Miracle-dz/UniFAR-FTUs huggingface dataset:
Parameter estimation and genetic evaluation of milk production traits from France and Germany with a multi-trait MACE model

A multi-trait MACE (MT-MACE) model was implemented for international bull comparison using daughter yield deviations of bulls. This MT-MACE model can better utilise the information derived from national genetic evaluations with a multi-trait model than the current single trait MACE (STMACE) model. Full pedigree information of bulls was used via sire and dam relationship. Milk production data from France and Germany were used to validate this MT-MACE model. Preconditioned conjugate gradients algorithm was applied to solve the equations together with the iteration on data technique. An approximate REML method specially developed for pre-corrected records was implemented to estimate genetic correlations between the two countries. Estimated genetic correlations of random regression coefficients of the German test day model with French lactation milk yields were high, resulting in genetic correlations, on a 305-day lactation basis, of 0.834, 0.937, 0.960, and 0.947 for first, second, third and combined lactation, respectively. Special test evaluations using zero genetic correlations were compared to the national evaluations for the bulls. Very high proof correlations and small proof differences confirmed the overall quality of the MTMACE model. However, the MT-MACE model gave proofs different from national proofs for the youngest bulls that have few daughters with short or missing lactations. The use of the data from bull dams did not lead to notable improvement in the international bull evaluations. With the estimated genetic correlations, a MT-MACE genetic evaluation was performed. As expected, local bulls had very high correlations between their national and international proofs, whereas the proof correlations were lower for common bulls due to the data from the other country. The correlations between national and international proofs increased with the number of daughters and with the average lactation length of daughters. Bulls with official national proofs had higher correlations than bulls with unofficial national proofs, and foreign proven bulls had lower correlations between national and international proofs than local bulls. The MT-MACE model can be extended to cow evaluation as well as to other traits.
Targeting microbiota-host interactions with resveratrol on cancer: Effects and potential mechanisms of action

Abstract Resveratrol (RSV) is a natural polyphenolic compound detected in grapes, berries, and red wine. The anticancer activities of RSV have been observed in vivo and in vitro studies. However, the pharmacology mechanism of RSV is confusing due to its low bioavailability. According to studies of the metabolic characteristics of RSV, the gut intestine is a crucial site of its health benefits. Dietary RSV exhibits a profound effect on the gut microbiota structure and metabolic function. In addition, emerging evidence demonstrates a protective effect of RSV metabolites against carcinogenesis. Therefore, to better understand the anticancer mechanisms of dietary RSV, it is vital to evaluate the role of RSV-microbiota-host interactions in cancer therapy. In this review, we summarized significant findings on the anticancer activities of RSV based on epidemiological, experimental and clinical studies involved in investigating the metabolic characteristics and the traditional anticancer mechanisms of RSV. Special attention is given to the putative mechanisms involving microbiota-host interactions, such as the modulation of gut microecology and the anticancer effects of RSV metabolites. The changes in microbiota-host interactions after RSV supplementation play vital roles in cancer prevention and thus offering a new perspective on nutritional interventions to treat cancer.
Hypolipogenic effects of Icariside E4 via phosphorylation of AMPK and inhibition of MID1IP1 in HepG2 cells

Though icariside E4 (IE4) is known to have anti‐noceptive, anti‐oxidant, anti‐Alzheimer and anti‐inflammatory effects, there was no evidence on the effect of IE4 on lipid metabolism so far. Hence, the hypolipogenic mechanism of IE4 was investigated in HepG2 hepatocellular carcinoma cells (HCCs) in association with MID1 Interacting Protein 1(MID1IP1) and AMPK signaling. Here, IE4 did not show any toxicity in HepG2 cells, but reduced lipid accumulation in HepG2 cells by Oil Red O staining. MID1IP1 depletion decreased the expression of SREBP‐1c and fatty acid synthase (FASN) and induced phosphorylation of ACC in HepG2 cells. Indeed, IE4 activated phosphorylation of AMPK and ACC and inhibited the expression of MID1IP1 in HepG2 cells. Furthermore, IE4 suppressed the expression of SREBP‐1c, liver X receptor‐α (LXR), and FASN for de novo lipogenesis in HepG2 cells. Interestingly, AMPK inhibitor compound C reversed the ability of IE4 to reduce MID1IP1, SREBP‐1c, and FASN and activate phosphorylation of AMPK/ACC in HepG2 cells, indicating the important role of AMPK/ACC signaling in IE4‐induced hypolipogenic effect. Taken together, these findings suggest that IE4 has hypolipogenic potential in HepG2 cells via activation of AMPK and inhibition of MID1IP1 as a potent candidate for treatment of fatty liver disease.
Chemical inhibition of the auxin inactivation pathway uncovers the roles of metabolic turnover in auxin homeostasis

Significance The phytohormone auxin, indole-3-acetic acid (IAA), is a key regulator in plant growth. The intracellular auxin level is precisely regulated in response to developmental and environmental cues. Auxin inactivation plays an important role in auxin homeostasis. Auxin is predominantly inactivated by conjugating it to amino acids—reactions catalyzed by the GH3 enzymes. Auxin rapidly induces the expression of auxin-inactivating GH3 family genes, thus forming a negative feedback loop for maintaining IAA levels. Using kakeimide, a selective inhibitor for auxin-inactivating GH3 enzymes, we demonstrate that auxin homeostasis is dynamically maintained by the rapid turnover of IAA (about 10 min) and that the GH3 pathway plays a central role in auxin inactivation in various plant species.
Structural insight and characterization of human Twinkle helicase in mitochondrial disease

Significance Twinkle, the helicase in the mitochondrial DNA replisome, unwinds DNA in a 5′–3′ direction and improves the efficiency of the DNA polymerase and replication. To date, there are no atomic models of Twinkle and it is the last member of the mitochondrial DNA replisome to be structurally characterized. Given that mutations in Twinkle helicase cause clinical effects, mapping the location of these residues is critical to understanding Twinkle-dependent mitochondria disease phenotypes. Here, we utilize cryo-electron microscopy to determine a full-length structure of Twinkle W315L in two oligomeric states. In addition to defining the location of the clinical mutations, we investigate flexibility at the interface and propose a model for the clinical effects of W315L.
Co-occurring ADHD symptoms in autistic adults are associated with less independence in daily living activities and lower subjective quality of life

Outcomes for autistic adults are generally poor across multiple foundational metrics, including activities of daily living and quality of life. Co-occurring psychiatric conditions contribute to these poor outcomes. Attention-deficit/hyperactivity disorder is one of the most common co-occurring conditions among autistic individuals; however, we know little about the association of attention-deficit/hyperactivity disorder symptoms with autistic adult outcomes. A total of 724 autistic adults (18–83 years; 58% female) recruited via Simons Foundation Powering Autism Research (SPARK) Research Match completed questionnaires on demographics, co-occurring attention-deficit/hyperactivity disorder symptoms, activities of daily living, and subjective quality of life. After controlling for age, birth-sex, socioeconomic status, and autistic traits, attention-deficit/hyperactivity disorder symptoms explained an additional 2%−10% of variance across activities of daily living and all domains of subjective quality of life. This is the first study to demonstrate that autistic adults who rated themselves as having more attention-deficit/hyperactivity disorder symptoms also rated themselves as less independent in activities of daily living and experiencing a lower subjective quality of life. These findings highlight that additional research and better supports for co-occurring attention-deficit/hyperactivity disorder symptoms may be critical to enhancing independence and quality of life for autistic adults. Lay abstract Outcomes for autistic adults are generally poor, including activities of daily living and self-ratings of quality of life. Co-occurring psychiatric conditions contribute to these poor outcomes. Attention-deficit/hyperactivity disorder is one of the most common co-occurring conditions in autistic individuals. However, we know little about the association between attention-deficit/hyperactivity disorder symptoms and outcomes in autistic adults. A total of 724 autistic adults (18–83 years; 58% female) recruited from the Simons Foundation Powering Autism Research participant registry completed questionnaires on demographics, co-occurring psychiatric conditions, activities of daily living, and subjective quality of life. Autistic adults who rated themselves as having more attention-deficit/hyperactivity disorder symptoms also rated themselves as having less independence in activities of daily living and a lower quality of life. This is the first study to show these relationships in autistic adults. These findings highlight that additional research and better supports for co-occurring attention-deficit/hyperactivity disorder symptoms may be critical to improving independence and quality of life for autistic adults.
P38α MAPK is a gatekeeper of uterine progesterone responsiveness at peri-implantation via Ube3c-mediated PGR degradation

Significance Uterine receptivity is indispensable for normal embryo implantation. Uterine receptivity is mainly dominated by ovarian estrogen and progesterone through their respective nuclear receptors ER and PR, expressed in the endometrium. However, how their homeostasis is maintained at protein level has been less studied. Here, we showed that the deficiency of uterine Mitogen-activated protein kinase p38 alpha (P38α) derailed normal uterine receptivity establishment, mainly due to the significant down-regulation of the PR protein rather than its transcript in the uterine stromal cells. Further exploration uncovered that the ubiquitin ligase Ube3c was afforded responsibility for PR polyubiquitination and protein degradation and that P38α could phosphorylate the Ube3c to restrain PR protein polyubiquitination. Our finding revealed a regulation manner for uterine progesterone responsiveness.
Admissibility analysis and control synthesis for switched linear singular systems

The problem of admissibility analysis and control synthesis of discrete-time switched linear singular (SLS) systems for arbitrary switching laws is solved. By using the switched Lyapunov function approach, some new sufficient conditions under which the SLS system is admissible for arbitrary switching laws are derived in terms of linear matrix inequalities (LMIs). Based on the admissibility results, control synthesis is then to design switched state feedback and static output feedback controllers, guaranteeing that the resulting closed-loop system is admissible. The presented results can be viewed as the extensions of previous works on switched Lyapunov function approach from the regular switched systems to singular switched cases. Examples are provided to demonstrate the reduced conservatism and effectiveness of the proposed conditions.
Heliosphere in the magnetized local interstellar medium' Results of a three-dimensional MHD

The results of a three-dimensional adaptive magnetohydrodynamic (MHD) model of the interaction of a magnetized solar wind with a magnetized very local interstellar medium in the presence of neutral interstellar hydrogen are presented. The interplanetary magnetic field is approximated by the Parker spiral, and the direction of the interstellar magnetic field is taken to be arbitrary. It is demonstrated that magnetic field interaction has a very pronounced effect on the structure of the global heliosphere. In particular, it is shown that the interaction of the interstellar wind with the shocked solar wind significantly depends on the direction of the interstellar magnetic field. This effect is mainly manifested in the distances to the heliospheric boundaries and the shape of the heliosphere. Depending on the orientation of the interstellar magnetic field the upstream location of the termination shock is expected to be at 80 ± 10 AU. The termination shock is predicted to be weak in agreement with the available body of observations. It is found that under quiet solar conditions the spiral structure of the interplanetery magnetic field remains imprinted in the solar wind far beyond the termination shock. Numerical simulations indicate that magnetic fields have a stabilizing effect on the heliopause.
Complete Genome Sequences of Three Mycoplasma gallisepticum 6/85-like Isolates

Control of Mycoplasma gallisepticum infection can be accomplished through vaccination. However, virulent field strains with genetic markers identical to vaccine strains have been identified. Here, we report the sequencing of three field isolates with genetic markers identical to the M. gallisepticum 6/85 vaccine strain. ABSTRACT Control of Mycoplasma gallisepticum infection can be accomplished through vaccination. However, virulent field strains with genetic markers identical to vaccine strains have been identified. Here, we report the sequencing of three field isolates with genetic markers identical to the M. gallisepticum 6/85 vaccine strain.
Chr21 protein–protein interactions: enrichment in proteins involved in intellectual disability, autism, and late-onset Alzheimer’s disease

A large-scale (82) yeast two-hybrid screen focusing on chromosome 21 proteins and their direct interactors revealed enrichment in proteins linked to synapse plasticity, autism, and Alzheimer’s disease. Down syndrome (DS) is caused by human chromosome 21 (HSA21) trisomy. It is characterized by a poorly understood intellectual disability (ID). We studied two mouse models of DS, one with an extra copy of the Dyrk1A gene (189N3) and the other with an extra copy of the mouse Chr16 syntenic region (Dp(16)1Yey). RNA-seq analysis of the transcripts deregulated in the embryonic hippocampus revealed an enrichment in genes associated with chromatin for the 189N3 model, and synapses for the Dp(16)1Yey model. A large-scale yeast two-hybrid screen (82 different screens, including 72 HSA21 baits and 10 rebounds) of a human brain library containing at least 107 independent fragments identified 1,949 novel protein–protein interactions. The direct interactors of HSA21 baits and rebounds were significantly enriched in ID-related genes (P-value < 2.29 × 10−8). Proximity ligation assays showed that some of the proteins encoded by HSA21 were located at the dendritic spine postsynaptic density, in a protein network at the dendritic spine postsynapse. We located HSA21 DYRK1A and DSCAM, mutations of which increase the risk of autism spectrum disorder (ASD) 20-fold, in this postsynaptic network. We found that an intracellular domain of DSCAM bound either DLGs, which are multimeric scaffolds comprising receptors, ion channels and associated signaling proteins, or DYRK1A. The DYRK1A-DSCAM interaction domain is conserved in Drosophila and humans. The postsynaptic network was found to be enriched in proteins associated with ARC-related synaptic plasticity, ASD, and late-onset Alzheimer’s disease. These results highlight links between DS and brain diseases with a complex genetic basis.
Flash drought early warning based on the trajectory of solar-induced chlorophyll fluorescence

Significance Flash drought has become increasingly common and threatens global food security. To help proactively manage and prevent the devastating effects of flash drought, we propose a flash drought early warning approach based on unusually slow increases or unusually fast decreases of a spaceborne proxy for plant photosynthesis, the solar-induced chlorophyll fluorescence (SIF). Relative to the operational US Drought Monitor, the SIF-based approach provides a lead time of 2 wk to 2 mo for flash drought onset and several weeks for drought recovery. It shows great potential to support the development of a global, agriculturally relevant early warning system that will help protect human food security, especially for regions where other drought indices are limited by sparse hydrometeorological data.
(cid:1) -Glucuronidase as a Sensitive and Versatile Reporter in Actinomycetes (cid:1)

Here we describe a versatile and sensitive reporter system for actinomycetes that is based on gusA , which encodes the (cid:1) -glucuronidase enzyme. A series of gusA- containing transcriptional and translational fusion vectors were constructed and utilized to study the regulatory cascade of the phenalinolactone biosynthetic gene cluster. Furthermore, these vectors were used to study the efﬁciency of translation initiation at the ATG, GTG, TTG, and CTG start codons. Surprisingly, constructs using a TTG start codon showed the best activity, whereas those using ATG or GTG were approximately one-half or one-third as active, respectively. The CTG fusion showed only 5% of the activity of the TTG fusion. A suicide vector, pKGLP2, carrying gusA in its backbone was used to visually detect merodiploid formation and resolution, making gene targeting in actino- mycetes much faster and easier. Three regulatory genes, plaR1 , plaR2 , and plaR3 , involved in phenalinolactone biosynthesis were efﬁciently replaced with an apramycin resistance marker
EFFECT OF SOME CHEMICAL ADDITIVES ON THE POTENCY OF BACILLUS THURINGIENSIS AGAINST THE COTTON LEAFWORM, SPODOPTERA LITTORALIS

Field experiments were conducted to investigate the effect of inorganic salts, zinc sulphate (ZnSO 4 ), Calcium carbonate (Ca CO 3 ) and Calcium oxide (Ca O) on potentiation of Bacillus thuringiensis (Bt) formulations against the 2 nd instar larvae of Spodoptera littoralis. Physico-chemical properties, suspensibility, surface tension and pH were also studied under field dilution rate (200 L water/ fed.). The results indicated that the tested inorganic salts decreased surface tension and increased PH value of candidate B.t. The initial and residual activity of the tested B.t, Dipel 2X, Protecto and Agerin can be markedly increased by using ZnSO 4 , CaCO 3 and Ca O at 0.1% in combination with their full recommended rates. Zinc sulphate was the most effective salt in increasing both initial and residual effect of Dipel 2X, Protecto and Agerin,. Zinc sulphate (ZnSO 4 ) also increased the residual half life value (RL50) of Diple 2X, Protecto and Agerin from 4.5, 3.6 and 3.2 days to 6.25, 7.0 and 7.0 days, respectively. The population of Spodoptera littoralis larvae were also reduced after 7 days after application. The addition of such salts decrease surface tension of Bt preparations, then increase their wettability and spreading on treated plant leaves, and increase their initial and residual activity. Also, to change pH of the gut, being more alkaline and thus enhancing the endotoxin breakdown and release of toxic fragments.
Institutional Determinants of the Prevalence of Start-ups and High-Growth Firms: Evidence from Sweden *

: The purpose of this study is to identify key institutional determinants of firm emergence and growth. We do this using various types of data from Sweden. A characterization of a number of institutions and policy measures shows that they are likely to have contributed to an environment that discourages entrepreneurial activity and firm growth. Aspects dealt with include: missing arenas for entrepreneurship in the care sectors and for household-related services, taxation of entrepreneurial income, incentives for wealth accumulation, wage-setting institutions and labor market regulations. Using original data, we provide evidence of a low prevalence of nascent entrepreneurs and a small net employment contribution by high-growth firms. We admit that indisputable evidence for the effects of institutional arrangements is almost impossible to establish. However, the consistency of our theoretical arguments and empirical data makes a strong case for the notion that the Swedish case illustrates the costs of giving too little weight to economic renewal in policy making.
Edinburgh Explorer Dominance of virus over host factors in cross-species activation of human cytomegalovirus early gene expression

Human cytomegalovirus (HCMV) exhibits a highly restricted host range. In this study, we sought to examine the relative signiﬁcance of host and viral factors in activating early gene expression of the HCMV UL54 (DNA polymerase) promoter in murine cells. Appropriate activation of the UL54 promoter at early times is essential for viral DNA replication. To study how the HCMV UL54 promoter is activated in murine cells, a transgenesis system based on yeast artiﬁcial chromosomes (YACs) was established for HCMV. A 178-kb YAC, containing a subgenomic fragment of HCMV encompassing the majority of the unique long (UL) region, was constructed by homologous recombination in yeast. This HCMV YAC backbone is defective for viral growth and lacks the major immediate-early (IE) gene region, thus permitting the analysis of essential cis -acting sequences when complemented in trans . To quantitatively measure the level of gene expression, we generated HCMV YACs containing a luciferase reporter gene inserted downstream of either the UL54 promoter or, as a control for late gene expression, the UL86 promoter, which directs expression of the major capsid protein. To determine the early gene activation pathway, point mutations were introduced into the inverted repeat 1 (IR1) element of the UL54 promoter of the HCMV YAC. In the transgenesis experiments, HCMV YACs and derivatives generated in yeast were introduced into NIH 3T3 murine cells by polyethylene glycol-mediated fusion. We found that infection of YAC, but not plasmid, transgenic lines with HCMV was sufﬁcient to fully recapitulate the UL54 expression program at early times of infection, indicating the importance of remote regulatory elements in inﬂuencing regulation of the UL54 promoter. Moreover, YACs containing a mutant IR1 in the UL54 promoter led to reduced ( ; 30-fold) reporter gene expression levels, indicating that HCMV major IE gene activation of the UL54 promoter is fully permissive in murine cells. In comparison with HCMV, infection of YAC transgenic NIH 3T3 lines with murine cytomegalovirus (MCMV) resulted in lower (more than one order of magnitude) efﬁciency in activating UL54 early gene expression. MCMV is therefore not able to fully activate HCMV early gene expression, indicating the signiﬁcance of virus over host determinants in the cross-species activation of key early gene promoters. Finally, these studies show that YAC transgenesis can be a useful tool in functional analysis of viral proteins and control of gene expression for large viral genomes.