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Empirical evidence indicates that conscious states, distinguished by the presence of phenomenal qualities, are closely linked to synchronized neural activity patterns whose dynamical characteristics can be attributed to self-organized criticality and phase transitions. These findings imply that insight into the mechanism by which the brain controls phase transitions will provide a deeper understanding of the fundamental mechanism by which the brain manages to transcend the threshold of consciousness. This article aims to show that the initiation of phase transitions and the formation of synchronized activity patterns is due to the coupling of the brain to the zero-point field (ZPF), which plays a central role in quantum electrodynamics (QED). The ZPF stands for the presence of ubiquitous vacuum fluctuations of the electromagnetic field, represented by a spectrum of normal modes. With reference to QED-based model calculations, the details of the coupling mechanism are revealed, suggesting that critical brain dynamics is governed by the resonant interaction of the ZPF with the most abundant neurotransmitter glutamate. The pyramidal neurons in the cortical microcolumns turn out to be ideally suited to control this interaction. A direct consequence of resonant glutamate-ZPF coupling is the amplification of specific ZPF modes, which leads us to conclude that the ZPF is the key to the understanding of consciousness and that the distinctive feature of neurophysiological processes associated with conscious experience consists in modulating the ZPF. Postulating that the ZPF is an inherently sentient field and assuming that the spectrum of phenomenal qualities is represented by the normal modes of the ZPF, the significance of resonant glutamate-ZPF interaction for the formation of conscious states becomes apparent in that the amplification of specific ZPF modes is inextricably linked with the excitation of specific phenomenal qualities. This theory of consciousness, according to which phenomenal states arise through resonant amplification of zero-point modes, is given the acronym TRAZE. An experimental setup is specified that can be used to test a corollary of the theory, namely, the prediction that normally occurring conscious perceptions are absent under experimental conditions in which resonant glutamate-ZPF coupling is disrupted.

Objectiveto analyze oncological, obstetrical, and surgical results of young early-stage cervical cancer patients who underwent radical trachelectomy (RT) surgery and wished to maintain their fertility.Methodologya retrospective cohort study was carried out concerning cases attended at the Brazilian National Cancer Institute Gynecology Oncology Service. Patients who underwent RT between January 2005 and January 2021 were included.ResultsA total of 32 patients with median age of 32 years old, 62.5% of whom were nulliparous, were assessed. Concerning cancer type, 65.6% squamous cell carcinoma (SCC) cases, 31.2% adenocarcinoma cases and 3.1% adenosquamous carcinoma cases were verified. Stage IA2 was evidenced in 12.5% of the patients and stage IB < 4 cm in 87.5%. Regarding surgical approaches, 68.25% of the patients underwent vaginal RT (VRT), 18.75%, abdominal RT (ART), 9.3%, the robotic radical trachelectomy (RORT) and 3.1%, video laparoscopy radical trachelectomy (VLRT). The median number of removed lymph nodes was 14, with only two detected as positive. Two cases of positive surgical margins were noted. A total of 3.1% intraoperative and 31.25% postoperative complications were observed, with cervical stenosis being the most common. The recurrence rate of the study was 3.1%, with a median follow-up time of 87 months, where 3.1% deaths occurred. The pregnancy rate of the study was 17.85% (5/28), with 54.5% evolving to live births and 45.5% evolving to abortion.ConclusionRadical trachelectomy is a feasible procedure presenting good oncological results and acceptable pregnancy rates.

The mucosal immunity is crucial for restricting SARS-CoV-2 at its entry site. Intramuscularly applied vaccines against SARS-CoV-2 stimulate high levels of neutralizing Abs in serum, but the impact of these intramuscular vaccinations on features of mucosal immunity is less clear. Here, we analyzed kinetic and functional properties of anti-SARS-CoV-2 Abs in the saliva after vaccination with BNT162b2. We analyzed a total of 24 healthy donors longitudinally for up to 16 months. We found that specific IgG appeared in the saliva after the second vaccination, declined thereafter and reappeared after the third vaccination. Adjusting serum and saliva for the same IgG concentration revealed a strong correlation between the reactivity in these two compartments. Reactivity to VoCs correlated strongly as seen by ELISAs against RBD variants and by live-virus neutralizing assays against replication-competent viruses. For further functional analysis, we purified IgG and IgA from serum and saliva. In vaccinated donors we found neutralizing activity towards authentic virus in the IgG, but not in the IgA fraction of the saliva. In contrast, IgA with neutralizing activity appeared in the saliva only after breakthrough infection. In serum, we found neutralizing activity in both the IgA and IgG fractions. Together, we show that intramuscular mRNA vaccination transiently induces a mucosal immunity that is mediated by IgG and thus differs from the mucosal immunity after infection. Waning of specific mucosal IgG might be linked to susceptibility for breakthrough infection.

IntroductionTo explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue interaction, we assessed their ability to penetrate, replicate and cause damage in a human 3D respiratory model.MethodsFor this, we used TEER measurements, real-time PCR, LDH, cytokine and complex confocal imaging analyses.Results and discussionWe observed that Delta readily penetrated deep into the respiratory epithelium and this was associated with major tissue destruction, high LDH activity, high viral loads and pronounced innate immune activation as observed by intrinsic C3 activation and IL-6 release at infection sites. In contrast, Omicron subvariants BA.5, BQ.1.1 and BF7 remained superficially in the mucosal layer resulting merely in outward-directed destruction of cells, maintenance of epithelial integrity, minimal LDH activity and low basolateral release of virus at infection sites, as well as significantly smaller areas of complement activation and lower IL-6 secretion. Interestingly, also within Omicron subvariants differences were observed with newer Omicron subvariants BQ.1.1 and BF.7 illustrating significantly reduced viral loads, IL-6 release and LDH activity compared to BA.5. Our data indicate that earliest interaction events after SARS-CoV-2 transmission may have a role in shaping disease severity.

TLR Agonists have promising activity in preclinical models of viral infection and cancer. However, clinical use is only in topical application. Systemic uses of TLR-ligands such as Resiquimod, have failed due to adverse effects that limited dose and thus, efficacy. This issue could be related to pharmacokinetic properties that include fast elimination leading to low AUC with simultaneously high cmax at relevant doses. The high cmax is associated with a sharp, poorly tolerated cytokine pulse, suggesting that a compound with a higher AUC/cmax-ratio could provide a more sustained and tolerable immune activation. Our approach was to design TLR7/8-agonist Imidazoquinolines intended to partition to endosomes via acid trapping using a macrolide-carrier. This can potentially extend pharmacokinetics and simultaneously direct the compounds to the target compartment. The compounds have hTLR7/8-agonist activity (EC50 of the most active compound in cellular assays: 75-120 nM hTLR7, 2.8-3.1 µM hTLR8) and maximal hTLR7 activation between 40 and 80% of Resiquimod. The lead candidates induce secretion of IFNα from human Leukocytes in the same range as Resiquimod but induce at least 10-fold less TNFα in this system, consistent with a higher specificity for human TLR7. This pattern was reproduced in vivo in a murine system, where small molecules are thought not to activate TLR8. We found that Imidazoquinolines conjugated to a macrolide or, substances carrying an unlinked terminal secondary amine, had longer exposure compared with Resiquimod. The kinetics of pro-inflammatory cytokine release for these substances in vivo were slower and more extended (for comparable AUCs, approximately half-maximal plasma concentrations). Maximal IFNα plasma levels were reached 4 h post application. Resiquimod-treated groups had by then returned to baseline from a peak at 1 h. We propose that the characteristic cytokine profile is likely a consequence of altered pharmacokinetics and, potentially, enhanced endosomal tropism of the novel substances. In particular, our substances are designed to partition to cellular compartments where the target receptor and a distinct combination of signaling molecules relevant to IFNα-release are located. These properties could address the tolerability issues of TLR7/8 ligands and provide insight into approaches to fine-tune the outcomes of TLR7/8 activation by small molecules.

The neural activity patterns associated with advanced cognitive processes are characterized by a high degree of collective organization, which raises the question of whether macroscopic quantum phenomena play a significant role in cortical dynamics. In order to pursue this question and scrutinize the feasibility of macroscopic quantum coherence in the brain, a model is developed regarding the functioning of microcolumns, which are the basic functional units of the cortex. This model assumes that the operating principle of a microcolumn relies on the interaction of a pool of neurotransmitter (glutamate) molecules with the vacuum fluctuations of the electromagnetic field, termed zero-point field (ZPF). Quantitative calculations reveal that the coupling strength of the glutamate pool to the resonant ZPF modes lies in the critical regime in which the criterion for the initiation of a phase transition is fulfilled, driving the ensemble of initially independent molecules toward a coherent state and resulting in the formation of a coherence domain that extends across the full width of a microcolumn. The formation of a coherence domain turns out to be an energetically favored state shielded by a considerable energy gap that protects the collective state against thermal perturbations and entails decoherence being greatly slowed down. These findings suggest that under the special conditions encountered in cortical microcolumns the emergence of macroscopic quantum phenomena is feasible. This conclusion is further corroborated by the insight that the presence of a coherence domain gives rise to downstream effects which may be crucial for the cortical communication and the formation of large-scale activity patterns. Taken together, the presented model sheds new light on the fundamental mechanism underlying cortical dynamics and suggests that long-range synchronization in the brain results from a bottom-up orchestration process involving the ZPF.

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.

The self-renewal and lineage-specific differentiation of stem cells are regulated by interactions with their microenvironments, called stem cell niche. Stem cells receive both biochemical and biophysical cues from their niche, which leads to the activation of signaling pathways, resulting in the modulation of gene expressions to guide their fate. Most of previous studies are focused on the effect of substrate stiffness using hydrogels with different Young’s moduli, and information is lacking on the effect of the discreteness of cell–substrate contacts on stem cells. Using mouse pluripotent, embryonic stem cells (mESCs) as the model system for early development, we quantitatively investigated the migration, dynamic deformation, and adhesion of mESCs on sparse and dense gelatin nanofibers deposited on glass surfaces, with a continuous layer of gelatin coated on glass substrates as the control. After confirming the maintenance of pluripotency on all the surfaces throughout the experiments, the centroid trajectories were monitored using timelapse imaging. The mean square displacement analysis indicated that both the diffusion coefficient and exponent were largest on sparse nanofibers, while the diffusion coefficient of mESCs on dense nanofibers was comparable to that on the control. Moreover, power spectral analysis of the shape deformation in the Fourier mode indicated that mESCs predominantly underwent elliptic deformation (mode 2), with the largest energy dissipation on sparse nanofibers. These data suggest that mESCs can deform and move on sparse nanofibers owing to the discrete cell–surface contact points. Intriguingly, using a self-developed technique based on laser-induced shock waves, a distinctly larger critical pressure was required to detach cells from nanofibers than from continuous gelatin. This finding suggests that the continuous but weak cell-substrate contacts suppress the deformation-driven mESC migration. As one of the key biological functions of stem cells, the proliferation rate of mESCs on these surfaces was determined. Although the observed difference was not statistically significant, the highest proliferation rate was observed on nanofibers, suggesting that the discreteness of cell–surface contacts can be used to regulate not only spatio-temporal dynamics but also the biological function of pluripotent stem cells.

Methane (CH4) emissions from aquatic systems have recently been comprised to account for up to 50% of global CH4 emissions, with lakes representing one of the largest CH4 sources within this pool. However, there is large uncertainty associated with CH4 emissions from freshwater environments to the atmosphere, because of a lack of understanding in the spatial and temporal dynamics of CH4 sources and sinks, as well as underlying mechanisms and processes. In this study, we investigated the concentrations and stable carbon (δ13C-CH4) and hydrogen (δ2H-CH4) isotope composition of CH4 in a small eutrophic lake (Lake Willersinnweiher) with seasonal stratification and its spatial and temporal variation. We found that while supersaturation of CH4 in the entire water column was present throughout the whole year, the isotopic composition of CH4 in sediment and water column varied depending on lake stratification, physiochemical conditions, and lake depth. During the stratification period, isotopic characteristics of pelagic surface water CH4 differed from littoral and sedimentary CH4, suggesting likely mixing of CH4 from different sources including vertical and lateral input as well as groundwater input and potentially oxic methane production in the mixed surface water layer. Aerobic CH4 oxidation indicated by a strong increase in both δ13C-CH4 and δ2H-CH4 values at the bottom of the oxycline was found to significantly reduce upward migrating CH4 released at the sediment-water interface. In the sediment, stable isotope characteristics of CH4 showed an increasing dominance of the acetoclastic CH4 formation pathway from the pelagic towards the littoral area. Furthermore, the occurrence of sulfate-dependent anaerobic methane oxidation in the sediment was suggested by an increase in δ13C-CH4 and δ2H-CH4 values. During the mixing period, the isotopic CH4 composition of the water column was distinctively less negative than during the stratification period potentially resulting from a greater impact of groundwater CH4 input compared to the stratification period. Our findings implicate that the application of concentrations and dual isotope measurements of CH4 is a promising approach for constraining CH4 sinks and sources in Lake Willersinnweiher and potentially other small lakes to clearly disentangle the complex CH4 dynamics in lakes both spatially and seasonally.

Objective: To strengthen future methodological choices regarding the measurement of cognition within the field of audiology, the current study aimed to examine the effect of, among other things, hearing sensitivity on the backward corsi tapping task (i.e., visual working memory and processing speed) and the letter-number sequencing task (i.e., verbal working memory and processing speed).Design and Study Sample: The backward corsi tapping task and the letter-number sequencing task were administered to 184 participants, aged between 18 and 69 years. The effect of age, sex, educational level, awakeness, and hearing sensitivity on verbal and visual working memory and processing speed was assessed using stepwise multiple regression analyses.Results: For all outcome variables, a decrease in performance was observed with increasing age. For visual and verbal working memory, males outperformed females, whereas no clear sex effect was observed for visual and verbal processing speed. Hearing sensitivity had only a significant impact on visual processing speed.Conclusion: The importance to evaluate cognitive construct validity within audiological research was highlighted. Further research should focus on investigating the associations between speech understanding on the one hand and the backward corsi tapping task and letter-number sequencing task on the other hand.

The goal of this work is to compile the basic components for the construction of an electromagnetic field theory of consciousness that meets the standards of a fundamental theory. An essential cornerstone of the conceptual framework is the vacuum state of quantum electrodynamics which, contrary to the classical notion of the vacuum, can be viewed as a vibrant ocean of energy, termed zero-point field (ZPF). Being the fundamental substrate mediating the electromagnetic force, the ubiquitous ZPF constitutes the ultimate bedrock of all electromagnetic phenomena. In particular, resonant interaction with the ZPF is critical for understanding rapidly forming, long-range coherent activity patterns that are characteristic of brain dynamics. Assuming that the entire phenomenal color palette is rooted in the vibrational spectrum of the ZPF and that each normal mode of the ZPF is associated with an elementary shade of consciousness, it stands to reason that conscious states are caused by the coupling of the brain to a particular set of normal modes selectively filtered from the full frequency spectrum of the ZPF. From this perspective, the brain is postulated to function as a resonant oscillator that couples to a specific range of ZPF modes, using these modes as a keyboard for the composition of an enormous variety of phenomenal states. Theoretical considerations suggest that the brain-ZPF interface is controlled by altering the concentrations of neurotransmitters, placing the detailed study of the neurotransmitter-ZPF interaction at the center of future research activities.

Humoral immunity is mainly mediated by a B cell population highly specialized to synthesize and secrete large quantities of antibodies – the antibody-secreting cells (ASC). In the gastrointestinal environment, a mixture of foreign antigens from the diet, commensal microbiota as well as occasional harmful pathogens lead to a constant differentiation of B cells into ASC. Due to this permanent immune response, more than 80% of mammalian ASC reside in the gut, of which most express immunoglobulin A (IgA). IgA antibodies contribute to intestinal homeostasis and can mediate protective immunity. Recent evidence points at a role for gut-derived ASC in modulating immune responses also outside of mucosal tissues. We here summarize recent evidence for wandering ASC, their antibodies and their involvement in systemic immune responses.

Spatial information of cells in their tissue microenvironment is necessary to understand the complexity of pathophysiological processes. Volumetric imaging of cleared organs provides this information; however, current protocols are often elaborate, expensive, and organ specific. We developed a simplified, cost-effective, non-hazardous approach for efficient tissue clearing and multi-organ volumetric imaging (EMOVI). EMOVI enabled multiplexed antibody-based immunolabeling, provided adequate tissue transparency, maintained cellular morphology and preserved fluorochromes. Exemplarily, EMOVI allowed the detection and quantification of scarce cell populations during pneumonitis. EMOVI also permitted histo-cytometric analysis of MHC-II expressing cells, revealing distinct populations surrounding or infiltrating glomeruli of nephritic kidneys. Using EMOVI, we found widefield microscopy with real-time computational clearing as a valuable option for rapid image acquisition and detection of rare cellular events in cleared organs. EMOVI has the potential to make tissue clearing and volumetric imaging of immune cells applicable for a broad audience by facilitating flexibility in organ, fluorochrome and microscopy usage.

Introduction: Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a nerve's capacity for axonal transport, it may be visualized by targeted application of a contrast agent and assessing the distribution through radiological imaging, thus revealing a nerve's continuity. This concept has not been explored, however, may potentially guide the treatment of peripheral nerve injuries. In this experimental proof-of-concept study, we tested imaging through MRI after administering gadolinium-based contrast agents which were then retrogradely transported.Methods: We synthesized MRI contrast agents consisting of paramagnetic agents and various axonal transport facilitators (HSA-DTPA-Gd, chitosan-DTPA-Gd or PLA/HSA-DTPA-Gd). First, we measured their relaxivity values in vitro to assess their radiological suitability. Subsequently, the sciatic nerve of 24 rats was cut and labeled with one of the contrast agents to achieve retrograde distribution along the nerve. One week after surgery, the spinal cords and sciatic nerves were harvested to visualize the distribution of the respective contrast agent using 7T MRI. In vivo MRI measurements were performed using 9.4 T MRI on the 1st, 3rd, and the 7th day after surgery. Following radiological imaging, the concentration of gadolinium in the harvested samples was analyzed using inductively coupled mass spectrometry (ICP-MS).Results: All contrast agents demonstrated high relaxivity values, varying between 12.1 and 116.0 mM−1s−1. HSA-DTPA-Gd and PLA/HSA-DTPA-Gd application resulted in signal enhancement in the vertebral canal and in the sciatic nerve in ex vivo MRI. In vivo measurements revealed significant signal enhancement in the sciatic nerve on the 3rd and 7th day after HSA-DTPA-Gd and chitosan-DTPA-Gd (p < 0.05) application. Chemical evaluation showed high gadolinium concentration in the sciatic nerve for HSA-DTPA-Gd (5.218 ± 0.860 ng/mg) and chitosan-DTPA-Gd (4.291 ± 1.290 ng/mg).Discussion: In this study a novel imaging approach for the evaluation of a peripheral nerve's integrity was implemented. The findings provide radiological and chemical evidence of successful contrast agent uptake along the sciatic nerve and its distribution within the spinal canal in rats. This novel concept may assist in the diagnostic process of peripheral nerve injuries in the future.

Coccidioides immitis and C. posadasii are soil dwelling dimorphic fungi found in North and South America. Inhalation of aerosolized asexual conidia can result in asymptomatic, acute, or chronic respiratory infection. In the United States there are approximately 350,000 new infections per year. The Coccidioides genus is the only known fungal pathogen to make specialized parasitic spherules, which contain endospores that are released into the host upon spherule rupture. The molecular determinants involved in this key step of infection remain largely elusive as 49% of genes are hypothetical with unknown function. An attenuated mutant strain C. posadasii Δcts2/Δard1/Δcts3 in which chitinase genes 2 and 3 were deleted was previously created for vaccine development. This strain does not complete endospore development, which prevents completion of the parasitic lifecycle. We sought to identify pathways active in the wild-type strain during spherule remodeling and endospore formation that have been affected by gene deletion in the mutant. We compared the transcriptome and volatile metabolome of the mutant Δcts2/Δard1/Δcts3 to the wild-type C735. First, the global transcriptome was compared for both isolates using RNA sequencing. The raw reads were aligned to the reference genome using TOPHAT2 and analyzed using the Cufflinks package. Genes of interest were screened in an in vivo model using NanoString technology. Using solid phase microextraction (SPME) and comprehensive two-dimensional gas chromatography – time-of-flight mass spectrometry (GC × GC-TOFMS) volatile organic compounds (VOCs) were collected and analyzed. Our RNA-Seq analyses reveal approximately 280 significantly differentially regulated transcripts that are either absent or show opposite expression patterns in the mutant compared to the parent strain. This suggests that these genes are tied to networks impacted by deletion and may be critical for endospore development and/or spherule rupture in the wild-type strain. Of these genes, 14 were specific to the Coccidioides genus. We also found that the wild-type and mutant strains differed significantly in their production versus consumption of metabolites, with the mutant displaying increased nutrient scavenging. Overall, our results provide the first targeted list of key genes that are active during endospore formation and demonstrate that this approach can define targets for functional assays in future studies.

The study of chemical bioactivity in the rhizosphere has recently broadened to include microbial metabolites, and their roles in niche construction and competition via growth promotion, growth inhibition, and toxicity. Several prior studies have identified bacteria that produce volatile organic compounds (VOCs) with antifungal activities, indicating their potential use as biocontrol organisms to suppress phytopathogenic fungi and reduce agricultural losses. We sought to expand the roster of soil bacteria with known antifungal VOCs by testing bacterial isolates from wild and cultivated cranberry bog soils for VOCs that inhibit the growth of four common fungal and oomycete plant pathogens, and Trichoderma sp. Twenty one of the screened isolates inhibited the growth of at least one fungus by the production of VOCs, and isolates of Chromobacterium vaccinii had broad antifungal VOC activity, with growth inhibition over 90% for some fungi. Fungi exposed to C. vaccinii VOCs had extensive morphological abnormalities such as swollen hyphal cells, vacuolar depositions, and cell wall alterations. Quorum-insensitive cviR− mutants of C. vaccinii were significantly less fungistatic, indicating a role for quorum regulation in the production of antifungal VOCs. We collected and characterized VOCs from co-cultivation assays of Phoma sp. exposed to wild-type C. vaccinii MWU328, and its cviR− mutant using stir bar sorptive extraction and comprehensive two-dimensional gas chromatography—time-of-flight mass spectrometry (SBSE-GC × GC-TOFMS). We detected 53 VOCs that differ significantly in abundance between microbial cultures and media controls, including four candidate quorum-regulated fungistatic VOCs produced by C. vaccinii. Importantly, the metabolomes of the bacterial-fungal co-cultures were not the sum of the monoculture VOCs, an emergent property of their VOC-mediated interactions. These data suggest semiochemical feedback loops between microbes that have co-evolved for sensing and responding to exogenous VOCs.

A series of 2-phenylbenzothiazole derivatives and their corresponding organometallic ruthenium(II) and osmium(II) complexes were synthesized, designed to exploit both, the attributes of the half-sandwich transition metal scaffold and the bioactivity spectrum of the applied 2-phenylbenzothiazoles. All synthesized compounds were characterized via standard analytical methods. The obtained organometallics showed antiproliferative activity in the low μM range and are thus at least an order of magnitude more potent than the free ligands. ESI-MS measurements showed that the examined compounds were stable in aqueous solution over 48 h. Additionally, their binding preferences to small biomolecules, their cellular accumulation and capacity of inducing apoptosis/necrosis were investigated. Based on the fluorescence properties of the selected ligand and the corresponding ruthenium complex, their subcellular distribution was studied by fluorescence microscopy, revealing a high degree of colocalization with acidic organelles of cancer cells.

Despite the progress made in studying the observable exteriors of conscious processes, which are reflected in the neural correlates of consciousness (NCC), there are still no satisfactory answers to two closely related core questions. These are the question of the origin of the subjective, phenomenal aspects of consciousness, and the question of the causal mechanisms underlying the generation of specific phenomenal states. In this article, we address these questions using a novel variant of cosmopsychism, a holistic form of panpsychism relying on the central idea that the universe is imbued with a ubiquitous field of consciousness (UFC). This field is understood as a foundational dual-aspect component of the cosmos, the extrinsic appearance of which is physical in nature and the intrinsic manifestation of which is phenomenological in nature. We argue that this approach brings a new perspective into play, according to which the organizational characteristics of the NCC are indicative of the brain’s interaction with and modulation of the UFC. Key insights from modern physics suggest that the modulation mechanism is identical with the fundamental mechanism underlying quantum systems, resulting in the conclusion that a coherently oscillating neural cell assembly acquires phenomenal properties by tapping into the universal pool of phenomenal nuances predetermined by the UFC, or more specifically, by entering into a temporary liaison with the UFC and extracting a subset of phenomenal tones from the phenomenal color palette inherent in the basic structure of the UFC. This hypothesis is supported by a substantial body of empirical evidence.

Understanding experiences of and responses to anxiety is foundational to developing robust theories of entrepreneurial behavior. Using open-ended, vignette and graphical elicitation interviews with 77 entrepreneurs, we inductively investigate the experience of and coping responses to anxiety during the entrepreneurship process. We develop a comprehensive and dynamic goal-striving model to explain experiencing and coping with entrepreneurial anxiety by integrating empirical findings with appraisal and control theories. In doing so, we theorize that entrepreneurial anxiety is endogenous to a cyclical conception of goal-striving, such that various sources of anxiety make sense only in consideration of the goals, standards or values to which they pertain. In this regard, entrepreneurs’ coping responses influence four different points of an iterative goal-striving cycle—an insight that moves beyond problematic static and binary coping classifications.

The main goal of this article consists in addressing two fundamental issues of consciousness research and cognitive science, namely, the question of why declarative memory functions are inextricably linked with phenomenal awareness and the question of the physical basis of memory traces. The presented approach proposes that high-level cognitive processes involving consciousness employ a universal mechanism by means of which they access and modulate an omnipresent background field that is identified with the zero-point field (ZPF) specified by stochastic electrodynamics (SED), a branch of physics that deals with the universal principles underlying quantum systems. In addition to its known physical properties and memory capacities, the ZPF is hypothesized to be an immanently sentient medium. It is propounded that linking up to a particular field mode of the ZPF activates a particular phenomenal nuance, implying that the phase-locked coupling of a set of field modes, i.e., the formation of a so-called ZPF information state, constitutes an appropriate mechanism for the amalgamation of elementary shades of consciousness into a complex state of consciousness. Since quantum systems rest exactly on this mechanism, conscious memory processes in the brain are expected to differ from unconscious processes by the presence of the typical features of many-body quantum systems, particularly long-range coherence and attractor formation, which is supported by a huge body of empirical evidence. On this basis, the conceptual framework set out in this article paves the way for a new understanding of the brain as a write–read head interacting with the ZPF, leading to self-consistent interpretations of the neural correlates of memory formation and memory retrieval and explaining why these memory processes are closely intertwined with phenomenal awareness. In particular, the neural correlates suggest that the brain produces consciously perceived memory traces by writing sequences of information states into the ZPF and retrieves consciously experienced memory traces by reading sequences of information states from the ZPF. Using these theoretical foundations, altered states of consciousness and memory disorders can be traced back to impairments of the ZPF write–read mechanism. The mechanism should reveal itself through characteristic photon emissions, resulting in testable predictions.

Biological methane formation is associated with anoxic environments and the activity of anaerobic prokaryotes (Archaea). However, recent studies have confirmed methane release from eukaryotes, including plants, fungi, and animals, even in the absence of microbes and in the presence of oxygen. Furthermore, it was found that aerobic methane emission in plants is stimulated by a variety of environmental stress factors, leading to reactive oxygen species (ROS) generation. Further research presented evidence that molecules with sulfur and nitrogen bonded methyl groups such as methionine or choline are carbon precursors of aerobic methane formation. Once generated, methane is widely considered to be physiologically inert in eukaryotes, but several studies have found association between mammalian methanogenesis and gastrointestinal (GI) motility changes. In addition, a number of recent reports demonstrated anti-inflammatory potential for exogenous methane-based approaches in model anoxia-reoxygenation experiments. It has also been convincingly demonstrated that methane can influence the downstream effectors of transiently increased ROS levels, including mitochondria-related pro-apoptotic pathways during ischemia-reperfusion (IR) conditions. Besides, exogenous methane can modify the outcome of gasotransmitter-mediated events in plants, and it appears that similar mechanism might be active in mammals as well. This review summarizes the relevant literature on methane-producing processes in eukaryotes, and the available results that underscore its bioactivity. The current evidences suggest that methane liberation and biological effectiveness are both linked to cellular redox regulation. The data collectively imply that exogenous methane influences the regulatory mechanisms and signaling pathways involved in oxidative and nitrosative stress responses, which suggests a modulator role for methane in hypoxia-linked pathologies.

Cell wall reinforcement with callose is a frequent plant response to infection. Poly(ADP-ribosyl)ation is a protein post-translational modification mediated by poly(ADP-ribose) polymerases (PARPs). Poly(ADP-ribosyl)ation has well-known roles in DNA damage repair and has more recently been shown to contribute to plant immune responses. 3-aminobenzamide (3AB) is an established PARP inhibitor and it blocks the callose deposition elicited by flg22 or elf18, two microbe-associated molecular patterns (MAMPs). However, we report that an Arabidopsis parp1parp2parp3 triple mutant does not exhibit loss of flg22-induced callose deposition. Additionally, the more specific PARP inhibitors PJ-34 and INH2BP inhibit PARP activity in Arabidopsis but do not block MAMP-induced callose deposition. These data demonstrate off-target activity of 3AB and indicate that 3AB inhibits callose deposition through a mechanism other than poly(ADP-ribosyl)ation. POWDERY MILDEW RESISTANT 4 (PMR4) is the callose synthase responsible for the majority of MAMP- and wound-induced callose deposition in Arabidopsis. 3AB does not block wound-induced callose deposition, and 3AB does not reduce the PMR4 mRNA abundance increase in response to flg22. Levels of PMR4-HA protein increase in response to flg22, and increase even more in flg22 + 3AB despite no callose being produced. The callose synthase inhibitor 2-deoxy-D-glucose does not cause similar impacts on PMR4-HA protein levels. Beyond MAMPs, we find that 3AB also reduces callose deposition induced by powdery mildew (Golovinomyces cichoracearum) and impairs the penetration resistance of a PMR4 overexpression line. 3AB thus reveals pathogenesis-associated pathways that activate callose synthase enzymatic activity distinct from those that elevate PMR4 mRNA and protein abundance.

Human immunodeficiency virus (HIV) relies heavily on the host cellular machinery for production of viral progeny. To exploit cellular proteins for replication and to overcome host factors with antiviral activity, HIV has evolved a set of regulatory and accessory proteins to shape an optimized environment for its replication and to facilitate evasion from the immune system. Several cellular pathways are hijacked by the virus to modulate critical steps during the viral life cycle. Thereby, post-translational modifications (PTMs) of viral and cellular proteins gain increasingly attention as modifying enzymes regulate virtually every step of the viral replication cycle. This review summarizes the current knowledge of HIV-host interactions influenced by PTMs with a special focus on acetylation, ubiquitination, and phosphorylation of proteins linked to cellular signaling and viral replication. Insights into these interactions are surmised to aid development of new intervention strategies.

This article presents a new interpretation of the consciousness-related neuroscientific findings using the framework of stochastic electrodynamics (SED), a branch of physics that sheds light on the basic principles underlying quantum systems. It is propounded that SED supplemented by two well-founded hypotheses leads to a satisfying explanation of the neural correlates of consciousness. The theoretical framework thus defined is based on the notion that all conceivable shades of phenomenal awareness are woven into the frequency spectrum of a universal background field, called zero-point field (ZPF), implying that the fundamental mechanism underlying conscious systems rests upon the access to information available in the ZPF. The body of evidence can be interpreted such that in the extroverted, stimulus-oriented operating mode the brain produces streams of consciousness by periodically writing persistent information states into the ZPF (theta cycle). In the introspective operating mode, which goes along with activations of the default mode network, the brain is receptive to the flow of ZPF information states that constitutes the record of conscious experiences, suggesting that the sense of self and the retrieval of memories is accomplished by periodically reading (filtering) persistent information states from the ZPF (alpha cycle). Moreover, the data support the conclusion that meditative practices and psychedelics detune the filter, thus preventing the instantiation of self-referential conscious states, which leads to the dissolution of the ego. Instead, the brain taps into a wider spectrum of ZPF modes and, hence, gains access to an extended phenomenal color palette, resulting in expanded consciousness.

Ionic liquids (ILs) are per definition salts with melting points below 100°C and might be green alternatives for the extraction of heavy metals from aqueous solutions due to their favorable environmental and physico-chemical properties. Partial solution during extraction, so-called leaching, however, limits their applicability. The present study synthesizes three novel ammonium and phosphonium ILs based on 3-hydroxy-2-naphthoic acid—trihexyltetradecylphosphonium—([P66614]), methyltrioctylphosphonium—([P1888]), and methyltrioctylammonium 3-hydroxy-2-naphthoate ([N1888][HNA])—by a deprotonation-metathesis route. The aims were to improve stability during extraction while still achieving high selectivity toward heavy metal ions, as well as to study the impact of different alkyl chains and the central atom of the cation on physico-chemical properties, extraction efficacy, and leaching. Extraction capabilities for the seven heavy metals Ag, Cd, Co, Cu, Mn, Ni, and Pb were studied in pure water at pH 8.0. Further experiments were conducted in water containing 30 g L−1 NaCl to simulate a seawater matrix and/or 30 mg L−1 humic acids, as well as metal-spiked natural water samples. All three ILs showed extraction efficacies ≥90% for Cu and Pb after 24 h. Overall, extraction efficacies for Ag, Cd, Cu, and Pb were highest for drinking water samples. Ag and Cd extraction was increased by up to 41% in (hyper-) saline samples using IL [P66614][HNA] compared with pure water samples. Leaching values were reduced down to 0.07% loss of the applied IL, which can be attributed to the hydrophobic character of 3-hydroxy-2-naphthoate. Our results represent a positive development toward a greener extraction of heavy metals from natural waters.

Conventional dendritic cells (cDCs) are versatile activators of immune responses that develop as part of the myeloid lineage downstream of hematopoietic stem cells. We have recently shown that in mice precursors of cDCs, but not of other leukocytes, are marked by expression of DNGR-1/CLEC9A. To genetically deplete DNGR-1-expressing cDC precursors and their progeny, we crossed Clec9a-Cre mice to Rosa-lox-STOP-lox-diphtheria toxin (DTA) mice. These mice develop signs of age-dependent myeloproliferative disease, as has been observed in other DC-deficient mouse models. However, despite efficient depletion of cDC progenitors in these mice, cells with phenotypic characteristics of cDCs populate the spleen. These cells are functionally and transcriptionally similar to cDCs in wild type control mice but show somatic rearrangements of Ig-heavy chain genes, characteristic of lymphoid origin cells. Our studies reveal a previously unappreciated developmental heterogeneity of cDCs and suggest that the lymphoid lineage can generate cells with features of cDCs when myeloid cDC progenitors are impaired.

The synthesis and in vitro cytotoxicity of a series of RuII(arene) complexes with carbohydrate-derived phosphite ligands and various arene co-ligands is described. The arene ligand has a strong influence on the in vitro anticancer activity of this series of compounds, which correlates fairly well with cellular accumulation. The most lipophilic compound bearing a biphenyl moiety and a cyclohexylidene-protected carbohydrate is the most cytotoxic with unprecedented IC50 values for the compound class in three human cancer cell lines. This compound shows reactivity to the DNA model nucleobase 9-ethylguanine, but does not alter the secondary structure of plasmid DNA indicating that other biological targets are responsible for its cytotoxic effect.