Unveiling hidden sources of noise.

Changes in neural activity thought to reflect brain aging may be partly influenced by age-dependent signals 'leaking' from the heart.

Differential effects of haloperidol on neural oscillations during wakefulness and sleep.

The electrical activity of the brain, characterized by its frequency components, reflects a complex interplay between periodic (oscillatory) and aperiodic components. These components are associated with various neurophysiological processes, such as the excitation-inhibition balance (aperiodic activity) or interregional communication (oscillatory activity). However, we do not fully understand whether these components are truly independent or if different neuromodulators affect them in different ways. The dopaminergic system has a critical role for cognition and motivation, being a potential modulator of these power spectrum components. To improve our understanding of these questions, we investigated the differential effects of this system on these components using electrocorticogram recordings in cats, which show clear oscillations and aperiodic 1/f activity. Specifically, we focused on the effects of haloperidol (a D2 receptor antagonist) on oscillatory and aperiodic dynamics during wakefulness and sleep. By parameterizing the power spectrum into these two components, our findings reveal a robust modulation of oscillatory activity by the D2 receptor across the brain. Surprisingly, aperiodic activity was not significantly affected and exhibited inconsistent changes across the brain. This suggests a nuanced interplay between neuromodulation and the distinct components of brain oscillations, providing insights into the selective regulation of oscillatory dynamics in awake states.

Evaluating and Comparing Measures of Aperiodic Neural Activity.

Neuro-electrophysiological recordings contain prominent aperiodic activity - meaning irregular activity, with no characteristic frequency - which has variously been referred to as 1/f (or 1/f-like activity), fractal, or 'scale-free' activity. Previous work has established that aperiodic features of neural activity is dynamic and variable, relating (between subjects) to healthy aging and to clinical diagnoses, and also (within subjects) tracking conscious states and behavioral performance. There are, however, a wide variety of conceptual frameworks and associated methods for the analyses and interpretation of aperiodic activity - for example, time domain measures such as the autocorrelation, fractal measures, and/or various complexity and entropy measures, as well as measures of the aperiodic exponent in the frequency domain. There is a lack of clear understanding of how these different measures relate to each other and to what extent they reflect the same or different properties of the data, which makes it difficult to synthesize results across approaches and complicates our overall understanding of the properties, biological significance, and demographic, clinical, and behavioral correlates of aperiodic neural activity. To address this problem, in this project we systematically survey the different approaches for measuring aperiodic neural activity, starting with an automated literature analysis to curate a collection of the most common methods. We then evaluate and compare these methods, using statistically representative time series simulations. In doing so, we establish consistent relationships between the measures, showing that much of what they capture reflects shared variance - though with some notable idiosyncrasies. Broadly, frequency domain methods are more specific to aperiodic features of the data, whereas time domain measures are more impacted by oscillatory activity. We extend this analysis by applying the measures to a series of empirical EEG and iEEG datasets, replicating the simulation results. We conclude by summarizing the relationships between the multiple methods, emphasizing opportunities for reexamining previous findings and for future work.

Changes in electrophysiological aperiodic activity during cognitive control in Parkinson's disease.

Cognitive symptoms in Parkinson's disease are common and can significantly affect patients' quality of life. Therefore, there is an urgent clinical need to identify a signature derived from behavioural and/or neuroimaging indicators that could predict which patients are at increased risk for early and rapid cognitive decline. Recently, converging evidence identified that aperiodic activity of the EEG reflects meaningful physiological information associated with age, development, cognitive and perceptual states or pathologies. In this study, we aimed to investigate aperiodic activity in Parkinson's disease during cognitive control and characterize its possible association with behaviour. Here, we recorded high-density EEG in 30 healthy controls and 30 Parkinson's disease patients during a Simon task. We analysed task-related behavioural data in the context of the activation-suppression model and extracted aperiodic parameters (offset, exponent) at both scalp and source levels. Our results showed lower behavioural performances in cognitive control as well as higher offsets in patients in the parieto-occipital areas, suggesting increased excitability in Parkinson's disease. A small congruence effect on aperiodic parameters in pre- and post-central brain areas was also found, possibly associated with task execution. Significant differences in aperiodic parameters between the resting-state, pre- and post-stimulus phases were seen across the whole brain, which confirmed that the observed changes in aperiodic activity are linked to task execution. No correlation was found between aperiodic activity and behaviour or clinical features. Our findings provide evidence that EEG aperiodic activity in Parkinson's disease is characterized by greater offsets, and that aperiodic parameters differ depending on arousal state. However, our results do not support the hypothesis that the behaviour-related differences observed in Parkinson's disease are related to aperiodic changes. Overall, this study highlights the importance of considering aperiodic activity contributions in brain disorders and further investigating the relationship between aperiodic activity and behaviour.

Role of MYO1F in neutrophil and macrophage recruitment and pro-inflammatory cytokine production in Aspergillus fumigatus keratitis.

PURPOSE: Myosin 1f (Myo1f), an unconventional long-tailed class Ⅰ myosin, plays significant roles in immune cell motility and innate antifungal immunity. This study was aimed to assess the expression and role of Myo1f in Aspergillus fumigatus (AF) keratitis. METHODS: Myo1f expression in the corneas of mice afflicted with AF keratitis and in AF keratitis-related cells was assessed using protein mass spectrometry, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunofluorescence. Myo1f expression following pre-treatment with inhibitors of dendritic cell-associated C-type lectin-1 (Dectin-1), Toll-like receptor 4 (TLR-4), and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was also examined. In AF keratitis mouse models, Myo1f small interfering RNA (siRNA) was administered via subconjunctival injection to observe disease progression, inflammatory cell recruitment, and protein production using slit lamp examination, immunofluorescence, hematoxylin-eosin (HE) staining, and western blotting. RESULTS: Myo1f expression was upregulated in both AF keratitis mouse models and AF keratitis-related cells. Dectin-1, TLR-4, and LOX-1 were found to be essential for the production of Myo1f in response to the infection with AF. In mice with AF keratitis, knockdown of Myo1f reduced disease severity, decreased the recruitment of neutrophils alongside macrophages to inflammatory areas, suppressed the myeloid differentiation factor 88 (MyD88)/ nuclear factor-kappaB (NF-κB) signaling pathway, and decreased the production of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, along with IL-6. Additionally, Myo1f was associated with apoptosis and pyroptosis in mice with AF keratitis. CONCLUSIONS: These findings demonstrated that Myo1f contributed to the recruitment of neutrophils and macrophages, the production of pro-inflammatory cytokines, and was associated with apoptosis and pyroptosis during AF keratitis.

PB1-F2 of low pathogenicity H7N7 restricts apoptosis in avian cells.

Avian influenza viruses (AIV) pose a continuous challenge to global health and economy. While countermeasures exist to control outbreaks in poultry, the persistent circulation of AIV in wild aquatic and shorebirds presents a significant challenge to effective disease prevention efforts. PB1-F2 is a non-structural protein expressed from a second open reading frame (+1) of the polymerase basic 1 (PB1) segment. The sequence and length of the PB1-F2 protein can vary depending on the host of origin. While avian isolates typically carry full-length PB1-F2, isolates from mammals, often express truncated forms. The selective advantage of the full-length PB1-F2 in avian isolates is not fully understood. Most research on the role of PB1-F2 in influenza virus replication has been conducted in mammalian systems, where PB1-F2 interfered with the host immune response and induced apoptosis. Here, we used Low Pathogenicity (LP) AIV H7N7 expressing full-length PB1-F2 as well as a knockout mutant. We found that the full-length PB1-F2 of LPAIV prolonged survival of infected cells by limiting apoptotic cell death. Furthermore, PB1-F2 knockout LPAIV significantly decreased MHC-I expression on fibroblasts, delayed tissue healing and increased phagocytic uptake of infected cells, whereas LPAIV expressing PB1-F2 has limited effects. These findings indicate that full-length PB1-F2 enables AIV to cause prolonged infections without severely harming the avian host. Our observations may explain maintenance of AIV in the natural bird reservoir in absence of severe clinical signs.

PPM1F regulates ovarian cancer progression by affecting the dephosphorylation of ITGB1.

PPM1F has been shown to play diverse biological functions in the progression of multiple tumors. PPM1F controls the T788/T789 phosphorylation switch of ITGB1 and regulates integrin activity. However, the impacts of PPM1F and ITGB1 on ovarian cancer (OV) progression remain unclear. Whether there is such a regulatory relationship between PPM1F and ITGB1 in ovarian cancer has not been studied. Therefore, the purpose of this study is to elucidate the function and the mechanism of PPM1F in ovarian cancer. The expression level and the survival curve of PPM1F were analyzed by databases. Gain of function and loss of function were applied to explore the function of PPM1F in ovarian cancer. A tumor formation assay in nude mice showed that knockdown of PPM1F inhibited tumor formation. We tested the effect of PPM1F on ITGB1 dephosphorylation in ovarian cancer cells by co-immunoprecipitation and western blotting. Loss of function was applied to investigate the function of ITGB1 in ovarian cancer. ITGB1-mut overexpression promotes the progression of ovarian cancer. Rescue assays showed the promoting effect of ITGB1-wt on ovarian cancer is attenuated due to the dephosphorylation of ITGB1-wt by PPM1F. PPM1F and ITGB1 play an oncogene function in ovarian cancer. PPM1F regulates the phosphorylation of ITGB1, which affects the occurrence and development of ovarian cancer.

Genetic diversity of Plasmodium malariae in sub-Saharan Africa: a two-marker genotyping approach for molecular epidemiological studies.

Introduction: Plasmodium malariae is the most common non-falciparum species in sub-Saharan Africa. Despite this, data on its genetic diversity is scarce. Therefore, we aimed to establish a P. malariae genotyping approach based on size polymorphic regions that can be easily applied in molecular epidemiological studies. Methods: Four potential genotyping markers, Pm02, Pm09, P. malariae thrombospondin-related anonymous protein (pmtrap), and P. malariae merozoite surface protein fragment 2 (pmmsp1 F2) were amplified via nested PCR and analysed using automated capillary gel electrophoresis. Results: We observed the highest allelic diversity for pmtrap (MOI = 1.61) and pmmsp1 F2 (He = 0.81). Further applying the two markers pmtrap and pmmsp1 F2 on a different sample set of 21 P. malariae positive individuals followed up over one week, we saw a high consistency in their performance. The results show a large complexity and high dynamics of P. malariae infections in the asymptomatic Gabonese study population. Discussion: We successfully implemented a new genotyping panel for P. malariae consisting of only two markers: pmtrap and pmmsp1 F2. It can be easily applied in other settings to investigate the genotype diversity of P. malariae populations, providing further important data on the molecular epidemiology of this parasite species.

Lasmiditan ameliorates serotonergic itch in mice: Possible involvement of 5-HT1F receptors.

Previously, some allergic conditions involving pruritus have been linked to migraine, raising the possibility that migraine and itching may be governed by similar underlying mechanisms. We aimed to investigate the efficacy of Lasmiditan, a highly selective agonist of the 5-hydroxytryptamine 1F (5-HT1F) receptor and a recently approved medication for the treatment of migraine headaches, in ameliorating serotonergic itching. Forty animals were employed in the present study (n = 40). Eight animals were randomly assigned to each of the following study groups (n = 8, in each group): (1) "Normal Saline": This group was given intradermal injections of normal saline (2) "5-HT": The animals were injected with intradermal 5-HT, which was used to induce itching. (3) "Lasmiditan 0.3", "Lasmiditan 1", and "Lasmiditan 3" groups: injected with 5-HT as well as intraperitoneal Lasmiditan at different dose levels (0.3, 1, and 3 mg/kg, respectively). Scratching behavior was recorded for 60 min, and the skin tissue of three mice was sampled at the end of the behavioral experiment to assess the levels of TLR-4, IL-31, 5-HT1F receptor, CGRP & TRPV4. In the present study, we found that Lasmiditan when administered at 1 mg/kg effectively reduced serotonin-induced itching compared to the "5-HT" group (P < 0.0001). Following the administration of Lasmiditan (1 mg/kg), the expression levels of the 5-HT1F receptor significantly increased (P < 0.01). Further, the levels of TLR-4, IL-31, CGRP & TRPV4 were substantially reduced upon the administration of Lasmiditan (1 mg/kg). We found that Lasmiditan is effective in reducing serotonergic itch in mice through its interaction with the 5-HT1F receptor in the skin tissue of mice.

Mitochondria-derived vesicles: potential nano-batteries to recharge the cellular powerhouse.

Mitochondria dysfunction is increasingly recognized as a critical factor in various pathogenic processes. The mechanism governing mitochondrial quality control serves as an adaptive response, ensuring the preservation of mitochondrial morphology, quantity, and overall function, crucial for cell survival. The generation of mitochondria-derived vesicles (MDVs) is one of the processes of mitochondrial quality control. Recent literature has suggested MDV heterogeneity; however, the detailed characteristics of various MDV subtypes still need to be studied better. Recent studies have shown that MDVs also play a role in inter-organelle communication for mitochondria besides quality control. For instance, Hazan et al. demonstrated that functional mitochondria from Saccharomyces cerevisiae release vesicles independent of the fission machinery. These vesicles, falling within the typical size range of MDVs, were selectively loaded with mitochondrial proteins, especially with functional ATP synthase subunits. Intriguingly, these MDVs maintained membrane potential and could generate ATP. Moreover, MDVs could fuse with naïve mitochondria, transferring their ATP generation machinery. Lastly, this study revealed a potential delivery mechanism of ATP-producing vesicles, presenting a promising avenue to rejuvenate ATP-deficient mitochondria. Overall, this study unveils a novel mechanism for inter-organelle communication by vesicles, which is crucial for maintaining cellular homeostasis and could also be important in pathological conditions.

Aperiodic Activity Indexes Neural Hyperexcitability in Generalized Epilepsy.

Generalized epilepsy (GE) encompasses a heterogeneous group of hyperexcitability disorders that clinically manifest as seizures. At the whole-brain level, distinct seizure patterns as well as interictal epileptic discharges (IEDs) reflect key signatures of hyperexcitability in magneto- and electroencephalographic (M/EEG) recordings. Moreover, it had been suggested that aperiodic activity, specifically the slope of the 1/ƒx decay function of the power spectrum, might index neural excitability. However, it remained unclear if hyperexcitability as encountered at the cellular level directly translates to putative large-scale excitability signatures, amenable to M/EEG. In order to test whether the power spectrum is altered in hyperexcitable states, we recorded resting-state MEG from male and female GE patients (n = 51; 29 females; 28.82 ± 12.18 years; mean ± SD) and age-matched healthy controls (n = 49; 22 females; 32.10 ± 12.09 years). We parametrized the power spectra using FOOOF ("fitting oscillations and one over f") to separate oscillatory from aperiodic activity to directly test whether aperiodic activity is systematically altered in GE patients. We further identified IEDs to quantify the temporal dynamics of aperiodic activity around overt epileptic activity. The results demonstrate that aperiodic activity indexes hyperexcitability in GE at the whole-brain level, especially during epochs when no IEDs were present (p = 0.0130; d = 0.52). Upon IEDs, large-scale circuits transiently shifted to a less excitable network state (p = 0.001; d = 0.68). In sum, these results uncover that MEG background activity might index hyperexcitability based on the current brain state and does not rely on the presence of epileptic waveforms.

Report of the Special-purpose Committee on Names of Fungi with the Same Epithet, established at the XIX International Botanical Congress in Shenzhen, China.

A Special-purpose Committee on Fungal Names with the Same Epithet was established at the XIX International Botanical Congress (IBC) in Shenzhen, China in 2017, with a mandate to report to the 12th International Mycological Congress (IMC) with recommendations on a preferred course of action with respect to names of pleomorphic fungi sharing the same epithet under the International Code of Nomenclature for algae, fungi, and plants. This report provides a synthesis of the deliberations from the Special-purpose Committee. We discuss the arguments for and against the proposed solution to the problems that have arisen regarding the nomenclature of fungi described in multiple morphs using the same epithet. We also propose a gentler method of addressing the problem using existing procedures.

Comparison three primer pairs for molecular sex determination in Eurasian pygmy owls (Glaucidium passerinum).

Bird sex determination is fundamental in various ecological and biological studies, although many avian species cannot be sexed visually due to their monomorphic and/or monochromatic appearance. Thus, reliable laboratory methods for sexing are a prerequisite. Most avian nestlings lack sex-related signs, including the Eurasian pygmy owl (Glaucidium passerinum). We performed laboratory sex determination analysis of this species using blood samples of 242 juveniles and nine adults. It relied on the qPCR of the specific intron from the chromo-helicase DNA-binding protein 1 gene. We tested three primer sets, the P2/P8, 2550F/2718R, and CHD1F/CHD1R, commonly used for bird laboratory sexing. The outcomes were displayed on an agarose gel electrophoresis and a plot from melt curve analysis, which had not been previously conducted in Eurasian pygmy owls. We found that only primer set CHD1F/CHD1R proved reliable, as the only one determined sex with one and two band/s and peak/s on the electrophoresis and the melt curve plot for males and females, respectively. The other two primer pairs failed and depicted one band/peak in all specimens regardless of their sex. Therefore, we recommend performing Eurasian pygmy owls' laboratory sexing by qPCR with CHD1F/CHD1R primers only.

Electrical, Optical and Thermal Properties of Ge-Si-Sn-O Thin Films.

This work evaluates the electrical, optical and thermal properties of Sn-doped GexSi1-xOy thin films for use as microbolometer sensing materials. The films were prepared using a combination of a radio frequency (RF) magnetron and direct current (DC) sputtering using a Kurt J Leskar Proline PVD-75 series sputtering machine. Thin films were deposited in an O2+Ar environment at a chamber pressure of 4 mTorr. The thicknesses of the thin films were varied between 300 nm-1.2 µm by varying the deposition time. The morphology and microstructure of thin films were investigated by atomic force microscope (AFM) imaging and X-ray diffraction (XRD), while the atomic composition was determined using the energy dispersive spectroscopy (EDS) function of a scanning electron microscope. The thin film with an atomic composition of Ge0.45Si0.05Sn0.15O0.35 was found to be amorphous. We used the Arrhenius relationship to determine the activation energy as well as temperature coefficient of resistance of the thin films, which were found to be 0.2529 eV and -3.26%/K, respectively. The noise voltage power spectral density (PSD) of the film was analyzed using a Primarius-9812DX noise analyzer using frequencies ranging from 2 Hz to 10 kHz. The noise voltage PSD of the film was found to be 1.76 × 10-11 V2/Hz and 2.78 × 10-14 V2/Hz at 2 Hz and 1KHz frequencies, respectively. The optical constants were determined using the ellipsometry reflection data of samples using an RC2 and infrared (IR) VASE Mark-II ellipsometer from J A Woollam. Absorption, transmission and reflection data for a wavelength range of 900 nm-5000 nm were also determined. We also determined the optical constant values such as the real and imaginary parts of refractive index (n and k, respectively) and real and imaginary part of permittivity (ε1 and ε2, respectively) for wavelength ranges between 193 nm to 35 µm. An optical band gap of 1.03 eV was determined from absorption data and using Tauc's equation. In addition, the thermal conductivity of the film was analyzed using a Linseis thin film analyzer employing the 3ω method. The thermal conductivity of a 780 nm thick film was found to be 0.38 Wm-1K-1 at 300 K. From the data, the Ge-Si-Sn-O alloy was found to be a promising material for use as a sensing material for microbolometers.

CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore.

Creatine kinases are essential for maintaining cellular energy balance by facilitating the reversible transfer of a phosphoryl group from ATP to creatine, however, their role in mitochondrial ATP production remains unknown. This study shows creatine kinases, including CKMT1A, CKMT1B, and CKB, are highly expressed in cells relying on the mitochondrial F1F0 ATP synthase for survival. Interestingly, silencing CKB, but not CKMT1A or CKMT1B, leads to a loss of sensitivity to the inhibition of F1F0 ATP synthase in these cells. Mechanistically, CKB promotes mitochondrial ATP but reduces glycolytic ATP production by suppressing mitochondrial calcium (mCa2+) levels, thereby preventing the activation of mitochondrial permeability transition pore (mPTP) and ensuring efficient mitochondrial ATP generation. Further, CKB achieves this regulation by suppressing mCa2+ levels through the inhibition of AKT activity. Notably, the CKB-AKT signaling axis boosts mitochondrial ATP production in cancer cells growing in a mouse tumor model. Moreover, this study also uncovers a decline in CKB expression in peripheral blood mononuclear cells with aging, accompanied by an increase in AKT signaling in these cells. These findings thus shed light on a novel signaling pathway involving CKB that directly regulates mitochondrial ATP production, potentially playing a role in both pathological and physiological conditions.

Casein kinase 1α mediates phosphorylation of the Merkel cell polyomavirus large T antigen for ß-TrCP destruction complex interaction and subsequent degradation.

Merkel cell polyomavirus (MCPyV) is a double-stranded tumor virus that is the main causative agent of Merkel cell carcinoma (MCC). The MCPyV large T antigen (LT), an essential viral DNA replication protein, maintains viral persistence by interacting with host Skp1-Cullin 1-F-box (SCF) E3 ubiquitin ligase complexes, which subsequently induces LT's proteasomal degradation, restricting MCPyV DNA replication. SCF E3 ubiquitin ligases require their substrates to be phosphorylated to bind them, utilizing phosphorylated serine residues as docking sites. The MCPyV LT unique region (MUR) is highly phosphorylated and plays a role in multiple host protein interactions, including SCF E3 ubiquitin ligases. Therefore, this domain highly governs LT stability. Though much work has been conducted to identify host factors that restrict MCPyV LT protein expression, the kinase(s) that cooperates with the SCF E3 ligase remains unknown. Here, we demonstrate that casein kinase 1 alpha (CK1α) negatively regulates MCPyV LT stability and LT-mediated replication by modulating interactions with the SCF ß-TrCP. Specifically, we show that numerous CK1 isoforms (α, δ, ε) localize in close proximity to MCPyV LT through in situ proximity ligation assays (PLA) and CK1α overexpression mainly resulted in decreased MCPyV LT protein expression. Inhibition of CK1α using short hairpin RNA (shRNA) and treatment of a CK1α inhibitor or an mTOR inhibitor, TORKinib, resulted in decreased ß-TrCP interaction with LT, increased LT expression, and enhanced MCPyV replication. The expression level of the CSNK1A1 gene transcripts is higher in MCPyV-positive MCC, suggesting a vital role of CK1α in limiting MCPyV replication required for establishing persistent infection. IMPORTANCE: Merkel cell polyomavirus (MCPyV) large tumor antigen is a polyphosphoprotein and the phosphorylation event is required to modulate various functions of LT, including viral replication. Therefore, cellular kinase pathways are indispensable for governing MCPyV polyomavirus infection and life cycle in coordinating with the immunosuppression environment at disease onset. Understanding the regulation mechanisms of MCPyV replication by viral and cellular factors will guide proper prevention strategies with targeted inhibitors for MCPyV-associated Merkel cell carcinoma (MCC) patients, who currently lack therapies.

Outbreaks of H5N1 High Pathogenicity Avian Influenza in South Africa in 2023 Were Caused by Two Distinct Sub-Genotypes of Clade 2.3.4.4b Viruses.

In 2023, South Africa continued to experience sporadic cases of clade 2.3.4.4b H5N1 high-pathogenicity avian influenza (HPAI) in coastal seabirds and poultry. Active environmental surveillance determined that H5Nx, H7Nx, H9Nx, H11Nx, H6N2, and H12N2, amongst other unidentified subtypes, circulated in wild birds and ostriches in 2023, but that H5Nx was predominant. Genome sequencing and phylogenetic analysis of confirmed H5N1 HPAI cases determined that only two of the fifteen sub-genotypes that circulated in South Africa in 2021-2022 still persisted in 2023. Sub-genotype SA13 remained restricted to coastal seabirds, with accelerated mutations observed in the neuraminidase protein. SA15 caused the chicken outbreaks, but outbreaks in the Paardeberg and George areas, in the Western Cape province, and the Camperdown region of the KwaZulu-Natal province were unrelated to each other, implicating wild birds as the source. All SA15 viruses contained a truncation in the PB1-F2 gene, but in the Western Cape SA15 chicken viruses, PA-X was putatively expressed as a novel isoform with eight additional amino acids. South African clade 2.3.4.4b H5N1 viruses had comparatively fewer markers of virulence and pathogenicity compared to European strains, a possible reason why no spillover to mammals has occurred here yet.

[Retracted] Mst1 regulates non­small cell lung cancer A549 cell apoptosis by inducing mitochondrial damage via ROCK1/F­actin pathways.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that certain of the EdU assay data shown in Fig. 7E on p. 2418 had already appeared in different form in a previously published paper written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused.  [International Journal of Oncology 53: 2409­2422, 2018; DOI: 10.3892/ijo.2018.4586].

Human Genetics of Ventricular Septal Defect.

Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field.