Miracle-dz/UniFAR-FTUs huggingface dataset:
A cascade of sulfur transferases delivers sulfur to the sulfur-oxidizing heterodisulfide reductase-like complex

A heterodisulfide reductase-like complex (sHdr) and novel lipoate-binding proteins (LbpAs) are central players of a wide-spread pathway of dissimilatory sulfur oxidation. Bioinformatic analysis demonstrate that the cytoplasmic sHdr-LbpA systems are always accompanied by sets of sulfur transferases (DsrE proteins, TusA, rhodaneses). The exact composition of these sets may vary depending on the organism and sHdr system type. To enable generalizations, we studied model sulfur oxidizers from distant bacterial phyla, i.e. Aquificota and Pseudomonadota. DsrE3C of the chemoorganotrophic Alphaproteobacterium Hyphomicrobium denitrificans and DsrE3B from the Gammaproteobacteria Thioalkalivibrio sp. K90mix, an obligate chemolithotroph, and Thiorhodospira sibirica, an obligate photolithotroph, are homotrimers that donate sulfur to TusA. Additionally, the hyphomicrobial rhodanese-like protein Rhd442 exchanges sulfur with both TusA and DsrE3C. The latter is essential for sulfur oxidation in Hm. denitrificans. TusA from Aquifex aeolicus (AqTusA) interacts physiologically with AqDsrE, AqLbpA and AqsHdr proteins. This is particularly significant as it establishes a direct link between sulfur transferases and the sHdr-LbpA complex that oxidizes sulfane sulfur to sulfite. In vivo, it is unlikely that there is a strict unidirectional transfer between the sulfur-binding enzymes studied. Rather, the sulfur transferases form a network, each with a pool of bound sulfur. Sulfur flux can then be shifted in one direction or the other depending on metabolic requirements. A single pair of sulfur-binding proteins with a preferred transfer direction, such as a DsrE3-type protein towards TusA, may be sufficient to push sulfur into the sink where it is further metabolized or needed. SIGNIFICANCE STATEMENT A network of bacterial sulfur transferases is uncovered and characterized that ultimately delivers sulfur to a complex cytoplasmic sulfur-oxidizing metalloenzyme, sHdr, that resembles heterodisulfide reductase from methanogenic archaea and interacts with lipoate-binding proteins. Similar sets of sulfur transferases occur in phylogenetically distant bacteria, underscoring the fundamental importance of the work.
Benchmarking Reverse Docking through AlphaFold2 Human Proteome

Predicting binding of a small molecule to the human proteome by reverse docking methods, we can predict the target interactions of drug compounds in the human body, as well as further evaluate their potential off-target effects or toxic side effects. In this study, we constructed 11 pipelines to evaluate and benchmark thoroughly the predictive capabilities of these reverse docking pipelines. The pipelines were built using site prediction tools (PointSite and SiteMap) based on the AF2 human proteome, docking programs (Glide and AutoDock Vina), and scoring functions (Glide, Autodock Vina, RTMScore, DeepRMSD, OnionNet-SFCT). The results show that pipeline glide_sfct (PS) exhibited the best target prediction ability and successfully predicted the similar proteins of native targets. This finding provides important clues for understanding the promiscuity between the drug ligand and the whole human proteome. In general, our study has the potential to increase the success rate and reduce the development timeline of drug discovery, thereby saving costs.
Cysteine String Protein alpha in Extracellular Vesicle Subtypes: a Proteomic Analysis

Cysteine string protein (CSPα /DnaJC5) is a presynaptic J-domain protein (JDP) that prevents neurodegeneration. CSPα/DnaJC5 is reported to facilitate export of distinct, highly oligomeric, disease-causing proteins in addition to wild-type TDP-43, tau and α-synuclein. Yet, detailed mechanistic knowledge of the full CSPα/DnaJC5 secreted proteome is lacking. Understanding the CSPα/DnaJC5 export pathway has implications for a growing number of neurodegenerative diseases. In humans, Leu115Arg or Leu116deletion mutations cause adult-onset neuronal ceroid lipofusinosis (ANCL), a rare neurodegenerative disorder. In the present study, we examined extracelular vesicles (EVs) released from CSPα/DnaJC5 expressing cells. Cells are known to secrete many types of EVs of different sizes and origins into the extracellular space. EV subpopulations were separated by their sedimentation speed and subjected to proteomic analysis. We find that CSPα/DnaJC5 and the CSPα/DnaJC5 mutants, Leu115Arg or Leu116del are enriched in multiple EV subpopulations. The exported protein profile is determined by proteomics. We report that several other J-domain proteins (JDPs), such as DnaJC7, DnaJA1 and DnaJA2 are exported and speculate that export of JDPs may facilitate the secretion of diverse client proteins. Our work provides a platform for further inquiry into the role of secreted CSPα/DnaJC5 and other JDPs in proteostasis.
Control of three-carbon amino acid homeostasis by promiscuous importers and exporters in Bacillus subtilis: Role of the sleeping beauty family of amino acid exporters

The Gram-positive model bacterium Bacillus subtilis can acquire amino acids by import, de novo biosynthesis, or by degradation of proteins and peptides. The accumulation of several amino acids inhibits growth of B. subtilis, probably due to misincorporation into cellular macromolecules such as proteins or peptidoglycan or due to interference with other amino acid biosynthetic pathways. Here, we studied the adaptation of B. subtilis to toxic concentrations of the three-carbon amino acids L-alanine, β-alanine, and 2,3-diaminopropionic acid as well as glycine. Resistance to the non-proteinogenic amino acid β-alanine, which is a precursor for the vitamin B5 and thus for coenzyme A biosynthesis is achieved by mutations that either activate a cryptic amino acid exporter, AexA (previously YdeD), or inactivate the amino acid importers AimA, AimB (previously YbxG), and BcaP. The aexA gene is very poorly expressed under most conditions studied. However, mutations afecting the transcription factor AerA (previously YdeC), can result in strong constitutive aexA expression. AexA is the founding member of a conserved family of amino acid exporters in B. subtilis, which are all very poorly expressed. Therefore, we suggest to call this family “sleeping beauty family of amino acid exporters”. 2,3-Diaminopropionic acid can also be exported by AexA, and this amino acid also seems to be a natural substrate of AerA/ AexA, as it can cause a slight but significant induction of aexA expression, and AexA also provides some natural resistance towards 2,3-diaminopropionic acid. Moreover, our work shows how low specificity amino acid transporters contribute to amino acid homeostasis in B. subtilis. IMPORTANCE Even though B. subtilis is of of the most-studied bacteria, amino acid homeostasis in this organism is not fully understood. We have identified import and export systems for the C2 and C3 amino acids. Our work demonstrates that the responsible amino acid permeases contribute in a rather promiscuitive way to amino acid uptake. In addition, we have discovered AexA, the first member of a family of very poorly expressed amino acid exporters, that we call “sleeping beauty amino acid exporters”. The expression of these transporters is typically triggered by mutations in corresponding regulator genes that are acquired upon exposure to toxic amino acids. These exporters are ubiquitous in all domains of life. It is tempting to speculate that many of them are not expressed until the cells experience a selective pressure by toxic compounds and that the protect the cells from rare but potentially dangerous accounters with such compounds.
Pseudoreplication and inappropriate statistical tests in the analysis of preference index data from the T-maze group assay for Drosophila behaviour

The binary choice chamber (T-maze) assay has been used as a standard behavioural screen in Drosophila research to test mutants in terms of sensory discrimination skills and synaptic plasticity during memory consolidation and decay. Typically, ca. 100 individuals are tested as a group at the same time and the behavioural readout consists in counting the number of individuals in the testing tube exposed to a stimulus versus the number of flies in the control tube, with the normalized difference in fly count being defined as the batch preference index (PI). Unfortunately, the batch PI has widely been taken as a precise metric of group behaviour, to the point where ANOVA/t-tests have been considered the most powerful statistical tests for analyzing samples in terms of batch PI values, which has led to a hyperinflation of apparently very highly significant effects for small differences in PI values (e.g. -0.1 vs 0.1), leading to problems with replicability. Here it is shown on the basis of a well-established statistical model for binary decisions that application of the t-test to PI data implicitly assumes that each fly in a batch is an independent biological replicate in the extremely strict sense that the decision of each individual was interrogated independently of the other flies. Therefore, t-test analysis of PI data obtained with the intrinsically pseudoreplicative group assay is the cause of extremely optimistic P-values, as suggested recently by Bassetto et al. (2023) on the basis of effect size considerations for proportions. Thus, rather than using inferential statistics, PI data should be assessed on the basis of effect size. A more fundamental problem with the batch PI value is the uncertainty in whether it measures the mean individual preference and if so, with what precision, given the simple readout? This aspect is illustrated here by modelling distributions of flies in the T-maze, which suggest that the effective precision of the PI value is clearly worse than the nominal precision of +/- 0.01 for 100 flies, so that the batch PI can only serve as a rough indicator of group tendencies.
Epigenetic disruption of the RARγ complex impairs its function to bookmark AR enhancer interactions required for enzalutamide sensitivity in prostate cancer

The current study in prostate cancer (PCa) focused on the genomic mechanisms at the cross-roads of pro-differentiation signals and the emergence of lineage plasticity. We explored an understudied cistromic mechanism involving RARγ’s ability to govern AR cistrome-transcriptome relationships, including those associated with more aggressive PCa features. The RARγ complex in PCa cell models was enriched for canonical cofactors, as well as proteins involved in RNA processing and bookmarking. Identifying the repertoire of miR-96 bound and regulated gene targets, including those recognition elements marked by m6A, revealed their significant enrichment in the RARγ complex. RARγ significantly enhanced the AR cistrome, particularly in active enhancers and super-enhancers, and overlapped with the binding of bookmarking factors. Furthermore, RARγ expression led to nucleosome-free chromatin enriched with H3K27ac, and significantly enhanced the AR cistrome in G2/M cells. RARγ functions also antagonized the transcriptional actions of the lineage master regulator ONECUT2. Similarly, gene programs regulated by either miR-96 or antagonized by RARγ were enriched in alternative lineages and more aggressive PCa phenotypes. Together these findings reveal an under-investigated role for RARγ, modulated by miR-96, to bookmark enhancer sites during mitosis. These sites are required by the AR to promote transcriptional competence, and emphasize luminal differentiation, while antagonizing ONECUT2.
Differential spatial regulation and activation of integrin nanoclusters inside focal adhesions

α5β1 and αvβ3 integrins are key components of focal adhesions (FAs) that play important roles in cell adhesion, migration and mechanobiology-dependent processes. Whether both integrins work in concert or their activities are differentially regulated inside FAs is not fully understood. Here, we exploited dual-color super-resolution stochastic optical reconstruction microscopy (STORM) to quantitatively assess the lateral nanoscale organization and activation state of both integrins and main adaptors inside FAs. Our results reveal that key FA proteins α5β1, αvβ3, paxillin, talin and vinculin organize into segregated nanoclusters of similar size (∼50 nm) and number of molecules, regardless of their partitioning in the membrane, confirming that integrin nanoclustering is force-independent. Both integrins further segregate as active or inactive nanoclusters that do not intermix at the nanoscale and with a higher fraction of active α5β1 nanoclusters as compared to αvβ3. We find a nearly 1:1 stoichiometry between active integrin and adaptor nanoclusters indicating that coordinated integrin nanocluster activation occurs via the concurrent engagement of talin and vinculin nanoclusters. Interestingly, active α5β1 nanoclusters preferentially localize at the FA periphery in proximity to paxillin, talin and vinculin nanoclusters, establishing multiprotein nano-hubs, whereas αvβ3 nanoclusters uniformly distribute throughout FAs. Overall, we reveal a highly complex lateral organization of integrins and main adaptors within FAs, where adhesion proteins arrange as modular nanoscale units that distinctively organize inside FAs to spatially regulate integrin activation. Such spatial control of integrin activity provides a physical mechanism to tune their functions having implications for their key roles in physiology and disease. Significance Statement Focal adhesions (FAs) are places for cell attachment to the extracellular matrix that influence multiple cellular processes as well as being sites for sensing and transducing mechanical stimuli. Integrins, core components of FAs, have different activation states and execute diversity of functions, but how their activity and roles are regulated remain mysterious. Using quantitative dual-color super-resolution microscopy we reveal that integrin activation is spatially regulated inside FAs. We show that main adhesion proteins organize as universal modular nanoscale units, spatially segregating from each other inside FAs. Remarkably, these modular units distinctively organize inside FAs selectively activating one type of integrin or another at specific locations within FAs, providing a physical mechanism to regulate integrin activation and possibly function.
Simple View of Reading Across the Transition from Kindergarten to Grade 1 in a Transparent Orthography

ABSTRACT Purpose This longitudinal study investigated the simple view of reading (SVR) model and its cognitive basis in a transparent orthography of the Lithuanian across the transition from kindergarten to Grade 1. Method The language and early literacy skills of 229 children (Mage = 6.79, SD = .47) were tested at the end of kindergarten (vocabulary, letter knowledge, phonological awareness, and RAN); listening comprehension and word reading fluency were tested at the start of Grade 1; and reading comprehension was measured at the end of Grade 1. Results Together with parental education, word reading fluency and listening comprehension predicted reading comprehension (R2 = 43.2%). The second model, which also included language and early literacy skills, showed that vocabulary and phonological awareness indirectly predicted reading comprehension via listening comprehension, while phonological awareness, letter knowledge, and rapid automatized naming (RAN) indirectly predicted reading comprehension via word reading fluency (R2 = 43.6%). However, after allowing the direct paths from language and early literacy skills in kindergarten to reading comprehension, listening comprehension and word reading fluency were no longer significant predictors of reading comprehension, whereas vocabulary and letter knowledge were (R2 = 58.9%). Conclusion The results provided support for the SVR model in transparent Lithuanian orthography in that linguistic and decoding components are important for early reading comprehension. However, the results also suggested that, in the Lithuanian context, kindergarten vocabulary and letter knowledge are stronger measures in predicting reading comprehension than listening comprehension and word reading fluency in Grade 1.
Cost-Based Storage of the R-tree Aggregated Values over Flash Memory

The flash memory due to its shock resistance, power economy and non-volatile nature is considered as a very popular storage device. It is widely used in mobile phones, sensor networks and hand-held devices. What attracts the attention is the data storage in the flash memory. Database vendors try to adapt their systems to the flash memory architecture. To make it efficient, database indexes, such as: B-tree or R-tree, must be implemented from the scratch in order to take into account the flash memory limitations. The R-tree is wildly used in the geographical databases for indexing the spatial objects. The aggregated R-tree (aR-tree) extends the original R-tree with the aggregated values, which are connected with the nodes. In this paper, we deal with the materialization technique of the aggregated values in the aR-tree index. We claim that not all the aggregated values should be explicitly stored in the flash memory. We propose a Cost-Based Method which chooses the most beneficial set of the aggregated values for materialization. Our method is particularly beneficial for devices with limited capacity and is optimized for the flash memory architecture.
Innovation and Its Discontents: How Our Broken Patent System is Endangering Innovation and Progress, and What to Do About It

Preface ix Introduction: They Fixed It, and Now It's Broke 1 CHAPTER 1: Today's Patent System at Work 25 CHAPTER 2: The Dark Side of Patents 56 CHAPTER 3: The Long Debate 78 CHAPTER 4: The Silent Revolution 96 CHAPTER 5: The Slow Starvation 127 CHAPTER 6: The Patent Reform Quagmire 151 CHAPTER 7: Innovation and Its Discontents 170 Notes 209 Index 229
Reﬁnement types in Jolie

Jolie is the ﬁrst language for microservices and it is currently dynamically type checked. This paper considers the opportunity to integrate dynamic and static type checking with the introduction of reﬁnement types, veriﬁed via SMT solver. The integration of the two aspects allows a scenario where the static veriﬁcation of internal services and the dynamic veriﬁcation of (potentially malicious) external services cooperates in order to reduce testing eﬀort and enhancing security
CORE Scholar CORE Scholar

Discussion forums provide a channel for students to engage with peers and course material outside of class, accessible even to commuter and nontraditional populations. Forums can build classroom community and aid learning, but students do not always take up these tools. We use network analysis to compare three semesters of forum logs from an introductory calculus-based physics course. The networks show dense structures of collaboration that differ significantly between semesters, even though aggregate participation statistics remain steady. After characterizing network structure for each semester, we correlate students ’ centrality — a numeric measure of network position — with final course grade. Finally, we use a backbone extraction procedure to clean up “ noise ” in the network and clarify centrality-grade correlations. We find that more central network positions are positively linked with course success in the two semesters with denser forum networks. Centrality is a more reliable indicator of grade than non-network measures such as postcount. Backbone extraction destroys these correlations, suggesting that the noise is in fact signal and further analysis of the discussion transcripts is required. DOI: 10.1103/PhysRevPhysEducRes.14. 020107
Minimization of Permuted Reed-Muller Trees and Reed-Muller Trees for Cellular Logic Programmable Gate Arrays

This Thesis is brought to you for free and open access. It has been accepted for inclusion in Dissertations and Theses by an authorized administrator of PDXScholar. For more information, please contact pdxscholar@pdx.edu. Recommended Citation Wu, Lifei, "Minimization of Permuted Reed-Muller Trees and Reed-Muller Trees for Cellular Logic Programmable Gate Arrays" (1993). Dissertations and Theses. Paper 4745.
The Online Waiting Experience: Using Temporal Information and The Online Waiting Experience: Using Temporal Information and Distractors to Make Online Waits Feel Shorter Distractors to Make Online Waits Feel Shorter

: Research on how to manage the online waiting experience has begun to emerge but has primarily focused on the use of distracting cues for online wait management (e.g., text and images that distract the user from the wait). The use of temporal information in waiting webpages (e.g., text and images that convey the duration of the wait) has received little attention from the information systems literature, and we have limited understanding about how the two types of cues (temporal information and distractors) affect wait time estimation. We address this gap by developing a theoretical model of how these cues affect the waiting experience and perceived waiting time. We tested the model with a 2 x 2 x 2 x 2 controlled lab experiment and 1025 participants using progress bar treatments that included temporal information (spatial and text description of the wait time duration) and distractors (progress bar animation and accelerated filling of the progress bar) with both short and long wait conditions. We found that the two types of cues reduced perceived waiting time through different nomological paths. Temporal cues reduced perceived uncertainty about the wait, while distractor cues directed attention away from the wait, increasing perceived enjoyment and wait time distortion. Further, the enhanced waiting experience reduced the perceived waiting time. Further, these cues were effective in managing the online waiting experience with both short and long waits.
ditlab at the NTCIR-17 Transfer Task

TheditlabteamparticipatedintheTransfertaskcomposedofdenseretrievalanddensererankingsubtasks.Wetrainedsentence-BERT byusingaJapaneseversionofmMARCOdatasetandcommonly usedforbothsubtasks.Wecomparedthreetypesofmodelsthat weretrainedaccordingtothreetypesoflosses:softmax,triplet, multiplenegativesrankinglosses.Theresultsshowthatthemul-tiplenegativesrankinglosswasthebestforbothsubtasks.Inad-dition,systemfusionssignificantlyimprovedtheperformancees-peciallyfortheretrievaltask.
SUSTAINABLE AGRICULTURAL GROWTH, DIVERSIFICATION AND FARM INCOME Transitioning to a Green Economy: A Narrative Overview of the Challenges and Opportunities in Indian Agriculture

The green economy refers to promoting economic activities that improve social equity and well-being, generate employment and income opportunities, and reduce environmental risks while restoring and effectively managing the natural resources. Agriculture is one of the core industries in achieving the green economy goals, especially in developing nations like India. In order to meet future food and raw material demands, India must reform rather than maintain its agricultural industry. Therefore, the present review comprehends the sector's economic, social, and environmental attributes and identifies its significant challenges and opportunities for green economy of the country. Based on the literature from across a range of disciplines, the study observed that the future requires transformation rather than sustaining the agricultural sector with an emphasis towards efficiency rather than growth, employment generation, nutritional security and management of surplus food in consonance with the agro-ecological backdrop.