbal fluency. However, these individuals' fluctuations in words or designs generation efficiency over time, a phenomenon that may significantly affect fluency, have never been studied. Thus, the aim of this research was to investigate if individuals with SCH may present with alternations in the dynamics of the information production and its control as well as to test if the potential abnormalities in this regard might affect these patients' overall performance on both verbal and non-verbal fluency tasks., Method: Forty-four patients with SCH and 40 healthy controls (HC) completed both verbal (phonological, semantic) and non-verbal fluency tests. To analyse processing efficiency changes over time, the period in which subjects had to generate words or designs (60 s) has been divided into 15-s sections., Results: In comparison to HCs, individuals with SCH obtained significantly lower total scores for all fluency measures. Furthermore, group differences in the dynamics of the test performance also emerged, with SCH patients having a significantly worse production during the initial 15 s of each fluency task. Additionally, the initial production deficiency seen in patients with SCH has accounted for these individuals' total performance. Moreover, comparisons of errors distribution over time during the phonemic and figural fluency performance also revealed differences, suggesting there was a rapid depletion in maintaining of cognitive control in the SCH sample., Conclusions: Inefficient fluency in SCH may arise from a more general initiation deficits that may partly account for these patients' cognitive problems.

Cells undergoing meiosis produce haploid gametes through one round of DNA replication followed by 2 rounds of chromosome segregation. This requires that cohesin complexes, which establish sister chromatid cohesion during S phase, are removed in a stepwise manner. At meiosis I, the separase protease triggers the segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase, recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it from cleavage. While chromatids disjoin upon cleavage of centromeric Rec8 at meiosis II, it was unclear how and when centromeric Rec8 is liberated from its protector PP2A. One proposal is that bipolar spindle forces separate PP2A from Rec8 as cells enter metaphase II. We show here that sister centromere biorientation is not sufficient to "deprotect" Rec8 at meiosis II in yeast. Instead, our data suggest that the ubiquitin-ligase APC/C Cdc20 removes PP2A from centromeres by targeting for degradation the shugoshin Sgo1 and the kinase Mps1. This implies that Rec8 remains protected until entry into anaphase II when it is phosphorylated concurrently with the activation of separase. Here, we provide further support for this model and speculate on its relevance to mammalian oocytes.

Background: Bipolar patients show high intra-individual variability during cognitive processing. However, it is not known whether there are a specific fluctuations of variability contributing to the overall high cognitive inconsistency. The objective was to compare dynamic profiles of patients and healthy controls to identify hypothetical differences and their associations with overall variability and processing speed., Methods: Changes of reaction times iSD during processing speed test performance over time was measured by dividing the iSD for whole task into four consecutive parts. Motor speed and cognitive effort were controlled., Results: Patients with BD exhibited significantly lower results regarding processing speed and higher intra-individual variability comparing with HC. The profile of intra-individual variability changes over time of performance was significantly different in BD versus HC groups: F(3, 207)=8.60, p<0.0001, η p 2 =0.11. iSD of BD patients in the initial phase of performance was three times higher than in the last. There was no significant differences between four intervals in HC group. Inter-group difference in the initial part of the profiles was significant also after controlling for several cognitive and clinical variables., Limitations: Applied computer version of Cognitive Speed Test was relatively new and, thus, replication studies are needed. Effect seen in the present study is driven mainly by the BD type I., Conclusions: Patients with BD exhibits problems with setting a stimulus-response association in starting phase of cognitive processing. This deficit may negatively interfere with the other cognitive functions, decreasing level of psychosocial functioning, therefore should be explored in future studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Meiosis consists of DNA replication followed by two consecutive nuclear divisions and gametogenesis or spore formation. While meiosis I has been studied extensively, less is known about the regulation of meiosis II. Here we show that Hrr25, the conserved casein kinase 1δ of budding yeast, links three mutually independent key processes of meiosis II. First, Hrr25 induces nuclear division by priming centromeric cohesin for cleavage by separase. Hrr25 simultaneously phosphorylates Rec8, the cleavable subunit of cohesin, and removes from centromeres the cohesin protector composed of shugoshin and the phosphatase PP2A. Second, Hrr25 initiates the sporulation program by inducing the synthesis of membranes that engulf the emerging nuclei at anaphase II. Third, Hrr25 mediates exit from meiosis II by activating pathways that trigger the destruction of M-phase-promoting kinases. Thus, Hrr25 synchronizes formation of the single-copy genome with gamete differentiation and termination of meiosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Processing speed turns out to be the central area of research on cognition in schizophrenia. So far the relationship between this dimension and the IQ level of patients and their healthy siblings has not been investigated., Aim: To investigate the differences in cognitive speed in patients with schizophrenia and their healthy siblings, and to determine whether cognitive speed as a covariate affects differences in IQ and cognitive profiles between groups., Methods: Forty-seven inpatients diagnosed with schizophrenia according to DSM-IV (SCH) and their 36 healthy siblings (HSB) were tested with cognitive speed tasks according to Bartzokis et al. method and Wechsler Intelligence Scale. Additional control for the possible impact of antipsychotic drugs and selected demographic variables on the cognitive performance was taken into account., Results: The siblings scored significantly higher in the cognitive speed task (p < 0.01) than patients, the WAIS-R cognitive test profiles were also significantly different in two ways: between groups, and between single test results in each of the assessed groups. The interaction effect: ANOVA, F(10, 770) = 2.798, p = 0.002. Similarly, the Performance and Full Scale IQs were significantly different, at p < 0.01. After controlling for cognitive speed, all significant differences no longer exist: e.g. Full Scale IQ, p = 0.459., Conclusions: Significant differences in cognitive speed between patients and their healthy siblings generate the differences in the cognitive profile assessed with Wechsler Intelligence Scale. Some problems of cognitive speed diagnosis and further research on the cognitive schizophrenia endophenotype were discussed.

Background: Ataxia telangiectasia mutated (ATM) is a detector of double-strand breaks (DSBs) and a crucial component of the DNA damage response (DDR) along with p53 and NF- κB transcription factors and Wip1 phosphatase. Despite the recent advances in studying the DDR, the mechanisms of cell fate determination after DNA damage induction is still poorly understood., Results: To investigate the importance of various DDR elements with particular emphasis on Wip1, we developed a novel mathematical model of ATM/p53/NF- κB pathways. Our results from in silico and in vitro experiments performed on U2-OS cells with Wip1 silenced to 25 % (Wip1-RNAi) revealed a strong dependence of cellular response to DNA damages on this phosphatase. Notably, Wip1-RNAi cells exhibited lower resistance to ionizing radiation (IR) resulting in smaller clonogenicity and higher apoptotic fraction., Conclusions: In this article, we demonstrated that Wip1 plays a role as a gatekeeper of apoptosis and influences the pro-survival behaviour of cells - the level of Wip1 increases to block the apoptotic decision when DNA repair is successful. Moreover, we were able to verify the dynamics of proteins and transcripts, apoptotic fractions and cells viability obtained from stochastic simulations using in vitro approaches. Taken together, we demonstrated that the model can be successfully used in prediction of cellular behaviour after exposure to IR. Thus, our studies may provide further insights into key elements involved in the underlying mechanisms of the DDR.

Protein-RNA and protein-DNA interactions play fundamental roles in many biological processes. A detailed understanding of these interactions requires knowledge about protein-nucleic acid complex structures. Because the experimental determination of these complexes is time-consuming and perhaps futile in some instances, we have focused on computational docking methods starting from the separate structures. Docking methods are widely employed to study protein-protein interactions; however, only a few methods have been made available to model protein-nucleic acid complexes. Here, we describe NPDock (Nucleic acid-Protein Docking); a novel web server for predicting complexes of protein-nucleic acid structures which implements a computational workflow that includes docking, scoring of poses, clustering of the best-scored models and refinement of the most promising solutions. The NPDock server provides a user-friendly interface and 3D visualization of the results. The smallest set of input data consists of a protein structure and a DNA or RNA structure in PDB format. Advanced options are available to control specific details of the docking process and obtain intermediate results. The web server is available at http://genesilico.pl/NPDock., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)