bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amino acid sequence assignment from single molecule peptide sequencing data using a two-stage classifier
Authors: Smith Matthew Beauregard , Simpson Zack Booth , Marcotte Edward M. 
Published: September 2022

AbstractWe present a machine learning-based interpretive framework (whatprot) for analyzing single molecule protein sequencing data produced by fluorosequencing, a recently developed proteomics technology that determines sparse amino acid sequences for many individual peptide molecules in a highly parallelized fashion [1] [2]. Whatprot uses Hidden Markov Models (HMMs) to represent the states of each peptide undergoing the various chemical processes during fluorosequencing, and applies these in a Bayesian classifier, in combination with pre-filtering by a k-Nearest Neighbors (kNN) classifier trained on large volumes of simulated fluorosequencing data. We have found that by combining the HMM based Bayesian classifier with the kNN pre-filter, we are able to retain the benefits of both, achieving both tractable runtimes and acceptable precision and recall for identifying peptides and their parent proteins from complex mixtures, outperforming the capabilities of either classifier on its own. Whatprot’s hybrid kNN-HMM approach enables the efficient interpretation of fluorosequencing data using a full proteome reference database and should now also enable improved sequencing error rate estimates.
Diel fluctuations inin-vivoSnRK1 activity in Arabidopsis rosettes during light-dark cycles
Authors: Avidan Omri , Moraes Thiago A. , Mengin Virginie , Feil Regina , Rolland Filip , Stitt Mark , Lunn John E. 
Published: September 2022

AbstractSUCROSE-NON-FERMENTING1 (SNF1)-RELATED KINASE1 (SnRK1) is a central hub in carbon and energy signalling in plants, and is orthologous with SNF1 in yeast and the AMP-ACTIVATED PROTEIN KINASE (AMPK) in animals. Previous studies of SnRK1 relied onin-vitroactivity assays or on monitoring the expression of putative marker genes. Neither approach gives unambiguous information aboutin-vivoSnRK1 activity. We have monitoredin-vivoSnRK1 activity using Arabidopsis (Arabidopsis thaliana) reporter lines that express a chimeric polypeptide with a SNF1/SnRK1/AMPK-specific phosphorylation site. We investigated responses during an equinoctial diel cycle, and after perturbing this cycle. As expected,in vivoSnRK1 activity rose towards the end of the night and rose even further when the night was extended. Unexpectedly, although sugars rose after dawn, SnRK1 activity did not decline until about 12 hours into the light period. The sucrose signal trehalose 6-phosphate (Tre6P) has been shown to inhibit SnRK1in vitro. We introduced the SnRK1 reporter into lines that harboured an inducibleTREHALOSE-6-PHOSPHATE SYNTHASEconstruct. Elevated Tre6P decreasedin-vivoSnRK1 activity in the light period, but not at the end of the night. Reporter polypeptide phosphorylation was sometimes negatively correlated with Tre6P, but a stronger and more widespread negative correlation was observed with glucose 6-phosphate. We propose that SnRK1 operates within a network that controls carbon utilization and maintains diel sugar homeostasis, and that Tre6P, hexose phosphates and the circadian clock contribute to regulation of SnRK1 activity in a context-dependent manner, and SnRK1-signalling is further modulated by factors that act downstream of SnRK1.One sentence summaryIn vivoSnRK1 activity shows an unexpected diel response and a complex relationship with trehalose 6-phosphate and other possible metabolic regulators.
A texture statistics encoding model reveals hierarchical feature selectivity across human visual cortex
Authors: Henderson Margaret M. , Tarr Michael J. , Wehbe Leila 
Published: September 2022

AbstractMid-level visual features, such as contour and texture, provide a computational link between low- and high-level visual representations. While the detailed nature of mid-level representations in the brain is not yet fully understood, past work has suggested that a texture statistics model (P-S model; Portilla and Simoncelli, 2000) is a candidate for predicting neural responses in areas V1-V4 as well as human behavioral data. However, it is not currently known how well this model accounts for the responses of higher visual cortex regions to natural scene images. To examine this, we constructed single voxel encoding models based on P-S statistics and fit the models to fMRI data from human subjects (male and female) from the Natural Scenes Dataset (Allen et al., 2021). We demonstrate that the texture statistics encoding model can predict the held-out responses of individual voxels in early retinotopic areas as well as higher-level category-selective areas. The ability of the model to reliably predict signal in higher visual cortex voxels suggests that the representation of texture statistics features is widespread throughout the brain, potentially playing a role in higher-order processes like object recognition. Furthermore, we use variance partitioning analyses to identify which features are most uniquely predictive of brain responses, and show that the contributions of higher-order texture features increases from early areas to higher areas on the ventral and lateral surface of the brain. These results provide a key step forward in characterizing how mid-level feature representations emerge hierarchically across the visual system.Significance StatementIntermediate visual features, like texture, play an important role in cortical computations and may contribute to tasks like object and scene recognition. Here, we used a texture model proposed in past work to construct encoding models that predict the responses of neural populations in human visual cortex (measured with fMRI) to natural scene stimuli. We show that responses of neural populations at multiple levels of the visual system can be predicted by this model, and that the model is able to reveal an increase in the complexity of feature representations from early retinotopic cortex to higher areas of ventral and lateral visual cortex. These results support the idea that texture-like representations may play a broad underlying role in visual processing.
The FELIX Project: Deep Networks To Detect Pancreatic Neoplasms
Authors: Xia Yingda , Yu Qihang , Chu Linda , Kawamoto Satomi , Park Seyoun , Liu Fengze , Chen Jieneng , Zhu Zhuotun , Li Bowen , Zhou Zongwei , Lu Yongyi , Wang Yan , Shen Wei , Xie Lingxi , Zhou Yuyin , Wolfgang Christopher , Javed Ammar , Fouladi Daniel Fadaei , Shayesteh Shahab , Graves Jefferson , Blanco Alejandra , Zinreich Eva S. , Klauss Miriam , Mayer Philipp , Kinny-Köster Benedict , Kinzler Kenneth , Hruban Ralph H. , Vogelstein Bert , Yuille Alan L. , Fishman Elliot K. 
Published: September 2022

ABSTRACTTens of millions of abdominal images are obtained with computed tomography (CT) in the U.S. each year but pancreatic cancers are sometimes not initially detected in these images. We here describe a suite of algorithms (named FELIX) that can recognize pancreatic lesions from CT images without human input. Using FELIX,>95% of patients with pancreatic ductal adenocarcinomas were detected at a specificity of>95% in patients without pancreatic disease. FELIX may be able to assist radiologists in identifying pancreatic cancers earlier, when surgery and other treatments offer more hope for long-term survival.
MSstatsPTM: Statistical relative quantification of post-translational modifications in bottom-up mass spectrometry-based proteomics
Authors: Kohler Devon , Tsai Tsung-Heng , Verschueren Erik , Huang Ting , Hinkle Trent , Phu Lilian , Choi Meena , Vitek Olga 
Published: September 2022

AbstractLiquid chromatography coupled with bottom up mass spectrometry (LC-MS/MS)-based proteomics is increasingly used to detect changes in post-translational modifications (PTMs) in samples from different conditions. Analysis of data from such experiments faces numerous statistical challenges. These include the low abundance of modified proteoforms, the small number of observed peptides that span modification sites, and confounding between changes in the abundance of PTM and the overall changes in the protein abundance. Therefore, statistical approaches for detecting differential PTM abundance must integrate all the available information pertaining to a PTM site, and consider all the relevant sources of confounding and variation. In this manuscript we propose such a statistical framework, which is versatile, accurate, and leads to reproducible results. The framework requires an experimental design, which quantifies, for each sample, both peptides with post-translational modifications and peptides from the same proteins with no modification sites. The proposed framework supports both label-free and tandem mass tag (TMT)-based LC-MS/MS acquisitions. The statistical methodology separately summarizes the abundances of peptides with and without the modification sites, by fitting separate linear mixed effects models appropriate for the experimental design. Next, model-based inferences regarding the PTM and the protein-level abundances are combined to account for the confounding between these two sources. Evaluations on computer simulations, a spike-in experiment with known ground truth, and three biological experiments with different organisms, modification types and data acquisition types demonstrate the improved fold change estimation and detection of differential PTM abundance, as compared to currently used approaches. The proposed framework is implemented in the free and open-source R/Bioconductor package MSstatsPTM.
The WW domain of IQGAP1 binds directly to the p110α catalytic subunit of PI 3-kinase
Authors: Bardwell A. Jane , Paul Madhuri , Yoneda Kiku C. , Andrade-Ludeña Maria D. , Nguyen Oanh T. , Fruman David A. , Bardwell Lee 
Published: September 2022

AbstractIQGAP1 is a multi-domain cancer-associated protein that serves as a scaffold protein for multiple signaling pathways. Numerous binding partners have been found for the calponin homology, IQ and GAP-related domains in IQGAP1. Identification of a binding partner for its WW domain has proven elusive, however, even though a cell-penetrating peptide derived from this domain has marked anti-tumor activity. Here, usingin vitrobinding assays with human proteins and co-precipitation from human cells, we show that the WW domain of human IQGAP1 binds directly to the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K). In contrast, the WW domain does not bind to ERK1/2, MEK1/2, or the p85α regulatory subunit of PI3K when p85α is expressed alone. However, the WW domain is able to bind to the p110α/p85α heterodimer when both subunits are co-expressed, as well as to the mutationally activated p110α/p65α heterodimer. We present a model of the structure of the IQGAP1 WW domain, and experimentally identify key residues in the hydrophobic core and beta strands of the WW domain that are required for binding to p110α. These findings contribute to a more precise understanding of IQGAP1-mediated scaffolding, and of how IQGAP1-derived therapeutic peptides might inhibit tumorigenesis.
Depletion of collagen IX alpha2 interferes osteochondral homeostasis of the knee joint which ultimately causing osteoarthritis-like articular cartilage damage
Authors: Dong Rui , Xu Huihui , Wang Pinger , Fang Liang , Xiao Luwei , Lv Shuaijie , Tong Peijian , Jin Hongting 
Published: September 2022

AbstractAs one of the branched chains of Type IX collagen (Col9), Collagen IX alpha2 (Col9α2) has been reported to be associated with several orthopedic conditions. To probe the relationship between Col9α2 and knee osteoarthritis (KOA), we performed a systematic analysis of Col9α2-deficient (Col9α-/-) mice using whole-mount skeletal staining, Micro-CT (μCT), biomechanics, histomorphometry, immunohistochemistry (IHC), immunofluorescence (IF) and Enzyme-linked immunosorbent (Elisa). Although whole-mount skeletal staining displayed no difference in bone length and ossification between Col9α-/- mice and wild-type (Col9α2+/+) mice at mid-gestation and adult stages, the knee joint exhibited dramatic discrepancies. Specifically, the subchondral bone (SCB) in the knee joint of Col9α-/- mice became sparse and deformed in the early stage, with altered bone morphometric parameters, reduced load-bearing capacity, dysfunctional bone homeostasis (decreased osteogenesis capacity and elevated bone resorption capacity), diminished cartilage proteoglycans and disrupted cartilage extracellular matrix (ECM) anabolism and catabolism compared with the Col9α2+/+ mice. In the late stage, the cartilage degeneration in Col9α2-/- mice were particularly pronounced compared to Col9α2+/+ mice, as evidenced by severe cartilage destruction and a marked reduction in cartilage thickness and area. Overall, Col9α2 is essential for maintaining osteochondral homeostasis in the knee joint of mice, and the absence of this gene is accompanied by distinct sclerosis of the SCB and a reduction in load-bearing capacity; in the late stage, in the lack of SCB stress inhibition, excessive load is consistently exerted on the cartilage, ultimately leading to osteoarthritic-like articular cartilage damage. Hence, Col9α2 may serve as a potential candidate biomarker associated with KOA.
Digestive exophagy of Bacterial Biofilms by an Amoeba Predator is Mediated by Specific Biofilm Recognition
Authors: Zanditenas Eva , Trebicz-Geffen Meirav , Domínguez-García Laura , Romero Diego , Kolodkin-Gal Ilana , Ankri Serge 
Published: September 2022

AbstractThe human protozoan parasite Entamoeba histolytica is responsible for amebiasis, a disease endemic to developing countries. E. histolytica trophozoites are released from the cysts to colonize the large intestine, where they primarily feed on bacterial cells. In these scenarios, bacterial cells form aggregates or structured communities too large for phagocytosis. Our results show that E. histolytica can degrade pre-established biofilms of Bacillus subtilis and Escherichia coli in a dose- and time-dependent manner. Surprisingly, trophozoites incubated with B. subtilis biofilm exhibit a unique transcriptome signature compared to those incubated with planktonic cells or without bacteria. Biofilm-induced genes include cysteine proteases (CPs), and the general inhibition of CPs by E64D or by the use of specific small-RNA (sRNA)-based RNA interference impairs the degradation of biofilms by E. histolytica. The degradation of B. subtilis extracellular matrix (ECM) protein TasA by CPs is associated with partial biofilm digestion and activation of the stress response in the interacting B. subtilis cells. The interaction with B. subtilis biofilms was also associated with lower levels of oxidoreductases. Oxidoreductase downregulation can be a readout of the embedding of E. histolytica trophozoites within the biofilm-produced extracellular matrix, reducing their exposure to oxidative stress (OS). Our results indicate that parasites may digest biofilms by a controlled mechanism of digestive exophagy as secretion of digestive enzymes as a conserved mechanism for biofilm degradation allows phagocytic digestion of biofilm cells. Furthermore, the partially digested biofilms can serve as an unexpected shield protecting parasites from oxidative environments and thereby may regulate the persistence and virulence of the parasite.
Crypt-top and crypt-bottom colonic epithelial cell population microRNA expression demonstrates cell type-specificity and correlation with endoscopic activity in ulcerative colitis
Authors: Inciuraite Ruta , Ramonaite Rima , Kupcinskas Juozas , Dalgediene Indre , Kulokiene Ugne , Kiudelis Vytautas , Varkalaite Greta , Zvirbliene Aurelija , Jonaitis Laimas Virginijus , Kiudelis Gediminas , Franke Andre , Schreiber Stefan , Juzenas Simonas , Skieceviciene Jurgita 
Published: September 2022

AbstractBackground and AimsColonic epithelial barrier loss and dysfunction are one of the early events in ulcerative colitis (UC) and microRNAs (miRNAs) participate in its regulation. However, cell type-specific profile of miRNAs during inflammation in UC is still unknown. Thus, we aimed to perform miRNA profiling on colon tissue and epithelial cell levels in active and quiescent UC.MethodsSmall RNA-sequencing in colon tissue, crypt-bottom (CD44+), and crypt-top (CD66a+) colonic epithelial cell populations from two independent cohorts of UC patients (active and quiescent, n=74), and healthy individuals (n=50) was performed. Data analysis encompassed differential expression, weighted gene co-expression network (WGCNA), correlation, gene-set enrichment analyses (GSEA).ResultsIn colon tissue of active and quiescent UC, differentially expressed miRNAs were shown to be potentially involved in intestinal barrier integrity regulation. Consecutive analysis of crypt-bottom and crypt-top colonic epithelial cells revealed distinct miRNA expression patterns in response to UC-caused inflammation. GSEA indicated that differentially expressed epithelial miRNAs are commonly involved in inflammation- and intestinal barrier integrity-related processes (such as signalling of interleukin-4 and interleukin-13), while miRNA differences between cell populations might reflect their function, i.e., crypt-bottom cell miRNA target genes involved in regulation of cell differentiation. Finally, pro-inflammatory miRNA co-expression module correlating with endoscopic UC activity was defined not only in both epithelial cell populations, but also in the colon tissue.ConclusionsmiRNA expression patterns are colon epithelial cell population- and UC state-specific and correlate with endoscopic UC activity. Irrespective of the UC stage deregulated epithelial miRNAs are potentially involved in regulation of intestinal barrier integrity.
Involvement of superior colliculus in complex figure detection of mice
Authors: Cazemier J. Leonie , Tran T. K. Loan , Hsu Ann T. Y. , Husić Medina , Kirchberger Lisa , Self Matthew W. , Roelfsema Pieter R. , Heimel J. Alexander 
Published: September 2022

AbstractObject detection is an essential function of the visual system. Although the visual cortex plays an important role in object detection, the superior colliculus can support detection when the visual cortex is ablated or silenced. Moreover, it has been shown that superficial layers of mouse SC (sSC) encode visual features of complex objects, and that this code is not inherited from the primary visual cortex. This suggests that mouse sSC may provide a significant contribution to complex object vision. Here, we use optogenetics to show that mouse sSC is causally involved in figure detection based on differences in figure contrast, orientation and phase. Additionally, our neural recordings show that in mouse sSC, image elements that belong to a figure elicit stronger activity than those same elements when they are part of the background. The discriminability of this neural code is higher for correct trials than incorrect trials. Our results provide new insight into the behavioral relevance of the visual processing that takes place in sSC.
VOCAL SIMILARITY AND DIFFERENCES IN FOUR SPECIES OF THE GENUSANTHUS: ACOUSTIC FEATURE ANALYSIS OF SOME COMMON CALLS
Authors: Dragonetti Marco 
Published: September 2022

ABSTRACTBirds of the same genus often share similar call repertoires, the aim of this paper is to find species-specific and common acoustic features across species. This can be a useful tool for identification purposes and for studying intra-interspecific communication. Similar flight call (tsip) in two closely related species (Anthus pratensis, Anthus spinoletta) were studied to find characteristics, that allows to discriminate the two species with acoustic means. Three different call types (tsip, softandalarm) of four species of the genus Anthus (A. pratensis, A. spinoletta, A. petrosus, A. cervinus) were also studied to find whether these common call types show different degrees of similarity. Discriminant function analysis correctly classified 98.4% ofA. pratensisandA. spinolettaflight calls. Three acoustic parameters showed the highest discrimination power: the frequency modulations, the maximum frequency value and the minimum frequency value of the peak frequency contour. Using these three values I proposed a simpler procedure for recognizing these two species, that allowed a correct classification of 96% of calls.The three call types of the fourAnthusspecies were studied using cross correlation among spectrogram contours.Alarmcalls of the four species showed stronger similarity, while the other call types were more distinctive, withsoftcall seeming to have a lower similarity between species and hence a higher distinctive power. These results suggest the hypothesis thatalarmcall is similar, because it retains features of a common ancestor easing heterospecific communication, while the other calls showed decreasing similarity and more species-specific features.
Cryo-EM structure of the Agrobacterium tumefaciens type IV secretion system-associated T-pilus reveals stoichiometric protein-phospholipid assembly
Authors: Kreida Stefan , Narita Akihiro , Johnson Matthew D , Tocheva Elitza I , Das Anath , Ghosal Debnath , Jensen Grant J. 
Published: September 2022

AbstractAgrobacterium tumefaciens is a plant pathogen that causes crown gall disease by the horizontal transfer of oncogenic DNA that is integrated into the host’s genome. The conjugation is mediated by the conjugative VirB/D4 type 4 secretion system (T4SS). A. tumefaciens T4SS assembles an extracellular filament, the T-pilus, that is involved in the formation of a mating pair between A. tumefaciens and the recipient plant cell by a not fully understood mechanism. Here, we present a 3 Å cryo-EM structure of the T-pilus, solved by helical reconstruction. Our structure reveals that the T-pilus comprises the major pilin protein VirB2 and phosphatidylglycerol (PG) phospholipid at a 1:1 stoichiometric ratio with 5-start helical symmetry. We further show that PG-headgroups and the positively charged Arg 91 residues of VirB2 protomers form extensive electrostatic interactions in the lumen of the T-pilus. Mutagenesis of Arg 91 destabilized the VirB2 protein and completely abolished pilus formation. While our T-pilus structure shows architectural similarity with previously published conjugative pili structures, positively charged sidechains protrude into the lumen and the lumen is narrower, raising questions whether the T-pilus is a conduit for ssDNA transfer. We also show that the VirB2 subunits in T-pilus filament are not cyclic, as previously thought.