Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-cell based elucidation of molecularly-distinct glioblastoma states and drug sensitivity

Glioblastoma heterogeneity and plasticity remain controversial, with proposed subtypes representing the average of highly heterogeneous admixtures of independent transcriptional states. Single-cell, protein-activity-based analysis allowed full quantification of >6,000 regulatory and signaling proteins, thus providing a previously unattainable single-cell characterization level. This helped identify four novel, molecularly distinct subtypes that successfully harmonize across multiple GBM datasets, including previously published bulk and single-cell profiles and single cell profiles from seven orthotopic PDX models, representative of prior subtype diversity. GBM is thus characterized by the plastic coexistence of single cells in two mutually-exclusive developmental lineages, with additional stratification provided by their proliferative potential. Consistently, all previous subtypes could be recapitulated by single-cell mixtures drawn from newly identified states. Critically, drug sensitivity was predicted and validated as highly state-dependent, both in single-cell assays from patient-derived explants and in PDX models, suggesting that successful treatment requires combinations of multiple drugs targeting these distinct tumor states. Significance We propose a new, 4-subtype GBM classification, which harmonizes across bulk and single-cell datasets. Single-cell mixtures from these subtypes effectively recapitulate all prior classifications, suggesting that the latter are a byproduct of GBM heterogeneity. Finally, we predict single-cell level activity of three clinically-relevant drugs, and validate them in patient-derived explant.
Crystal structure of m4-1BB/4-1BBL complex reveals an unusual dimeric ligand that undergoes structural changes upon receptor binding

The interaction between the 4-1BB and its ligand 4-1BBL provides co-stimulatory signals for T cell activation and proliferation, but differences in the mouse and human molecules might result in differential engagement of this pathway. Here, we report the crystal structure of mouse 4-1BBL and of the mouse 4-1BB/4-1BBL complex, together provide insights into the molecular recognition of the cognate receptor by m4-1BBL. In contrast to all human or mouse TNF ligands that form non-covalent mostly trimeric assemblies, the m4-1BBL structure formed a novel disulfide linked dimeric assembly. The structure showed that certain differences in the amino acid composition along the intramolecular interface, together with two specific residues (Cys 246 and Ser 256) that are exclusively present in m4-1BBL, are responsible for unique dimerization. Unexpectedly, upon binding to m4-1BB, m4-1BBL undergoes structural changes within each protomer, in addition the individual m4-1BBL protomers rotate with respect to each other, leading to a different dimerization interface with more inter-subunit interactions. In the m4-1BB/4-1BBL complex, each receptor monomer binds exclusively to a single ligand subunit with contributions of cysteine-rich domain (CRD) 1, CRD2 and CRD3. Furthermore, structure-guided mutagenesis of the binding interface revealed that novel binding interactions with the GH loop, rather than the DE loop, are energetically critical and define the species based receptor selectivity for m4-1BBL. A comparison with the human 4-1BB/4-1BBL complex highlighted several differences between the ligand and receptor binding interfaces and provide an explanation for the absence of inter species cross-reactivity between human and mouse 4-1BB and 4-1BBL molecules.
Effect of liquid medium on shoots amplification, in vitro flowering and ex vitro rooting of Oldenlandia umbellata L. - A dye yielding medicinal herb

Oldenlandia umbellata L. gains importance due to its medicinal properties and the presence of anthraquinones based natural dyes in the roots. Present study describes the effect of Murashige and Skoog’s (MS) liquid medium (full strength) on in vitro regeneration, flower bud induction and ex vitro rooting in O. umbellata. Shoot segments with 2-3 nodes (each node with 2 axillary buds) served as explants for establishment of cultures. The liquid medium augmented with 2.0 mg L-1 6-benzylaminopurine (BAP) with additives (50 mg L-1 of ascorbic acid and 25 mg L-1 each of arginine, adenine sulphate and citric acid) was effective for shoot bud induction (6.4±0.19 shoots per explant within 2-3 weeks). The shoots were further multiplied (89.3±1.07 shoots, 2-3 weeks) when the shoot clusters obtained from the culture initiation directly transferred to the full-strength MS liquid medium incorporated with 1.0 mg L-1 BAP and 0.5 mg L-1 indole-3 acetic acid (IAA) with additives. Flower buds were induced (12.0±0.15 buds per shoot) when the shoots were cultured on 1.0 mg L-1 BAP and kinetin (Kin, 6-furfurylaminopurine) and 0.5 mg L-1 of IAA at 45 µmol m−2 s−1 SFPD (Spectral Flux Photon Density) light intensity for 14/10h (light/dark) photoperiod. The adventitious roots were induced on 1/4 strength MS medium supplemented with 1.5 mg L-1 indole-3 butyric acid (IBA). Ex vitro rooting was achieved (16.0±0.53 roots per shoot) by pulse treatment of the shoots with 300 mg L-1 IBA for 2 min. The in vitro produced plantlets were acclimatized in the greenhouse and finally translocated to the in vivo conditions with 93 % success rate. This is the foremost (use of liquid MS medium) and cost-effective method for large scale multiplication of O. umbellata.
A comprehensive formula for decomposing change in community similarity into introduction and extinction events

Biological invasion, climate change and urbanization are presently altering species compositions worldwide (McKinney and Lockwood 1999, McKinney 2006, Qian and Ricklefs 2006, Magurran et al. 2015, Gossner et al. 2016, Newbold et al. 2018), while changes in community composition are generally associated with higher community similarities and losses of community distinctiveness (McKinney and Lockwood 1999, Olden et al. 2004). The underlying processes of homogenization are still unclear and especially lack theoretical underpinnings (Olden and Poff 2003, Rosenblad and Sax 2017). It was theoretically and empirically proposed that similarity changes are determined by different events (Olden and Poff 2003, Villeger and Brosse 2012, Rosenblad and Sax 2017). For example, the introduction of the same species to two sites would result in an increase in similarity, while the extinction of same native species from two sites would lead to a decrease in similarity. In complement to earlier works on the mathematical description of homogenization (Olden and Poff 2003, Villeger and Brosse 2012). Rosenblad and Sax (2017) provided a concise framework of six types of introduction and extinction events with formula derivations to qualify the relative importance of these events on changes in community similarity. They found that the effects of these events vary according to event type and initial similarity. However, their conclusions mainly derive from simplified assumptions of species richness and number of events, which prevent us from understanding the precise relationships among initial similarity, different event types and total number of species. Through mathematical derivation and simulations (Fig. 1), we thus aim to: 1) combine previously identified determinants of change in similarity into a single comprehensive formula; 2) illustrate how these determinants interact with each other; and 3) highlight the important role of gradient in species richness in affecting the magnitude of similarity changes.
Tonotopic and multisensory organization of the mouse dorsal inferior colliculus revealed by two-photon imaging

The dorsal (DCIC) and lateral cortices (LCIC) of the inferior colliculus are major targets of the auditory and non-auditory cortical areas, suggesting a role in complex multimodal information processing. However, relatively little is known about their functional organization. We utilized in vivo two-photon Ca2+ imaging in awake mice expressing GCaMP6s in GABAergic or non-GABAergic neurons in the IC to investigate their spatial organization. We found different classes of temporal response, which we confirmed with simultaneous juxtacellular electrophysiology. Both GABAergic and non-GABAergic neurons showed spatial microheterogeneity in their temporal responses. In contrast, a robust reversed rostromedial-caudolateral gradient of frequency tuning was conserved between the two groups, and even among the subclasses. This, together with the existence of a subset of neurons sensitive to spontaneous movements, provides functional evidence for redefining the border between DCIC and LCIC.
The role of substrate characteristics in Populus tremuloides (MICHX.) seed germination in post-disturbance black spruce-feathermoss forest in northwestern Quebec

Trembling aspen (Populus tremuloides (Michx.)) has become established along a mining road in the lower northern Quebec region (49°39' to 49°45'N and 79°01' to 79°02' W) in areas that have not supported aspen in the past. The primary means of regeneration of aspen is through vegetative root suckers, but it is doubtful that it could progress through this region at such a fast rate solely by asexual reproduction. Aspen are known to produce large amounts of seeds that could account for aspen's rapid progression, but sexual reproduction of aspen is rare; very little is known about Populus tremuloides seed germination and seed survival in natural conditions. The aim of this study was to determine seedbed conditions that facilitate the emergence and survival of Populus tremuloides seedlings, and to identify the key factors involved in these processes. Observations of established saplings and a sowing experiment were conducted on both post harvest and post fire sites. Our data on established saplings showed that there were seed-origin trembling aspen located in both post-harvest and burned areas indicating that Populus tremuloides can and has established from seed in areas where aspen was previously absent. Both our sowing experiment and our greenhouse experiment showed that the emergence of seedlings was relatively low, but that Polytrichum strictum moss and exposed mineral soil depressions were the best seedbeds for seed germination. Extreme temperatures and availability of moisture appeared to be controlling factors on seed germination, but ultimately the physical and biological characteristics of each substrate influenced the substrate's response to these factors in a different way. We conclude that sexual reproduction of trembling aspen may and has occurred in this region, and is promoted by the presence of exposed mineral soil and Polytrichum strictum moss. %%%%Keywords: Bryophytes, Populus tremuloides, Polytrichum, Sphagnum, seedling, seedbed, germination, seed.
Use of high protein distiller’s dried grains (HPDDG) with enzyme phytase as a cost effective ingredient in the diet of fingerlings European sea bass, Dicentrarchus labrax

The present study was conducted to evaluate the effect of various dietary levels of high protein distiller’s dried grains (HPDDG) supplemented with enzyme phytase on growth performance, feed utilization and haematological indices of European sea bass Dicentrarchus labrax fingerlings. A total of 150 D. labrax fingerlings with an average body weight of 7.5 ± 0.5g were divided in the five experimental treatments (in triplicates each). The experiment was conducted for 56 days. Fish were fed to apparent the satiation six days a week. Five isonitrogenous 45% CP experimental diets were formulated. The control (C) diet had no high protein distiller’s dried grains (HPDDG) and phytase enzyme added. Diet 2 (C+) was formulated as control diet and supplemented with phytase at a level of 0.5 g/kg. Diets 3-5 each contained HPDDG at levels of 20, 30, and 40 %, respectively with soybean meal and supplemented each with phytase at a level of 0.5 g/kg. Over the 56 days feeding period, all fish fed HPDDG-supplemented with phytase diets resulted in higher growth than the control diet, suggesting that the using of HPDDG-supplemented with phytase enhanced the growth performance of sea bass fingerlings. The same trend was recorded for the best FCR and PER. The hematology and serum biochemistry (hemoglobin (Hb), red blood cells (RBCs) count, white blood cells (WBCs) and hematocrit (Hct %) and immune parameters (total protein, albumin, globulin, cholestorl, lysozyme activity and total antioxidant capacity) of D. labrax fingerlings significantly (P ≥ 0.05) increased with increasing dietary HPDDG with phytase. Result indicates that HPDDG with phytase is a good alternative protein source for compromising growth performance and physiological parameters of European sea bass, Dicentrarchus labrax Fingerlings
Evolution of C4 photosynthesis predicted by constraint-based modelling

Evolutionary constraint-based modelling is a powerful tool for the analysis of evolutionary trajectories in bacteria with unknown usefulness in eukaryotes. We hypothesised that the agriculturally important trait of C4 photosynthesis is accessible to modelling because it evolved from an ancestral ground state of C3 photosynthesis. All genes required for C4 are present in C3 but not arranged in a pathway. Plants performing C4 metabolism are capable of highly efficient carbon fixation and consequentially are adapted to adverse growth conditions and/or are capable of high growth rates. We hypothesised that constraint-based modelling will identify the selective pressures under which C4 photosynthesis evolves. Indeed, a carefully curated two-celled model predicts C4 under two different selective pressures. The model attributed differences between extant metabolic flavours of C4 to light availability and distribution. Likely kinetic constraints on reactions were identified for flux solutions which did not match known physiological fluxes. The data shows evolutionary constraint-based modelling in eukaryotes predicts molecular evolution with precision.
Overview of Image Reconstruction

Image reconstruction (or computerized tomography, etc.) is any process whereby a function, f, on Rn is estimated from empirical data pertaining to its integrals, If(x) dx, for some collection of hyperplanes of dimension k < n. The paper begins with background information on how image reconstruction problems have arisen in practice, and describes some of the application areas of past or current interest; these include radioastronomy, optics, radiology and nuclear medicine, electron microscopy, acoustical imaging, geophysical tomography, nondestructive testing, and NMR zeugmatography. Then the various reconstruction algorithms are discussed in five classes: summation, or simple back-projection; convolution, or filtered back-projection; Fourier and other functional transforms; orthogonal function series expansion; and iterative methods. Certain more technical mathematical aspects of image reconstruction are considered from the standpoint of uniqueness, consistency, and stability of solution. The paper concludes by presenting certain open problems. 73 references. (RWR)
A circadian zip code guides leukocyte homing

Circadian rhythms are important for organisms to anticipate predictable environmental changes. Evidence indicates that the oscillation of murine blood numbers is closely related to the lighting schedule. However, the dynamics and the mechanisms of the migration of leukocyte subsets over 24 hours are unknown. Here, we could show that that numbers of circulating leucocyte subsets exhibit circadian rhythms in murine blood, which was regulated by rhythmic homing, with a co-contribution of both microenvironmental and leukocyte-autonomous oscillations. We identified leukocyte and vascular bed specific surface expression oscillations of adhesion molecules and chemokine receptors over 24 hours. To test the relevance of these oscillations, functional blocking experiments using antibodies or functional blockers directed against pro-migratory molecules were performed. Our data indicate the adhesion molecules CD11a, CD49d and L-selectin and the chemokine receptor CXCR4 on the leukocyte side, as well as VCAM-1 and ICAM-1 on the endothelial side to be important in the rhythmic recruitment process of leukocyte subsets. A stronger blocking effect targeting these molecules was found at night for leukocyte subsets. In the homing experiments, we found donor leukocytes preferentially migrated to organs at night, and that the recruitment process of different leukocyte subsets to various organs could be blocked by distinct inhibitors. We exposed the role of circadian genes in the rhythmic recruitment process using B-cell and myeloid-cell-specific knockouts of the circadian gene Bmal1, which demonstrated altered expression levels of specific oscillatory molecules and leukocyte numbers in tissues, suggesting that rhythmicity in these factors may be directly regulated by the circadian clock. Furthermore, we detected inverse oscillation patterns of human blood cell numbers compared to murine cells as well as of the expression levels of CXCR4 on leukocyte subsets. Together, our data demonstrate that circadian genes control a rhythmic leukocyte- and tissue-specific molecular signature in the expression of pro-migratory factors, which allows for the recruitment of select leukocyte subsets at distinct times.
In vitro anti-bacterial activity of Tinospora cordifolia leaf extract and its phytochemical screening

Background: Antimicrobial resistance is the main concern worldwide to combat infectious. Over the years studies on leaf extracts Tinospora cordifolia have demonstrated the potent role its antibacterial property. The current study is an attempt to test its antibacterial property against Escherichia coli cell division. Material and methods: Phytochemical screening assay of T. cordifolia leaf extract was done using standard procedure and the results showed the presence of alkaloid, carbohydrate, terpenoid, steroid, tannin, amino acid, flavonoid and glycoside components. Results: HPLC analysis revealed the presence of berberine in T. cordifolia leaf extract. Further E. coli cells were treated with berberine to study its efficacy in inhibiting cell division. Antibacterial assay was performed by using disc diffusion method. Conclusion: Among aqueous, methanolic, ethanolic, chloroform, hexane and acetone extract only methanolic extract showed zone of inhibition.
A Novel Algorithm for the Reduction of Irregular Noise in Corrupted Speech Signals

One of the main problems associated with the use of two-sensor noise cancellation systems is the nature of the noise signals. This problem imposes the use of high complexity algorithms to reduce the noise in useful signals. This can be impractical for many real time applications, where computational power is a critical issue. Most of existing literature approaches is based on a single and usually complex adaptation algorithm to do the job. In this paper, a new mechanism is devised to eliminate background noise from speech communications. The procedure is based on a two-sensor adaptive noise canceller that is capable of assigning a suitable algorithm according to properties of the noise. The criterion used here is based on calculating the eigenvalue spread of the autocorrelation of the input noise. The new smart noise canceller (SNC) applies a suitable adaptive algorithm according to the eigenvalue characteristics of the input signal. This approach showed its capability in executing noise cancellation under different types of environmental noise. Fast convergence rates, improvement in signal-to-noise ratio and substantial reduction in computational power are obtained using this SNC technique. Experiments are conducted using real life signals to demonstrate the success of the method.
Cyanidium chilense (Cyanidiophyceae, Rhodophyta) from tuff rocks of the archeological site of Cuma, Italy

Phlegrean Fields is a large volcanic area situated southwest of Naples (Italy), including both cave and thermoacidic habitats. These extreme environments host the genus Cyanidium; the species C. chilense represents a common phototrophic microorganism living in anthropogenic caves. With a view to provide a comprehensive characterization for a correct taxonomic classification, morpho‐ultrastructural investigations of C. chilense from Sybil's cave (Phlegren Fields) was herein carried out and compared with the thermoacidophilic C. caldarium. The biofilm was also analyzed to define the role of C. chilense in the establishment of a biofilm within cave environments. Despite the peculiar ecological and molecular divergences, C. chilense and C. caldarium shared all the main diacritic features, suggesting morphological convergence within the genus; cytological identity was found among C. chilense strains geographically distant and adapted to different substrates, such as the porous yellow tuff of Sybil cave, and calcyte, magnesite and basaltic rocks from other caves. C. chilense is generally dominant in all biofilms, developing monospecific islets, developing both superficially or between fungal hyphae and coccoid cyanobacteria. Extracellular polymeric substances (EPS) were recorded in C. chilense biofilms from Sybil cave, confirming the role of EPS in facilitating cells adhesion to the surface, creating a cohesive network of interconnecting biofilm cells.
An Evaluation of Retrieval Performance Using Farsi Text

A series of experiments has been conducted on the Farsi language in the University of Tehran during past three years. The goal of these experiments was to establish the characteristics of Farsi text with respect to different retrieval models and weight schemes. These experiments included different Fuzzy methods and Vector Space, Probablistic and N-gram models of retrieval. The results show that vectore space model with ltu.Lnu weighting outperforms other models and weighting schemes.
Comparison between transgenic and AAV-PHP.eB-mediated expression of GCaMP6s using in vivo wide-field functional imaging of brain activity

Abstract. We employ transcranial wide-field single-photon imaging to compare genetically encoded calcium sensors under transgenic or viral vector expression strategies. Awake, head-fixed animals and brief visual flash stimuli are used to assess function. The use of awake transcranial imaging may reduce confounds attributed to cranial window implantation or anesthesia states. We report differences in wide-field epifluorescence brightness and peak ΔF / F0 response to visual stimulation between expression strategies. Other metrics for indicator performance include fluctuation analysis (standard deviation) and regional correlation maps made from spontaneous activity. We suggest that multiple measures, such as stimulus-evoked signal-to-noise ratio, brightness, and averaged visual ΔF / F0 response, may be necessary to characterize indicator sensitivity and methods of expression. Furthermore, we show that strategies using blood brain barrier-permeable viruses, such as PHP.eB, yield comparable expression and function as those derived from transgenic mice. We suggest that testing of new genetically engineered activity sensors could employ a single-photon, wide-field imaging pipeline involving visual stimulation in awake mice that have been intravenously injected with PHP.eB.
Estimating snow particle size using TM band-4

The snowpack parameters are important to climatological and hydrological investigations. Using data acquired with the Landsat Thematic Mapper (TM) over the Oetztal Alps and Wapta, the authors derived snow particle size maps from TM band-4. The information with temporal and spatial variations in snow properties will prove our understanding of the processes of natural snowpacks and provide the quantitative measurements for climatological and hydrological studies. <<ETX>>