Miracle-dz/UniFAR-FTUs huggingface dataset:
Cultural-Historical Activity Theory as a Framework for Exploring Pre-service Teachers’ Use of an Intelligent Tutoring System for English Language Proficiency

Abstract The purpose of this study was to examine pre-service teachers’ perceptions of their use of an intelligent tutoring system (ITS) as an English language proficiency tool. Pre-service teachers’ perceptions were analysed using Engeström’s second-generation cultural-historical activity theory (CHAT). A qualitative interpretivist paradigm was used. Six pre-service teachers who were learning to be English home language teachers but were not English home language speakers were interviewed. The study’s findings indicated that when the ITS was integrated into an activity system for teaching and learning, participants had a favourable opinion of it. The ITS was perceived to aid pre-service teachers in enhancing their language skills and to be instrumental in achieving goals and objectives as a tool for learning.
Repetitive Negative Thinking and Sexual Functioning in Portuguese Men and Women: A Cross-Sectional Study

Abstract Objective: Repetitive negative thinking (RNT) is a transdiagnostic process involved in the development and maintenance of emotional disorders that negatively affect sexual functioning. However, empirical evidence for the role of RNT on sexual functioning is still lacking. The current study aimed to investigate the role of RNT on sexual functioning in men and women by examining differences in RNT between men and women and between individuals with and without subclinical sexual difficulties. It also aimed to investigate the predictive role of RNT on sexual function indices in men and women. Methods: A total of 424 participants (270 women) completed online a sociodemographic questionnaire and Portuguese versions of the Persistent and Intrusive Negative Thoughts Scale, the Female Sexual Functioning Index, and the International Index of Erectile Function. Results: The main findings showed that women scored significantly higher than men on the RNT. Similarly, individuals with subclinical sexual difficulties scored significantly higher on the RNT compared with individuals without sexual difficulties. RNT was a statistically significant and negative predictor of sexual functioning in women and men. The role of RNT on sexual functioning in women and men was found, with men and women with subclinical sexual difficulties more likely to express persistent and intrusive negative thoughts compared with men and women without sexual difficulties. Conclusions: In summary, RNT appears to be a negative predictor of sexual functioning in both women and men, suggesting that individuals with more intrusive and negative persistent thoughts also have more difficulty in their sexual response.
Time is money, but sometimes it costs more: an economic history perspective into nuclear projects’ pitfalls

Abstract The changing socio-economic context has a crucial impact in nuclear decisions and execution of the projects. The nuclear projects initiated over the past 20 years reduced their construction times relative to those initiated before. Of the over 600 the nuclear projects built over the past 70 years only 3% took longer than 15 years to complete. Analysing the lengthiest projects within their economic context, reveals that ‘when and where’, (i.e., the contextual risks) explains most the delays, thus questioning whether nuclear power plant projects are inherently examples of the megaproject ‘pathologies. ’ The analysis of the lengthiest nuclear power projects makes evident that the failure to deliver nuclear plants on time and within budget was related to the historical period and/or the specific location more than to any inherent characteristics of nuclear power plants. Stakeholders of nuclear projects (and megaprojects in general) should be attentive to socio-economic changes and macro-economic impacts to avoid pitfalls.
Ultrafast molecular dynamics observed within a dense protein condensate

Many biological macromolecules can phase-separate in the cell and form highly concentrated condensates. The mesoscopic dynamics of these assemblies have been widely characterized, but their behavior at the molecular scale has remained more elusive. Here we investigate condensates of two highly charged disordered human proteins as a characteristic example of liquid-liquid phase separation. The dense phase is 1000 times more concentrated and has 300 times higher bulk viscosity than the dilute phase. However, single-molecule spectroscopy in individual droplets reveals that the polypeptide chains are remarkably dynamic, with sub-microsecond reconfiguration times. We rationalize this behavior with large-scale all-atom molecular-dynamics simulations, which reveal an unexpectedly similar short-range molecular environment in the dense and dilute phases, suggesting that local biochemical processes and interactions can remain exceedingly rapid in phase-separated systems.
Mean Dimension of Generative Models for Protein Sequences

Generative models for protein sequences are important for protein design, mutational effect prediction and structure prediction. In all of these tasks, the introduction of models which include interactions between pairs of positions has had a major impact over the last decade. More recently, many methods going beyond pairwise models have been developed, for example by using neural networks that are in principle able to capture interactions between more than two positions from multiple sequence alignments. However, not much is known about the inter-dependency patterns between positions in these models, and how important higher-order interactions involving more than two positions are for their performance. In this work, we introduce the notion of mean dimension for generative models for protein sequences, which measures the average number of positions involved in interactions when weighted by their contribution to the total variance in log probability of the model. We estimate the mean dimension for different model classes trained on different protein families, relate it to the performance of the models on mutational effect prediction tasks and also trace its evolution during training. The mean dimension is related to the performance of models in biological prediction tasks and can highlight differences between model classes even if their performance in the prediction task is similar. The overall low mean dimension indicates that well-performing models are not necessarily of high complexity and encourages further work in interpreting their performance in biological terms.
The Kelch13 compartment is a hub of highly divergent vesicle trafficking proteins in malaria parasites

Single amino acid changes in the parasite protein Kelch13 (K13) result in reduced susceptibility of P. falciparum parasites to artemisinin and its derivatives (ART). Recent work indicated that K13 and other proteins co-localising with K13 (K13 compartment proteins) are involved in the endocytic uptake of host cell cytosol (HCCU) and that a reduction in HCCU results in ART resistance. HCCU is critical for parasite survival but is poorly understood, with the K13 compartment proteins among the few proteins so far functionally linked to this process. Here we further defined the composition of the K13 compartment by analysing more hits from a previous BioID, showing that MyoF and MCA2 as well as Kelch13 interaction candidate (KIC) 11 and 12 are found at this site. Functional analyses, tests for ART susceptibility as well as comparisons of structural similarities using AlphaFold2 predictions of these and previously identified proteins showed that canonical vesicle trafficking and endocytosis domains were frequent in proteins involved in resistance or endocytosis (or both), comprising one group of K13 compartment proteins. While this strengthened the link of the K13 compartment to endocytosis, many proteins of this group showed unusual domain combinations and large parasite-specific regions, indicating a high level of taxon-specific adaptation of this process. Another group of K13 compartment proteins did not influence endocytosis or ART susceptibility and lacked detectable vesicle trafficking domains. We here identified the first protein of this group that is important for asexual blood stage development and showed that it likely is involved in invasion. Overall, this work identified novel proteins functioning in endocytosis and at the K13 compartment. Together with comparisons of structural predictions it provides a repertoire of functional domains at the K13 compartment that indicate a high level of adaption of endocytosis in malaria parasites.
Enteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy

Digestive Chagas disease (DCD) is an enteric neuropathy caused by Trypanosoma cruzi infection. There is a lack of evidence on the mechanism of pathogenesis and rationales for treatment. We used a mouse model that recapitulates key clinical manifestations to study how infection dynamics shape DCD pathology, and the impact of treatment with the front-line drug benznidazole. Curative treatment at 6 weeks post-infection resulted in sustained recovery of GI transit function, whereas sub-curative treatment led to infection relapse and gradual return of DCD symptoms. Neuro-immune gene expression profiles shifted from chronic inflammation to a tissue repair signature after cure, accompanied by increased glial cell activity and regenerative neurogenesis in the myenteric neuronal plexus. Delaying treatment until 24 weeks post-infection led to a partial reversal of the DCD phenotype, suggesting the accumulation of permanent tissue damage over the course of chronic infection. Our study shows that murine DCD pathogenesis is sustained by chronic T. cruzi infection and is not an inevitable consequence of acute stage denervation. The risk that irreversible enteric neuromuscular tissue damage and dysfunction will develop highlights the importance of prompt diagnosis and treatment. Finally, these findings support the concept of treating asymptomatic T. cruzi infected individuals with benznidazole to prevent DCD development.
The phased diploid genome assembly of Vitis vinifera cv. Shiraz

Shiraz (Syrah) is a dark-skinned cultivar of the wine grape Vitis vinifera that forms the basis of some of the world’s most iconic wines. Worldwide, Shiraz is the fourth most planted grapevine cultivar, however it represents the most planted cultivar in Australia. Given the importance of Shiraz to worldwide wine production, a long-read based reference genome assembly for this cultivar was produced and used to investigate the unique genetic diversity and ancestral origins of this iconic variety. Phylogenetic reconstruction using high-quality genome assemblies for wine grape cultivars provided further support of a kinship between Shiraz and Pinot Noir. Harnessing long-read data, transposable element insertions potentially affecting gene function were characterized in Shiraz and assessed relative to other cultivars. This revealed a heterogenous landscape of transposon insertion points across cultivars and uncovered a specific combination of allelic variants at the TPS24 terpene synthase locus, which when combined with appropriate environmental triggers, may allow Shiraz to produce high levels of rotundone, the aroma compound responsible for the distinctive peppery characteristics of this cultivar.
Developmentally Programmed Switches in DNA Replication: Gene Amplification and Genome-Wide Endoreplication in Tetrahymena

Locus-specific gene amplification and genome-wide endoreplication generate the elevated copy number of ribosomal DNA (rDNA, 9000 C) and non-rDNA (45 C) chromosomes in the developing macronucleus of Tetrahymena thermophila. Subsequently, all macronuclear chromosomes replicate once per cell cycle during vegetative growth. Here we describe an unanticipated, programmed switch in the regulation of replication initiation in the rDNA minichomosome. Early in development the 21 kb rDNA minichromosome is preferentially amplified from 2 C to ~800 C from well-defined origins, concurrent with genome-wide endoreplication (2 C to 8-16 C) in starved mating Tetrahymena (endoreplication (ER) Phase 1). Upon refeeding, rDNA and non-rDNA chromosomes achieve their final copy number through resumption of just the endoreplication program (ER Phase 2). Unconventional rDNA replication intermediates are generated primarily during ER phase 2, consistent with delocalized replication initiation and possible formation of persistent RNA-DNA hybrids. Origin usage and replication fork elongation are affected in non-rDNA chromosomes as well. Despite the developmentally programmed 10-fold reduction in the ubiquitous eukaryotic initiator, the Origin Recognition Complex (ORC), active initiation sites are more closely spaced in ER phases 1 and 2 compared to vegetative growing cells. We propose that initiation site selection is relaxed in endoreplicating macronuclear chromosomes and may be less dependent on ORC.
Stresses in a plate containing an infinite row of holes

It is well known that the presence of a hole in a stressed plate has a very great influence upon the maximum stress, and a number of investigations, both mathematical and experimental, have been directed towards determining the exact extent of this influence. When the hole is isolated and the boundaries of the plate are distant the mathematical method of binding the stresses in its neighbourhood is elementary. But the presence of adjacent boundaries introduces great complications. The problem has been solved for a circular hole near to a single straight boundary by effery, and for a hole mid-way between two straight boundaries by the present writer and others. Here appears, however, to have been no theoretical investigationof the stresses in the neighbourhood of a group of holes sufficiently close together to influence each other to a marked extent. Capper, using optical methods, obtained the stress distributions in a narrow plate under tension when there were three holes in line across the plate or six holes in triangular formation. His results will be referred to at a later stage. The simplest case for mathematical investigation is that of an infinite row of equal and equally spaced holes in a plate of indefinite extent. If the applied tractions are of such a kind that all the holes are similar with regard to them, we have a periodic stress distribution. It will be shown that this is always expressible by means of a set of periodic functions all derivable from one fundamental function. The solution so obtained will be applied to the special cases of tensions applied either parallel to the line of centres or perpendicular to this line. Numerical results will be given.
Macromolecular Crowding Is Surprisingly Unable to Deform the Structure of a Model Biomolecular Condensate

The crowded interior of a living cell makes experiments on simpler in vitro systems attractive. Although these reveal interesting phenomena, their biological relevance can be questionable. A topical example is the phase separation of intrinsically-disordered proteins into biomolecular condensates, which is proposed to underlie the membraneless compartmentalisation of many cellular functions. How a cell reliably controls biochemical reactions in compartments open to the compositionally-varying cytoplasm is an important question for understanding cellular homeostasis. Computer simulations are often used to study the phase behaviour of model biomolecular condensates, but the number of relevant parameters explodes as the number of protein components increases. It is unfeasible to exhaustively simulate such models for all parameter combinations, although interesting phenomena are almost certainly hidden in the jungle of their high-dimensional parameter space. Here we have studied the phase behaviour of a model biomolecular condensate in the presence of a polymeric crowding agent. We used a novel compute framework to execute dozens of simultaneous simulations spanning the protein/crowder concentration space. We then combined the results into a graphical representation for human interpretation, which provided an efficient way to search the model’s high-dimensional parameter space. We found that steric repulsion from the crowder drives a near-critical system across the phase boundary, but the molecular arrangement within the resulting biomolecular condensate is rather insensitive to the crowder concentration and molecular weight. We propose that a cell may use the local cytoplasmic concentration to assist formation of biomolecular condensates, while relying on the dense phase reliably providing a stable, structured, fluid milieu for cellular biochemistry despite being open to its changing environment.
A multi-omics analysis identifies molecular features associated with heifer fertility in a case-control design including Angus and Holstein cattle

Background Infertility or subfertility is a critical barrier to sustainable cattle production, including in heifers. The development of heifers that do not produce a calf within an optimum window of time is a critical factor for the profitability and sustainability of the cattle industry. The early identification of heifers with optimum fertility using molecular phenotyping is a promising approach to improving sustainability in beef and dairy cattle production. Results Using a high-density single nucleotide polymorphism (SNP) chip, we collected genotypic data from 575,053 SNPs. We also produced quantitative transcriptome data for 12,445 genes (12,105 protein-coding genes, 228 long non-coding RNAs, and 112 pseudogenes) and proteome data for 213 proteins. We identified two SNPs significantly associated with heifer fertility (rs110918927, chr12: 85648422, P = 6.7×10-7; and rs109366560, chr11:37666527, P = 2.6×10-5). We identified two genes with differential transcript abundance (eFDR ≤ 0.002) between the two groups (Fertile and Sub-Fertile): Adipocyte Plasma Membrane Associated Protein (APMAP, 1.16 greater abundance in the Fertile group) and Dynein Axonemal Intermediate Chain 7 (DNAI7, 1.23 greater abundance in the Sub-Fertile group). Our analysis revealed that the protein Alpha-ketoglutarate-dependent dioxygenase FTO was more abundant in the plasma collected from Fertile heifers relative to their Sub-Fertile counterparts (FDR < 0.05). Interestingly, two proteins did not reach the significance threshold in the model accounting for all samples (Apolipoprotein C-II, APOC2 (FDRglmm = 0.06) and Lymphocyte cytosolic protein 1, LCP1 (FDRglmm = 0.06)), but both proteins were less abundant in the plasma of Fertile Holstein heifers (P < 0.05). Lastly, an integrative analysis of the three datasets identified a series of features (SNPs, gene transcripts, and proteins) that can be useful for the discrimination of heifers based on their fertility. When all features were utilized together, 21 out of 22 heifers were classified correctly based on their fertility category. Conclusions Our multi-omics analyses confirm the complex nature of female fertility. Very importantly, our results also highlight differences in the molecular profile of heifers associated with fertility that transcend the constraints of breed-specific genetic background.
Anesthesia alters cortical spike sequences in rodent visual cortex

Recurring spike sequences are thought to underlie cortical computations and may be essential for information processing in the conscious state. How anesthesia at graded levels may influence spontaneous and stimulus-related spike sequences in visual cortex has not been systematically examined. We recorded extracellular single-unit activity in the rat primary visual cortex in vivo during wakefulness and three levels of anesthesia produced by desflurane. The latencies of spike sequences within 0~200ms from the onset of spontaneous UP states and visual flash-evoked responses were compared. During wakefulness, spike latency patterns linked to the local field potential theta cycle were similar to stimulus-evoked patterns. Under anesthesia, spontaneous UP state sequences differed from flash-evoked sequences due to the recruitment of low-firing excitatory neurons to the UP state. Flash-evoked spike sequences showed higher reliability and longer latency when stimuli were applied during DOWN states compared to UP states. At deeper levels, anesthesia altered both UP state and flash-evoked spike sequences by selectively suppressing inhibitory neuron firing. The results reveal anesthesia-induced complex changes in cortical firing sequences that may influence visual information processing.
A transcriptome atlas of Striga hermonthica germination

Societal Impact Statement Witchweeds, parasitic plants of the genus Striga, are nicknamed “cereal killers” because of their devasting destruction of Africa’s most staple cereals, including maize, sorghum, millets, and upland rice. The parasite relies on biomolecules emitted from the host roots to germinate and therefore initiate its infectious lifecycle. Some sorghum varieties have evolved to not produce effective germination stimulants, making them resistant to the parasite. Here, we assess genetic factors that underpin Striga germination. We discuss how such knowledge can be used to develop new Striga management strategies through the disruption of host-parasite communication exchange. Summary Seeds of the parasitic plant Striga are dormant. They only germinate in response to biomolecules emitted from the host’s root exudate, strigolactones (SL). But, it is now emerging that Striga germination is a much more complex process regulated by crosstalk of hormone signaling pathways. To further understand the genetic basis of the communication exchange between Striga and its host sorghum, we performed a comparative transcriptomic analysis. We sought to identify major transcriptomic changes that define the germination process in Striga and a set of genes that may contribute to the differences in germination rates. Results showed that germination proceeds immediately after SL perception and is marked by a wave of transcriptional reprogramming to allow for metabolic processes of energy mobilization. Cluster analysis using self-organizing maps (SOMs) revealed a time-phased and genotype-differentiated response to germination stimulation. The variation in germination was also a function of hormonal crosstalk. The early germination stage was associated with significant repression of genes in the abscisic acid (ABA) biosynthesis pathway. Other hormones influenced germination as follows: (i) ABA and auxin repressed germination, (ii) brassinosteroid, ethylene and jasmonic acid promoted germination, and (iii) cytokinin had a more prominent role post-germination rather than during germination. Perception of SL sets the germination programme leading to different rates of germination in sorghum followed by a complex hormonal regulation network that acts to either repress or enhance germination. These results have far-reaching implications for developing Striga management strategies by disrupting hormonal communication exchange.