Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Trust on Gaze-Mediated Attentional Orienting

The last two decades have witnessed growing interest in the study of social cognition and its multiple facets, including trust. Interpersonal trust is generally understood as the belief that others are not likely to harm you. When meeting strangers, judgments of trustworthiness are mostly based on fast evaluation of facial appearance, unless information about past behavior is available. In the past decade, studies have tried to understand the complex relationship between trust and gaze-cueing of attention (GCA) (i.e., attentional orienting following another person’s gaze). This review will focus on the studies that used a gaze-cueing paradigm to explore this relationship. While the predictivity of the gaze-cue seems to consistently influence trustworthiness judgments, the impact of trust on gaze-cueing is less clear. Four studies found enhanced gaze-cueing effects with trustworthy faces; one found stronger effects of gaze-cueing with faces associated with undesirable behavior, but only when the observer’s personal evaluations were taken into account. Four studies did not observe an effect of trust on gaze-cueing. Overall, studies have highlighted the complexity of this relationship, suggesting that multiple factors (including age, gender, the characteristics of the observer, and whether or not a threat is perceived) are likely to intervene in the interplay between trust and gaze-triggered attentional orienting. After discussing results in the context of existing theories of gaze-cueing and trust, we conclude that further investigation is needed to better understand this relationship and the contribution of social factors to attentional shifts guided by gaze.
Design and Synthesis of Chitosan—Gelatin Hybrid Hydrogels for 3D Printable in vitro Models

The development of 3D printable hydrogels based on the crosslinking between chitosan and gelatin is proposed. Chitosan and gelatin were both functionalized with methyl furan groups. Chemical modification was performed by reductive amination with methyl furfural involving the lysine residues of gelatin and the amino groups of chitosan to generate hydrogels with tailored properties. The methyl furan residues present in both polymers were exploited for efficient crosslinking via Diels-Alder ligation with PEG-Star-maleimide under cell-compatible conditions. The obtained chitosan-gelatin hybrid was employed to formulate hydrogels and 3D printable biopolymers and its processability and biocompatibility were preliminarily investigated.
Compartmentalized Neuronal Culture for Viral Transport Research

Neuron-invading viruses usually enter via the peripheral organs/tissues of their mammalian hosts and are transported to the neurons. Virus trafficking is critical for transport or spread within the nervous system. Primary culture of neurons is a valuable and indispensable method for neurobiological research, allowing researchers to investigate basic mechanisms of diverse neuronal functions as well as retrograde and anterograde virus transport in neuronal axons. Primary ganglion sensory neurons from mice can be cultured in a compartmentalized culture device, which allows spatial fluidic separation of cell bodies and distal axons. These neurons serve as an important model for investigating the transport of viruses between the neuronal soma and distal axons. Alphaherpesviruses are fascinating and important human and animal pathogens, they replicate and establish lifelong latent infection in the peripheral nervous system, the mechanism of the viral transport along the axon is the key to understand the virus spread in the nervous system. In this review, we briefly introduce and evaluate the most frequently used compartmentalization tools in viral transport research, with particular emphasis on alphaherpesviruses.
Graded fMRI Neurofeedback Training of Motor Imagery in Middle Cerebral Artery Stroke Patients: A Preregistered Proof-of-Concept Study

Ischemic stroke of the middle cerebral artery (MCA), a major brain vessel that supplies the primary motor and premotor cortex, is one of the most common causes for severe upper limb impairment. Currently available motor rehabilitation training largely lacks satisfying efficacy with over 70% of stroke survivors showing residual upper limb dysfunction. Motor imagery-based functional magnetic resonance imaging neurofeedback (fMRI-NF) has been suggested as a potential therapeutic technique to improve motor impairment in stroke survivors. In this preregistered proof-of-concept study (https://osf.io/y69jc/), we translated graded fMRI-NF training, a new paradigm that we have previously studied in healthy participants, to first-time MCA stroke survivors with residual mild to severe impairment of upper limb motor function. Neurofeedback was provided from the supplementary motor area (SMA) targeting two different neurofeedback target levels (low and high). We hypothesized that MCA stroke survivors will show (1) sustained SMA-region of interest (ROI) activation and (2) a difference in SMA-ROI activation between low and high neurofeedback conditions during graded fMRI-NF training. At the group level, we found only anecdotal evidence for these preregistered hypotheses. At the individual level, we found anecdotal to moderate evidence for the absence of the hypothesized graded effect for most subjects. These null findings are relevant for future attempts to employ fMRI-NF training in stroke survivors. The study introduces a Bayesian sequential sampling plan, which incorporates prior knowledge, yielding higher sensitivity. The sampling plan was preregistered together with a priori hypotheses and all planned analysis before data collection to address potential publication/researcher biases. Unforeseen difficulties in the translation of our paradigm to a clinical setting required some deviations from the preregistered protocol. We explicitly detail these changes, discuss the accompanied additional challenges that can arise in clinical neurofeedback studies, and formulate recommendations for how these can be addressed. Taken together, this work provides new insights about the feasibility of motor imagery-based graded fMRI-NF training in MCA stroke survivors and serves as a first example for comprehensive study preregistration of an (fMRI) neurofeedback experiment.
Novel Therapeutic Targets for Hypoxia-Related Cardiovascular Diseases: The Role of HIF-1

Insufficient oxygen availability (hypoxia) is a precursor to numerous cardiovascular diseases, including atherosclerosis, pulmonary hypertension, and heart failure. The main site of hypoxic injury in the human body is the mitochondria, where oxygen acts as the final electron acceptor in the process of oxidative phosphorylation. Hypoxia-inducible factor (HIF) is activated in hypoxic conditions and acts as an important modulator of diverse target genes in the human body. The downstream genes of HIF include vital modulators of cardiovascular-related signaling pathways. Therefore, it is hypothesized that HIF represents a potential therapeutic target for the treatment and prevention of cardiovascular diseases. In this short review, we introduce the pathophysiology of hypoxic injury in cardiovascular disease, and we conclude from convincing evidence that HIF can modulate relevant cardioprotective signaling pathways.
RNA Binding Motif 5 (RBM5) in the CNS—Moving Beyond Cancer to Harness RNA Splicing to Mitigate the Consequences of Brain Injury

Gene splicing modulates the potency of cell death effectors, alters neuropathological disease processes, influences neuronal recovery, but may also direct distinct mechanisms of secondary brain injury. Therapeutic targeting of RNA splicing is a promising avenue for next-generation CNS treatments. RNA-binding proteins (RBPs) regulate a variety of RNA species and are prime candidates in the hunt for druggable targets to manipulate and tailor gene-splicing responses in the brain. RBPs preferentially recognize unique consensus sequences in targeted mRNAs. Also, RBPs often contain multiple RNA-binding domains (RBDs)—each having a unique consensus sequence—suggesting the possibility that drugs could be developed to block individual functional domains, increasing the precision of RBP-targeting therapies. Empirical characterization of most RBPs is lacking and represents a major barrier to advance this emerging therapeutic area. There is a paucity of data on the role of RBPs in the brain including, identification of their unique mRNA targets, defining how CNS insults affect their levels and elucidating which RBPs (and individual domains within) to target to improve neurological outcomes. This review focuses on the state-of-the-art of the RBP tumor suppressor RNA binding motif 5 (RBM5) in the CNS. We discuss its potent pro-death roles in cancer, which motivated our interest to study it in the brain. We review recent studies showing that RBM5 levels are increased after CNS trauma and that it promotes neuronal death in vitro. Finally, we conclude with recent reports on the first set of RBM5 regulated genes identified in the intact brain, and discuss how those findings provide new clues germane to its potential function(s) in the CNS, and pose new questions on its therapeutic utility to mitigate CNS injury.
Cerebral Oxygenation and Autoregulation in Very Preterm Infants Developing IVH During the Transitional Period: A Pilot Study

Background: The transitional period, defined as the first 72 h after preterm birth, is often characterized by a significant hemodynamic instability, which represents an important risk factor for such neurological complications of prematurity as intraventricular hemorrhage (IVH). The impairment of cerebral autoregulation plays a key role in the pathogenesis of IVH, whose incidence is highest during the transitional period. This pilot study aimed to evaluate whether patterns of cerebral autoregulation and oxygenation differ in relation to IVH development in very preterm infants during the transitional period. Methods: Infants <32 weeks' gestation were enrolled within 12 h from birth. A simultaneous monitoring of cerebral oxygenation (CrSO2) by near-infrared spectroscopy and of heart rate and peripheral oxygen saturation by pulse oximetry was performed over the first 72 h. Cerebral fractional oxygen extraction (cFTOE) and tissue oxygenation-heart rate reactivity index (TOHRx), which represents a marker of cerebrovascular reactivity, were calculated. Daily cranial and cardiac ultrasound scans were performed, in order to assess the hemodynamic status and to detect a possible IVH onset. CrSO2 and cFTOE, clustered on 6-hour epochs, were compared between infants who developed IVH during the study period and those who did not. A between-group comparison of TOHRx before and after IVH detection was also performed. Results: Twenty preterm infants with a median gestational age of 27 weeks (interquartile range, IQR: 25-30 weeks) and median birth weight of 895 g (IQR: 822-1208 g) were enrolled. Of these, 8 developed IVH. The median age at IVH detection was 40 h (IQR: 30-48 h). Pre-IVH TOHRx was significantly higher compared to matched control periods (p <0.001). CrSO2 was significantly lower from 12 to 30 h and from 42 h onwards in cases compared to controls; however, a temporary CrSO2 rise preceded IVH detection. Similarly, cFTOE was significantly higher in IVH infants from 12 to 30 h and from 48 to 72 h, with a transient decrease between the two periods. Conclusions: In preterm infants during the transitional period, the development of IVH is preceded by transient changes in cerebral oxygenation and oxygen extraction which, in turn, may underlie an early impairment of cerebral autoregulation. Larger studies are needed to confirm these preliminary findings.
Improving recombinant protein production using TISIGNER.com

Planning experiments using accurate prediction algorithms could mitigate failures in recombinant protein production. We have developed TISIGNER.com with the aim of addressing the technical challenges in recombinant protein production. We offer two web services, TIsigner (Translation Initiation coding region designer) and SoDoPE (Soluble Domain for Protein Expression), which are specialised in prediction/optimisation of recombinant protein expression and solubility, respectively. Importantly, TIsigner and SoDoPE are linked, which allows users to switch between the tools when optimising their genes of interest.
Alpha/beta power decreases during episodic memory formation predict the magnitude of alpha/beta power decreases during subsequent retrieval

Episodic memory retrieval is characterised by the vivid reinstatement of information about a personally-experienced event. Growing evidence suggests that the reinstatement of such information is supported by reductions in the spectral power of alpha/beta activity. Given that the amount of information that can be recalled depends on the amount of information that was originally encoded, information-based accounts of alpha/beta activity would suggest that retrieval-related alpha/beta power decreases similarly depend upon decreases in alpha/beta power during encoding. To test this hypothesis, seventeen human participants completed a sequence-learning task while undergoing concurrent MEG recordings. Regression-based analyses were then used to estimate how alpha/beta power decreases during encoding predicted alpha/beta power decreases during retrieval, on a trial-by-trial basis. When subjecting these parameter estimates to group-level analysis, we find evidence to suggest that retrieval-related alpha/beta (7-15Hz) power decreases fluctuate as a function of encoding-related alpha/beta power decreases. These results suggest that retrieval-related alpha/beta power decreases are contingent on the decrease in alpha/beta power that arose during encoding. Subsequent analysis uncovered no evidence to suggest that these alpha/beta power decreases reflect stimulus identity, indicating that the contingency between encoding- and retrieval-related alpha/beta power reflects the reinstatement of a neurophysiological operation, rather than neural representation, during episodic memory retrieval.
Effect of Storage Temperature and S-Alk(en)yl-L-Cysteine Sulfoxide on Green Pigment Formation in Crushed Garlic (Allium sativum L.) Cloves

After complete maceration of garlic (Allium sativum L.) cloves, green pigments were occasionally formed. The green pigment formation was evaluated with five garlic cultivars stored at 0, 10, and 20℃. Regardless of the cultivar, harvest time, and sprouting, the greening was observed only in garlics stored at 0 and 10℃ over 4 and 5 months, respectively, whereas garlics stored at 20℃ did not develop greening under all the experimental conditions. Three major flavor precursors in garlic cloves, (+)-S-methyl-(MCSO), (+)-S-2-propenyl (or allyl)-(2-PRENCSO, alliin), and trans-(+)-S-1-propenyl-L-cysteine sulfoxide (1-PRENCSO) were detected in this experiment. 1- and 2-PRENCSO gradually increased, but MCSO decreased with storage time at all the temperatures and in all the cultivars examined. 1-PRENCSO was detected only in greening garlics stored at 0 and 10℃ for over 4 and 5 months, respectively. Through the addition of three flavor precursors individually into the homogenates of greening garlic cloves, the possible roles of 1- and 2-PRENCSO for inducing greening were also confirmed with highly positive correlations between greening and their concentrations, r² = 0.92 and r² = 0.77, respectively, showing an increased absorbance at 590 ㎚. On the other hand, the homogenates of non-greening garlic cloves were not greened by the addition of flavor precursors, preserving their creamy colors. An alliinase inhibitor, hydroxylamine at 100 mM completely inhibited greening. Greening was finally considered as one of the various physiological responses that could be induced by prolonged low temperature storage after harvest. It was associated with an alliinase activity and the increased levels of flavor precursors, particularly 1- and 2-PRENCSO on which alliinase acted when garlic cells were finely disrupted.
Corticohippocampal Neuroenergetics and histomorphology in aluminium-induced neurotoxicity: Putative therapeutic roles of ascorbic acid and nicotine

Alzheimer’s disease (AD) is the most common cause of dementia and is hallmarked by β-amyloid plaque and neurofibrillary tangles deposition in the central nervous system. The complex mechanism that underlies AD pathogenesis has made the development of a definitive cure futile. Exploring the possible therapeutic advantages of combining two neuromodulatory molecules with different mechanisms of neuroprotection is an interesting way of drug discovery. Ascorbic acid (AA), a potent antioxidant molecule, and nicotine (NIC), an allosteric modulator of nAChRs, have both been documented to independently proffer neuroprotection in experimental and clinical neurodegenerative cases. This study elucidated the putative therapeutic advantages of combining ascorbic acid and nicotine as a treatment regimen against the aluminium-induced Alzheimer-like corticohippocampal histopathology, anxiety, and perturbed neuroenergetics in rats induced with Rats treated with 100 mg/kg aluminium chloride for 28 days presented with significantly increased stretch attend posture frequency and centre square entry. Aluminium significantly depleted the activities of glucose-6-phosphate dehydrogenase (G6PDH) while increasing lactate levels. Corticohippocampal histomorphology of these animals showed poor histoarchitecture, increased congophilic and argentophilic densities that were coupled with increased anti-NSE immunopositivity. Animals post-treated with NIC (10mg/kg) and AA (100mg/kg) for 28 days presented with reduced anxiety level and improved corticohippocampal histomorphology. AA normalized G6PDH and lactate levels while the congophilic density was reduced by NIC. Corticohippocampal argentophilic density anti-NSE immunopositivity were also normalized by AA+NIC. The findings from this study have shown that a combination of ascorbic acid and nicotine effectively mitigated aluminium-induced corticohippocampal histopathology and perturbed neuroenergetics.
Innovation of heterochromatin functions drives rapid evolution of essential ZAD-ZNF genes in Drosophila

Contrary to prevailing dogma, evolutionarily young and dynamic genes can encode essential functions. Here, we investigate genetic innovation in ZAD-ZNF genes, which encode the most abundant class of insect transcription factors. We find that evolutionarily dynamic ZAD-ZNF genes are more likely to encode essential functions in Drosophila melanogaster than ancient, conserved ZAD-ZNF genes. To understand the basis of this unexpected correlation, we focus on the Nicknack ZAD-ZNF gene. Nicknack is an evolutionarily young, poorly retained in Drosophila species, and evolves under strong positive selection, yet we find that it is necessary for larval development in D. melanogaster. We show that Nicknack encodes a heterochromatin-localizing protein like its closely related paralog Oddjob, also an evolutionarily dynamic, essential ZAD-ZNF gene. We find that the divergent D. simulans Nicknack protein can still localize to D. melanogaster heterochromatin and rescue viability of female but not male Nicknack-null D. melanogaster. Our findings suggest that innovation for rapidly changing heterochromatin functions might provide a general explanation for the essential functions of many evolutionarily dynamic ZAD-ZNF genes in insects.
Using a GTR+Γ substitution model for dating sequence divergence when stationarity and time-reversibility assumptions are violated

Motivation As the number and diversity of species and genes grow in contemporary datasets, two common assumptions made in all molecular dating methods, namely the time-reversibility and stationarity of the substitution process, become untenable. No software tools for molecular dating allow researchers to relax these two assumptions in their data analyses. Frequently the same General Time Reversible (GTR) model across lineages along with a gamma (+Γ) distributed rates across sites is used in relaxed clock analyses, which assumes time-reversibility and stationarity of the substitution process. Many reports have quantified the impact of violations of these underlying assumptions on molecular phylogeny, but none have systematically analyzed their impact on divergence time estimates. Results We quantified the bias on time estimates that resulted from using the GTR+Γ model for the analysis of computer-simulated nucleotide sequence alignments that were evolved with non-stationary (NS) and non-reversible (NR) substitution models. We tested Bayesian and RelTime approaches that do not require a molecular clock for estimating divergence times. Divergence times obtained using a GTR+Γ model differed only slightly (∼3% on average) from the expected times for NR datasets, but the difference was larger for NS datasets (∼10% on average). The use of only a few calibrations reduced these biases considerably (∼5%). Confidence and credibility intervals from GTR+Γ analysis usually contained correct times. Therefore, the bias introduced by the use of the GTR+Γ model to analyze datasets, in which the time-reversibility and stationarity assumptions are violated, is likely not large and can be reduced by applying multiple calibrations. Availability All datasets are deposited in Figshare: https://doi.org/10.6084/m9.figshare. 12594638. Contact s.kumar@temple.edu
Sensitive and reproducible determination of clinical HDL proteotypes

Background High-density lipoprotein (HDL) is a heterogenous mixture of blood-circulating multimolecular particles containing many different proteins, lipids, and RNAs. Recent advancements in mass spectrometry-based proteotype analysis strategies enable the sensitive and reproducible quantification of proteins across large patient cohorts. Methods HDL particles were isolated from plasma of more than 300 healthy individuals or patients with a multiplicity of physiological HDL states. From these, peptides were extracted and HDL proteome spectral libraries were generated. This is a prerequisite for using data-independent acquisition (DIA) strategies to analyze HDL particles from clinical cohorts using mass spectrometry. Results The resulting HDL proteome spectral libraries consist of 296 protein groups and 341 peptidoforms of potential biological significance identified with high confidence. We used the HDL proteome libraries to evaluate HDL proteotype differences in between healthy individuals and patients suffering from diabetes mellitus type 2 (T2DM) and/or coronary heart disease (CHD). Bioinformatic interrogation of the data revealed significant quantitative differences in the HDL proteotypes including a significant depletion of phosphatidylinositol-glycan-specific phospholipase D (PHLD) from disease-derived HDL particles. Conclusion The DIA-based HDL proteotyping strategy enabled sensitive and reproducible digitization of HDL proteotypes derived from patient cohorts and provides new insights into the composition of HDL particles as a rational basis to decode structure-function-disease relationships of HDL. List of human genes and protein names discussed in the paper - APOA1 (Apolipoprotein A-I) - APOA2 (Apolipoprotein A-II) - APOE (Apolipoprotein E) - APOC3 (Apolipoprotein C3) - CLUS (Clusterin) - PHLD (Phosphatidylinositol-glycan-specific phospholipase D) - PON1 (Serum paraoxonase/arylesterase 1) - PON3 (Serum paraoxonase/lactonase 3) - PSPB (Pulmonary surfactant-associated protein B) - RAB1B (Ras-related protein Rab-1B) - RAB6A (Ras-related protein Rab-6A) - RB11A/B (Ras-related protein Rab-11A/B) - RP1BL (Ras-related protein Rap-1b-like protein) - RAB10 (Ras-related protein Rab-10) - SAA1 (Serum amyloid A-1 protein) - SAA2 (Serum amyloid A-2 protein) - SAA4 (Serum amyloid A-4 protein) - SCRB1 (Scavenger receptor class B member 1)