Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Prediction and Genome-Wide Association Studies of Flour Yield and Alveograph Quality Traits Using Advanced Winter Wheat Breeding Material

Use of genetic markers and genomic prediction might improve genetic gain for quality traits in wheat breeding programs. Here, flour yield and Alveograph quality traits were inspected in 635 F6 winter wheat breeding lines from two breeding cycles. Genome-wide association studies revealed single nucleotide polymorphisms (SNPs) on chromosome 5D significantly associated with flour yield, Alveograph P (dough tenacity), and Alveograph W (dough strength). Additionally, SNPs on chromosome 1D were associated with Alveograph P and W, SNPs on chromosome 1B were associated with Alveograph P, and SNPs on chromosome 4A were associated with Alveograph L (dough extensibility). Predictive abilities based on genomic best linear unbiased prediction (GBLUP) models ranged from 0.50 for flour yield to 0.79 for Alveograph W based on a leave-one-out cross-validation strategy. Predictive abilities were negatively affected by smaller training set sizes, lower genetic relationship between lines in training and validation sets, and by genotype–environment (G×E) interactions. Bayesian Power Lasso models and genomic feature models resulted in similar or slightly improved predictions compared to GBLUP models. SNPs with the largest effects can be used for screening large numbers of lines in early generations in breeding programs to select lines that potentially have good quality traits. In later generations, genomic predictions might be used for a more accurate selection of high quality wheat lines.
Local and Global Changes in Brain Metabolism during Deep Brain Stimulation for Obsessive-Compulsive Disorder

Recent approaches have suggested that deep brain stimulation (DBS) for obsessive-compulsive disorder relies on distributed networks rather than local brain modulation. However, there is insufficient data on how DBS affects brain metabolism both locally and globally. We enrolled three patients with treatment-refractory obsessive-compulsive disorder with ongoing DBS of the bilateral ventral capsule/ventral striatum. Patients underwent resting-state 18F-fluorodeoxyglucose and positron emission tomography in both stimulation ON and OFF conditions. All subjects showed relative hypometabolism in prefronto-basal ganglia-thalamic networks compared to a healthy control cohort when stimulation was switched OFF. Switching the stimulation ON resulted in differential changes in brain metabolism. Locally, volumes of activated tissue at stimulation sites (n = 6) showed a significant increase in metabolism during DBS ON compared to DBS OFF (Mean difference 4.5% ± SD 2.8; p = 0.012). Globally, differential changes were observed across patients encompassing prefrontal increase in metabolism in ON vs. OFF condition. Bearing in mind limitations of the small sample size, we conclude that DBS of the ventral capsule/ventral striatum for obsessive-compulsive disorder increases brain metabolism locally. Across distributed global networks, DBS appears to exert differential effects, possibly depending on localization of stimulation sites and response to the intervention.
Plasma Membrane-Associated Restriction Factors and Their Counteraction by HIV-1 Accessory Proteins

The plasma membrane is a site of conflict between host defenses and many viruses. One aspect of this conflict is the host’s attempt to eliminate infected cells using innate and adaptive cell-mediated immune mechanisms that recognize features of the plasma membrane characteristic of viral infection. Another is the expression of plasma membrane-associated proteins, so-called restriction factors, which inhibit enveloped virions directly. HIV-1 encodes two countermeasures to these host defenses: The membrane-associated accessory proteins Vpu and Nef. In addition to inhibiting cell-mediated immune-surveillance, Vpu and Nef counteract membrane-associated restriction factors. These include BST-2, which traps newly formed virions at the plasma membrane unless counteracted by Vpu, and SERINC5, which decreases the infectivity of virions unless counteracted by Nef. Here we review key features of these two antiviral proteins, and we review Vpu and Nef, which deplete them from the plasma membrane by co-opting specific cellular proteins and pathways of membrane trafficking and protein-degradation. We also discuss other plasma membrane proteins modulated by HIV-1, particularly CD4, which, if not opposed in infected cells by Vpu and Nef, inhibits viral infectivity and increases the sensitivity of the viral envelope glycoprotein to host immunity.
Three-Dimensional Modeling of Avascular Tumor Growth in Both Static and Dynamic Culture Platforms

Microfluidic cell culture platforms are ideal candidates for modeling the native tumor microenvironment because they can precisely reconstruct in vivo cellular behavior. Moreover, mathematical modeling of tumor growth can pave the way toward description and prediction of growth pattern as well as improving cancer treatment. In this study, a modified mathematical model based on concentration distribution is applied to tumor growth in both conventional static culture and dynamic microfluidic cell culture systems. Apoptosis and necrosis mechanisms are considered as the main inhibitory factors in the model, while tumor growth rate and nutrient consumption rate are modified in both quiescent and proliferative zones. We show that such modification can better predict the experimental results of tumor growth reported in the literature. Using numerical simulations, the effects of the concentrations of the nutrients as well as the initial tumor radius on the tumor growth are investigated and discussed. Furthermore, tumor growth is simulated by taking into account the dynamic perfusion into the proposed model. Subsequently, tumor growth kinetics in a three-dimensional (3D) microfluidic device containing a U-shaped barrier is numerically studied. For this case, the effect of the flow rate of culture medium on tumor growth is investigated as well. Finally, to evaluate the impact of the trap geometry on the tumor growth, a comparison is made between the tumor growth kinetics in two frequently used traps in microfluidic cell culture systems, i.e., the U-shaped barrier and microwell structures. The proposed model can provide insight into better predicting the growth and development of avascular tumor in both static and dynamic cell culture platforms.
Polyphenolic Characterization, Antioxidant, and Cytotoxic Activities of Mangifera indica Cultivars from Costa Rica

The phenolic profile of skin and flesh from Manifera indica main commercial cultivars (Keitt and Tommy Atkins) in Costa Rica was studied using ultra performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-ESI-MS) on enriched phenolic extracts. A total of 71 different compounds were identified, including 32 gallates and gallotannins (of different polymerization degree, from galloyl hexose monomer up to decagalloyl hexoses and undecagalloyl hexoses); seven hydroxybenzophenone (maclurin and iriflophenone) derivatives, six xanthonoids (including isomangiferin and mangiferin derivatives); 11 phenolic acids (hydroxybenzoic and hydroxycinnamic acid derivatives); and eight flavonoids (rhamnetin and quercetin derivatives). The findings for T. Atkins skin constitute the first report of such a high number and diversity of compounds. Also, it is the first time that the presence of gallotannin decamers and undecamers are reported in the skin and flesh of Keitt cultivar and in T. Atkins skins. In addition, total phenolic content (TPC) was measured with high values especially for fruits’ skins, with a TPC of 698.65 and 644.17 mg gallic acid equivalents/g extract, respectively, for Keitt and T. Atkins cultivars. Antioxidant potential using 2,2-diphenyl-1-picrylhidrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) methods were evaluated, with T. Atkins skin showing the best values for both DPPH (IC50 = 9.97 µg/mL) and ORAC (11.02 mmol TE/g extract). A significant negative correlation was found for samples between TPC and DPPH antioxidant values (r = −0.960, p < 0.05), as well as a significant positive correlation between TPC and ORAC (r = 0.910, p < 0.05) and between DPPH and ORAC antioxidant methods (r = 0.989, p < 0.05). Also, cytotoxicity was evaluated in gastric adenocarcinoma (AGS), hepatocarcinoma (HepG2), and colon adenocarcinoma (SW620), with T. Atkins skin showing the best results (IC50 = 138–175 µg/mL). Finally, for AGS and SW 620 cell lines particularly, a high significant negative correlation was found between cytotoxic activity and gallotannins (r = −0.977 and r = −0.940, respectively) while for the HepG2 cell line, the highest significant negative correlation was found with xanthonoids compounds (r = −0.921).
Towards a standard model of musical improvisation

Musical improvisation is a sophisticated cognitive process that combines creativity, goal‐directed action, sensory monitoring and social interaction. With a renewed interest in quantifying creative processes facilitated by recent advances in neuroimaging technology, musical improvisation has emerged as an ideal paradigm to study creativity. However, many studies isolate the top‐down processes related to creativity from those related to production and auditory perception, leaving the question of how creative behaviours integrate sensory information with higher cognitive processes unanswered. The bottom‐up neural correlates of music perception have been extensively quantified, comprising networks for auditory processing and parsing semantic and syntactic content. In studies of spontaneously generated music and domain‐general creativity, executive control and goal‐directed movement networks are added to the perceptual foundation. This review summarises previous work on music perception and improvisation and presents a conceptual model of musical improvisation with known neural correlates. We make recommendations on future directions for the study of improvisation and discuss the challenges posed by this endeavour.
Biofouling of Polyamide Membranes: Fouling Mechanisms, Current Mitigation and Cleaning Strategies, and Future Prospects

Reverse osmosis and nanofiltration systems are continuously challenged with biofouling of polyamide membranes that are used almost exclusively for these desalination techniques. Traditionally, pretreatment and reactive membrane cleanings are employed as biofouling control methods. This in-depth review paper discusses the mechanisms of membrane biofouling and effects on performance. Current industrial disinfection techniques are reviewed, including chlorine and other chemical and non-chemical alternatives to chlorine. Operational techniques such as reactive membrane cleaning are also covered. Based on this review, there are three suggested areas of additional research offering promising, polyamide membrane-targeted biofouling minimization that are discussed. One area is membrane modification. Modification using surface coatings with inclusion of various nanoparticles, and graphene oxide within the polymer or membrane matrix, are covered. This work is in the infancy stage and shows promise for minimizing the contributions of current membranes themselves in promoting biofouling, as well as creating oxidant-resistant membranes. Another area of suggested research is chemical disinfectants for possible application directly on the membrane. Likely disinfectants discussed herein include nitric oxide donor compounds, dichloroisocyanurate, and chlorine dioxide. Finally, proactive cleaning, which aims to control the extent of biofouling by cleaning before it negatively affects membrane performance, shows potential for low- to middle-risk systems.
Revealing misfit dislocations in InAsxP1−x-InP core–shell nanowires by x-ray diffraction

InAsxP1−x nanowires are promising building blocks for future optoelectronic devices and nanoelectronics. Their structure may vary from nanowire to nanowire, which may influence their average optoelectronic properties. Therefore, it is highly important for their applications to know the average properties of an ensemble of the nanowires. Structural properties of the InAsxP1−x-InP core–shell nanowires were investigated using the coplanar x-ray diffraction performed at a synchrotron facility. Studies of series of symmetric and asymmetric x-ray Bragg reflections allowed us to determine the 26% ± 3% of As chemical composition in the InAsxP1−x core, core–shell relaxation, and the average tilt of the nanowires with respect to the substrate normal. Based on the x-ray diffraction, scanning, and transmission electron microscopy measurements, a model of the core–shell relaxation was proposed. Partial relaxation of the core was attributed to misfit dislocations formed at the core–shell interface and their linear density was estimated to be 3.3 ± 0.3 × 104 cm−1.
Remission of Type 2 Diabetes Mellitus after Bariatric Surgery: Fact or Fiction?

Although type 2 diabetes mellitus (T2DM) has been traditionally viewed as an intractable chronic medical condition, accumulating evidence points towards the notion that a complete remission of T2DM is feasible following a choice of medical and/or surgical interventions. This has been paralleled by increasing interest in the establishment of a universal definition for T2DM remission which, under given circumstances, could be considered equivalent to a “cure”. The efficacy of bariatric surgery in particular for achieving glycemic control has highlighted surgery as a candidate curative intervention for T2DM. Herein, available evidence regarding available surgical modalities and the mechanisms that drive metabolic amelioration after bariatric surgery are reviewed. Furthermore, reports from observational and randomized studies with regard to T2DM remission are reviewed, along with concepts relevant to the variety of definitions used for T2DM remission and other potential sources of discrepancy in success rates among different studies.
The fidelity of cancer cells in PDX models: Characteristics, mechanism and clinical significance

Patient‐derived xenograft (PDX) models are widely used as preclinical cancer models and are considered better than cell culture models in recapitulating the histological features, molecular characteristics and intratumoral heterogeneity (ITH) of human tumors. While the PDX model is commonly accepted for use in drug discovery and other translational studies, a growing body of evidence has suggested its limitations. Recently, the fidelity of cancer cells within a PDX has been questioned, which may impede the future application of these models. In this review, we will focus the variable phenotypes of xenograft tumors and the genomic instability and molecular inconsistency of PDX tumors after serial transplantation. Next, we will discuss the underlying mechanism of ITH and its clinical relevance. Stochastic selection bias in the sampling process and/or deterministic clonal dynamics due to murine selective pressure may have detrimental effects on the results of personalized medicine and drug screening studies. In addition, we aim to identify a possible solution for the issue of fidelity in current PDX models and to discuss emerging next‐generation preclinical models.
Daily administration of Sake Lees (Sake Kasu) reduced psychophysical stress-induced hyperalgesia and Fos responses in the lumbar spinal dorsal horn evoked by noxious stimulation to the hindpaw in the rats

ABSTRACT We tested whether Sake Lees (SL) had inhibitory effects on hyperalgesia in the hindpaw under psychophysical stress conditions. Male rats were subjected to repeated forced swim stress treatments (FST) from Day −3 to Day −1. Intraperiotoneal administration of SL which contained low concentration of ethanol (SLX) was conducted after each FST. On Day 0, formalin-evoked licking behaviors and Fos responses in the lumbar spinal cord (DH) and several areas within the rostral ventromedial medulla (RVM) were quantified as nociceptive responses. FST-induced hyperalgesia in the hindpaw was prevented by repeated SL and SLX treatments. Fos expression was significantly increased in DH and some areas within the RVM under FST, which was prevented by repeated SL or SLX. These findings indicated that daily administration of SL had the potential to alleviate stress-induced hyperalgesia. Graphical Abstract Modulatory roles of Sake Lees on stress-induced hyperalgesia.
Insulin Receptor Isoform A Modulates Metabolic Reprogramming of Breast Cancer Cells in Response to IGF2 and Insulin Stimulation

Previously published work has demonstrated that overexpression of the insulin receptor isoform A (IR-A) might play a role in cancer progression and metastasis. The IR has a predominant metabolic role in physiology, but the potential role of IR-A in cancer metabolic reprogramming is unknown. We aimed to characterize the metabolic impact of IR-A and its ligand insulin like growth factor 2 (IGF2) in human breast cancer (BC) cells. To establish autocrine IGF2 action, we generated human BC cells MCF7 overexpressing the human IGF2, while we focused on the metabolic effect of IR-A by stably infecting IGF1R-ablated MCF7 (MCF7IGF1R-ve) cells with a human IR-A cDNA. We then evaluated the expression of key metabolism related molecules and measured real-time extracellular acidification rates and oxygen consumption rates using the Seahorse technology. MCF7/IGF2 cells showed increased proliferation and invasion associated with aerobic glycolysis and mitochondrial biogenesis and activity. In MCF7IGF1R-ve/IR-A cells insulin and IGF2 stimulated similar metabolic changes and were equipotent in eliciting proliferative responses, while IGF2 more potently induced invasion. The combined treatment with the glycolysis inhibitor 2-deoxyglucose (2DG) and the mitochondrial inhibitor metformin blocked cell invasion and colony formation with additive effects. Overall, these results indicate that IGF2 and IR-A overexpression may contribute to BC metabolic reprogramming.
The Impact of the Epigenetic Cancer Drug Azacitidine on Host Immunity: The Role of Myelosuppression, Iron Overload and tp53 Mutations in a Zebrafish Model

The unsatisfactory real-world efficacy of the hypomethylating agent azacitidine in treating myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) has prompted us to investigate the hematological adverse events and host variables that may compromise the use of this epigenetic drug. Using the zebrafish, we found that azacitidine destroyed their myeloid precursors and impaired myeloid function by inhibiting antigen processing, allogeneic response and phagocytic activity, resulting in increased susceptibility to infection even by the normal flora E. coli. In addition, iron overload, a MDS-associated condition following repeated transfusions, exacerbated bacterial infection especially by V. vulnificus with known iron dependence. Furthermore, we show that the tp53M214K mutant zebrafish survived longer than the wild-type (WT) when challenged with bacteria following azacitidine treatment. This was attributed to the mutant’s hematopoietic cells rather than its general genetic background, since the WT animals reconstituted with the tp53M214K mutant kidney marrow became more resistant to bacterial infection following treatment with azacitidine. The clinical relevance of our findings was indicated by a MDS case with severe azacitidine-induced bone marrow suppression and by the association of hyperferritinemia with bacteremia in azacitidine-treated patients, while tp53M214K-mediated resistance to azacitidine-induced myelosuppression may explain the survival advantage of malignant MDS and AML clones over their normal counterparts under azacitidine treatment. Together, we propose that myelosuppression, iron overload and TP53 mutations may represent the host variables that compromise the azacitidine efficacy.
The Emerging Proteomic Research Facilitates in-Depth Understanding of the Biology of Honeybees

Advances in instrumentation and computational analysis in proteomics have opened new doors for honeybee biological research at the molecular and biochemical levels. Proteomics has greatly expanded the understanding of honeybee biology since its introduction in 2005, through which key signaling pathways and proteins that drive honeybee development and behavioral physiology have been identified. This is critical for downstream mechanistic investigation by knocking a gene down/out or overexpressing it and being able to attribute a specific phenotype/biochemical change to that gene. Here, we review how emerging proteome research has contributed to the new understanding of honeybee biology. A systematic and comprehensive analysis of global scientific progress in honeybee proteome research is essential for a better understanding of research topics and trends, and is potentially useful for future research directions.
The Non-Covalent Interactions and In Vitro Radical Scavenging Activities of the Caseinate-Galangin and Caseinate-Genistein Complexes

Non-covalent interactions and in vitro radical scavenging activities of the complexes formed by the commercial milk protein product caseinate and one of the two polyphenols (galangin and genistein) were assessed by the multi-spectroscopic techniques, molecular docking, and detection of scavenging activities against the 1,1–diphenyl-2-picryl-hydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hydroxyl radicals. The caseinate bound with the two polyphenols showed conformational changes and increased scavenging activities, compared with original caseinate. The caseinate-polyphenol binding was driven by the hydrophobic interaction and hydrogen-bonds, while hydrophobic interaction was the main binding force. Meanwhile, sodium dodecyl sulfate and urea could damage the essential hydrophobic interaction and hydrogen-bonds, respectively, and thus led to decreased apparent binding constants for the caseinate-polyphenol binding. Based on the measured values of several apparent thermodynamic parameters like ΔH, ΔS, ΔG, and donor–acceptor distance as well as the detected radical scavenging activity, galangin having more planar stereochemical structure and random B-ring rotation always had higher affinity for caseinate than genistein having location isomerism and twisted stereochemical structure, while the caseinate-galangin complex showed higher radical scavenging activity than the caseinate-genistein complex. It is thus concluded that both chemical and stereochemical structures of polyphenols are crucial to the affinity of polyphenols for protein and antioxidant activities of the protein-polyphenol complexes.