Miracle-dz/UniFAR-FTUs huggingface dataset:
Working Memory Performance after Daily Caffeine Intake: Compromised Performance and Reduced Hippocampal Activity

Neuroprotective effects of caffeine have been frequently reported in the context of disease and cognitive dysfunction as well as in epidemiological studies in humans. However, evidence on caffeine effects on neural and memory functions during daily intake in a healthy cognitive state remains scarce. This randomized double-blind placebo-controlled crossover study investigated working memory functions by N-back tasks and functional magnetic resonance imaging (fMRI) after daily caffeine intake compared to a placebo baseline and to acute caffeine withdrawal in 20 young healthy volunteers. Each volunteer was given 3 times 150 mg caffeine for 10 days in the daily caffeine condition, 3 times 150 mg mannitol for 10 days in the placebo condition, and 9-day caffeine plus 1-day mannitol in the acute withdrawal condition. During the 10th day, participants performed 4 N-back sessions (two loads each: 0- and 3-back) under controlled laboratory conditions. During the 4th session of N-Back (i.e. at 5.5 h, 36.5 h and > 10 days after the last caffeine intake in the caffeine, withdrawal, and placebo condition, respectively) we assessed blood-oxygen-level-dependent (BOLD) activity. During the entire 10th day, in 0-back tasks, we observed longer reaction times (RTs) in the withdrawal compared to the placebo (Cohen’s d = 0.7) and caffeine condition (Cohen’s d = 0.6), but no significant effects of conditions on error rates. In contrast, in 3-back tasks (controlled for 0-back), the RTs in the caffeine condition were longer compared to placebo (Cohen’s d = 0.6) and withdrawal (Cohen’s d = 0.5). Error rates were higher during both caffeine and withdrawal conditions compared to placebo (Cohen’s d of both contrasts = 0.4). Whole-brain analyses on fMRI data did not reveal significant condition-dependent differences in activities between task loads. Across task loads, however, we observed a reduced hippocampal activation (Cohen’s d = −1.3) during the caffeine condition compared to placebo, while no significant difference in brain activities between withdrawal and placebo conditions. Taken together, the worse working memory function and the hippocampal hypoactivation implicate a potential detrimental effect of daily caffeine intake on neurocognitive functions of healthy adults. Moreover, they echo the hippocampal volumetric reduction reported previously in the same volunteers. Lastly, acute withdrawal from daily caffeine intake impairs both low-order cognitive processes and working memory performance. Taking earlier studies on acute caffeine effects into account, our findings indicate that daily caffeine intake elicits a dynamic change in cerebral activities during the course of repeated consumption, with unknown consequences in the long run.
Selective attention is insensitive to reward and to dopamine in Parkinson’s disease

Patients with Parkinson’s disease exhibit reduced reward sensitivity in addition to early cognitive deficits, among which attention impairments are common. Attention allocation is controlled at multiple levels and recent work has shown that reward, in addition to its role in the top-down goal-directed control of attention, also guides the automatic allocation of attention resources, a process thought to rely on striatal dopamine. Whether Parkinson’s patients, due to their striatal dopamine loss, suffer from an inability to use reward information to guide the allocation of their attention is unknown. To address this question, we tested Parkinson’s patients (n=43) ON and OFF their dopaminergic medication, and compared them to a group of older controls (n=31). We used a standard two-phase attention capture task in which subjects were first implicitly trained to make colour-reward associations. In the second phase, the previously reward-associated colours were used as distractors in a visual search task. We found that patients did not use reward information to modulate their attention; they were similarly distracted by the presence of low and high-reward distractors. However, contrary to our predictions, we did not find evidence that dopamine modulated this inability to use reward to guide attention allocation. Additionally, we found slightly increased overall distractibility in Parkinson’s patients compared to older controls, but interestingly, the degree of distractibility was not influenced by dopamine replacement. Our results suggest that loss of reward-guided attention allocation may contribute to early attention deficits and raise the possibility that this inability to prioritize cognitive resource allocation could contribute to executive deficits more broadly in Parkinson’s disease.
Augmentation of CD47-SIRPα signaling protects cones in genetic models of retinal degeneration

Inherited retinal diseases such as retinitis pigmentosa (RP) can be caused by thousands of different mutations, a small number of which have been successfully treated with gene replacement. However, this approach has yet to scale and may be infeasible in many cases, highlighting the need for interventions that could benefit more patients. Here, we found that microglial phagocytosis is upregulated during cone degeneration in RP, suggesting that expression of “don’t eat me” signals such as CD47 might confer protection to cones. To test this, we delivered an adeno-associated viral (AAV) vector expressing CD47 on cones, which promoted cone survival in three mouse models of RP and preserved visual function. Cone rescue with CD47 required signal regulatory protein alpha (SIRPα) but not microglia or thrombospondin-1 (TSP1), suggesting that CD47 interacts with SIRPα on non-microglial cells to alleviate degeneration. These findings establish augmentation of CD47-SIRPα signaling as a potential treatment strategy for RP and possibly other forms of neurodegeneration.
Determination of Polyphenols in Lycium barbarum Leaves by High-Performance Liquid Chromatography–Tandem Mass Spectrometry

ABSTRACT High-performance liquid chromatography coupled with high-resolution mass spectrometry was used for the determination of polyphenols in Lycium barbarum leaves. Twenty compounds extracted by methanol–water were tentatively identified that included chlorogenic acids, flavonoids, and phenolic acids. Neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, and isochlorogenic acid C were identified in Chinese cultivated L. barbarum leaves for the first time. Caffeic acid and isoquercitrin were also present. The concentrations of these compounds in L. barbarum leaves were determined. The results showed that all analytes had linear calibration relationships with limits of detection from 0.318 to 3.35 ng mL−1. The polyphenols and flavonoids in L. barbarum leaves provided strong 2,2-diphenyl-1-picrylhydrazyl radical-scavenging capacity (IC50 of 23.1 ± 0.4 to 26.0 ± 0.4 µg mL−1). This method is suitable for the determination of polyphenols in L. barbarum leaves, which provide polyphenols with suitable antioxidant activity.
A fed-batch technique to evaluate biodegradation rates of inhibitory compounds with anaerobic biofilms attached to granular activated carbon

Adsorption kinetics render measurements of substrate utilization rates in biofilms attached to adsorbing materials difficult. A fed-batch technique which maintains a constant concentration of substrate in the presence of biomass attached to granular activated carbon (GAC) was developed to measure biological kinetics independent of adsorption kinetics. The fed-batch technique used pre-adsorbed substrate on GAC as a source of substrate. During the experiment, the mass of substrate that is biodegraded is negligible when compared to the large mass of adsorbed substrate. Near equilibrium adsorption phenomena maintains the concentration of substrate constant throughout the experiment and eliminates mass transport resistance within the biofilms. Substrate utilization rates were measured at a specific substrate concentration by monitoring methane gas production rates. Samples of GAC with attached biomass were removed from two expanded-bed anaerobic reactors. GAC samples from a 3-ethylphenol (3-ep) fed reactor were used in batch experiments with 3-ep as the substrate and GAC samples from an orthochlorophenol (OCP) fed reactor were used in batch experiments with OCP as the substrate. Data were observed to fit Haldane kinetics and predictions from the Haldane kinetic parameters were in agreement with transient behavior from the 3-ep fed reactor. This technique was useful in predicting threshold inhibitory levels for continuous treatment of inhibitory wastewaters in expanded-bed GAC reactors. The fed-batch technique light also be applied to measure substrate utilization rates of biomass attached to other adsorbable materials such as soils.
A trade-off between stress resistance and tolerance underlies the adaptive response to hydrogen peroxide

In response to environmental stress, cellular defense strategies may be divided into two categories: those, as in homeostatic systems, that seek to maintain cell proliferation by degrading the stressor (i.e., resistance); and those that ensure cell survival (i.e. tolerance), even if this is often at the expense of cell proliferation. In this study, we have explored the genetic bases of the antagonism between resistance and tolerance during the response to hydrogen peroxide (H2O2) in budding yeast. We show that inactivation of protein kinase A (PKA) by H2O2 signaling induces an abrupt transition from normal homeostatic function to a stress-tolerant state by protecting the growth machinery, hence maximizing cellular fitness in a changing environment. This model system paves the way for developing antiproliferative strategies that target both resistance and tolerance mechanisms to prevent relapse.
Review of Multi-Modal Imaging in Urea Cycle Disorders: The Old, the New, the Borrowed, and the Blue

The urea cycle disorders (UCD) are rare genetic disorder due to a deficiency of one of six enzymes or two transport proteins that act to remove waste nitrogen in form of ammonia from the body. In this review, we focus on neuroimaging studies in OTCD and Arginase deficiency, two of the UCD we have extensively studied. Ornithine transcarbamylase deficiency (OTCD) is the most common of these, and X-linked. Hyperammonemia (HA) in OTCD is due to deficient protein handling. Cognitive impairments and neurobehavioral disorders have emerged as the major sequelae in Arginase deficiency and OTCD, especially in relation to executive function and working memory, impacting pre-frontal cortex (PFC). Clinical management focuses on neuroprotection from HA, as well as neurotoxicity from other known and yet unclassified metabolites. Prevention and mitigation of neurological injury is a major challenge and research focus. Given the impact of HA on neurocognitive function of UCD, neuroimaging modalities, especially multi-modality imaging platforms, can bring a wealth of information to understand the neurocognitive function and biomarkers. Such information can further improve clinical decision making, and result in better therapeutic interventions. In vivo investigations of the affected brain using multimodal neuroimaging combined with clinical and behavioral phenotyping hold promise. MR Spectroscopy has already proven as a tool to study biochemical aberrations such as elevated glutamine surrounding HA as well as to diagnose partial UCD. Functional Near Infrared Spectroscopy (fNIRS), which assesses local changes in cerebral hemodynamic levels of cortical regions, is emerging as a non-invasive technique and will serve as a surrogate to fMRI with better portability. Here we review two decades of our research using non-invasive imaging and how it has contributed to an understanding of the cognitive effects of this group of genetic conditions.
Corrosion control of mild steel in 0.1 M H2SO4 solution by benzimidazole and its derivatives: an experimental and theoretical study

The corrosion inhibition performances of four imidazolium-based corrosion inhibitors on mild steel in acidic medium, namely benzimidazole (BI), 2-aminobenzimidazole (ABI), 2-phenylbenzimidazole (PBI), and omeprazole (OP) were investigated in this work. The experimental results confirmed by electrochemical measurements and a scanning electron microscopy study show that OP may exhibit the best inhibitive performance among the four compounds for mild steel in sulfuric acid solution. Furthermore, quantum chemical calculations of density function theory (DFT) and molecular dynamics (MD) simulations were applied to theoretically determine the relationship between molecular structure and inhibition efficiency. OP shows the highest reaction activity among the four molecules. The binding energies of the corrosion inhibitor molecules and iron surface follow the order of OP > PBI > ABI > BI, which agrees well with the experimental findings.
Modeling the effect of intercalative particle binding on the overstretching transition of double-stranded DNA

DNA is best known from the perspective of genetics, but its mechanical properties are also an interesting and important field of study. These mechanical properties play an important role in cellular processes such as replication and transcription. To characterize the mechanics of DNA, physicists measure force-extension curves of individual double-stranded DNA molecules. They observe that the DNA molecule cooperatively overstretches to a length 1.7 times longer than B-DNA at a well-defined force of about 65 pN: the overstretching transition. To visualize these DNA mechanics, fluorescent molecules are bound to the DNA via the process of intercalation. However, these intercalators are known to perturb the DNA structure and thus change the features of the force-extension curve. In particular, the overstretching transition is found experimentally to shift to higher forces than 65 pN, as a function of intercalator concentration. In this work, we develop multi-state freely jointed chain models to gain an understanding of the physical principles behind the effect of intercalative particle binding on the overstretching transition of double-stranded DNA. We show that a freely jointed chain like model with three possible segment lengths reproduces experimental force-extension curves, and that this model captures the physical principles behind the effect of intercalation on the force-extension curve. The three segment lengths represent B-DNA, overstretched DNA, and intercalated DNA. Moreover, our model agrees quantitatively with the experimentally found linear dependence of the overstretching force on the intercalator concentration. Finally, our theory predicts a further elongation to twice the length of B-DNA, induced by intercalative binding at every base pair, in the force-regime beyond the overstretching transition.
Seismic Hazard Function Mapping Using Estimated Horizontal Crustal Strain Off West Coast Northern Sumatra

A seismic hazard study and analysis of the megathrust source off the west coast of North Sumatra, Indonesia, were conducted based on the estimated horizontal crustal strain using the surface displacement data. This area was selected due to the availability of pre- and co-seismic Global Positioning System (GPS) data for the 2005 Nias–Simeulue Mw 8.6 event. This study aimed to estimate the seismic hazard function (SHF), which is expressed as peak ground acceleration (PGA) versus probability of exceedance (PE), for a 500 years return period using GPS data. The source area model of the Mw 8.6 event is determined based on the co-seismic GPS data. The horizontal crustal strain of the source area is estimated using least square prediction employing local covariance functions based on the horizontal displacement data. The Mw 8.6 return period is estimated by dividing the sum of the co-seismic seismic moment by the pre-seismic seismic moment based on GPS data. The seismicity rate model above a magnitude of completeness is then estimated assuming the b-value of 1 obtained on the previous study’s earthquake catalog data in the region. We show that the SHF based on the study area’s horizontal crustal strain is higher than the one based on earthquake catalogs and estimated geological sliprate data. This discrepancy is associated with the static stress increase (Coulomb failure stress, CFS) of about 0.25 bar imparted by the 2004 Aceh Mw 9.1 event that occurred in the north of the study region. We interpreted that the increase of the SHF was due to the increase in the region’s stress load, which was well documented by the GPS data.
Comparison of fixation characteristics of new acid fixing reactive dyes derived from 5, 10 -phenophosphazine ring with commercial reactive dyes on nylon 66 and wool substrates

The traditional alkaline reactive dyes were found unsuitable for the continuous dyeing of the polyester/cotton blends. This and other problems lead to the search for the acid fixing reactive dyes. Calcobond and Procion T dyes were thus introduced. However, these series of dyes have suffered diminishing acceptability because of the expensive application conditions. Dyes derived from the 5,10-phenophosphazine ring were accidentally found to form covalent bonds with cellulose at neutral pH earlier. This report extends application of these groups of dyes to wool and nylon substrates. The effect of pH on exhaustion and fixation was investigated. The kinetics of dyeing was also studied and compared with some commercial alkaline fixing reactive dyes. The dyes have been established to be acid fixing on wool and nylon. A reaction mechanism has also been proposed.
Transcriptional Profiling of Myceliophthora thermophila on Galactose and Metabolic Engineering for Improved Galactose Utilization

Efficient biological conversion of all sugars from lignocellulosic biomass is necessary for the cost-effective production of biofuels and commodity chemicals. Galactose is one of the most abundant sugar in many hemicelluloses, and it will be important to capture this carbon for an efficient bioconversion process of plant biomass. Thermophilic fungus Myceliophthora thermophila has been used as a cell factory to produce biochemicals directly from renewable polysaccharides. In this study, we draw out the two native galactose utilization pathways, including the Leloir pathway and oxido-reductive pathway, and identify the significance and contribution of them, through transcriptional profiling analysis of M. thermophila and its mutants on galactose. We find that galactokinase was necessary for galactose transporter expression, and disruption of galK resulted in decreased galactose utilization. Through metabolic engineering, both galactokinase deletion and galactose transporter overexpression can activate internal the oxido-reductive pathway and improve the consumption rate of galactose. Finally, the heterologous galactose-degradation pathway, De Ley–Doudoroff (DLD) pathway, was successfully integrated into M. thermophila, and the consumption rate of galactose in the engineered strain was increased by 57%. Our study focuses on metabolic engineering for accelerating galactose utilization in a thermophilic fungus that will be beneficial for the rational design of fungal strains to produce biofuels and biochemicals from a variety of feedstocks with abundant galactose.
Movement Matters! Understanding the Developmental Trajectory of Embodied Planning

Human motor skills are exceptional compared to other species, no less than their cognitive skills. In this perspective paper, we suggest that “movement matters! ,” implying that motor development is a crucial driving force of cognitive development, much more impactful than previously acknowledged. Thus, we argue that to fully understand and explain developmental changes, it is necessary to consider the interaction of motor and cognitive skills. We exemplify this argument by introducing the concept of “embodied planning,” which takes an embodied cognition perspective on planning development throughout childhood. From this integrated, comprehensive framework, we present a novel climbing paradigm as the ideal testbed to explore the development of embodied planning in childhood and across the lifespan. Finally, we outline future research directions and discuss practical applications of the work on developmental embodied planning for robotics, sports, and education.
Random-Walk, Agent-Level Pandemic Simulation (RAW-ALPS) for Analyzing Effects of Different Lockdown Measures

This article develops an agent-level stochastic simulation model, termed RAW-ALPS, for simulating the spread of an epidemic in a community. The mechanism of transmission is agent-to-agent contact, using parameters reported for the COVID-19 pandemic. When unconstrained, the agents follow independent random walks and catch infections due to physical proximity with infected agents. Under lockdown, an infected agent can only infect a coinhabitant, leading to a reduction in the spread. The main goal of the RAW-ALPS simulation is to help quantify the effects of preventive measures—timing and durations of lockdowns—on infections, fatalities, and recoveries. The model helps measure changes in infection rates and casualties due to the imposition and maintenance of restrictive measures. It considers three types of lockdowns: 1) whole population (except the essential workers), 2) only the infected agents, and 3) only the symptomatic agents. The results show that the most effective use of lockdown measures is when all infected agents, including both symptomatic and asymptomatic, are quarantined, while the uninfected agents are allowed to move freely. This result calls for regular and extensive testing of a population to isolate and restrict all infected agents.
Multiple Drivers of High Species Diversity and Endemism Among Alyssum Annuals in the Mediterranean: The Evolutionary Significance of the Aegean Hotspot

The Mediterranean Basin is a significant hotspot of species diversity and endemism, with various distribution patterns and speciation mechanisms observed in its flora. High species diversity in the Mediterranean is also manifested in the monophyletic lineage of Alyssum annuals (Brassicaceae), but little is known about its origin. These species include both diploids and polyploids that grow mainly in open and disturbed sites across a wide elevational span and show contrasting distribution patterns, ranging from broadly distributed Eurasian species to narrow island endemics. Here, we investigated the evolution of European representatives of this lineage, and aimed to reconstruct their phylogeny, polyploid and genome size evolution using flow cytometric analyses, chloroplast and nuclear high- and low-copy DNA markers. The origin and early diversification of the studied Alyssum lineage could be dated back to the Late Miocene/Pliocene and were likely promoted by the onset of the Mediterranean climate, whereas most of the extant species originated during the Pleistocene. The Aegean region represents a significant diversity center, as it hosts 12 out of 16 recognized European species and comprises several (sub)endemics placed in distinct phylogenetic clades. Because several species, including the closest relatives, occur here sympatrically without apparent niche differences, we can reject simple allopatric speciation via vicariance as well as ecological speciation for most cases. Instead, we suggest scenarios of more complex speciation processes that involved repeated range shifts in response to sea-level changes and recurrent land connections and disconnections since the Pliocene. In addition, multiple polyploidization events significantly contributed to species diversity across the entire distribution range. All seven polyploids, representing both widespread species and endemics to the western or eastern Mediterranean, were inferred to be allopolyploids. Finally, the current distribution patterns have likely been affected also by the human factor (farming and grazing). This study illustrates the complexity of evolutionary and speciation processes in the Mediterranean flora.