Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultrastructural analysis of dendritic spine necks reveals a continuum of spine morphologies

Dendritic spines are membranous protrusions, with a bulbous head connected to the dendrite by a thin neck, and receive essentially all excitatory inputs in most mammalian neurons. Spines have a wide variety of morphologies that likely have a significant effect on their biochemical and electrical properties. The question of whether spines belong to distinct morphological or functional subtypes or constitute a continuum is still open. To discern this, it is important to measure spine necks objectively. Recent advances in electron microscopy enable automatic reconstructions of 3D spines with nanometer precision. Analyzing ultrastructural reconstructions from mouse neocortical neurons with computer vision algorithms, we demonstrate that the vast majority of spines can be rigorously separated into head and neck components. Analysis of the head and neck morphologies reveals a continuous distribution of parameters. The spine neck diameter, but not the neck length, was correlated with the head volume. Spines with larger head volumes often had a spine apparatus and pairs of spines in a post-synaptic cell contacted by the same axon had similar head volumes. Our data are consistent with a lack of morphological categories of spines and indicate that the morphologies of the spine neck and head are independently regulated. These results have repercussions for our understanding of the function of dendritic spines in neuronal circuits.
Seasonal Dynamics in the Number and Composition of Coliform Bacteria in Drinking Water Reservoirs

Worldwide, surface waters like lakes and reservoirs are one of the major sources for drinking water production, especially in regions with water scarcity. In the last decades, they have undergone significant changes due to climate change. This includes not only an increase of the water temperature but also microbiological changes. In recent years, increased numbers of coliform bacteria have been observed in these surface waters. In our monitoring study we analyzed two drinking water reservoirs (Klingenberg and Kleine Kinzig Reservoir) over a two-year period in 2018 and 2019. We detected high numbers of coliform bacteria up to 2.4 x 104 bacteria per 100 ml during summer months, representing an increase of four orders of magnitude compared to winter. Diversity decreased to one or two species that dominated the entire water body, namely Enterobacter asburiae and Lelliottia spp. , depending on the reservoir. Interestingly, the same, very closely related strains have been found in several reservoirs from different regions. Fecal indicator bacteria Escherichia coli and enterococci could only be detected in low concentrations. Furthermore, fecal marker genes were not detected in the reservoir, indicating that high concentrations of coliform bacteria were not due to fecal contamination. Microbial community revealed Frankiales and Burkholderiales as dominant orders. Enterobacterales, however, only had a frequency of 0.04% within the microbial community, which is not significantly affected by the extreme change in coliform bacteria number. Redundancy analysis revealed water temperature, oxygen as well as nutrients and metals (phosphate, manganese) as factors affecting the dominant species. We conclude that this sudden increase of coliform bacteria is an autochthonic process that can be considered as a mass proliferation or “coliform bloom” within the reservoir. It is correlated to higher water temperatures in summer and is therefore expected to occur more frequently in the near future, challenging drinking water production. Highlights Coliform bacteria proliferate in drinking water reservoirs to values above 104 per 100 ml The genera Lelliottia and Enterobacter can form these “coliform blooms” Mass proliferation is an autochthonic process, not related to fecal contaminations It is related to water temperature and appears mainly in summer It is expected to occur more often in future due to climate change Graphical abstract
Potent Neutralization Antibodies Induced by a Recombinant Trimeric Spike Protein Vaccine Candidate Containing PIKA Adjuvant for COVID-19

Neutralizing antibodies are critical to prevent corona virus infection. The structures of immunogens to elicit most potent neutralization antibodies are still under investigation. Here we tested the immunogenicity of the trimeric, full length Spike protein with 2 proline mutations to preserve its prefusion conformation. Recombinant trimeric Spike protein expressed by CHO cells was used with polyI:C (PIKA) adjuvant to immunize mice by 0-7-14 day schedule. The results showed that Spike-specific antibody was induced at day 21 with titer of more than 50,000 in average as measured by direct binding to Spike protein. The titer of neutralization reached more than 1000 in average when tested by a pseudo-virus system, using monoclonal antibodies (40592-MM57 and 40591-MM43) with neutralizing IC50 at 1 μg/ml as standards. Protein/peptide array showed that the antibodies induced by trimeric S protein vaccine bind similarly to natural infection with the receptor binding domain (RBD) as major immunodominant region. No linear epitopes were found in RBD, although several linear epitopes were found in C-terminal domain right after RBD, and heptad repeat regions. Our study supports the efficacy of recombinant trimeric Spike protein vaccine candidate for COVID-19, with excellent safety and readiness for storage and distribution in developing countries.
“A compressed representation of spatial distance in the rodent hippocampus’’

Principal cells in the rodent hippocampus often fire in response to traversal through a specific spatial location (place cells), as well as elapsed time during an imposed temporal delay or after stimulus offset (time cells). Sequences of time cells unfold rapidly at first, with many time cells with narrow time fields. As the triggering event recedes into the past, time cells are fewer and have broader fields. This means that the representation of time in the hippocampus is compressed with greater resolution for time points near the present. Using tetrode recordings we measured individual CA1 units while rats traveled along a track that could be changed in length. Consistent with previous results, most place cells coded for distance from the starting point of the trajectory. Critically, place cells became less numerous and showed gradually widening fields with distance from the starting location. These results suggest that as the animal leaves a landmark, the hippocampal place code forms a compressed representation of distance from the starting location. The representation of time and space in the hippocampus have similar properties suggesting that they arise from similar computational mechanisms. Significance Statement The hippocampus represents relationships between events in time and space. It has been hypothesized that temporal and spatial relationships are the result of a common computational mechanism. Previous work has shown that the representation of time in the hippocampus is compressed, with less neural resolution for more temporally remote events, consistent with the observation that temporal memory is worse for events further in the past. This paper shows an analogous result for spatial relationships. Place cells coded for distance from the start of a journey. As distance increased, place fields became broader and less numerous, showing a decrease in spatial resolution. This result suggests a unified coding scheme for the dimensions of time and space in the rodent hippocampus.
Interacting rhythms enhance sensitivity of target detection in a fronto-parietal computational model of visual attention

Even during sustained attention, enhanced processing of attended stimuli waxes and wanes rhythmically, with periods of enhanced and relatively diminished visual processing (and subsequent target detection) alternating at 4 or 8 Hz in a sustained visual attention task. These alternating attentional states occur alongside alternating dynamical states, in which lateral intraparietal cortex (LIP), the frontal eye field (FEF), and the mediodorsal pulvinar (mdPul) exhibit different activity and functional connectivity at α, β, and γ frequencies—rhythms associated with visual processing, working memory, and motor suppression. To assess whether and how these multiple interacting rhythms contribute to periodicity in attention, we propose a detailed computational model of FEF and LIP. When driven by θ-rhythmic inputs simulating experimentally-observed mdPul activity, this model reproduced the rhythmic dynamics and behavioral consequences of observed attentional states, revealing that the frequencies and mechanisms of the observed rhythms allow for peak sensitivity in visual target detection while maintaining functional flexibility.
A unified genealogy of modern and ancient genomes

The sequencing of modern and ancient genomes from around the world has revolutionised our understanding of human history and evolution1,2. However, the general problem of how best to characterise the full complexity of ancestral relationships from the totality of human genomic variation remains unsolved. Patterns of variation in each data set are typically analysed independently, and often using parametric models or data reduction techniques that cannot capture the full complexity of human ancestry3,4. Moreover, variation in sequencing technology5,6, data quality7 and in silico processing8,9, coupled with complexities of data scale10, limit the ability to integrate data sources. Here, we introduce a non-parametric approach to inferring human genealogical history that overcomes many of these challenges and enables us to build the largest genealogy of both modern and ancient humans yet constructed. The genealogy provides a lossless and compact representation of multiple datasets, addresses the challenges of missing and erroneous data, and benefits from using ancient samples to constrain and date relationships. Using simulations and empirical analyses, we demonstrate the power of the method to recover relationships between individuals and populations, as well as to identify descendants of ancient samples. Finally, we show how applying a simple non-parametric estimator of ancestor geographical location to the inferred genealogy recapitulates key events in human history. Our results demonstrate that whole-genome genealogies are a powerful means of synthesising genetic data and provide rich insights into human evolution.
Skillful prediction of tropical Pacific fisheries provided by Atlantic Niños

Tropical Pacific upwelling-dependent ecosystems are the most productive and variable worldwide, mainly due to the influence of El Niño Southern Oscillation (ENSO). ENSO can be forecasted seasons ahead thanks to assorted climate precursors (local-Pacific processes, pantropical interactions). However, due to observational data scarcity, little is known about the importance of these precursors for marine ecosystem prediction. Previous studies based on Earth System Model simulations forced by observed climate have shown that multiyear predictability of tropical Pacific marine primary productivity is possible. With recently released global marine ecosystem simulations forced by historical climate, full examination of tropical Pacific ecosystem predictability is now feasible. By complementing historical fishing records with marine ecosystem model data, we show herein that equatorial Atlantic sea surface temperatures (SSTs) constitute a valuable predictability source for tropical Pacific fisheries, which can be forecasted over large-scale areas up to three years in advance. A detailed physical-biological mechanism is proposed whereby equatorial Atlantic SSTs influence upwelling of nutrient-rich waters in the tropical Pacific, leading to a bottom-up propagation of the climate-related signal across the marine food web. Our results represent historical and near-future climate conditions and provide a useful springboard for implementing a marine ecosystem prediction system in the tropical Pacific.
The Serine Protease HtrA2 mediates radiation-induced senescence in cancer cells

Radiation therapy can induce cellular senescence in cancer cells leading to short-term tumor growth arrest, yet increased long-term recurrence. To better understand the molecular mechanisms involved, we developed a model of radiation-induced senescence in cultured cancer cells, which exhibited a typical senescent phenotype, including upregulation of p53 and its target p21, followed by sustained reduction in cellular proliferation, changes in cell size and cytoskeleton organization, and senescence-associated beta-galactosidase activity. A functional siRNA screen using a cell death-related library identified the mitochondrial Ser protease HtrA2 as necessary for senescence development. Mass spectrometry-based proteomic profiling of the senescent cells indicated downregulation of proteins involved in cell cycle progression and DNA repair, and upregulation of proteins associated with malignancy, while irradiation with HtrA2 inhibition upregulated cell proliferation components. In search of direct HtrA2 substrates following radiation, we determined that HtrA2 cleaves the intermediate filament protein vimentin, affecting its cytoplasmic organization. Ectopic expression of active cytosolic HtrA2 resulted in similar changes to vimentin filament assembly. Thus HtrA2, contributes to several hallmarks of senescence and is involved in the cytoskeletal reorganization that accompanies radiation-induced senescence. Summary Here the authors identify the Ser protease HtrA2 as a novel mediator of radiation-induced senescence, necessary for sustained proliferation arrest and reorganization of the vimentin filament network.
Single cell transcriptome mapping identifies a local innate B cell population driving local antibody production and chronic rejection after lung transplantation

Bronchiolitis obliterans syndrome (BOS) due to chronic rejection is the main reason for poor outcomes after lung transplantation (LTx). We and others have recently identified B cells as major contributors to BOS after LTx. The extent of B cell heterogeneity, however, as well as those B cell populations that determine chronic rejection of the lung, remain entirely unclear. Here, we provide a map of cell population heterogeneity and their gene expression patterns during chronic rejection after orthotopic LTx in mice. Out of a total of 14 major comprehensive cell clusters, corresponding to 11 known major cell subpopulations, Mzb1-expressing plasma cells (PCs) were the most prominently increased cell population in lungs with BOS. Scgb1a1-expressing bronchial epithelial cells were depleted, while Cd14-expressing monocytes and Pdgfra-expressing fibroblasts were enriched in BOS grafts. These findings were validated in two different cohorts of human BOS after LTx. MZB1-IgG-double positive PCs infiltrated the airways of patients with BOS, while they were absent from healthy lungs. IgG, but not IgA, IgD, IgE or IgM, were significantly increased in bronchoalveolar lavage from BOS patients, compared with LTx patients who did not develop BOS. Pseudotime and trajectory analysis revealed that a Bhlhe41, Cxcr3, Itgb1-triple positive-B cell subset, also expressing classical markers of the innate-like B-1 B cell population, served as the progenitor pool for Mzb1+ PCs. This progenitor B cell subset accounted for the increase in IgG2c expression and production in BOS lung grafts. Importantly, Aicda−/− mice, which lack all isotypes of Ig (except IgM) were protected from the onset of BOS after LTx. In summary, we provide a detailed atlas of cell population changes of chronic rejection after LTx. We have identified IgG-positive PCs and their progenitors – an innate B cell subpopulation characterized by a specific subset of markers - as the major source of local antibody production and a major contributor to both mouse and human BOS after LTx.
Cholecystokinin 1 Receptor (Cck1R) Normalizes mTORC1 signaling and is Protective to Purkinje cells of SCA Mice

Spinocerebellar Ataxias (SCAs) are a group of genetic diseases characterized by progressive ataxia and neurodegeneration, often in cerebellar Purkinje neurons. A SCA1 mouse model, Pcp2-ATXN1[30Q]D776, has severe ataxia in absence of progressive Purkinje neuron degeneration and death. Previous RNA-seq analyses identified cerebellar up-regulation of the peptide hormone Cholecystokinin (Cck) in Pcp2-ATXN1[30Q]D776 mice. Importantly, absence of Cck1 receptor (Cck1R) in Pcp2-ATXN1[30Q]D776 mice confers a progressive disease with Purkinje neuron death. A Cck1R agonist, A71623 administered to Pcp2-ATXN1[30Q]D776;Cck-/- and Pcp2-AXTN1[82Q] mice dampened Purkinje neuron pathology and associated deficits in motor performance. In addition, A71623 administration improved motor performance of Pcp2-ATXN2[127Q] SCA2 mice. Moreover, the Cck1R agonist A71623 corrected mTORC1 signaling and improved expression of calbindin in cerebella of AXTN1[82Q] and ATXN2[127Q] mice. These results indicate that manipulation of the Cck-Cck1R pathway is a potential therapeutic target for treatment of diseases involving Purkinje neuron degeneration.
Modeling Solids Friction for Dense-Phase Pneumatic Conveying of Powders

This article results from an ongoing investigation aimed at developing a new validated test-design procedure for the accurate prediction of pressure drop for dense-phase pneumatic conveying of powders. Models for combined pressure drop coefficient (“K”) for solids-gas mixture were derived using the concept of “suspension density” by using the steady-state “straight pipe” pressure drop data between two different tapping locations of the same pipe and also for two different diameter pipes. It was observed that the derived models were different depending on the location of tapping points (for the same pipe) and selected pipe diameters. The derived models were then evaluated by predicting the pressure drop for pipelines with various diameters or lengths (69 mm I.D. × 168 m, 105 mm I.D. × 168 m, 69 mm I.D. × 554 m) for the conveying of power station fly ash. A comparison between the predicted pneumatic conveying characteristics (PCC) and the experimental plots showed that the models resulted in significant over-predictions. In the second part of the article, the “system” approach of scaleup was evaluated. “Total” pipeline pressure drop characteristics for test-rig pipelines were scaled up to predict the PCC for larger/longer pipes. It was found that the “system” approach generally resulted in grossly inaccurate predictions. It was concluded that further studies are needed for a better understanding of the solids-gas flow mechanism under dense-phase conditions.
The Limitations of X-ray Absorption Spectroscopy for Determining the Structure of Zinc Sites in Proteins. When Is a Tetrathiolate Not a Tetrathiolate?

X-ray absorption fine structure (XAFS) spectra have been measured for a series of structurally characterized zinc model complexes that mimic the zinc sites found in metalloproteins. These include both inorganic zinc coordination complexes and small zinc binding peptides. These data have been analyzed to determine the extent to which Zn XAFS can be used to determine reliably the ligation environment of the zinc. Because Zn−N and Zn−S XAFS oscillations are nearly out of phase over the accessible energy range, it is difficult to determine the relative number of sulfur and nitrogen scatterers, and in some cases, it is even difficult to determine whether a low-Z (N or O) ligand is bound in the presence of high-Z (S) ligands. We describe a protocol that, by controlling the number of variable parameters, can be used to obtain an accurate quantitation of the number of low-Z ligands. We also show that two of the variables that are often treated as freely adjustable parameters, the scale factor and shift in the thr.
In Situ IR Characterization of CO Interacting with Rh Nanoparticles Obtained by Calcination and Reduction of Hydrotalcite-Type Precursors

Supported Rh nanoparticles obtained by reduction in hydrogen of severely calcined Rh/Mg/Al hydrotalcite-type (HT) phases have been characterized by FT-IR spectroscopy of adsorbed CO [both at room temperature (r.t.) and nominal liquid nitrogen temperature] and Transmission Electron Microscopy (TEM). The effect of reducing temperature has been investigated, showing that Rh crystal size increases from 1.4 nm to 1.8 nm when the reduction temperature increases from 750°C to 950°C. The crystal growth favours the formation of bridged CO species and linear monocarbonyl species with respect to gem-dicarbonyl species; when CO adsorbs at r.t. , CO disproportionation occurs on Rh and it accompanies the formation of (CO)2. The role of interlayer anions in the HT precursors to affect the properties of the final materials has been also investigated considering samples prepared from silicate-instead of carbonate-containing precursors. In this case, formation of (CO)2 and CO disproportionation do not occur, and this evidence is discussed in terms of support effect.
How to Train for a 5K—What Does the Science Say?

This article provides insight into developing an individualized training program for an intermediate runner. The exercise professional should hope to gain knowledge on initial testing, exercise prescription, and monitoring of training. Apply It! • This article provides a realistic and scientific approach for developing a 12-week training program for an intermediate-level recreational runner preparing for their first 5K race. • The fitness professional should expect to gain knowledge on an effective field test used to determine initial fitness and estimate the lactate threshold. • Rating of perceived exertion (RPE) is a valuable tool for prescribing endurance exercise to an intermediate-level runner. RPE is simple to use and relates to the three-zone intensity model. • Using different tools, such as the Profile of Mood State Questionnaire, will help to monitor your client. This approach may assist in your prevention of overtraining and decreased motivation and may keep training exciting so that the client can meet their goals.
Electrophilic aromatic substitution. Part I. The nitration of some reactive aromatic compounds in concentrated sulphuric and perchloric acids

The nitration of benzene and some more reactive compounds in sulphuric acid (and to a smaller extent in perchloric acid) has been studied. In both media a limit is reached beyond which the introduction of further activating substituents does not increase the rate of nitration. This limit is the rate of encounter of the nitronium ions and the aromatic molecules. Up to 68% sulphuric acid the slope of the plot of the stoicheiometric second-order rate constant for the nitration of benzene against –(HR+ log aH2O) at 25° is unity, but above this acidity the slope increases. These facts diminish the value of a comparison of the rate of nitration of a given substrate with that of benzene as a means of studying aromatic reactivity, for the comparison would be dependent on the acidity. Further, at the higher end of the acidity range studied, the rate of nitration of benzene approaches to within a sixth of the observed encounter rate, and if the former is then to some degree encounter-controlled, the significance of comparison with other substrates is reduced.
Large-Eddy Simulation of Subsonic-Supersonic Flow and Heat Transfer in a Hybrid Gas-Water Stabilized Arc

The paper presents numerical simulations of the turbulence effect in the discharge and near-outlet regions of the hybrid-stabilized argon-water electric arc. Calculations were carried out for the assumption of laminar and turbulent plasma flow models, respectively. Results of simulation for currents 300-600 A on a fine numerical grid show that the influence of turbulence is weak and the maximum difference for all the monitored physical quantities is less than 2% in the discharge region and less than 6% in the near-outlet region. Comparison with experimental temperature profiles exhibits good agreement.