Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of computational methods for the determination of biomass composition and evaluation of its impact in genome-scale models predictions

The use of genome-scale metabolic models is rapidly increasing in fields such as metabolic engineering. An important part of a metabolic model is the biomass equation, since this reaction will be used as the objective function in most simulation approaches. In order to obtain a reliable metabolic model, the biomass precursors and their coefficients must be as precise as possible. Ideally, the determination of the biomass composition would be performed experimentally, but due to technical limitations in cellular components quantification, budget restraints and time limitations, this is often established by approximation to closely related organisms. Computational methods however, can extract some information from the genome, such as amino acid and nucleotide compositions. One main objective in this study was to evaluate how biomass precursor coefficients computationally determined, affected the predictability of several genome-scale metabolic models by comparison with experimental data. Sensitivity analysis studies were performed with the Escherichia coli iAF1260 metabolic model concerning specific growth rate and flux distribution. Several metabolic models, whose biomass composition had been experimentally determined, were used to evaluate the impact of biomass coefficients on growth rates and flux distributions. In this study, biomass precursor coefficients were changed based on data obtained from computational methods and from closely related organisms. The results obtained from these two changes were then compared to the results obtained from the model using the experimentally determined biomass composition. Finally, analytical methods were established for macromolecule quantification and protein, DNA and RNA content of Helicobacter pylori biomass were experimentally determined. The results obtained suggest that small modifications (around 1×10-) in biomass precursor coefficients have no significant impact on the computed specific growth rate and flux distributions. We also observed that, despite computationally determined biomass coefficients present differences to those experimentally determined, the growth rate and flux distributions have similar results (differences below 1,5 %). Surprisingly, specific growth rates and flux distributions were more distant from experimental data when adopting biomass precursor coefficients from closely related organisms.
Collagen fingerprinting traces the introduction of caprines to island Eastern Africa

The human colonization of eastern Africa's near- and offshore islands was accompanied by the translocation of several domestic, wild and commensal fauna, many of which had long-term impacts on local environments. To better understand the timing and nature of the introduction of domesticated caprines (sheep and goat) to these islands, this study applied collagen peptide fingerprinting (Zooarchaeology by Mass Spectrometry or ZooMS) to archaeological remains from eight Iron Age sites, dating between ca 300 and 1000 CE, in the Zanzibar, Mafia and Comoros archipelagos. Where previous zooarchaeological analyses had identified caprine remains at four of these sites, this study identified goat at seven sites and sheep at three, demonstrating that caprines were more widespread than previously known. The ZooMS results support an introduction of goats to island eastern Africa from at least the seventh century CE, while sheep in our sample arrived one–two centuries later. Goats may have been preferred because, as browsers, they were better adapted to the islands' environments. The results allow for a more accurate understanding of early caprine husbandry in the study region and provide a critical archaeological baseline for examining the potential long-term impacts of translocated fauna on island ecologies.
Male age alone predicts paternity success under sperm competition when effects of age and past mating effort are experimentally separated

Older males often perform poorly under post-copulatory sexual selection. It is unclear, however, whether reproductive senescence is because of male age itself or the accumulated costs of the higher lifetime mating effort that is usually associated with male age. To date, very few studies have accounted for mating history and sperm storage when testing the effect of male age on sperm traits, and none test how age and past mating history influence paternity success under sperm competition. Here, we experimentally manipulate male mating history to tease apart its effects from that of age on ejaculate traits and paternity in the mosquitofish, Gambusia holbrooki. We found that old, naive males had more sperm than old, experienced males, while the reverse was true for young males. By contrast, neither male age nor mating history affected sperm velocity. Finally, using artificial insemination to experimentally control the number of sperm per male, we found that old males sired significantly more offspring than young males independently of their mating history. Our results highlight that the general pattern of male reproductive senescence described in many taxa may often be affected by two naturally confounding factors, male mating history and sperm age, rather than male age itself.
Multicellularity and sex helped shape the Tree of Life

Across the Tree of Life, there are dramatic differences in species numbers among groups. However, the factors that explain the differences among the deepest branches have remained unknown. We tested whether multicellularity and sexual reproduction might explain these patterns, since the most species-rich groups share these traits. We found that groups with multicellularity and sexual reproduction have accelerated rates of species proliferation (diversification), and that multicellularity has a stronger effect than sexual reproduction. Patterns of species richness among clades are then strongly related to these differences in diversification rates. Taken together, these results help explain patterns of biodiversity among groups of organisms at the very broadest scales. They may also help explain the mysterious preponderance of sexual reproduction among species (the ‘paradox of sex’) by showing that organisms with sexual reproduction proliferate more rapidly.
Dysregulation of the AP2M1 phosphorylation cycle by LRRK2 impairs endocytosis and leads to dopaminergic neurodegeneration

Clathrin-mediated endocytosis in neurons is sensitive to the abundance and activity of the kinase LRRK2. LRRK2 links endocytosis to Parkinson’s disease Defects in endocytosis and mutations in the kinase LRRK2 are associated with Parkinson’s disease. Liu et al. found that LRRK2 directly regulates endocytosis by phosphorylating a protein critical to clathrin coating and uncoating cycles. In cultured neurons and animal models, LRRK2-mediated phosphorylation of the AP2 complex subunit M1 was essential for initiating clathrin coating of budding endocytic vesicles. However, increased activation of LRRK2—such as that caused by a Parkinson’s disease–associated mutation—prevented the uncoating of AP2M1 after internalization, thereby impairing endocytic trafficking. This effect was implicated in the loss of dopaminergic neurons in a fly model of LRRK2-mutant PD, suggesting that it may underlie pathology in patients. Mutations in the kinase LRRK2 and impaired endocytic trafficking are both implicated in the pathogenesis of Parkinson’s disease (PD). Expression of the PD-associated LRRK2 mutant in mouse dopaminergic neurons was shown to disrupt clathrin-mediated endocytic trafficking. Here, we explored the molecular mechanism linking LRRK2 to endocytosis and found that LRRK2 bound to and phosphorylated the μ2 subunit of the adaptor protein AP2 (AP2M1), a core component of the clathrin-mediated endocytic machinery. Analysis of human SH-SY5Y cells and mouse neurons and tissues revealed that loss of LRRK2 abundance or kinase function resulted in decreased phosphorylation of AP2M1, which is required for the initial formation of clathrin-coated vesicles (CCVs). In contrast, overexpression of LRRK2 or expression of a Parkinson’s disease–associated gain-of-function mutant LRRK2 (G2019S) inhibited the uncoating of AP2M1 from CCVs at later stages and prevented new cycles of CCV formation. Thus, the abundance and activity of LRRK2 must be calibrated to ensure proper endocytosis. Dysregulated phosphorylation of AP2M1 from the brain but not thyroid tissues of LRRK2 knockout and G2019S-knockin mice suggests a tissue-specific regulatory mechanism of endocytosis. Furthermore, we found that LRRK2-dependent phosphorylation of AP2M1 mediated dopaminergic neurodegeneration in a Drosophila model of PD. Together, our findings provide a mechanistic link between LRRK2, AP2, and endocytosis in the pathogenesis of PD.
Effects of ternary elements on the ductility of TiAl

TiAl alloys have great potential for applications at high temperature due to their excellent material properties. However, the low ductility at the room-temperature restricted its application greatly. It is very important to find approaches of improving the ductility of the material. In this study, effects of ternary elements (Zr, Hf, V, Nb, Ta, Cr, Mo, W, Cu and Zn) on the ductility of TiAl were investigated by first-principle calculations. Results revealed that the addition of the atoms of Zr, Hf, Cu and Zn could improve the ductility of TiAl by changing the lattice parameter, the electronic structure, and the elastic constants of TiAl. The calculation results can be used as a reference for selecting alloying elements for ductility improvement of TiAl alloys.
Gender bias in dictionary-derived word embeddings

Existing methods for generating word embeddings offer great results and coverage of non-standard or colloquial terms but can often suffer from bias. Such bias may arise from the corpora used like Wikipedia and Google News. We suspect that dictionaries may be less likely to embed biases, and thus methods that are able to generate embeddings from dictionaries may side-step these biases. To do this, we evaluate the bias found in 2 dictionary-based methods (CPAE and dict2vec) and 2 common methods (word2vec and GLoVe) for generating word embeddings. We ﬁnd that dictionary-based methods do seem promising in containing less bias, but are unable to completely avoid the issue. We then make a few attempts at identifying why bias may appear in these embeddings, and ﬁnd evidence for two hypotheses that may contribute.
A passive mechanism for decoupling energy storage and return in ankle–foot prostheses: A case study in recycling collision energy

Abstract Individuals with lower limb amputation experience reduced ankle push-off work in the absence of functional muscles spanning the joint, leading to decreased walking performance. Conventional energy storage and return (ESR) prostheses partially compensate by storing mechanical energy during midstance and returning this energy during the terminal stance phase of gait. These prostheses can provide approximately 30% of the push-off work performed by a healthy ankle–foot during walking. Novel prostheses that return more normative levels of mechanical energy may improve walking performance. In this work, we designed a Decoupled ESR (DESR) prosthesis which stores energy usually dissipated at heel-strike and loading response, and returns this energy during terminal stance, thus increasing the mechanical push-off work done by the prosthesis. This decoupling is achieved by switching between two different cam profiles that produce distinct, nonlinear torque–angle mechanics. The cams automatically interchange at key points in the gait cycle via a custom magnetic switching system. Benchtop characterization demonstrated the successful decoupling of energy storage and return. The DESR mechanism was able to capture energy at heel-strike and loading response, and return it later in the gait cycle, but this recycling was not sufficient to overcome mechanical losses. In addition to its potential for recycling energy, the DESR mechanism also enables unique mechanical customizability, such as dorsiflexion during swing phase for toe clearance, or increasing the rate of energy release at push-off.
Experimental study of a turbulent boundary layer with a rough-to-smooth change in surface conditions at high Reynolds numbers

Abstract This study presents an experimental dataset documenting the evolution of a turbulent boundary layer downstream of a rough-to-smooth surface transition. To investigate the effect of upstream flow conditions, two groups of experiments are conducted. For the Group-Re cases, a nominally constant viscous-scaled equivalent sand grain roughness $k_{s0}^{+}\approx 160$ is maintained on the rough surface, while the friction Reynolds number $Re_{\tau 0}$ ranges from 7100 to 21 000. For the Group-ks cases, $Re_{\tau 0}\approx 14\,000$ is maintained while $k_{s0}^{+}$ ranges from 111 to 228. The wall-shear stress on the downstream smooth surface is measured directly using oil-film interferometry to redress previously reported uncertainties in the skin-friction coefficient recovery trends. In the early development following the roughness transition, the flow in the internal layer is not in equilibrium with the wall-shear stress. This conflicts with the common practise of modelling the mean velocity profile as two log laws below and above the internal layer height, as first proposed by Elliott (Trans. Am. Geophys. Union, vol. 39, 1958, pp. 1048–1054). As a solution to this, the current data are used to model the recovering mean velocity semi-empirically by blending the corresponding rough-wall and smooth-wall profiles. The over-energised large-scale motions leave a strong footprint in the near-wall region of the energy spectrum, the frequency and magnitude of which exhibit dependence on $Re_{\tau 0}$ and $k_{s0}^{+}$, respectively. The energy distribution in near-wall small scales is mostly unaffected by the presence of the outer flow with rough-wall characteristics, which can be used as a surrogate measure to extract the local friction velocity.
Peak Running Intensities in Field Hockey - A Positional Analysis

Abstract The aim of this study was to investigate the positional mean peak running periods during a field hockey match using a moving average method. The secondary aim was to investigate how the peak periods changed between quarters and playing positions. The moving average method was used to analyse the data because of the nature of field hockey, which has natural fluctuations of high and low intensity periods of play. The time periods included periods from 1 to 10 minutes. The level of significance for results was set at p ≤ 0.05. The study found that forwards had a peak running intensity of 194 ± 24.2 m·min-1, midfielders 189 ± 11.9 m·min-1, and defenders 182.6 ± 17.9 m·min-1. These results showed that forwards had the highest maximum running speed, with defenders having the lowest one (p = 0.0025). Additionally, running output started to plateau after 7/8-min periods for each of the three positions. Forwards did not show any statistically significant changes across the four quarters. Midfielders showed effect sizes ranging from >0.6 to >2.0 (moderate, large and very large) significance when comparing the first three quarters to the fourth one. Defenders showed >0.6 to <2.0 (moderate to large) effect sizes to occur when comparing the first and second quarter to the fourth. There are three main practical implications from the results of this study: 1) the creation of conditioning drills, 2) substitution patterns, and 3) knowledge to be able to plan and train at or above peak match demands.
Artificial neural network (ANN) approach for prediction and modeling of breakthrough curve analysis of fixed-bed adsorption of iron ions from aqueous solution by activated carbon from Limonia acidissima shell

Abstract The present research article explored the potential of activated carbon prepared from Limonia acidissima shell to adsorb total Fe ions from aqueous solution in a packed bed up-flow column. The effect of essential factors such as bed height (3–5 cm), initial concentration (30–50 mg/L), and flow rate (3.32–5.4 mL/min) on the performance of the column bed was investigated. The adsorption capacity augmented with an increase in bed height and initial adsorbate concentration but declined with an increase in flow rate. The maximum uptake capacity of 209.6 mg/g was achieved at 5 cm bed height, 3.32 mL/min, and 50 mg/L initial concentration. The bed depth service time (BDST) model was used to analyze the experimental data and determine the characteristic parameters of the packed bed reactor suitable for designing large-scale column studies. The Adams–Bohart, Thomas, and Yoon–Nelson models were applied to the experimental data to predict breakthrough curves using non-linear regression. The artificial neural network (ANN) based model was able to efficaciously predict the column performance using the Levenberg–Marquardt (LM) algorithm. A comparison between the experimental data and model results contributed to a high degree of correlation, specifying that the preliminary information was in good agreement with the ANN predicted data.
Association of NFKB1, NKX2-5, GATA4 and RANKL Gene Polymorphisms with Sporadic Congenital Heart Disease in Greek Patients

Abstract Congenital heart disease (CHD) is a group of structural defects of the heart and the great vessels, and one of the leading causes of death among infants and young adults. Several gene variants are involved in diverse mechanisms of cardiac and vessel development and could thus be considered candidate mutated genes for a congenital heart defect or a specific variant could predispose a person to CHD. In the present study, variants in four such genes are investigated for the first time in a group of young Greek CHD patients: the NFKB1 gene polymorphism (–94ins/ delATTG), rs28362491, NKX2-5 gene polymorphism rs2277923, GATA4 gene polymorphism rs11785481 and RANKL gene polymorphism rs4531631. A total of 43 CHD patients and 100 healthy adults were included in the study. The polymerase chain reaction-restriction fragment length polymorphism (PRC-RFLP) method was used to genotype the aforementioned polymorphisms of NFKB1, NKX2-5, GATA4 and RANKL. The association analysis identified that there was a protective association between CHD and the A allele of rs2277923 polymorphism (p = 0.004). The D allele of the rs28362491 polymorphism is also a likely risk factor for causing CHD (p = 0.006). The differences of the rs4531631 and rs11785481 variant contribution had no statistical significance between the groups (p >0.05). In conclusion, our results revealed that the rs28362491 and rs2277923 gene polymorphisms, but not the rs4531631 and rs11785481 polymorphisms, may contribute to CHD risk in a cohort of Greek CHD patients.
Simultaneously both Expression of LMP-1 and Methylation of E-cadherin: Molecular Biomarker in Stage IV of Nasopharyngeal Carcinoma Patients

Abstract The phenome of E-cadherin gene methylation and the expression of latent membrane protein 1 (LMP-1) gene are associated with nasopharyngeal carcinoma (NPC). In order to determine whether cooperative LMP-1 expression or methylation of E-cadherin could serve as the potential molecule biomarker target for diagnosis and therapy of NPC, a case-control study including 93 NPC biopsy samples and 100 non cancerous nasopharyngeal swab samples were examined, as well as the strength of association among them by the quantitative polymerase chain reaction (qPCR) and nested-methylation-specific PCR methods. The significantly higher frequency of LMP-1 expression and E-cadherin methylation in NPC biopsy samples, accounting for 76.34 and 73.12%, respectively, compared to non cancerous samples, accounting for 0.00 and 30.00%, respectively, were observed. The significant correlation between the LMP-1 expression and E-cadherin methylation in NPC samples was reported. In detail, in the stage IV of NPC, in case of LMP-1-positive samples, 35 of 37 samples (accounting for 94.60%) were positive for methylation of E-cadherin. It was demonstrated that cooperative LMP-1 expression and E-cadherin gene methylation could serve as a molecular biomarker in NPC.
Widespread germline genetic heterogeneity of human ribosomal RNA genes

Polymorphism drives survival under stress and provides adaptability. Genetic polymorphism of ribosomal RNA (rRNA) genes derives from internal repeat variation of this multicopy gene, and from interindividual variation. A considerable amount of rRNA sequence heterogeneity has been proposed but has been challenging to estimate given the scarcity of accurate reference sequences. We identified four rDNA copies on chromosome 21 (GRCh38) with 99% similarity to recently introduced reference sequence KY962518.1. Pairwise alignment of the rRNA coding sequences of these copies showed differences in sequence and length. We customized a GATK bioinformatics pipeline using the four rDNA loci, spanning a total 145 kb, for variant calling. We employed whole genome sequencing (WGS) data from the 1000 Genomes Project phase 3 and analyzed variants in 2,504 individuals from 26 populations. Using the pipeline, we identified a total of 3,790 variant positions. The variants positioned non-randomly on the rRNA gene. Invariant regions included the promoter, early 5’ ETS, 5.8S, ITS1 and certain regions of the 28S rRNA, and large areas of the intragenic spacer. 18S rRNA coding region had very few variants, while a total of 470 variant positions were observed on 28S rRNA. The majority of the 28S rRNA variants located on highly flexible human-expanded rRNA helical folds ES7L and ES27L, suggesting that these represent positions of diversity and are potentially under continuous evolution. These findings provide a genetic view for rRNA heterogeneity and raise the need to functional assess how the 28S rRNA variants affect ribosome functions.
Epithelial-mesenchymal plasticity determines estrogen receptor positive (ER+) breast cancer dormancy and reacquisition of an epithelial state drives awakening

Estrogen receptor α-positive (ER+) breast cancers (BCs) represent more than 70% of all breast cancers and pose a particular clinical challenge because they recur up to decades after initial diagnosis and treatment. The mechanisms governing tumor cell dormancy and latent disease remain elusive due to a lack of adequate models. Here, we compare tumor progression of ER+ and triple-negative (TN) BC subtypes with a clinically relevant mouse intraductal xenografting approach (MIND). Both ER+ and TN BC cells disseminate already during the in situstage. However, TN disseminated tumor cells (DTCs) proliferate at the same rate as cells at the primary site and give rise to macro-metastases. ER+ DTCs have low proliferative indices, form only micro-metastases and lose epithelial characteristics. Expression of CDH1 is decreased whereas the mesenchymal marker VIM and the transcription factors, ZEB1/ZEB2, which control epithelial-mesenchymal plasticity (EMP) are increased. EMP is not detected earlier during ER+ BC development and not required for invasion or metastasis. In vivo, forced transition to the epithelial state through ectopic E-cadherin expression overcomes dormancy with increased growth of lung metastases. We conclude that EMP is essential for the generation of a dormant cell state and the development of latent disease. Targeting exit from EMP is of therapeutic potential.