Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictive Neuronal Adaptation as a Basis for Consciousness

Being able to correctly predict the future and to adjust own actions accordingly can offer a great survival advantage. In fact, this could be the main reason why brains evolved. Consciousness, the most mysterious feature of brain activity, also seems to be related to predicting the future and detecting surprise: a mismatch between actual and predicted situation. Similarly at a single neuron level, predicting future activity and adapting synaptic inputs accordingly was shown to be the best strategy to maximize the metabolic energy for a neuron. Following on these ideas, here we examined if surprise minimization by single neurons could be a basis for consciousness. First, we showed in simulations that as a neural network learns a new task, then the surprise within neurons (defined as the difference between actual and expected activity) changes similarly to the consciousness of skills in humans. Moreover, implementing adaptation of neuronal activity to minimize surprise at fast time scales (tens of milliseconds) resulted in improved network performance. This improvement is likely because adapting activity based on the internal predictive model allows each neuron to make a more “educated” response to stimuli. Based on those results, we propose that the neuronal predictive adaptation to minimize surprise could be a basic building block of conscious processing. Such adaptation allows neurons to exchange information about own predictions and thus to build more complex predictive models. To be precise, we provide an equation to quantify consciousness as the amount of surprise minus the size of the adaptation error. Since neuronal adaptation can be studied experimentally, this can allow testing directly our hypothesis. Specifically, we postulate that any substance affecting neuronal adaptation will also affect consciousness. Interestingly, our predictive adaptation hypothesis is consistent with multiple ideas presented previously in diverse theories of consciousness, such as global workspace theory, integrated information, attention schema theory, and predictive processing framework. In summary, we present a theoretical, computational, and experimental support for the hypothesis that neuronal adaptation is a possible biological mechanism of conscious processing, and we discuss how this could provide a step toward a unified theory of consciousness.
Synergistic Effects of Combined Nurr1 Overexpression and Natural Inducers on the More Efficient Production of Dopaminergic Neuron-Like Cells From Stem Cells

The development of dopaminergic (DA) neurons is a very complex process, and a combination of extrinsic and intrinsic factors involves their differentiation. Transcription factor, Nurr1 plays an essential role in the differentiation and maintenance of midbrain DA neurons. Nurr1-based therapies may restore DA function in Parkinson's disease (PD) by replacing damaged cells with differentiated cells derived from stem cells. Providing tissue-specific microenvironments such as brain extract can effectively induce dopaminergic gene expression in stem cells. The present study aimed to investigate the combined effects of Nurr1 gene overexpression and a neonatal rat brain extract (NRBE) induction on dopaminergic differentiation of P19 stem cells. In order to neural differentiation induction, stably Nurr1-transfected cells were treated with 100 μg/ml of NRBE. The differentiation potential of the cells was then evaluated during a period of 1–3 weeks via various methods. The initial evaluation of the cells by direct observation under a light microscope and cresyl violet specific staining, confirmed neuron-like morphology in the differentiated cells. In addition, different molecular and cellular techniques, including real-time PCR, immunofluorescence, and flow cytometry, demonstrated that the treated cells expressed pan-neuronal and dopaminergic markers. In all experimental groups, neuronal phenotype with dopaminergic neuron-like cells characteristics mainly appeared in the second week of the differentiation protocol. Overall, the results of the present study revealed for the first time the synergistic effects of Nurr1 gene overexpression and possible soluble factors that existed in NRBE on the differentiation of P19 stem cells into dopaminergic neuron-like cells.
Differential Effects of One Meal per Day in the Evening on Metabolic Health and Physical Performance in Lean Individuals

Background: Generally, food intake occurs in a three-meal per 24 h fashion with in-between meal snacking. As such, most humans spend more than ∼ 12–16 h per day in the postprandial state. It may be reasoned from an evolutionary point of view, that the human body is physiologically habituated to less frequent meals. Metabolic flexibility (i.e., reciprocal changes in carbohydrate and fatty acid oxidation) is a characteristic of metabolic health and is reduced by semi-continuous feeding. The effects of time-restricted feeding (TRF) on metabolic parameters and physical performance in humans are equivocal. Methods: To investigate the effect of TRF on metabolism and physical performance in free-living healthy lean individuals, we compared the effects of eucaloric feeding provided by a single meal (22/2) vs. three meals per day in a randomized crossover study. We included 13 participants of which 11 (5 males/6 females) completed the study: age 31.0 ± 1.7 years, BMI 24.0 ± 0.6 kg/m2 and fat mass (%) 24.0 ± 0.6 (mean ± SEM). Participants consumed all the calories needed for a stable weight in either three meals (breakfast, lunch and dinner) or one meal per day between 17:00 and 19:00 for 11 days per study period. Results: Eucaloric meal reduction to a single meal per day lowered total body mass (3 meals/day –0.5 ± 0.3 vs. 1 meal/day –1.4 ± 0.3 kg, p = 0.03), fat mass (3 meals/day –0.1 ± 0.2 vs. 1 meal/day –0.7 ± 0.2, p = 0.049) and increased exercise fatty acid oxidation (p < 0.001) without impairment of aerobic capacity or strength (p > 0.05). Furthermore, we found lower plasma glucose concentrations during the second half of the day during the one meal per day intervention (p < 0.05). Conclusion: A single meal per day in the evening lowers body weight and adapts metabolic flexibility during exercise via increased fat oxidation whereas physical performance was not affected.
Composite Bioinks With Mesoporous Bioactive Glasses—A Critical Evaluation of Results Obtained by In Vitro Experiments

Besides osteoconductivity and a high degradation rate, mesoporous bioactive glasses (MBGs) are specific for their highly ordered channel structure and high specific surface area, making them suitable as drug and/or growth factor delivery systems. On the other hand, the mesoporous channel structure and MBG composition can have an effect on common cell evaluation assays, leading to inconclusive results. This effect is especially important when MBG is mixed in composite bioinks, together with cells. Additionally, the hydrogel component of the ink can influence the degradation of MBG, leading to different ion releases, which can additionally affect the analyses. Hence, our aim here was to show how the MBG structure and composition influence common cell viability and differentiation assays when calcium (Ca)- or magnesium (Mg)-containing glass is part of an alginate-based composite bioink. We suggested pre-labeling of cells with DiI prior to bioprinting and staining with calcein-AM to allow identification of metabolically active cells expressing signals in both green and red channels, allowing the use of fluorescence imaging for cell viability evaluations in the presence of high amounts (7 wt %) of MBGs. The release and uptake of ions during degradation of CaMBG and MgMBG were significantly changed by alginate in the composite bioinks, as confirmed by higher release and uptake from bulk glasses. Additionally, we detected a burst release of Mg2+ from composites only after 24 h of incubation. Furthermore, we demonstrated that released ions and the mesoporous channel structure affect the measurement of lactate dehydrogenase (LDH) and alkaline phosphatase activity (ALP) in bioprinted composite scaffolds. Measured LDH activity was significantly decreased in the presence of CaMBG. On the other hand, the presence of MgMBG induced increased signal measured for the ALP. Taken together, our findings show how composite bioinks containing MBGs can interfere with common analyses, obtaining misleading results.
Long-Term Amelioration Practices Reshape the Soil Microbiome in a Coastal Saline Soil and Alter the Richness and Vertical Distribution Differently Among Bacterial, Archaeal, and Fungal Communities

Globally soil salinity is one of the most devastating environmental stresses affecting agricultural systems and causes huge economic losses each year. High soil salinity causes osmotic stress, nutritional imbalance and ion toxicity to plants and severely affects crop productivity in farming systems. Freezing saline water irrigation and plastic mulching techniques were successfully developed in our previous study to desalinize costal saline soil. Understanding how microbial communities respond during saline soil amelioration is crucial, given the key roles soil microbes play in ecosystem succession. In the present study, the community composition, diversity, assembly and potential ecological functions of archaea, bacteria and fungi in coastal saline soil under amelioration practices of freezing saline water irrigation, plastic mulching and the combination of freezing saline water irrigation and plastic mulching were assessed through high-throughput sequencing. These amelioration practices decreased archaeal and increased bacterial richness while leaving fungal richness little changed in the surface soil. Functional prediction revealed that the amelioration practices, especially winter irrigation with saline water and film mulched in spring, promoted a community harboring heterotrophic features. β-null deviation analysis illustrated that amelioration practices weakened the deterministic processes in structuring coastal saline soil microbial communities. These results advanced our understanding of the responses of the soil microbiome to amelioration practices and provided useful information for developing microbe-based remediation approaches in coastal saline soils.
A Combination of Chest Radiography and Estimated Plasma Volume May Predict In-Hospital Mortality in Acute Heart Failure

Background: Patients with heart failure (HF) often display dyspnea associated with pulmonary congestion, along with intravascular congestion, both may result in urgent hospitalization and subsequent death. A combination of radiographic pulmonary congestion and plasma volume might screen patients with a high risk of in-hospital mortality in the emergency department (ED). Methods: In the pathway of dyspneic patients in emergency (PARADISE) cohort, patients admitted for acute HF were stratified into 4 groups based on high or low congestion score index (CSI, ranging from 0 to 3, high value indicating severe congestion) and estimated plasma volume status (ePVS) calculated from hemoglobin/hematocrit. Results: In a total of 252 patients (mean age, 81.9 years; male, 46.8%), CSI and ePVS were not correlated (Spearman rho <0 .10, p > 0.10). High CSI/high ePVS was associated with poorer renal function, but clinical congestion markers (i.e., natriuretic peptide) were comparable across CSI/ePVS categories. High CSI/high ePVS was associated with a four-fold higher risk of in-hospital mortality (adjusted-OR, 95%CI = 4.20, 1.10-19.67) compared with low CSI/low ePVS, whereas neither high CSI nor ePVS alone was associated with poor prognosis (all-p-value > 0.10; Pinteraction = 0.03). High CSI/high ePVS improved a routine risk model (i.e., natriuretic peptide and lactate)(NRI = 46.9%, p = 0.02), resulting in high prediction of risk of in-hospital mortality (AUC = 0.85, 0.82-0.89). Conclusion: In patients hospitalized for acute HF with relatively old age and comorbidity burdens, a combination of CSI and ePVS was associated with a risk of in-hospital death, and improved prognostic performance on top of a conventional risk model.
Liver Fibrosis—From Mechanisms of Injury to Modulation of Disease

The Transregional Collaborative Research Center “Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease” (referred to as SFB/TRR57) was funded for 13 years (2009–2021) by the German Research Council (DFG). This consortium was hosted by the Medical Schools of the RWTH Aachen University and Bonn University in Germany. The SFB/TRR57 implemented combined basic and clinical research to achieve detailed knowledge in three selected key questions: (i) What are the relevant mechanisms and signal pathways required for initiating organ fibrosis? (ii) Which immunological mechanisms and molecules contribute to organ fibrosis? and (iii) How can organ fibrosis be modulated, e.g., by interventional strategies including imaging and pharmacological approaches? In this review we will summarize the liver-related key findings of this consortium gained within the last 12 years on these three aspects of liver fibrogenesis. We will highlight the role of cell death and cell cycle pathways as well as nutritional and iron-related mechanisms for liver fibrosis initiation. Moreover, we will define and characterize the major immune cell compartments relevant for liver fibrogenesis, and finally point to potential signaling pathways and pharmacological targets that turned out to be suitable to develop novel approaches for improved therapy and diagnosis of liver fibrosis. In summary, this review will provide a comprehensive overview about the knowledge on liver fibrogenesis and its potential therapy gained by the SFB/TRR57 consortium within the last decade. The kidney-related research results obtained by the same consortium are highlighted in an article published back-to-back in Frontiers in Medicine.
Disruptions of the Human Connectome Associated With Hemispatial Neglect

Background and Objectives Hemispatial neglect is a heterogeneous and complex disorder that can be classified by frame of reference for “left” vs “right,” including viewer-centered neglect (VCN, affecting the contralesional side of the view), stimulus-centered neglect (SCN, affecting the contralesional side of the stimulus, irrespective of its location with respect to the viewer), or both. We investigated the effect of acute stroke lesions on the connectivity of neural networks that underlie VCN or SCN. Methods A total of 174 patients within 48 hours of acute right hemispheric infarct underwent a detailed hemispatial neglect assessment that included oral reading, scene copy, line cancellation, gap detection, horizontal line bisection tests, and MRI. Each patient's connectivity map was generated. We performed a linear association analysis between network connectivity strength and continuous measures of neglect to identify lesion-induced disconnections associated with the presence or severity of VCN and SCN. Results were corrected for multiple comparisons. Results About 42% of the participants with right hemisphere stroke had at least one type of neglect. The presence of any type of neglect was associated with lesions to tracts connecting the right inferior parietal cortex, orbitofrontal cortex, and right thalamus to other right-hemispheric structures. VCN only was strongly associated with tracts connecting the right putamen to other brain regions and tracts connecting right frontal regions with other brain regions. The presence of both types of neglect was most strongly associated with tracts connecting the right inferior and superior parietal cortex to other brain regions and those connecting left or right mesial temporal cortex to other brain regions. Discussion Our study provides new evidence for the specific white matter tracts where disruption can cause hemispatial neglect in a relatively large number of participants and homogeneous time after onset. We obtained MRI and behavioral testing acutely, before the opportunity for rehabilitation or substantial recovery. Classification of Evidence This study provides Class II evidence that damage to specific white matter tracts identified on MRI are associated with the presence of neglect following right hemispheric stroke.
Acaricide-impaired functional and numerical responses of the predatory mite, Amblyseius largoensis (Acari: Phytoseiidae) to the pest mite Raoiella indica (Acari: Tenuipalpidae)

Abstract The suppression of pest populations by a predator depends on two basic components of the predator-prey interaction: the functional and the numerical responses of the predator. Such responses can be affected by exposure to acaricides. In the present study, the effects of acaricides (abamectin, azadirachtin, fenpyroximate, and chlorfenapyr) on the functional and numerical responses of the predatory mite, Amblyseius largoensis (Acari: Phytoseiidae) an important natural enemy of the pest mite, Raoiella indica (Acari: Tenuipalpidae), were investigated. The exposure of A. largoensis to acaricides occurred through contact with a surface contaminated with dried acaricide residue. Subsequently, A. largoensis exhibited a type II functional response, which was not altered by exposure of any acaricides. However, exposure to abamectin resulted in a decrease in the average mean numbers of prey consumed by a predator. Exposure to acaricides increased prey handling time by 67%, 25%, 38%, and 35% for abamectin, azadirachtin, fenpyroximate, and chlorfenapyr, respectively. Exposure to abamectin reduced the attack rate of A. largoensis by 52%. The numerical response of A. largoensis was only affected by exposure to abamectin, where just 60% of the females oviposited, and regardless of the prey density, the average mean numbers of eggs/female/day was always less than 0.4. The food conversion efficiency into biomass of A. largoensis eggs decreased with increasing prey density, and this trend was not altered by exposure to any acaricides. However, exposure to abamectin drastically compromised the oviposition of A. largoensis, showing no increase in egg production with increasing prey density.
Immunoprotection against Cryptococcosis Offered by Znf2 Depends on Capsule and the Hyphal Morphology

Cryptococcosis claims close to 200,000 lives annually. There is no vaccine clinically available for this fungal disease. ABSTRACT Systemic cryptococcosis is fatal without treatment. Globally, this disease kills 180,000 of the 225,000 infected people each year, even with the use of antifungal therapies. Currently, there is no vaccine to prevent cryptococcosis. Previously, we discovered that Znf2, a morphogenesis regulator that directs Cryptococcus yeast-to-hyphal transition, profoundly affects cryptococcal interaction with the host—overexpression of ZNF2 drives filamentous growth, attenuates cryptococcal virulence, and elicits protective host immune responses. Importantly, immunization with cryptococcal cells overexpressing ZNF2, either in live or heat-inactivated form, offers significant protection to the host from a subsequent challenge by the otherwise lethal wild-type H99 strain. We hypothesize that cellular components enriched in ZNF2oe cells are immunoprotective. Here, we discovered that serum from protected animals vaccinated with inactivated ZNF2oe cells recognizes cryptococcal antigens that reside within the capsule. Consistently, capsule is required for immunoprotection offered by ZNF2oe cells. Interestingly, the serum from protective animals recognizes antigens in both wild-type yeast cells and ZNF2oe cells, with higher abundance in the latter. Consequently, even the heat-inactivated wild-type cells become immunoprotective with an increased vaccination dose. We also found that disruption of a chromatin remodeling factor Brf1, which is important for initiation of filamentation by Znf2, reduces the antigen level in ZNF2oe cells. Deletion of BRF1 drastically reduces the protective effect of ZNF2oe cells in both live and heat-killed forms even though the ZNF2oebrf1Δ strain itself is avirulent. Collectively, our findings underscore the importance of identifying the subset of cryptococcal surface factors that are beneficial in host protection. IMPORTANCE Cryptococcosis claims close to 200,000 lives annually. There is no vaccine clinically available for this fungal disease. Many avirulent mutant strains do not provide protection against cryptococcosis. We previously discovered that hyphal ZNF2oe strains elicit protective host immune responses both in the live and heat-inactivated forms. Here we seek to understand the mechanism underlying the host protection provided by ZNF2oe cells. We discovered increased accumulation of antigens located within the caspusle of ZNF2oe cells and consequently the requirement of the capsule for ZNF2oe strain-elicited host protection. Furthermore, genetically blocking the ability of ZNF2oe cells to grow in the hyphal form significantly reduces antigen accumulation and impairs the ability of ZNF2oe strain to provide host protection. Our findings highlight the importance of identifying the Znf2-regulated capsular surface factors that are fundamental in host protection.
Bandwidth enhancement of microstripline‐to‐waveguide transitions for broadband E‐band module applications

In this work, a broadband microstripline‐to‐waveguide (MSL‐to‐WG) transition has been presented for E‐band module applications. In order to extend its bandwidth (BW), extended ground (eGND) planes and patch‐type probe are designed and their dimension and structure are optimized. Compared to the ordinary transition using a simple electric probe (S‐probe), the optimized eGND plane on the dielectric substrate and triple‐patch probe enhance the operational BW of 56.4 and 71.7%, respectively. The designed transition on the low‐loss liquid crystal polymer (LCP) dielectric substrate was fabricated. Its measured operational BW for the reflection loss (S11) below −10 dB is over 28 GHz at all test frequencies from 67 to 95 GHz. The measured insertion loss of the fabricated transition can be analyzed as −1.45 and −1.59 dB per a transition at 70 and 80 GHz, respectively, considering the loss contribution of the cable adapter and waveguide transition. © 2016 Wiley Periodicals, Inc. Microwave Opt Technol Lett 58:1398–1401, 2016
yggS Encoding Pyridoxal 5′-Phosphate Binding Protein Is Required for Acidovorax citrulli Virulence

Bacterial fruit blotch, caused by seed-borne pathogen Acidovorax citrulli, poses a serious threat to the production of cucurbits globally. Although the disease can cause substantial economic losses, limited information is available about the molecular mechanisms of virulence. This study identified that, a random transposon insertion mutant impaired in the ability to elicit a hypersensitive response on tobacco. The disrupted gene in this mutant was determined to be Aave_0638, which is predicted to encode a YggS family pyridoxal phosphate-dependent enzyme. YggS is a highly conserved protein among multiple organisms, and is responsible for maintaining the homeostasis of pyridoxal 5′-phosphate and amino acids in cells. yggS deletion mutant of A. citrulli strain XjL12 displayed attenuated virulence, delayed hypersensitive response, less tolerance to H2O2 and pyridoxine, increased sensitivity to antibiotic β-chloro-D-alanine, and reduced swimming. In addition, RNA-Seq analysis demonstrated that yggS was involved in regulating the expression of certain pathogenicity-associated genes related to secretion, motility, quorum sensing and oxidative stress response. Importantly, YggS significantly affected type III secretion system and its effectors in vitro. Collectively, our results suggest that YggS is indispensable for A.citrulli virulence and expands the role of YggS in the biological processes.