bluuebunny/crossref_metadata_2025_split huggingface dataset:
A glimpse of the paleome in endolithic microbial communities
Authors: Wegner Carl-Eric , Stahl Raphaela , Velsko Irina , Hübner Alex , Fagernäs Zandra , Warinner Christina , Lehmann Robert , Ritschel Thomas , Totsche Kai U. , Küsel Kirsten 
Published: September 2022

AbstractThe terrestrial subsurface houses a significant proportion of the Earth’s microbial biomass. Our understanding about terrestrial subsurface microbiomes is almost exclusively derived from groundwater and porous sediments. To obtain more insights about endolithic microbiomes and their metabolic status, we investigated rock samples from the vadose zone, fractured aquifers, and deep aquitards. Using methods from paleogenomics, we recovered sufficient DNA for metagenomics from rock specimens independent of porosity, lithology, and depth. We estimated between 2.81 and 4.25 × 105 cells × g−1 rock. DNA damage patterns revealed paleome signatures (genetic records of past microbial communities) for three rock specimens from the vadose zone. The taxonomy and functional potential of paleome communities revealed increased abundances of chemolithoautotrophs, and a broader metabolic potential for aromatic hydrocarbon breakdown. Our study suggests that limestones represent ideal archives for genetic records of past microbial communities, due to their specific conditions facilitating long-term DNA preservation.
Genome-wide association studies of seed metabolites identify loci controlling specialized metabolites in Arabidopsis thaliana
Authors: Naake Thomas , Scossa Federico , de Souza Leonardo Perez , Borghi Monica , Brotman Yariv , Mori Tetsuya , Nakabayashi Ryo , Tohge Takayuki , Fernie Alisdair R. 
Published: September 2022

AbstractPlants synthesize specialized metabolites to facilitate environmental and ecological interactions. During evolution, plants diversified in their potential to synthesize these metabolites. Quantitative differences in metabolite levels of natural Arabidopsis thaliana accessions can be employed to unravel the genetic basis for metabolic traits using genome-wide association studies (GWAS). Here, we performed metabolic GWAS (mGWAS) on seeds of a panel of 315 A. thaliana natural accessions, including the reference genotypes C24 and Col-0, for polar and semi-polar seed metabolites using untargeted ultra-performance liquid chromatography-mass spectrometry. As a complementary approach, we performed quantitative trait locus (QTL) mapping of near-isogenic introgression lines between C24 and Col-0 for specific seed specialized metabolites. Besides common QTL between seeds and leaves, GWAS revealed seed-specific QTL for specialized metabolites indicating differences in the genetic architecture of seeds and leaves. In seeds, aliphatic methylsulfinylalkyl and methylthioalkyl glucosinolates associated with the GS-ALK and GS-OHP locus on chromosome 4 containing alkenyl hydroxyalkyl producing 2 (AOP2) and 3 (AOP3) and/or with the GS-ELONG locus on chromosome 5 containing methylthioalkyl malate synthase (MAM1) and MAM3. We detected two unknown sulfur-containing compounds that were also mapped to these loci. In GWAS, some of the annotated flavonoids (kaempferol 3-O-rhamnoside-7-O-rhamnoside, quercetin 3-O-rhamnoside-7-O-rhamnoside) were mapped to transparent testa 7 (AT5G07990), encoding a cytochrome P450 75B1 monooxygenase. Three additional mass signals corresponding to quercetin-containing flavonols were mapped to UGT78D2 (AT5G17050). The association of the loci and associating metabolic features were functionally verified in knockdown mutant lines. By performing GWAS and QTL mapping, we were able to leverage variation of natural populations and parental lines to study seed specialized metabolism. The GWAS data set generated here is a high-quality resource that can be interrogated in further studies.
Tug-of-peace: Visual Rivalry and Atypical Visual Motion Processing in MECP2 duplication Syndrome of Autism
Authors: Bogatova Daria , Smirnakis Stelios M. , Palagina Ganna 
Published: September 2022

AbstractExtracting common patterns of neural circuit computations in the autism spectrum and confirming them as a cause of specific core traits of autism is the first step towards identifying cell- and circuit-level targets for effective clinical intervention. Studies in human subjects with autism have identified functional links and common anatomical substrates between core restricted behavioral repertoire, cognitive rigidity, and over-stability of visual percepts during visual rivalry. To be able to study these processes with single-cell precision and comprehensive neuronal population coverage, we developed the visual bi-stable perception paradigm for mice. Our task is based on plaid patterns consisting of two transparent gratings drifting at an angle of 120° relative to each other. This results in spontaneous reversals of the perception between local component motion (motion of the plaid perceived as two separate moving grating components) and integrated global pattern motion (motion of the plaid perceived as a fused moving texture). Furthermore, this robust paradigm does not depend on the explicit report of the mouse, since the direction of the optokinetic nystagmus (OKN, rapid eye movements driven by either pattern or component motion) is used to infer the dominant percept. Using this paradigm, we found that the rate of perceptual reversals between global and local motion interpretations of the stimulus is reduced in the MECP2 duplication mouse model of autism.Moreover, the stability of local motion percepts is greatly increased in MECP2 duplication mice at the expense of global motion percepts. Thus, our model reproduces a subclass of the core features in human autism (reduced rate of visual rivalry and atypical perception of visual motion). This further offers a well-controlled approach for dissecting neuronal circuits underlying these core features.
Using genomic scars to select immunotherapy beneficiaries in advanced non-small cell lung cancer
Authors: Donker H. C. , van Es B. , Tamminga M. , Lunter G. A. , van Kempen L. C. L. T. , Schuuring E. , Hiltermann T. J. N. , Groen H. J. M. 
Published: September 2022

AbstractIn advanced non-small cell lung cancer (NSCLC), response to immunotherapy is difficult to predict from pre-treatment information. Given the toxicity of immunotherapy and its financial burden on the healthcare system, we set out to identify patients for whom treatment is effective. To this end, we used mutational signatures from DNA mutations in pre-treatment tissue. Single base substitutions, doublet base substitutions, indels, and copy number alteration signatures were analysed inm= 101 patients (the discovery set). We found that tobacco smoking signature (SBS4) and thiopurine chemotherapy exposure-associated signature (SBS87) were linked to durable benefit. Combining both signatures in a machine learning model separated patients with a progression-free survival hazard ratio ofon the cross-validated discovery set andon an independent external validation set (m= 56). This paper demonstrates that the fingerprints of mutagenesis, codified through mutational signatures, select advanced NSCLC patients who may benefit from immunotherapy, thus potentially reducing unnecessary patient burden.
Resolving chaperone-assisted protein folding on the ribosome at the peptide level
Authors: Wales Thomas E. , Pajak Aleksandra , Roeselová Alžběta , Shivakumaraswamy Santosh , Howell Steven , Hartl F. Ulrich , Engen John R. , Balchin David 
Published: September 2022

AbstractThe cellular environment is critical for efficient protein maturation, but how proteins fold during biogenesis remains poorly understood. We used hydrogen/deuterium exchange (HDX) mass spectrometry (MS) to define, at peptide resolution, the cotranslational chaperone-assisted folding pathway ofEscherichia colidihydrofolate reductase. On the ribosome, the nascent polypeptide folds via structured intermediates not populated during refolding from denaturant. Association with the ribosome allows these intermediates to form, as otherwise destabilizing C-terminal sequences remain confined in the ribosome exit tunnel. We find that partially-folded nascent chains recruit the chaperone Trigger factor, which uses a large composite hydrophobic/hydrophilic interface to engage folding intermediates without disrupting their structure. In addition, we comprehensively mapped dynamic interactions between the nascent chain and ribosomal proteins, tracing the path of the emerging polypeptide during synthesis. Our work provides a high-resolution description ofde novoprotein folding dynamics, thereby revealing new mechanisms by which cellular factors shape the conformational search for the native state.
Bill shape imposes biomechanical tradeoffs in cavity-excavating birds
Authors: Chhaya Vaibhav , Reddy Sushma , Krishnan Anand 
Published: September 2022

ABSTRACTOrganisms are subject to a host of physical forces that influence morphological evolution. Birds, for instance, use their bills as implements to perform various functions, each exerting unique physical demands and selective influences on bill morphology. For example, birds that use their bills to excavate nesting or roosting cavities must resist a range of mechanical stresses to prevent fracture. However, the contribution of bill geometry and material composition to excavation stress resistance remains poorly understood. Here, we study the biomechanical consequences of bill diversification in two clades of cavity-excavating, frugivorous birds, the paleotropical barbets. Using multilayered finite element models and beam theory, we compare the excavation performance of different maxillary geometries for two loading regimes experienced by barbet bills during cavity excavation-dorsoventral impact and torsion. We find that deeper and wider maxillae perform better for impact loads than for torsional loads, with the converse for narrower maxillae. This results in a tradeoff between impact and torsion resistance imposed by bill geometry. Analytical beam models validate this prediction, showing that this relationship holds even when maxillae are simplified to solid elliptical beams. Finally, we find that composite bill structures broadly exhibit lower stresses than homogenous structures of the same geometry, indicating a functional synergy between the keratinous rhamphotheca and bony layers of the bill. Overall, our findings demonstrate the strong link between morphological evolution, behavior, and functional performance in organisms.
Rapid expansion and visual specialization of learning and memory centers in Heliconiini butterflies
Authors: Couto Antoine , Young Fletcher J , Atzeni Daniele , Marty Simon , Melo-Flórez Lina , Hebberecht Laura , Monllor Monica , Neal Chris , Cicconardi Francesco , McMillan W Owen , Montgomery Stephen H. 
Published: September 2022

AbstractHow do neural systems evolve to support new behaviors? Changes in the abundance and diversity of neural cell types, and their connectivity, shape brain composition and provide the substrate for behavioral variation. We describe a striking example of neural elaboration in an ecologically diverse tribe of Heliconiini butterflies. By building extensive new datasets of neural traits across the tribe, we identify major bursts in the size and cellular composition of the mushroom bodies, central brain structures essential for learning and memory. These expansion events are associated with increased innervation form visual centers and coincide with enhanced performance in multiple cognitive assays. This suite of neural and cognitive changes is likely tied to the emergence of derived foraging behaviors, facilitated by localized specialization of neural networks.One-Sentence SummaryMajor shifts in brain composition and behavior in butterflies with unique foraging and dietary behaviors.
Odor-gated oviposition behavior in an ecological specialist
Authors: Álvarez-Ocaña Raquel , Shahandeh Michael P. , Ray Vijayaditya , Auer Thomas O. , Gompel Nicolas , Benton Richard 
Published: September 2022

AbstractColonization of a novel ecological niche can require, or be driven by, evolution of an animal’s behaviors promoting their reproductive success in the new environment. Little is known about the underlying mechanisms. We have exploited an emerging genetic model for behavioral neuroecology, Drosophila sechellia – a close relative of Drosophila melanogaster that exhibits extreme specialism for Morinda citrifolia noni fruit – to study the evolution and sensory basis of oviposition. D. sechellia produces fewer eggs compared to other drosophilids, but lays these almost exclusively on noni substrates, contrasting with avoidance or indifference of noni by generalist species. Visual, textural and social cues do not explain the species-specificity of this preference. By contrast, loss of olfactory input in D. sechellia, but not D. melanogaster, essentially abolishes egg-laying, suggesting that this sensory modality gates gustatory-driven noni preference. We find the noni bouquet is detected by redundant olfactory pathways. By parsing the fruit’s volatile chemicals and genetic perturbation of individual olfactory pathways in D. sechellia, we discover a key role for hexanoic acid and its cognate receptor, the Ionotropic receptor Ir75b, in odor-evoked oviposition. Through receptor exchange in D. melanogaster, we provide evidence for a causal contribution of odor-tuning changes in Ir75b to the evolution of oviposition behavior during D. sechellia’s host specialization.
Multimodal system for recording individual-level behaviors in songbird groups
Authors: Rüttimann L. , Wang Y. , Rychen J. , Tomka T. , Hörster H. , Hahnloser R.H.R. 
Published: September 2022

AbstractThe implicit goal of longitudinal observations of animal groups is to identify individuals and to reliably detect their behaviors, including their vocalizations. Yet, to segment fast behaviors and to extract individual vocalizations from sound mixtures remain challenging problems. Promising approaches are multimodal systems that record behaviors with multiple cameras, microphones, and animal-borne wireless sensors. The instrumentation of these systems must be optimized for multimodal signal integration, which is an overlooked steppingstone to successful behavioral tracking.We designed a modular system (BirdPark) for simultaneously recording small animals wearing custom low-power frequency-modulated radio transmitters. Our custom software-defined radio receiver makes use of a multi-antenna demodulation technique that eliminates data losses due to radio signal fading and that increases the signal-to-noise ratio of the received radio signals by 6.5 dB compared to best single-antenna approaches. Digital acquisition relies on a single clock, allowing us to exploit cross-modal redundancies for dissecting rapid behaviors on time scales well below the video frame period, which we demonstrate by reconstructing the wing stroke phases of free-flying songbirds. By separating the vocalizations among up to eight vocally interacting birds, our work paves the way for dissecting complex social behaviors.
Comparative Study between In-silico and Clinical Works on the Control of Blood Glucose Level in People with Type 1 Diabetes using Improved Hovorka Equations
Authors: Mohd Sohadi Nur Amanina , Som Ayub Md , Mohd Nor Noor Shafina , Ali Sherif Abdulbari , Ahmad Mohd Aizad 
Published: September 2022

AbstractBackgroundHovorka model is one of the diabetic models which is widely used in the artificial pancreas device (APD) also known as closed loop system, meant for people with type 1 diabetes (T1D). Previous workers had modified some equations in the sub-sections of the Hovorka model, which is also known as improved Hovorka equations, in regulating the blood glucose level (BGL) within normoglycemic range (4.0 to 7.0 mmol/L). However, the improved Hovorka equations have not been tested yet in terms of its usability to regulate and control the BGL in safe range for two or more people with T1D. This study aims to simulate their BGL with meal disturbances for 24 hours using the improved Hovorka equations.MethodsData for people with T1D were obtained from Clinic 1, Clinical Training Centre (CTC), UiTM Medical Specialist Centre, Sungai Buloh, Selangor. Data collected include gender, age, body weight, mealtimes, meal amount, and duration. Three patients whose ages range from 11 to 14 years old were selected. All patients consumed three meals daily: breakfast, lunch, and dinner. The simulation (in-silico work) was done using MATLAB software, and the BGL profile from both in-silico and clinical works were compared and analysed.ResultsIt was revealed that the BGLs for all three people with T1D were far better in the in-silico work compared to the clinical work. The BGL for patient 1 was able to achieve normoglycaemia 73% of the time in the in-silico work. Meanwhile, patient 2 managed to stay in the normoglycemic range for 85% of the time in the in-silico work compared to clinical work, which was merely 31%. For Patient 3, the time duration spent in the normoglycemic range was only 16% in the in-silico work compared to none as in the clinical work. The p-values obtained in the study were less than 0.05, indicating that the in-silico work using the improved Hovorka equations was acceptable for predicting the BGL for people with T1D.ConclusionsIt can be concluded that the improved Hovorka equations are reliable in simulating the meal disturbances effect on BGL and increasing people in T1D times’ duration in the normoglycemic range compared to the clinical work.
Allele-specific expression reveals genetic drivers of tissue regeneration in mice
Authors: Talbott Heather E. , Mack Katya L. , Griffin Michelle , Guardino Nicholas J. , Parker Jennifer B.L. , Spielman Amanda F. , Davitt Michael F. , Mascharak Shamik , Berger Mark J. , Wan Derrick C. , Fraser Hunter B. , Longaker Michael T. 
Published: September 2022

SummaryIn adult mammals, skin wounds typically heal by scarring rather than through regeneration. In contrast, “super-healer” MRL mice have the unusual ability to regenerate ear punch wounds, yet the molecular basis for this regeneration remains elusive. Here, in hybrid crosses between MRL and non-regenerating mice, we use allele-specific gene expression to identifycis-regulatory variation associated with ear regeneration. Analyzing three major wound cell populations, we identified extensive strain- and tissue- specificcis-regulatory divergence associated with differences in healing outcomes. Genes withcis-regulatory differences specifically in fibroblasts were associated with wound healing phenotypes and pathways, and were enriched near genetic markers associated with ear-healing in a genetic cross. Finally, we demonstrated that one of these genes,Cfh, could be applied ectopically to accelerate wound repair and induce regeneration in typically fibrotic wounds. Overall, our results provide insight into the molecular drivers of regeneration in MRL mice with potential clinical implications.
Whole Plant Transpiration Responses of Common Bean (Phaseolus vulgarisL.) to Drying Soil: Water Channels and Transcription Factors
Authors: Cordoba-Novoa H. , Zhang B. , Guo Y. , Aslam M.M. , Fristchi F.B. , Hoyos-Villegas V. 
Published: September 2022

AbstractCommon bean (Phaseolus vulgarisL.) is the main legume crop for direct human consumption worldwide. Among abiotic factors affecting common bean, drought is the most limiting. This study aimed at characterizing genetic variability and architecture of transpiration, stomatal regulation and whole plant water use within the Mesoamerican germplasm. A critical fraction of transpirable soil water (FTSWc) was estimated as the inflection point at which NTR starts decreasing linearly. Genome-wide association (GWA) analyses for mean NTR and FTSWc were performed. High variation on mean NTR and FTSWc was found among genotypes. Genomic signals controlling the variation of these traits were identified onPv01 andPv07 some located in intergenic, intronic and exonic regions. A set of novel candidate genes and putative regulatory elements located in these QTL were identified. Some of the genes have been previously reported to be involved in abiotic tolerance in model species, including some of the five transcription factors (TF) identified. Four candidate genes, one with potential water transportation activity and three TFs were validated. The genePhvul.001G108800,an aquaporin SIP2-1 related gene, showed water channel activity through oocyte water assays. MutantArabidopsis thaliana(Ath) lines for the homologous genes of common bean were evaluated in transpiration experiments. Two of the three evaluated TFs, UPBEAT1 and C2H2-type ZN finger protein, were involved in the control of transpiration responses to drying soil. Our results provide evidence of novel genes to accelerate the drought tolerance improvement in the crop and study the physiological basis of drought response in plants.
Establishing Thrombolysis in Myocardial Infarction Frame Count as a Clinical Measure of Coronary Microvascular Disease in Women
Authors: Wayne Nicole , Wu Qufei , Moore Stephen C. , Ferrari Victor A. , Metzler Scott D. , Guerraty Marie A. 
Published: September 2022

AbstractBackgroundDespite growing awareness of the crucial role of the coronary vasculature in cardiovascular health and disease, diagnosing coronary microvascular disease (CMVD) remains challenging because it often requires advanced cardiac imaging that are available at only a few centers. For example, perfusion positron emission tomography (PET) allows for the quantification of the myocardial blood flow (MBF) and, thus, the calculation of the MBF reserve (MBFR), which is the ratio of MBF under rest conditions and MBF under hyperemic or stress conditions. In the absence of obstructive coronary artery disease, MBFR is a measure of CMVD. However, the availability of perfusion PET is limited. Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) is an angiography-based measure of coronary flow that has been proposed, but not well established, as a measure of CMVD. We aim to demonstrate a relationship between TFC and MBFR and to establish cut-off measures from clinical coronary angiograms for the diagnosis of CMVD.MethodsWe identified a cohort of 123 patients (age 58 +/− 12.1, 63% female, 41% Caucasian) who had no obstructive coronary artery disease and had undergone perfusion PET stress testing and clinical coronary angiography for clinical indications. We compared TFC for each coronary territory with regional perfusion PET parameters using linear regression modeling. We then used two mathematical models of the coronary circulation to understand the relationship between these parameters. We performed ROC analysis to determine the ability of TFC to diagnose CMVD, defined as global MBFR < 2.ResultsThere is a very tight sex-dependent correlation between TFC and MBFR, but no association between resting coronary flow and TFC and only a weak association between stress coronary flow and TFC. Mathematical modeling of the coronary circulation highlights an uncoupling between TFC and flow in larger vessels where TFC is measured, providing a likely explanation for the surprising empiric result. ROC analysis shows TFC as an excellent measure of CMVD in women (AUC 0.84-0.89) and establishes TFC cutoffs.ConclusionsTFC from clinical coronary angiograms reflects coronary microvascular function in a sex-dependent manner and performs well in identifying women with CMVD.Clinical PerspectiveWhat is new?Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) is highly correlated with myocardial blood flow reserve (MBFR), which reflects coronary vasodilatory potential, in patients without obstructive coronary artery disease.Computational modeling establishes how the relationship between TFC and MBFR can exist.TFC performs much better in women than in men for the diagnosis of coronary microvascular disease (CMVD) and thresholds for the diagnosis of CMVD with TFC are identified.What are the clinical implications?TFC from clinical coronary angiograms can be used to assess CMVD in women.