Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylogenomic patterns of divergence and gene flow detail the evolution of reinforcement and hybrid speciation in Phlox wildflowers

The tree of life is riddled with reticulate evolutionary histories, and some clades, such as the eastern standing Phlox, appear to be hotspots of hybridization. In this group there are two cases of reinforcement and nine hypothesized hybrid species. Given the historical importance of this group for our understanding of plant speciation, the relationships of these taxa and the role of hybridization and gene flow in their diversification require genomic validation. Using phylogenomic analyses, we resolve the evolutionary relationships of the eastern standing Phlox and test hypotheses about if and how hybridization and gene flow were creative forces in their diversification. Our results provide novel resolution of the phylogenetic relationships in this group, including well-supported paraphyly across some species. We identify gene flow during one of two cases of reinforcement and find support for one of the five hypothesized homoploid hybrid speciation events. Additionally, we infer the ancestries of four allotetraploid hybrid species. Hybridization has contributed to diverse evolutionary outcomes within this Phlox group; although, not as extensively as previously hypothesized. This study demonstrates the importance of phylogenomics in confirming hypothesized histories of non-model systems and adds to the growing evidence of interspecific genetic exchange in the generation of biodiversity.
Dynamic mode structure of active turbulence

Dense suspensions of swimming bacteria exhibit chaotic flow patterns that promote the mixing and transport of resources and signalling chemicals within cell colonies. While the importance of active turbulence is widely recognized, the structure and dynamics of the resulting collective flows are the subject of intense investigation. Here, we combine microfluidic experiments with proper orthogonal decomposition (POD) analysis to quantify the dynamical flow structure of this model active matter system under a variety of conditions. In isotropic bulk turbulence, the modal representation shows that the most energetic flow structures dictate the spatio-temporal dynamics across a range of suspension activity levels. In confined geometries, POD analysis illustrates the role of boundary interactions for the transition to bacterial turbulence, and it quantifies the evolution of coherent active structures in externally applied flows. Beyond establishing the physical flow structures under-pinning the complex dynamics of bacterial turbulence, the low-dimensional representation afforded by this modal analysis offers a potential path toward data-driven modelling of active turbulence.
Accelerated mass transfer from frozen thin films during thin-film freeze-drying

Freeze-drying, or lyophilization, is widely used to produce pharmaceutical solids from temperature-sensitive materials but the process is time and energy inefficient. Herein, using E. coli as a model live organism, whose viability in dry powders is highly sensitive to the water content in the powders, we demonstrated that the drying rate of thin-film freeze-drying (TFFD) is significantly higher than that of the conventional shelf freeze-drying, likely because the large total surface area from the loosely stacked frozen thin films and the low thickness of the thin-films enable faster and more efficient mass transfer during freeze-drying. The highly porous nature and high specific surface area of the thin-film freeze-dried powders may have contributed to the faster mass transfer as well. Moreover, we demonstrated that TFFD can be applied to produce dry powders of E. coli and L. acidophilus with minimum bacterial viability loss (i.e., within one log reduction), and the L. acidophilus dry powder is suitable for intranasal delivery. It is concluded that TFFD technology is promising in addressing the time-and cost-inefficient issue of conventional shelf freeze-drying.
Structural Characterization of L-Galactose Dehydrogenase: A Key Enzyme for Vitamin C Biosynthesis

In plants, it is well-known that ascorbic acid (vitamin C) can be synthesized via multiple metabolic pathways but there is still much to be learnt concerning their integration and control mechanisms. Furthermore, the structural biology of the component enzymes has been poorly exploited. Here we describe the first crystal structure for an L-galactose dehydrogenase (SoGDH from spinach), from the D-mannose/L-galactose (Smirnoff Wheeler) pathway which converts L-galactose into L-galactono-1,4-lactone. The kinetic parameters for the enzyme are similar to those from its homologue from camu-camu, a super-accumulator of vitamin C found in the Peruvian amazon. Both enzymes are monomers in solution, have a pH optimum of 7 and their activity is largely unaffected by high concentrations of ascorbic acid, suggesting the absence of a feedback mechanism acting via GDH. Previous reports may have been influenced by changes of the pH of the reaction medium as a function of ascorbic acid concentration. The structure of SoGDH is dominated by a (β/α)8 barrel closely related to aldehyde-keto reductases (AKRs). The structure bound to NAD+ shows that the lack of Arg279 justifies its preference for NAD+ over NADP+, as employed by many AKRs. This favours the oxidation reaction which ultimately leads to ascorbic acid accumulation. When compared with other AKRs, residue substitutions at the C-terminal end of the barrel (Tyr185, Tyr61, Ser59 and Asp128) can be identified to be likely determinants of substrate specificity. The present work contributes towards a more comprehensive understanding of structure-function relationships in the enzymes involved in vitamin C synthesis.
Vibrio tarriae sp. nov., a novel member of the Cholerae clade isolated from across the United States

A number of bacteria with close resemblance to Vibrio cholerae has been isolated over the years by the Centers for Disease Control and Prevention (CDC), which could not be assigned a proper taxonomic designation based on preliminary identification methods. Nine such isolates have been found to share 16S rRNA gene identity exceeding 99% with V. cholerae, yet DNA-DNA hybridization (60.4-62.1%) and average nucleotide identity values (94.4-95.1%) were below the species cut-off, indicating a potentially novel species. Phylogenetic analysis of core genomes places this group of isolates in a monophyletic clade, within the “Cholerae clade,” but distinct from any other species. Extensive phenotypic characterization reveals unique biochemical properties that distinguish this novel species from V. cholerae. Comparative genomic analysis reveals a unique set of siderophore genes, suggesting that iron acquisition strategies could be vital for the divergence of the novel species from a common ancestor with V. cholerae. Based on genetic, phylogenetic, and phenotypic differences observed, we propose these isolates represent a novel species of the genus Vibrio, for which the name Vibrio tarriae sp. nov. is proposed. Strain 2521-89 (= DSM 112461 = CCUG 75318), isolated from lake water, is the type strain. Author Notes The GenBank/EMBL/DDBJ accession number for the 16S rRNA gene sequence of strain 2521-89 is MW773202.1. The genome sequences (genome assemblies) of strains 2521-89, 2523-88, 2015V-1076, 2016V-1018, 2016V-1062, 2017V-1038, 2017V-1070 and 2017V-1124 are deposited under the accession number NZ_CP022353. 1, QKKG01000001.1, QKKH00000000.1, QKKI00000000.1, QKKJ00000000.1, QKKK00000000.1, QKKM00000000.1, and QKKN00000000.1, respectively. All the whole genome sequences are deposited under bioproject ID: PRJNA391152.
Experimental and Theoretical Analysis of Soft Magnetic Materials for Power applications

The efficiency of electrical machines carries a global impact because they fulfill about three-quarters of global electrical energy consumption. Its improvement requires a sound knowledge of energy loss properties of magnetic materials used in the core of electrical machines, especially non-conventional supply conditions, such as non-sinusoidal, high induction, alternating (1-D) and rotating (2-D) flux waveforms that have been posed with the incorporation of new electronic devices and materials in the systems. For these reasons, novel theoretical models and experimental techniques need to be developed to obtain the loss behavior under these complex flux regimes. To address these issues, experimental investigation and theoretical analysis have been carried out in this thesis on different magnetic materials and a wide ensemble of supply conditions. The aim of the theoretical analysis was to fill the gap between the physicists and the engineers by developing simple models that can be applied to compute the loss under realistic supply conditions. This theoretical frame is rooted in the physical principle of the separation of loss and the Statistical Theory of Loss (STL) by which the loss can be separated into the hysteresis, classical, and excess components. The concept of loss separation has been exploited under 1-D flux and extended to 2-D fluxes, where the relations between alternating and rotational losses have been obtained on a number of different materials, this analysis restricted to the region not influenced by skin effect. The proposed theoretical models have been tested by comparing loss figure of different magnetic materials over a wide range of frequencies, induction levels, and conventional or non-conventional supply conditions. To this purpose, loss characterization of non-oriented Fe-(3.2wt \%)Si steels have been performed using a three phase magnetizer able to generate 1-D and 2-D flux patterns, up to saturation magnetization. Fieldmetric and Thermometric methods have been applied at low and very high induction levels. Loss characterization of other non-oriented Fe-Si and low carbon steels have also been performed under 1-D flux at very low and high sinusoidal inductions using Epstein frame, single sheet tester or ring samples, over frequencies ranging from quasi-static conditions up to 10 kHz. Systematic uncertainties have been observed in measurements using a Single Sheet Tester due to MMF drop in flux closing yoke and a compensated Permeameter has been designed to reduce these uncertainties by compensating the MMF drop in the flux closing yoke.
Coupling and heterogeneity modulate pacemaking capability in healthy and diseased two-dimensional sinoatrial node tissue models

Both experimental and modeling studies have attempted to determine mechanisms by which a small anatomical region, such as the sinoatrial node (SAN), can robustly drive electrical conduction in the human heart. However, despite important advances from prior research, important questions remain unanswered. This study aimed to investigate, through mathematical modeling, the role of intercellular coupling and cellular heterogeneity in synchronization and pacemaking within the healthy and diseased SAN. In a multicellular computational model of a monolayer of either human or rabbit SAN cells, simulations revealed that heterogenous cells synchronize their discharge frequency into a unique beating rhythm across a wide range of cellular heterogeneity and intercellular coupling. However, an insightful and unanticipated behavior appears in pathological conditions precipitated by perturbations of certain ionic currents (gCaL = 0.5): an intermediate range of intercellular coupling (900-4000 MΩ) is beneficial to the human SAN automaticity, enabling a very small portion of tissue (3.4%) to drive propagation, which fails with both lower and higher resistances. This protective effect of intercellular coupling and heterogeneity, seen in both human and rabbit tissues, highlights the remarkable resilience of the SAN. Overall, the model here developed allowed insight into the mechanisms of automaticity of the human sinoatrial node. The simulations suggest that certain degrees of gap junctional expressions protect the SAN from ionic perturbations that might be caused by drugs or mutations.
of 12 now-deleted genes of 19 identified and predicted Myb family DNA binding proteins directly involved in rice Magnaporthe oryzae pathogenicity

Proteins with DNA binding Myb domains have been suggested to be involved in regulating development and stress responses in Eukaryotes. Magnaporthe oryzae is considered the most destructive fungal pathogen of rice, and we screened the genome for all genes encoding proteins containing Myb domains since these could be essential during pathogenesis. We found 19 genes Myb1-19 . Only a few have previously been investigated, and one has been shown to be involved in pathogenesis. We tried to delete the other 18 genes and succeeded with 12. RT-qPCR showed that all 19 genes are expressed with different expression profiles during pathogenesis. Only deletions of the genes encoding proteins MoMyb2, MoMyb13, and MoMyb15 showed growth, conidiation, or infection phenotypes, indicating that they are singly needed for successful infection. Even more important, the lack of phenotypes for 9 mutants surprised us, and we extended the analysis to expression co-regulation of all 19 Myb proteins and found 5 co-regulated groups of predicted Myb-domain proteins. We point to likely compensatory regulations of other genes compensating and hiding the effect of many deletions. Further studies of the Myb-family genes are thus of interest since revealing their functions with a possible effect on pathogenicity could be targeted for future measures to control M. oryzae in rice.
Opponent Learning with Different Representations in the Cortico-Basal Ganglia Circuits

Abstract The direct and indirect pathways of the basal ganglia (BG) have been suggested to learn mainly from positive and negative feedbacks, respectively. Since these pathways unevenly receive inputs from different cortical neuron types and/or regions, they may preferentially use different state/action representations. We explored whether such a combined use of different representations, coupled with different learning rates from positive and negative reward prediction errors (RPEs), has computational benefits. We modeled animal as an agent equipped with two learning systems, each of which adopted individual representation (IR) or successor representation (SR) of states. With varying the combination of IR or SR and also the learning rates from positive and negative RPEs in each system, we examined how the agent performed in a dynamic reward navigation task. We found that combination of SR-based system learning mainly from positive RPEs and IR-based system learning mainly from negative RPEs could achieve a good performance in the task, as compared with other combinations. In such a combination of appetitive SR-based and aversive IR-based systems, both systems show activities of comparable magnitudes with opposite signs, consistent with the suggested profiles of the two BG pathways. Moreover, the architecture of such a combination provides a novel coherent explanation for the functional significance and underlying mechanism of diverse findings about the cortico-BG circuits. These results suggest that particularly combining different representations with appetitive and aversive learning could be an effective learning strategy in certain dynamic environments, and it might actually be implemented in the cortico-BG circuits.
Variation in ubiquitin system genes creates substrate-specific effects on proteasomal protein degradation

Ubiquitin-proteasome system (UPS) protein degradation regulates protein abundance and eliminates mis-folded and damaged proteins from eukaryotic cells. Variation in UPS activity influences numerous cellular and organismal phenotypes. However, to what extent such variation results from individual genetic differences is almost entirely unknown. Here, we developed a statistically powerful mapping approach to characterize the genetic basis of variation in UPS activity. Using the yeast Saccharomyces cerevisiae, we systematically mapped genetic influences on the N-end rule, a UPS pathway that recognizes N-degrons, degradation-promoting signals in protein N-termini. We identified 149 genomic loci that influence UPS activity across the complete set of N-degrons. Resolving four loci to individual causal nucleotides identified regulatory and missense variants in ubiquitin system genes whose products process (NTA1), recognize (UBR1 and DOA10), and ubiquitinate (UBC6) cellular proteins. Each of these genes contained multiple causal variants and several individual variants had substrate-specific effects on UPS activity. A cis-acting promoter variant that modulates UPS activity by altering UBR1 expression also alters the abundance of 36 proteins without affecting levels of the corresponding mRNAs. Our results demonstrate that natural genetic variation shapes the full sequence of molecular events in protein ubiquitination and implicate genetic influences on the UPS as a prominent source of post-translational variation in gene expression.
Prediction of Fertilization Disorders in the In Vitro Fertilization/Intracytoplasmic Sperm Injection: A Retrospective Study of 106,728 Treatment Cycles

Purpose This study aimed to develop a risk prediction of fertilization disorders during the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods A retrospective study was performed with 106,728 fresh embryo IVF/ICSI cycles from 2009 to 2019. Basic characteristics of patients, clinical treatment data, and laboratory parameters were involved. The associations between the selected variables and risks for low fertilization rate (LFR) and total fertilization failure (TFF) were investigated. Ordinal logistic regression and the receiver operating characteristic curves (ROCs) were used to construct and evaluate the prediction models. Results A total of 97,181 controls, 4,343 LFR and 5,204 TFF cases were involved in this study. The model based on clinical characteristics (the ages of the couples, women’s BMI, types of infertility, ART failure history, the diminished ovarian reserve, sperm quality, insemination method, and the number of oocytes retrieved) had an AUC of 0.743 for TFF. The laboratory model showed that primary infertility, ART failure history, minimal-stimulation cycle/natural cycle, numbers of oocyte retrieved < 5, IVF, and Anti-Mullerian hormone (AMH) level < 1.1ng/ml are predictors of TFF, with an AUC of 0.742. Conclusion We established a clinical and a laboratory prediction model for LFR/TFF. Both of the models showed relatively high AUCs.
Phytotoxic Azaphilones From the Mangrove-Derived Fungus Penicillium sclerotiorum HY5

Mangrove is a unique marine ecosystem growing in the intertidal zone of tropical and subtropical coast, with the characteristics of hypoxia tolerance, high salinity, and high humidity. In order to discover novel leading compounds with potent phytotoxicity, seven pairs of azaphilones E/Z isomers, isochromophilone H (1a/1b), sclerotiorins A and B (2a/2b and 3a/3b), ochlephilone (4a/4b), isochromophilone IV (5a/5b), isochromophilone J (6a/6b), and isochromophilone I (7a/7b), were isolated from the culture broth of the mangrove-derived fungus, the Penicillium sclerotiorum HY5, by various chromatographic methods. Among them, 1a, 1b, 2a, 3a, 4a, 5a, 6a, and 6b were new compounds. Their chemical structures and absolute configurations were elucidated based on high resolution electrospray ionization mass spectroscopy (HRESIMS), 1D/2D nuclear magnetic resonance (NMR) spectroscopic analysis, and comparisons of electronic circular dichroism (ECD) data. Compounds 3, 4, and 7 exhibited potent phytotoxicity against the growth of radicle and plumule on Amaranthus retroflexus L. , with EC50 values ranging from 234.87 to 320.84 μM, compared to the positive control glufosinate-ammonium, with EC50 values of 555.11 μM for radicle, and 656.04 μM for plumule. Compounds 4 and 7 also showed inhibitory effects on the growth of velvetleaf (Abutilon theophrasti Medikus), with EC50 values ranging from 768.97 to 1,201.52 μM. This study provides new leading compounds for the research and development of marine-derived bioherbicides. Graphical Abstract Representative phytotoxic azaphilones from Penicillium sclerotiorum HY5.
ENTT/ENTTR: A Family of Improved Emerging NVM-Based Trojan Triggers and Resets

Hardware Trojans in Integrated Circuits (ICs), that are inserted as hostile modifications in the design phase and/or the fabrication phase, are a security threat since the semiconductor manufacturing process is increasingly becoming globalized. These Trojans are devised to stay hidden during standard structural and functional testing procedures and only activate under pre-determined rare conditions (e.g., after a large number of clock cycles or the assertion of an improbable net). Once triggered, they can deliver malicious payloads (e.g., denial-of-service and information leakage attacks). Current literature identifies a collection of logic Trojans (both trigger circuits and payloads), but minimal research exists on memory Trojans despite their high feasibility. Emerging Non-Volatile Memories (NVMs), such as Resistive RAM (RRAM), have special properties such as non-volatility and gradual drift in bitcell resistance under a pulsing voltage input that make them prime targets to deploy hardware Trojans. In this paper, we present two delay-based and two voltage-based Trojan triggers using emerging NVM (ENTT) by utilizing RRAM’s resistance drift under a pulsing voltage input. Simulations show that ENTTs can be triggered by reading/writing to a specific memory address N times (N could be 2,500–3,500 or a different value for each ENTT design). Since the RRAM is non-volatile, address accesses can be intermittent and therefore stay undetected from system-level techniques that can identify continuous hammering as a possible security threat. We also present three reset techniques to de-activate the triggers. The resulting static/dynamic power overhead and maximum area overhead incurred by the proposed ENTTs are 104.24 μW/0.426 μW and 9.15 μm2, respectively in PTM 65 nm technology. ENTTs are effective against contemporary Trojan detection techniques and system level protocols. We also propose countermeasures to detect ENTT during the test phase and/or prevent fault-injection attacks during deployment.
Antitumor Effect of Simvastatin in Combination With DNA Methyltransferase Inhibitor on Gastric Cancer via GSDME-Mediated Pyroptosis

Gasdermin E (GSDME) is one of the executors of pyroptosis, a type of programmed lytic cell death, which can be triggered by caspase-3 activation upon stimulation. Silenced GSDME expression due to promoter hypermethylation is associated with gastric cancer (GC), which is confirmed in the present study by bioinformatics analysis and methylation-specific PCR (MSP) test of GC cell lines and clinical samples. GC cell lines and mouse xenograft models were used to investigate the pyroptosis-inducing effect of the common cholesterol-depleting, drug simvastatin (SIM), allied with upregulating GSDME expression by doxycycline (DOX)- inducible Tet-on system or DNA methyltransferase inhibitor 5-Aza-2′-deoxycytidine (5-Aza-CdR). Cell viability assessment and xenograft tumour growth demonstrated that the tumour inhibition effects of SIM can be enhanced by elevated GSDME expression. Morphological examinations and assays measuring lactate dehydrogenase (LDH) release and caspase-3/GSDME protein cleavage underlined the stimulation of pyroptosis as an important mechanism. Using short hairpin RNA (shRNA) knockdown of caspase-3 or GSDME, and caspase-3-specific inhibitors, we provided evidence of the requirement of caspase-3/GSDME in the pyroptosis process triggered by SIM. We conclude that reactivating GSDME expression and thereby inducing cancer cell-specific pyroptosis could be a potential therapeutic strategy against GC.