bluuebunny/crossref_metadata_2025_split huggingface dataset:
Net charges of the ribosomal proteins of theS10andspcclusters of halophiles are inversely related to the degree of halotolerance
Authors: Tirumalai Madhan R , Anane-Bediakoh Daniela , Rajesh Siddharth , Fox George. E. 
Published: November 2021

AbstractNet positive charge(s) on ribosomal proteins (r-proteins) have been reported to influence the assembly and folding of ribosomes. A high percentage of r-proteins from extremely halophilic archaea are known to be acidic or even negatively charged. Those proteins that remain positively charged are typically far less so. Herein the analysis is extended to the non-archaeal halophilic bacteria, eukaryotes and halotolerant archaea. The net charges (pH 7.4) of r-proteins that comprise theS10-spcoperon/cluster from individual microbial and eukaryotic genomes were estimated and intercompared. It was observed that as a general rule, as the salt tolerance of the bacterial strains increased from 5 to 15%, the net charges of the individual proteins remained mostly basic. The most striking exceptions were the extremely halophilic bacterial strains,Salinibacter ruberSD01,Acetohalobium arabaticumDSM 5501 andSelenihalanaerobacter shriftiiATCC BAA-73, which are reported to require a minimum of 18%-21% of salt for their growth. All three strains have a higher number of acidicS10-spccluster r-proteins than what is seen in the moderate halophiles or the halotolerant strains. Of the individual proteins, only uL2 never became acidic. uS14 and uL16 also seldom became acidic. The net negative charges on several of theS10-spccluster r-proteins is a feature generally shared by all extremely halophilic archaea and bacteria. TheS10-spccluster r-proteins of halophilic fungi and algae (eukaryotes) were exceptions. They were positively charged despite the halophilicity of the organisms.ImportanceThe net charges (at pH 7.4) of the ribosomal proteins (r-proteins) that comprise theS10-spccluster show an inverse relationship with the halophilicity/halotolerance levels in both bacteria and archaea. In non-halophilic bacteria, theS10-spccluster r-proteins are generally basic (positively charged), while the rest of the proteomes in these strains are generally acidic. On the other hand, the whole proteomes of the extremely halophilic strains are overall negatively charged including theS10-spccluster r-proteins. Given that the distribution of charged residues in the ribosome exit tunnel influences co-translational folding, the contrasting charges observed in theS10-spccluster r-proteins has potential implications for the rate of passage of these proteins through the ribosomal exit tunnel. Furthermore, the universal protein uL2 which lies in the oldest part of the ribosome is always positively charged irrespective of the strain/organism it belongs to. This has implications for its role in the prebiotic context.
Structural comparative modeling of multi-domain ΔF508 CFTR
Authors: McDonald Eli Fritz , Woods Hope , Smith Shannon T. , Kim Minsoo , Schoeder Clara T. , Plate Lars , Meiler Jens 
Published: November 2021

ABSTRACTCystic Fibrosis (CF) is a common genetic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), an epithelial anion channel expressed in several vital organs. Absence of functional CFTR results in imbalanced osmotic equilibrium and subsequent mucus build up in the lungs - which increases the risk of infection and eventually causes death. CFTR is an ATP binding cassette (ABC) transporter composed of two transmembrane domains (TMDs), two nucleotide binding domains (NBDs), and an unstructured regulatory domain. The most prevalent patient mutation is the deletion of F508 (ΔF508), making ΔF508 CFTR the primary target for current FDA approved CF therapies. However, no experimental multi-domain ΔF508 CFTR structure has been determined and few studies have modeled ΔF508 using multi-domain WT CFTR structures. Here, we used cryo-EM density data and Rosetta comparative modeling (RosettaCM) to compare a ΔF508 model with published experimental data on CFTR NBD1 thermodynamics. We then apply this modeling method to generate multi-domain WT and ΔF508 CFTR structural models. These models demonstrate the destabilizing effects of ΔF508 on NBD1 and the NBD1/TMD interface in both the closed and open conformation of CFTR. Furthermore, we modeled ΔF508/R1070W and ΔF508 bound to the CFTR corrector VX-809. Our models reveal the stabilizing effects of R1070W and VX-809 on multi-domain models of ΔF508 CFTR and pave the way for rational design of additional drugs that target ΔF508 CFTR for treatment of CF.Author SummaryProtein’s three-dimension shape determines their function, so when genetic mutation compromises the shape of vital proteins, it may cause disease. Such is the case in Cystic Fibrosis, a chronic genetic disease caused by mutations in the protein Cystic Fibrosis Transmembrane Conductance Regulator. Here, we work backwards from the shape of the wild-type protein – found in healthy people, to computationally model the shape of the most common Cystic Fibrosis mutant. Our computer models reveal distinct defects in the shape of the mutant Cystic Fibrosis Transmembrane Conductance Regulator protein in the area surrounding the mutation. We also model an important FDA approved Cystic Fibrosis drug, VX-809, into the mutant protein structure and show how VX-809 stabilizes the protein around the location of the mutation. The method we developed will pave the way for computational drug design for Cystic Fibrosis.
Virtual reality validation of naturalistic modulation strategies to counteract fading in retinal stimulation
Authors: Thorn Jacob Thomas , Chenais Naïg Aurelia Ludmilla , Hinrichs Sandrine , Chatelain Marion , Ghezzi Diego 
Published: November 2021

AbstractObjectiveTemporal resolution is a key challenge in artificial vision. Several prosthetic approaches are limited by the perceptual fading of evoked phosphenes upon repeated stimulation from the same electrode. Therefore, implanted patients are forced to perform active scanning, via head movements, to refresh the visual field viewed by the camera. However, active scanning is a draining task, and it is crucial to find compensatory strategies to reduce it.ApproachTo address this question, we implemented perceptual fading in simulated prosthetic vision using virtual reality. Then, we quantified the effect of fading on two indicators: the time to complete a reading task and the head rotation during the task. We also tested if stimulation strategies previously proposed to increase the persistence of responses in retinal ganglion cells to electrical stimulation could improve these indicators.Main resultsThis study shows that stimulation strategies based on interrupted pulse trains and randomisation of the pulse duration allows significant reduction of both the time to complete the task and the head rotation during the task.SignificanceThe stimulation strategy used in retinal implants is crucial to counteract perceptual fading and to reduce active head scanning during prosthetic vision. In turn, less active scanning might improve the patient’s comfort in artificial vision.
Effects of food availability cycles on phase and period of activity/rest rhythm inDrosophila melanogaster
Authors: Singh Viveka Jagdish , Potdar Sheetal , Sheeba Vasu 
Published: November 2021

AbstractForaging and feeding are indispensable for survival and their timing depends not only on the metabolic state of the animal but also on the availability of food resources in their environment. Since both these aspects are subject to change over time, these behaviours exhibit rhythmicity in occurrence. As the locomotor activity of an organism is related to its disposition to acquire food, and peak feeding in fruit flies has been shown to occur at a particular time of the day, we asked if cyclic food availability can entrain their rhythmic activity. By subjecting flies to cyclic food availabilityi.e., feeding/starvation (FS) cycles, we provided food cues contrasting to the preferred activity times and observed if this imposed cycling in food availability could entrain the activity/rest rhythm. We found that phase control, which is a property integral to entrainment, was not achieved despite increasing starvation duration of FS cycles (FS12:12, FS10:14 and FS8:16). We also found that flies subjected to T21 and T26 FS cycles were unable to match period of the activity rhythm to short or long T-cycles. Taken together these results show that external food availability cycles do not entrain the activity/rest rhythm of fruit flies. However, we find that starvation induced hyperactivity causes masking which results in phase changes. Additionally, T-cycle experiments resulted in minor period changes during FS treatment. These findings highlight that food cyclicity by itself may not be a potent zeitgeber but may act in unison with other abiotic factors like light and temperature to help flies time their activity appropriately.
CRAFT: a bioinformatics software for custom prediction of circular RNA functions
Authors: Molin Anna Dal , Gaffo Enrico , Difilippo Valeria , Buratin Alessia , Parenzan Caterina Tretti , Bresolin Silvia , Bortoluzzi Stefania 
Published: November 2021

AbstractCircular RNAs (circRNAs), transcripts generated by backsplicing, are particularly stable and pleiotropic molecules, whose dysregulation drives human diseases and cancer by modulating gene expression and signaling pathways. CircRNAs can regulate cellular processes by different mechanisms, including interaction with microRNAs (miRNAs) and RNA-binding proteins (RBP), and encoding specific peptides. The prediction of circRNA functions is instrumental to interpret their impact in diseases, and to prioritize circRNAs for functional investigation. Currently, circRNA functional predictions are provided by web databases that do not allow custom analyses, while self-standing circRNA prediction tools are mostly limited to predict only one type of function, mainly focusing on the miRNA sponge activity of circRNAs. To solve these issues, we developed CRAFT (CircRNA Function prediction Tool), a freely available computational pipeline that predicts circRNA sequence and molecular interactions with miRNAs and RBP, along with their coding potential. Analysis of a set of circRNAs with known functions has been used to appraise CRAFT predictions and to optimize its setting. CRAFT provides a comprehensive graphical visualization of the results, links to several knowledge databases, and extensive functional enrichment analysis. Moreover, it originally combines the predictions for different circRNAs. CRAFT is a useful tool to help the user explore the potential regulatory networks involving the circRNAs of interest and generate hypotheses about the cooperation of circRNAs into the modulation of biological processes.Key pointsCRAFT is a self standing tool for comprehensive circRNA function prediction.CRAFT functions include circRNA sequence reconstruction, microRNA and RNA-binding protein response elements and coding potential prediction.Predictions for multiple circRNAs are connected to infer possible cooperation networks and illustrate the potential impact of circRNAs on biological and disease processes.
Reconstructing disease dynamics for mechanistic insights and clinical benefit
Authors: Frishberg Amit , Milman Neta , Alpert Ayelet , Spitzer Hannah , Asani Ben , Schiefelbein Johannes B. , Priglinger Siegfried G. , Schultze Joachim L. , Theis Fabian J. , Shen-Orr Shai S. 
Published: November 2021

AbstractDiseases change over time, both phenotypically and in underlying driving molecular processes. Though understanding disease progression dynamics is critical for diagnostics and treatment, capturing these dynamics is difficult, due to their complexity and the high heterogeneity between individuals. We developed TimeAx, an algorithm which builds a comparative framework for capturing disease dynamics using high-dimensional short time-series data. We demonstrate TimeAx utility by studying disease progression dynamics for multiple diseases and data types. Notably, for urothelial bladder cancer tumorigenesis, we identified a stromal pro-invasion point on the disease progression axis, characterized by massive immune cell infiltration to the tumor microenvironment and increased mortality. Moreover, the continuous TimeAx model differentiated between early and late tumors within the same tumor subtype, uncovering novel molecular transitions and potential targetable pathways. Overall, we present a powerful approach for studying disease progression dynamics, providing improved molecular interpretability and clinical benefits for patient stratification and outcome prediction.
A new lineage of non-photosynthetic green algae with extreme organellar genomes
Authors: Pánek Tomáš , Barcytė Dovilė , Treitli Sebastian C. , Záhonová Kristína , Sokol Martin , Ševčíková Tereza , Zadrobílková Eliška , Jaške Karin , Yubuki Naoji , Čepička Ivan , Eliáš Marek 
Published: November 2021

AbstractBackgroundThe plastid genomes of the green algal order Chlamydomonadales tend to expand their non-coding regions, but this phenomenon is poorly understood. Here we shed new light on organellar genome evolution in Chlamydomonadales by studying a previously unknown non-photosynthetic lineage. We established cultures of two new Polytoma-like flagellates, defined their basic characteristics and phylogenetic position, and obtained complete organellar genome sequences and a transcriptome assembly for one of them.ResultsWe discovered a novel deeply diverged chlamydomonadalean lineage that has no close photosynthetic relatives and represents an independent case of photosynthesis loss. To accommodate these organisms we establish the new genus Leontynka, with two species (L. pallida and L. elongata) distinguishable through both their morphological and molecular characteristics. Notable features of the colourless plastid of L. pallida deduced from the plastid genome (plastome) sequence and transcriptome assembly include the retention of ATP synthase, thylakoid-associated proteins, the carotenoid biosynthesis pathway, and a plastoquinone-based electron transport chain, the latter two modules having an obvious functional link to the eyespot present in Leontynka. Most strikingly, the ~362 kbp plastome of L. pallida is by far the largest among the non-photosynthetic eukaryotes investigated to date due to an extreme proliferation of sequence repeats. These repeats are also present in coding sequences, with one repeat type found in the exons of 11 out of 34 protein-coding genes, with up to 36 copies per gene, thus affecting the encoded proteins. The mitochondrial genome of L. pallida is likewise exceptionally large, with its >104 kbp surpassed only by the mitogenome of Haematococcus lacustris among all members of Chlamydomonadales hitherto studied. It is also bloated with repeats, though entirely different from those in the L. pallida plastome, which contrasts with the situation in H. lacustris where both the organellar genomes have accumulated related repeats. Furthermore, the L. pallida mitogenome exhibits an extremely high GC content in both coding and non-coding regions and, strikingly, a high number of predicted G-quadruplexes.ConclusionsWith its unprecedented combination of plastid and mitochondrial genome characteristics, Leontynka pushes the frontiers of organellar genome diversity and is an interesting model for studying organellar genome evolution.
Identification of antibiotic resistance proteins via MiCId’s augmented workflow. A mass spectrometry-based proteomics approach
Authors: Alves Gelio , Ogurtsov Aleksey , Karlsson Roger , Jaén-Luchoro Daniel , Piñeiro-Iglesias Beatriz , Salvà-Serra Francisco , Andersson Björn , Moore Edward R.B. , Yu Yi-Kuo 
Published: November 2021

AbstractFast and accurate identifications of pathogenic bacteria along with their associated antibiotic resistance proteins are of paramount importance for patient treatments and public health. While mass spectrometry has become an important, technique for diagnostics of infectious disease, there is a need for mass spectrometry workflows offering this capability. To meet this need, we have augmented the previously published Microorganism Classification and Identification (MiCId) workflow for this capability. To evaluate the performance of the newly augmented MiCId workflow, we have used MS/MS datafiles from samples of 10 antibiotic resistance bacterial strains belonging to three different species: Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The evaluation results show that MiCId’s workflow has a sensitivity value around 85% (with a lower bound at about 72%) and a precision greater than 95% in the identification of antibiotic resistance proteins. Using MS/MS datasets from samples of two bacterial clonal isolates, one being antibiotic-sensitive while the other (obtained from the same patient at different times) being multidrug-resistant, we applied MiCId’s workflow to investigate possible mechanisms of antibiotic resistance in these pathogenic bacteria; the results showed that MiCId’s conclusions are in agreement with the published study. Furthermore, we show that MiCId’s workflow is fast. It pro-vides microorganismal identifications, protein identifications, sample biomass estimates, and antibiotic resistance protein identifications in 6–17 minutes per MS/MS sample using computing resources that are available in most desktop and laptop computers, making it a highly portable workflow. This study demonstrated that MiCId’s workflow is fast, portable, and with high sensitivity and high precision, making it a valuable tool for rapid identifications of bacteria as well as detection of their antibiotic resistance proteins. The new version of MiCId (v.07.01.2021) is freely available for download at https://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads.html.
Phylogenomic analyses using genomes and transcriptomes do not “resolve” relationships among major clades in Phrymaceae
Authors: Morales-Briones Diego F. , Lin Nan , Huang Eileen Y. , Grossenbacher Dena L. , Sobel James M. , Gilmore Caroline D. , Tank David C. , Yang Ya 
Published: November 2021

AbstractPremise of the studyPhylogenomic datasets using genomes and transcriptomes provide rich opportunities beyond resolving bifurcating phylogenetic relationships. Monkeyflower (Phrymaceae) is a model system for evolutionary ecology. However, it lacks a well-supported phylogeny for a stable taxonomy and for macroevolutionary comparisons.MethodsWe sampled 24 genomes and transcriptomes in Phrymaceae and closely related families, including eight newly sequenced transcriptomes. We reconstructed the phylogeny using IQ-TREE and ASTRAL, evaluated gene tree discordance using PhyParts, Quartet Sampling, and cloudogram, and carried out phylogenetic network analyses using PhyloNet and HyDe. We searched for whole genome duplication (WGD) events using chromosome numbers, synonymous distance, and gene duplication events.Key resultsMost gene trees support the monophyly of Phrymaceae and each of its tribes. Most gene trees also support the tribe Mimuleae being sister to Phrymeae + Diplaceae + Leucocarpeae, with extensive gene tree discordance among the latter three. Despite the discordance, polyphyly of Mimulus s.l. is strongly supported, and no particular reticulation event among the Phrymaceae tribes is well supported. Reticulation likely occurred among Erythranthe bicolor and close relatives. No ancient WGD event was detected in Phrymaceae. Instead, small-scale duplications are among potential drivers of macroevolutionary diversification of Phrymaceae.ConclusionsWe show that analysis of reticulate evolution is sensitive to taxon sampling and methods used. We also demonstrate that genome-scale data do not always fully “resolve” phylogenetic relationships. They present rich opportunities to investigate reticulate evolution, and gene and genome evolution involved in lineage diversification and adaptation.
Hippocampal Neuropeptide Y2receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism
Authors: Méndez-Couz Marta , González-Pardo Héctor , Arias Jorge L. , Conejo Nélida M. 
Published: November 2021

ABSTRACTIntroductionThe neuropeptide Y (NPY) is broadly distributed in the central nervous system (CNS), and it has been related to neuroprotective functions. NPY seems to be an important component to counteract brain damage and cognitive impairment mediated by drugs of abuse and neurodegenerative diseases, and both NPY and its Y2receptor (Y2R) are highly expressed in the hippocampus, critical for learning and memory. We have recently demonstrated its influence on cognitive functions; however, the specific mechanism and involved brain regions where NPY modulates spatial memory by acting on Y2R remain unclear.MethodsHere, we examined the involvement of the hippocampal NPY Y2R in spatial memory and associated changes in brain metabolism by bilateral administration of the selective antagonist BIIE0246 into the rat dorsal hippocampus. To further evaluate the relationship between memory functions and neuronal activity, we analysed the regional expression of the mitochondrial enzyme cytochrome c oxidase (CCO) as an index of oxidative metabolic capacity in limbic and non-limbic brain regions.ResultsThe acute blockade of NPY Y2R significantly improved spatial memory recall in rats trained in the Morris water maze that matched metabolic activity changes in spatial memory processing regions. Specifically, CCO activity changes were found in the dentate gyrus of the dorsal hippocampus and CA1 subfield of the ventral hippocampus, the infralimbic region of the PFC and the mammillary bodies.ConclusionsThese findings suggest that the NPY hippocampal system, through its Y2R receptor, influences spatial memory recall (retrieval) and exerts control over patterns of brain activation that are relevant for associative learning, probably mediated by Y2R modulation of long-term potentiation and long-term depression.HighlightsUnder hippocampal Y2R antagonism, place preference memory retrieval is enhancedSpatial retrieval enhancement under Y2R blockade is correlated with changes in regional brain energy metabolismEnhanced retrieval associated CCO activity increases in the dorsal DG, while decreasing in the ventral CA1, IL cortex and mammillary bodiesY2R exert control over patterns of brain activation that are relevant for spatial memory expression