Miracle-dz/UniFAR-FTUs huggingface dataset:
Autosomal Microsatellite Investigation Reveals Multiple Genetic Components of the Highlanders from Thailand

The hill tribes of northern Thailand comprise nine officially recognized groups: the Austroasiatic-speaking (AA) Khmu, Htin and Lawa; the Hmong-Mien-speaking (HM) IuMien and Hmong; and the Sino-Tibetan-speaking (ST) Akha, Karen, Lahu and Lisu. Except the Lawa, the rest of the hill tribes migrated into their present habitats only very recently. The Thai hill tribes were of much interest to research groups focusing on study of cultural and genetic variation because of their unique languages and cultures. So far, there have been several genetic studies of the Thai hill tribes. However, complete forensic microsatellite database of the Thai hill tribes is still lacking. To construct such database, we newly generated 654 genotypes of 15 microsatellites commonly used in forensic investigation that belong to all the nine hill tribes and also non-hill tribe highlanders from northern Thailand. We also combined 329 genotypes from previous studies of northern Thai populations bringing to a total of 983 genotypes, which were then subjected to genetic structure and population relationships analyses. Our overall results indicated homogenous genetic structure within the HM- and Tai-Kadai (TK)-speaking groups, large genetic divergence of the HM-speaking Hmong but not IuMien from the other Thai groups, and genetic heterogeneity within the ST- and AA-speaking groups, reflecting different population interactions and admixtures. In addition to establishing genetic relationships within and among these populations, our finding, which provides a more complete picture of the forensic microsatellite database of the multiple Thai highland dwellers, would not only serve to expand and strengthen forensic investigation in Thailand, but would also benefit its neighboring countries of Laos and Myanmar, from which many of the Thai hill tribes originated and where large populations of these ethnic groups still reside.
Extra-Nuclear Functions of the Transcription Factor Grainyhead-Like 3 in the Endothelium—Interaction with Endothelial Nitric Oxide Synthase

We previously demonstrated that the transcription factor Grainyhead-like 3 (GRHL3) has essential functions in endothelial cells by inhibiting apoptosis and promoting migration as well as activation of endothelial nitric oxide synthase (eNOS). We now show that a large portion of the protein is localized to myo-endothelial projections of murine arteries suggesting extra-nuclear functions. Therefore, we generated various deletion mutants to identify the nuclear localization signal (NLS) of GRHL3 and assessed potential extra-nuclear functions. Several large-scale deletion mutants were incapable of activating a GRHL3-dependent reporter construct, which could either be due to deficiencies in transcriptional activation or to impaired nuclear import. One of these mutants encompassed a predicted bipartite NLS whose deletion led to the retention of GRHL3 outside the nucleus. Interestingly, this mutant retained functions of the full-length protein as it could still inhibit pathways inducing endothelial cell apoptosis. As apoptosis protection by GRHL3 depends on NO-production, we examined whether GRHL3 could interact with eNOS and showed a direct interaction, which was enhanced with the extra-nuclear GRHL3 variant. The observation that endogenous GRHL3 also interacts with eNOS in intact murine arteries corroborated these findings and substantiated the notion that GRHL3 has important extra-nuclear functions in the endothelium.
Differential Diagnosis of Cachexia and Refractory Cachexia and the Impact of Appropriate Nutritional Intervention for Cachexia on Survival in Terminal Cancer Patients

Cancer cachexia subsequently shifts to refractory cachexia, however, it is not easy to properly differentiate them in clinical settings. Patients considered refractory cachexia may include cachectic patients with starvation. This study aimed to identify these cachectic patients and to evaluate the effect of nutritional intervention for them. Study subjects were terminal cancer patients admitted for palliative care and were judged refractory cachexia in the last five years. We retrospectively examined to find useful indices for identifying such cachectic patients and for evaluating the effect of nutritional intervention. Out of 223 patients in refractory cachexia, 26 were diagnosed cachexia with starvation after symptom management. Comparing before and one week after this management, Palliative Performance Scale (PPS) and transthyretin significantly improved (p < 0.0001, p = 0.0002, respectively) Then, we started nutritional intervention for these cachectic patients and divided into effective group (n = 17) and non-effective group (n = 9) using the criteria for cachexia. Comparing between the two groups, PPS significantly improved2 weeks after intervention in effective group (p = 0.006). Survival time was significantly longer in effective group (p = 0.008). PPS and transthyretin were useful for differential diagnosis of cachexia and refractory cachexia. PPS was useful for evaluating nutritional intervention for cachectic patients. Appropriate nutritional intervention improved survival.
Polyphenolic Characterization of Merlot, Tannat and Syrah Skin Extracts at Different Degrees of Maturity and Anti-Inflammatory Potential in RAW 264.7 Cells

(1) Background: Both sensory quality and healthy attributes of Vitis vinifera grapes used for winemaking are closely related with the polyphenolic composition of their skins. (2) Methods: In this study, the polyphenolic characterization (flavan-3-ols, procyanidins, flavonols, stilbenes, anthocyanins) was investigated by ultra performance liquid chromatography coupled to a triple quadrupole mass spectrometer (UPLC-QqQ-MS). Skins from Vitis vinifera Merlot, Tannat, and Syrah red grape varieties cultivated in the south of France at different stages of ripening in 2018 were used. The anti-inflammatory and the antioxidant potential of the extracts were evaluated by the measure of nitric oxide (NO) and the intracellular reactive oxygen species production (ROS) in lipopolysaccharide (LPS)-stimulated macrophages. (3) Results: 41 polyphenols were quantified in all samples. Generally, the flavan-3-ol and procyanidin content decreased during ripening whereas the anthocyanins and stilbenes increased. In addition, as a novelty of this work, a wide identification and characterization of monomeric and oligomeric stilbenes was assessed by using authentic standards isolated in our laboratory, some of them (parthenocissin A and miyabenol C) reported for the first time in Merlot, Tannat and Syrah cultivars. The before-veraison skin extracts of all studied varieties, exhibited higher NO and ROS productions inhibition (>50%) proving both antioxidant and anti-inflammatory properties.
Polydatin Prevents Calcium Pyrophosphate Crystal-Induced Arthritis in Mice

Background: Polydatin is a stilbenoid with important antioxidant, anti-inflammatory, and immunomodulating properties. The aim of this study was to assess the anti-inflammatory preventive effect of polydatin in the mouse model of acute arthritis induced by calcium pyrophosphate (CPP) crystals. Methods: Acute arthritis was induced by the injection of a suspension of sterile CPP crystals into the ankle joint of Balb/c mice. Animals were randomized to receive polydatin or colchicine (the control drug) according to a prophylactic and a therapeutic protocol. The primary outcome was the variation of ankle swelling obtained after crystal injection and treatment, while histological parameters such as leukocyte infiltration, IL-1ß and CXCL1 levels and tissue expression were considered as secondary outcomes. Results: Prophylactic treatment with PD significantly diminished ankle swelling after 48 h from crystal injection. Secondary outcomes such as leukocyte infiltration, necrosis, edema, and synovitis were also decreased. PD caused a reduction in circulating levels of IL-1ß and CXCL1, as well as their tissue expression. By contrast, the therapeutic administration of PD did not have any beneficial effect. Conclusions: PD can effectively prevent acute inflammatory response to crystals in the mouse model of CPP crystal-induced arthritis. These results suggest that this bioactive compound might be used in the prevention of crystal-induced acute attacks in humans.
Meaning in Life Mediates the Association between Environmental Engagement and Loneliness

Although the positive outcomes of human–environment interactions have been established, research examining the motivation between engagement in pro-environmental activities and psychological well-being is limited. In this mixed-methods study, the relationship between pro-environmental engagement, meaning in life, and well-being, including loneliness and depression, were investigated in a sample of 112 young adults in Canada. It was found that engaging in pro-environmental activities was negatively associated with loneliness. This association was mediated by meaning in life (e.g., an intrinsic motive of caring for future generations). In addition, qualitative analyses explored how engaging in pro-environmental activities has a meaningful impact on meaning in life, and on well-being. A thematic analysis generated three unique themes: (1) responsibility to teach the next generation about the environment, (2) deep appreciation for and connection to nature, and (3) renewed agency through self-directed learning. Overall, findings suggest that meaning in life is a core motive that underlies the association between environmental engagement and loneliness. The present study enriched the relationship between pro-environmentalism and well-being with a mixed-methods perspective.
Wheat Varietal Response to Tilletia controversa J. G. Kühn Using qRT-PCR and Laser Confocal Microscopy

Tilletia controversa J. G. Kühn is a causal organism of dwarf bunt in wheat. Understanding the interaction of wheat and T. controversa is of practical and scientific importance for disease control. In this study, the relative expression of TaLHY and TaPR-4 and TaPR-5 genes was higher in a resistant (Yinong 18) and moderately resistant (Pin 9928) cultivars rather than susceptible (Dongxuan 3) cultivar at 72 h post inoculation (hpi) with T. controversa. Similarly, the expression of defensin, TaPR-2 and TaPR-10 genes was observed higher in resistant and moderately resistant cultivars after exogenous application of phytohormones, including methyl jasmonate, salicylic acid, and abscisic acid. Laser confocal microscopy was used to track the fungal hyphae in the roots, leaves, and tapetum cells, which of susceptible cultivar were infected harshly by T. controversa than moderately resistant and resistant cultivars. There were no fungal hyphae in tapetum cells in susceptible cultivar after methyl jasmonate, salicylic acid and abscisic acid treatments. Moreover, after T. controversa infection, the pollen germination was of 80.06, 58.73, and 0.67% in resistant, moderately resistant and susceptible cultivars, respectively. The above results suggested that the use using of resistant cultivar is a good option against the dwarf bunt disease.
Eribulin Efficacy on Brain Metastases in Heavily Pretreated Patients with Metastatic Breast Cancer

The onset of brain metastases (BM) is a major turning point during advanced breast cancer (ABC) evolution, with only few treatment options when local therapies have failed. The therapeutic effect of eribulin, a wildly used drug in the treatment of ABC, remains unclear in this setting. Patients and Methods: We performed a retrospective observational study to assess eribulin efficacy in patients with ABC who displayed BM at time of eribulin initiation. We collected data from the medical files of all ABC patients who received eribulin at our institution from 2012 until 2020. Our main endpoint was the central nervous system (CNS) progression-free survival. (CNS-PFS). Other evaluation criteria were extra-cranial progression free survival (PFS) and overall survival (OS). Results: Twenty patients with BM monitoring data available were selected out of the 549 who received eribulin during the inclusion period. Fifteen patients (75%) had BM progressive as the best response, three patients (15%) had disease stabilization for more than 6 months and only one patient had a partial response according to RECIST 1.1 criteria. Median CNS-PFS was 3.39 months (95CI (3.02–3.76)). Cox univariate analysis identified molecular subtype as the only prognostic parameter in our cohort, with patients with hormone-receptor positive tumors less likely to experience CNS progression than those with triple-negative MBC (HR = 0.23 (95CI = 0.07–0.80), p = 0.021). Median extra-cranial PFS was 2.67 months (95CI (2.33–3.01)). Median OS was 7.68 months (95CI (0–17.41)). Conclusion: Eribulin seems to have only a limited impact on BM evolution. Hormone receptors expression may identify a subset of patients with better BM control.
Dinuclear Lanthanide(III) Complexes from the Use of Methyl 2-Pyridyl Ketoxime: Synthetic, Structural, and Physical Studies

The first use of methyl 2-pyridyl ketoxime (mepaoH) in homometallic lanthanide(III) [Ln(III)] chemistry is described. The 1:2 reactions of Ln(NO3)3·nH2O (Ln = Nd, Eu, Gd, Tb, Dy; n = 5, 6) and mepaoH in MeCN have provided access to complexes [Ln2(O2CMe)4(NO3)2(mepaoH)2] (Ln = Nd, 1; Ln = Eu, 2; Ln = Gd, 3; Ln = Tb, 4; Ln = Dy, 5); the acetato ligands derive from the LnIII—mediated hydrolysis of MeCN. The 1:1 and 1:2 reactions between Dy(O2CMe)3·4H2O and mepaoH in MeOH/MeCN led to the all-acetato complex [Dy2(O2CMe)6(mepaoH)2] (6). Treatment of 6 with one equivalent of HNO3 gave 5. The structures of 1, 5, and 6 were solved by single-crystal X-ray crystallography. Elemental analyses and IR spectroscopy provide strong evidence that 2–4 display similar structural characteristics with 1 and 5. The structures of 1–5 consist of dinuclear molecules in which the two LnIII centers are bridged by two bidentate bridging (η1:η1:μ2) and two chelating-bridging (η1:η2:μ2) acetate groups. The LnIII atoms are each chelated by a N,N’-bidentate mepaoH ligand and a near-symmetrical bidentate nitrato group. The molecular structure of 6 is similar to that of 5, the main difference being the presence of two chelating acetato groups in the former instead of the two chelating nitrato groups in the latter. The geometry of the 9-coordinate LnIII centers in 1, 5 and 6 can be best described as a muffin-type (MFF-9). The 3D lattices of the isomorphous 1 and 5 are built through H-bonding, π⋯π stacking and C-H⋯π interactions, while the 3D architecture of 6 is stabilized by H bonds. The IR spectra of the complexes are discussed in terms of the coordination modes of the organic and inorganic ligands involved. The Eu(III) complex 2 displays a red, metal-ion centered emission in the solid state; the TbIII atom in solid 4 emits light in the same region with the ligand. Magnetic susceptibility studies in the 2.0–300 K range reveal weak antiferromagnetic intramolecular GdIII…GdIII exchange interactions in 3; the J value is −0.09(1) cm−1 based on the spin Hamiltonian Ĥ = −J(ŜGd1·ŜGd2).
Old Parasitoids for New Mealybugs: Host Location Behavior and Parasitization Efficacy of Anagyrus vladimiri on Pseudococcus comstocki

Simple Summary Anagyrus vladimiri has been widely employed as a biological control agent (BCA) against the vine mealybugs Planococcus ficus but the knowledge about its employment against other mealybug species is limited. In this study, we investigated the potential efficacy of A. vladimiri for Pseudococcus comstocki management, considering the increasing threat represented by this mealybug pest in Mediterranean vineyards and fruit orchards. No-choice and two-choice tests were conducted to quantify parasitoid behavior against P. ficus and P. comstocki. Our results pointed out that A. vladimiri successfully parasitized both pests, showing no host preference between the two species. Our observations highlight that this parasitoid can be successfully deployed as BCA against P. comstocki populations. Abstract The Comstock mealybug, Pseudococcus comstocki (Hemiptera: Pseudococcidae) is a primary pest of orchards in the North and Northwest of China. This pest appeared recently in Europe, including Italy, where it is infesting mainly vineyards as well as apple and pear orchards. The present study investigated the efficacy of Anagyrus vladimiri, a known biological control agent (BCA) of Planococcus ficus, on P. comstocki to evaluate a potential use for the management of this new pest. No-choice tests were conducted to quantify the parasitoid behavior against P. ficus and P. comstocki. The parasitoid successfully parasitized both species (parasitization rate: 51% and 67% on P. comstocki and P. ficus, respectively). The A. vladimiri developmental time (19.67 ± 1.12 vs. 19.70 ± 1.07 days), sex ratio (1.16 ± 1.12 vs. 1.58 ± 1.07) and hind tibia length of the progeny showed no differences when P. comstocki and P. ficus, respectively, were exploited as hosts. Two-choice tests, conducted by providing the parasitoid with a mixed population of P. ficus and P. comstocki, showed no host preference for either of the two mealybug species (23 vs. 27 first choices on P. comstocki and P. ficus, respectively). The parasitization rate (61.5% and 64.5% in P. comstocki and P. ficus, respectively) did not differ between the two hosts. Overall, our study adds basic knowledge on parasitoid behavior and host preferences and confirms the use of this economically important encyrtid species as an effective BCA against the invasive Comstock mealybug.
Medically Important Alterations in Transport Function and Trafficking of ABCG2

Several polymorphisms and mutations in the human ABCG2 multidrug transporter result in reduced plasma membrane expression and/or diminished transport function. Since ABCG2 plays a pivotal role in uric acid clearance, its malfunction may lead to hyperuricemia and gout. On the other hand, ABCG2 residing in various barrier tissues is involved in the innate defense mechanisms of the body; thus, genetic alterations in ABCG2 may modify the absorption, distribution, excretion of potentially toxic endo- and exogenous substances. In turn, this can lead either to altered therapy responses or to drug-related toxic reactions. This paper reviews the various types of mutations and polymorphisms in ABCG2, as well as the ways how altered cellular processing, trafficking, and transport activity of the protein can contribute to phenotypic manifestations. In addition, the various methods used for the identification of the impairments in ABCG2 variants and the different approaches to correct these defects are overviewed.
Protection against Glucolipotoxicity by High Density Lipoprotein in Human PANC-1 Hybrid 1.1B4 Pancreatic Beta Cells: The Role of microRNA

Simple Summary Loss of the cells which secrete insulin, the hormone which controls blood sugar levels, can occur due to the damaging effects of high levels of sugar and fat in the bloodstream, and is a key factor which triggers type 2 diabetes. Protection against this damage is provided by one of the fat and protein complexes which carry the ‘good’ cholesterol in the bloodstream, a complex which is called high-density lipoprotein. This study looks at the changes in the expression of small pieces of RNA, called microRNA, triggered in insulin-secreting cells by treatment with high density lipoprotein. These small RNA sequences can help to regulate the expression of genes which can contribute to the protective effect of high-density lipoproteins. Delivery of one of these sequences was able to modulate gene expression in cells, but could not provide enough protection against the damaging effects of high sugar and fat. We conclude that the complex changes in numerous microRNA sequences caused by high density lipoproteins cannot be replicated by a single sequence, suggesting that networks of regulatory microRNA sequences are more important than single sequences. The results will inform drug discovery strategies which focus on high density lipoprotein and microRNA. Abstract High-density lipoproteins provide protection against the damaging effects of glucolipotoxicity in beta cells, a factor which sustains insulin secretion and staves off onset of type 2 diabetes mellitus. This study examines epigenetic changes in small non-coding microRNA sequences induced by high density lipoproteins in a human hybrid beta cell model, and tests the impact of delivery of a single sequence in protecting against glucolipotoxicity. Human PANC-1.1B4 cells were used to establish Bmax and Kd for [3H]cholesterol efflux to high density lipoprotein, and minimum concentrations required to protect cell viability and reduce apoptosis to 30mM glucose and 0.25 mM palmitic acid. Microchip array identified the microRNA signature associated with high density lipoprotein treatment, and one sequence, hsa-miR-21-5p, modulated via delivery of a mimic and inhibitor. The results confirm that low concentrations of high-density lipoprotein can protect against glucolipotoxicity, and report the global microRNA profile associated with this lipoprotein; delivery of miR-21-5p mimic altered gene targets, similar to high density lipoprotein, but could not provide sufficient protection against glucolipotoxicity. We conclude that the complex profile of microRNA changes due to HDL treatment may be difficult to replicate using a single microRNA, findings which may inform current drug strategies focused on this approach.
Multiple Sclerosis-Associated hnRNPA1 Mutations Alter hnRNPA1 Dynamics and Influence Stress Granule Formation

Evidence indicates that dysfunctional heterogeneous ribonucleoprotein A1 (hnRNPA1; A1) contributes to the pathogenesis of neurodegeneration in multiple sclerosis. Understanding molecular mechanisms of neurodegeneration in multiple sclerosis may result in novel therapies that attenuate neurodegeneration, thereby improving the lives of MS patients with multiple sclerosis. Using an in vitro, blue light induced, optogenetic protein expression system containing the optogene Cryptochrome 2 and a fluorescent mCherry reporter, we examined the effects of multiple sclerosis-associated somatic A1 mutations (P275S and F281L) in A1 localization, cluster kinetics and stress granule formation in real-time. We show that A1 mutations caused cytoplasmic mislocalization, and significantly altered the kinetics of A1 cluster formation/dissociation, and the quantity and size of clusters. A1 mutations also caused stress granule formation to occur more quickly and frequently in response to blue light stimulation. This study establishes a live cell optogenetics imaging system to probe localization and association characteristics of A1. It also demonstrates that somatic mutations in A1 alter its function and promote stress granule formation, which supports the hypothesis that A1 dysfunction may exacerbate neurodegeneration in multiple sclerosis.