Miracle-dz/UniFAR-FTUs huggingface dataset:
Individual Differences in Peripheral Hearing and Cognition Reveal Sentence Processing Differences in Healthy Older Adults

When viewed cross-sectionally, aging seems to negatively affect speech comprehension. However, aging is a heterogeneous process, and variability among older adults is typically large. In this study, we investigated language comprehension as a function of individual differences in older adults. Specifically, we tested whether hearing thresholds, working memory, inhibition, and individual alpha frequency would predict event-related potential amplitudes in response to classic psycholinguistic manipulations at the sentence level. Twenty-nine healthy older adults (age range 61-76 years) listened to English sentences containing reduced relative clauses and object-relative clauses while their electroencephalogram was recorded. We found that hearing thresholds and working memory predicted P600 amplitudes early during reduced relative clause processing, while individual alpha frequency predicted P600 amplitudes at a later point in time. The results suggest that participants with better hearing and larger working memory capacity simultaneously activated both the preferred and the dispreferred interpretation of reduced relative clauses, while participants with worse hearing and smaller working memory capacity only activated the preferred interpretation. They also suggest that participants with a higher individual alpha frequency had a higher likelihood of successfully reanalysing the sentence towards the reduced relative clause reading than participants with a lower individual alpha frequency. By contrast, we found no relationship between object-relative clause processing and working memory or hearing thresholds. Taken together, the results support the view that older adults employ different strategies during auditory sentence processing dependent on their hearing and cognitive abilities and that there is no single ability that uniformly predicts sentence processing outcomes.
Saliva-Based Molecular Testing for SARS-CoV-2 that Bypasses RNA Extraction

Convenient, repeatable, large-scale molecular testing for SARS-CoV-2 would be a key weapon to help control the COVID-19 pandemic. Unfortunately, standard SARS-CoV-2 testing protocols are invasive and rely on numerous items that can be subject to supply chain bottlenecks, and as such are not suitable for frequent repeat testing. Specifically, personal protective equipment (PPE), nasopharyngeal (NP) swabs, the associated viral transport media (VTM), and kits for RNA isolation and purification have all been in short supply at various times during the COVID-19 pandemic. Moreover, SARS-CoV-2 is spread through droplets and aerosols transmitted through person-to-person contact, and thus saliva may be a relevant medium for diagnosing SARS-CoV-2 infection status. Here we describe a saliva-based testing method that bypasses the need for RNA isolation/purification. In experiments with inactivated SARS-CoV-2 virus spiked into saliva, this method has a limit of detection of 500-1000 viral particles per mL, rivalling the standard NP swab method, and initial studies also show excellent performance with 100 clinical samples. This saliva-based process is operationally simple, utilizes readily available materials, and can be easily implemented by existing testing sites, thus allowing for high-throughput, rapid, and repeat testing of large populations. Graphical Abstract
Effect of Ginger and Garlic on the Microbial Load and Shelf- Life of Burukutu

Burukutu was produced using the modified method. After production, the product was analyzed physicochemically and the following values were obtained, using parameters like p (3.94), total titratable acidity H (0.55), specific gravity (0.8273g/m ), alcoholic content (4.10) and temperature (29°C). Diverse microbial genera 3 such as Staphylococcus sp, Bacillus sp, Lactibacillus sp, Saccharomyces sp and Escherichia coli dominated the spoilt burukutu. Isolates of the above mentioned genera were treated with the ethanolic extract of these spices; ginger and garlic in the ratio of 20 grams of spice to 10ml of 90% ethanol (20: 100ml). These spice had an effect on the spoilage organisms but the combination of the spices ginger-garlic in equal proportions (401g: 100ml) gave a synergistic effect that was better off. So, of all the treatments, ginger - garlic (40g: 20ml) was the most effective followed by garlic and ginger respectively. Shelf-life of the product can be extended beyond 2 weeks of production, by blending burukutu with a combination of these spices.
Phytochemical and antimicrobial studies on extractives of Calyptrochilum emarginatum (SW) Schltr (Orchidaceae) growing in Nigeria

Calyptrochilum emarginatum is an epiphytic shrub belonging to the orchid family with numerous medicinal uses. Phytochemical investigation of the leaf extractives revealed the presence of tannins, flavonoids, carbohydrates, terpenes, sterols and saponins. Alkaloids and cardiac glycosides could not be detected. Antimicrobial studies of the extracts revealed that at a minimum inhibitory concentration (MIC) of 1.6 mg/ml, the hexane and methanol successive extracts exhibited bactericidal activities against Staphylococcus aureus. The straight run methanol extract and the successive ethyl acetate extract did not show any activity against all the microorganisms investigated namely, S. aureus, Candida albicans, Klebsiella pneumonia, Escherichia coli and Salmonella paratyphi at the same concentration. Key words: Calyptrochilum emarginatum, orchid, phytochemicals, antimicrobial, minimum inhibitory concentration (MIC).
Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins

Mitotic spindle microtubules (MTs) undergo continuous poleward flux, whose driving force and function in humans remain unclear. Here, we combined loss-of-function screenings with analysis of MT dynamics in human cells to investigate the molecular mechanisms underlying MT-flux. We report that kinesin-7/CENP-E at kinetochores (KTs) is the predominant driver of MT-flux in early prometaphase, while kinesin-4/KIF4A on chromosome arms facilitates MT-flux during late prometaphase and metaphase. We show that both of these activities work in coordination with MT-crosslinking motors kinesin-5/EG5 and kinesin-12/KIF15. Our data further indicate that MT-flux driving force is transmitted from non-KT MTs to KT-MTs via MT-coupling by HSET and NuMA. Moreover, we found that MT-flux rate correlates with spindle size and this correlation depends on the establishment of stable end-on KT-MT attachments. Strikingly, we revealed that flux is required to counteract the kinesin 13/MCAK-dependent MT-depolymerization to regulate spindle length. Thus, our study demonstrates that MT-flux in human cells is driven by the coordinated action of four kinesins, and is required to regulate mitotic spindle size in response to MCAK-mediated MT-depolymerizing activity at KTs.
Glacial survival does not matter – II: RAPD phylogeography of Nordic Saxifraga cespitosa

It has been suggested that many arctic‐alpine plant species have limited dispersal ability and cannot have arrived in Scandinavia and the arctic archipelago of Svalbard by long‐distance dispersal after a total glaciation. It has therefore been proposed that such species must have survived the entire glaciation(s) in ice‐free refugia in southern Norway, northern Norway and Svalbard. We investigated random amplified polymorphic DNA (RAPD) variation among 28 populations from Norway and Svalbard of one of these arctic‐alpine ‘short‐distance dispersers’, the selfing polyploid Saxifraga cespitosa. In an analysis of molecular variance (AMOVA), more variation was found among populations within the three postulated refugia regions (45%) than among these regions (25%). Spatial autocorrelation (Mantel) analyses showed that the genetic distance monotonously increased with increasing geographical distance. In UPGMA and PCO analyses, the populations from Norway and Svalbard formed a south–north cline that continued across the Barents Sea barrier. The results suggest that there has been recent dispersal among the three postulated refugia regions and thus that postglacial dispersal into these refugia regions from other distant areas also must represent a possibility. The observed geographical pattern of the genetic variation may have been established after expansion from different source areas outside the North European ice sheet and/or from different refugia areas ‘within’ the ice sheet, but it is probably not possible to distinguish among these alternatives. The results for S. cespitosa are consistent with a dynamic late‐ and postglacial scenario with extensive plant dispersal, and support the conclusion from our previous study of the outbreeding Saxifraga oppositifolia; the hypothesis of glacial survival in Norway and/or Svalbard is superfluous.
Changes in the functional connectome and behavior after exposure to chronic stress and increasing neurogenesis

Addition of new neurons to the dentate gyrus might change the activity of neural circuitry in the areas which the hippocampus projects to. The size of the hippocampus and the number of adult newborn granule cells are decreased by unpredictable chronic mild stress (UCMS). Additionally, one of the notable effects of chronic stress is the induction of ΔFosB, an unusually stable transcription factor which accumulates over time in several brain areas. This accumulation has been observed in many animal models of depression and it could have a protective role against stress, but no studies so far have explored how a specific increase in neurogenesis might regulate the induction and which brain networks might be predominately affected. We attempted to investigate the role of increasing adult hippocampal neurogenesis on stress-related behavior and the functional brain circuitry involved in mice exposed to UCMS. We used iBax mice, in which the pro-apoptotic gene Bax can be selectively ablated in neural stem cells, therefore inducibly enhancing survival of newborn neurons after tamoxifen administration. The animals were exposed to UCMS for 9 weeks and treated with tamoxifen in week 3 after the beginning of UCMS. In week 8, they were submitted to a battery of behavioral tests to assess depressive-like and anxiety-like behavior. In week 9, blood was collected to assess basal corticosterone levels, and the animals were sacrificed and their brain collected for ΔFosB immunohistochemistry. Brain-wide maps of ΔFosB expression were constructed and graph theoretical analyses were used to study the changes in brain networks after stress. UCMS induced negative correlations between the lateral entorhinal cortex and both the hippocampal structures and the nucleus accumbens in the VEH-treated mice, which were not present in other groups. Ranking nodes by degree reveals a strong thalamic-cortical signature in both non-stress (NS) groups. Exposure to UCMS seems to induce activity in thalamic areas and cerebral nuclei, with a different signature in the UCMS TAM group, which seems to completely “disengage” the neocortex and has most of its nodes with the most connections in the thalamic areas.
Predicting precision grip grasp locations on three-dimensional objects

We rarely experience difficulty picking up objects, yet of all potential contact points on the surface, only a small proportion yield effective grasps. Here, we present extensive behavioral data alongside a normative model that correctly predicts human precision grasping of unfamiliar 3D objects. We tracked participants’ forefinger and thumb as they picked up objects of 10 wood and brass cubes configured to tease apart effects of shape, weight, orientation, and mass distribution. Grasps were highly systematic and consistent across repetitions and participants. We employed these data to construct a model which combines five cost functions related to force closure, torque, natural grasp axis, grasp aperture, and visibility. Even without free parameters, the model predicts individual grasps almost as well as different individuals predict one another’s, but fitting weights reveals the relative importance of the different constraints. The model also accurately predicts human grasps on novel 3D-printed objects with more naturalistic geometries and is robust to perturbations in its key parameters. Together, the findings provide a unified account of how we successfully grasp objects of different 3D shape, orientation, mass, and mass distribution.
Intraspecific trait variability mediates the response of subalpine grassland communities to extreme drought events

Climate change is expected to increase the magnitude and the frequency of extreme climatic events such as droughts. Better understanding how plant communities will respond to these droughts is a major challenge. We expect the response to be a shift in functional trait values resulting from both species turnover and intraspecific trait variability, but little research has addressed the relative contribution of both components. We analysed the short‐term functional response of subalpine grassland communities to a simulated drought by focusing on four leaf traits (LDMC: leaf dry matter content, SLA: specific leaf area, LNC: leaf nitrogen concentration and LCC: leaf carbon concentration). After evaluating species turnover and intraspecific variability separately, we determined their relative contribution in the community functional response to drought, reflected by changes in community‐weighted mean traits. We found significant species turnover and intraspecific variability, as well as significant changes in community‐weighted mean for most of the traits. The relative contribution of intraspecific variability to the changes in community mean traits was more important (42–99%) than the relative contribution of species turnover (1–58%). Intraspecific variability either amplified (for LDMC, SLA and LCC) or dampened (for LNC) the community functional response mediated by species turnover. We demonstrated that the small contribution of species turnover to the changes in community mean LDMC and LCC was explained by a lack of covariation between species turnover and interspecific trait differences. Synthesis. These results highlight the need for a better consideration of intraspecific variability to understand and predict the effect of climate change on plant communities. While both species turnover and intraspecific variability can be expected following an extreme drought, we report new evidence that intraspecific variability can be a more important driver of the short‐term functional response of plant communities.
Electrophysiology of Stimulus-Secretion Coupling in Human β-Cells

Herein, we review the applicability to human β-cells of an electrophysiologically based hypothesis of the coupling of glucose metabolism to insulin secretion. According to this hypothesis, glucose metabolism leads to the generation of intracellular intermediates (including ATP), which leads to closure of ATP-sensitive K+ channels. Channel closure results in membrane depolarization, the onset of electrical activity, and voltage-dependent Ca2+ entry. The resultant rise in cytosolic Ca2+ leads to Ca2+-dependent exocytosis of insulin granules. We found that most of the published experimental evidence for human β-cells supports this hypothesis. In addition, we present three other emerging lines of evidence in support of this hypothesis for human islet β-cells: 1) the effects of pH1-altering maneuvers on insulin secretion and electrical activity; 2) preliminary identification of LVA and HVA single Ca2+ channel currents; and 3) validation of the feasibility of Cm measurements to track insulin granule exocytosis. On the basis of this last new line of evidence, we suggest that combinations of Cm measurements and electrical activity/membrane current measurements may help define the roles of diverse electrical activity patterns, displayed by human β-cells, in stimulus-induced insulin secretion.
GluD2- and Cbln1-mediated Competitive Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells

The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, yet this hypothesis has not been causally tested in vivo in the mammalian brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner. A generative model of dendritic growth based on competitive synaptogenesis largely recapitulates GluD2 sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis.
Accessory ESCRT-III proteins selectively regulate Rab11-exosome biogenesis in Drosophila secondary cells

Exosomes are secreted nanovesicles with potent signalling activity that are initially formed as intraluminal vesicles (ILVs) in multivesicular endosomes, which subsequently fuse with the plasma membrane. These ILVs are made in both late endosomes and recycling endosomes, the latter marked by the small GTPase Rab11 and generating exosomes with different cargos and functions. Core proteins within four Endosomal Sorting Complex Required for Transport (ESCRT) assemblies (0-III) play key sequential roles in late endosomal exosome biogenesis and ILV-mediated destruction of ubiquitinylated cargos through the endolysosomal system. They also control additional cellular processes, such as cytokinesis and other vesicle budding. By contrast, the functions of several accessory ESCRTs are not well defined. Here we assess the ESCRT-dependency of Rab11-exosomes, using RNA knockdown in Drosophila secondary cells (SCs) of the male accessory gland, which have unusually enlarged Rab11-positive compartments. Unexpectedly, not only are core proteins in all four ESCRT complexes required for Rab11-exosome formation, but also accessory ESCRT-III proteins, CHMP1, CHMP5 and IST1. Suppressing expression of these accessory proteins does not affect other aspects of cell morphology, unlike most core ESCRT knockdowns, and does not lead to accumulation of ubiquitinylated cargos. We conclude that accessory ESCRT-III components have a specific and potentially ubiquitin-independent role in Rab11-exosome generation, which might provide a target for blocking the pro-tumorigenic activities of these vesicles in cancer.
Reward-predictive cues elicit maladaptive reward seeking in adolescent rats

Impulsive behavior during adolescence may stem from a developmental imbalance between motivational and impulse control systems, producing greater urges to pursue reward and weakened capacities to inhibit such actions. Here, we developed a Pavlovian-instrumental transfer (PIT) protocol to assay rats’ ability to suppress cue-motivated reward seeking based on changes in reward expectancy. Traditionally, PIT studies focus on how reward-predictive cues motivate instrumental reward-seeking behavior (lever pressing). However, cues signaling imminent reward delivery also elicit countervailing focal-search responses (food-cup approach). We first examined how reward expectancy (cue-reward probability) influences expression of these competing behaviors. Adult male rats increased rates of lever pressing when presented with cues signaling lower probabilities of reward but focused their activity at the food cup on trials with cues that signaled higher probabilities of reward. We then compared adolescent and adult male rats in their responsivity to cues signaling different reward probabilities. In contrast to adults, adolescent rats did not flexibly adjust their pattern of responding based on the expected likelihood of reward delivery but increased their rate of lever pressing for both weak and strong cues. These findings indicate that impulse control over cue-motivated behavior is fundamentally dysregulated during adolescence, providing a model for studying neurobiological mechanisms of adolescent impulsivity.
A circuit model of auditory cortex

The mammalian sensory cortex is composed of multiple types of inhibitory and excitatory neurons, which form sophisticated microcircuits for processing and transmitting sensory information. Despite rapid progress in understanding the function of distinct neuronal populations, the parameters of connectivity that are required for the function of these microcircuits remain unknown. Recent studies found that two most common inhibitory interneurons, parvalbumin- (PV) and somatostatin-(SST) positive interneurons control sound-evoked responses, temporal adaptation and network dynamics in the auditory cortex (AC). These studies can inform our understanding of parameters for the connectivity of excitatory-inhibitory cortical circuits. Specifically, we asked whether a common microcircuit can account for the disparate effects found in studies by different groups. By starting with a cortical rate model, we find that a simple current-compensating mechanism accounts for the experimental findings from multiple groups. They key mechanisms are two-fold. First, PVs compensate for reduced SST activity when thalamic inputs are strong with less compensation when thalamic inputs are weak. Second, SSTs are generally disinhibited by reduced PV activity regardless of thalamic input strength. These roles are augmented by plastic synapses. These differential roles reproduce the differential effects of PVs and SSTs in stimulus-specific adaptation, forward suppression and tuning-curve adaptation, as well as the influence of PVs on feedforward functional connectivity in the circuit. This circuit exhibits a balance of inhibitory and excitatory currents that persists on stimulation. This approach brings together multiple findings from different laboratories and identifies a circuit that can be used in future studies of upstream and downstream sensory processing. Significance Statement The mammalian auditory cortex is composed of multiple types of inhibitory and excitatory neurons, which form sophisticated microcircuits for processing and transmitting sensory information. Distinct inhibitory neuron subtypes play distinct functions in auditory processing, but it remains unknown what simple set of underlying mechanisms is responsible for inhibitory cortical function. Here, we built minimal rate and spiking models and identified a specific set of synaptic mechanisms that could best reproduce the broad set of experimental results in the auditory cortex. The simplicity of our model provides an understanding of inhibitory cortical processing at the circuit level, which explains results from different laboratories, and provides for a novel computational framework for future studies of cortical function.