Miracle-dz/UniFAR-FTUs huggingface dataset:
Plastome Sequences Help to Resolve Deep-Level Relationships of Populus in the Family Salicaceae

Populus, a core genus of Salicaceae, plays a significant ecological role as a source of pioneer species in boreal forests. However, interspecific hybridization and high levels of morphological variation among poplars have resulted in great difficulty in classifying species for systematic and comparative evolutionary studies. Here, we present phylogenetic analyses of 24 newly sequenced Populus plastomes and 36 plastomes from GenBank, which represent seven genera of Salicaceae, in combination with a matrix of eighteen morphological characters of 40 Populus taxa to reconstruct highly supported relationships of genus Populus. Relationships among the 60 taxa of Salicaceae strongly supported two monophyletic genera: Populus and Salix. Chosenia was nested within the genus Salix, and five clades within Populus were divided. Clade I included the three taxa P. euphratica, P. pruinosa, and P. ilicifolia. Clade II contained thirteen taxa [P. adenopoda, P. alba, P. bolleana, P. davidiana, P. hopeiensis, P. nigra, P. qiongdaoensis, P. rotundifolia, P. rotundifolia var. duclouxiana, P. tremula, P. tremula × alba, P. tomentosa, and P. tomentosa (NC)]. Clade III included the ten taxa P. haoana, P. kangdingensis, P. lasiocarpa, P. pseudoglauca, P. qamdoensis, P. schneideri, P. simonii, P. szechuanica, P. szechuanica var. tibetica, and P. yunnanensis. Clade IV included P. cathayana, P. gonggaensis, P. koreana, P. laurifolia, P. trinervis, P. wilsonii, and P. xiangchengensis. The last clade comprised P. angustifolia, P. balsamifera, P. deltoides, P. deltoides × nigra, P. fremontii, P. mexicana, and P. trichocarpa. This phylogeny is also supported by morphological traits, including bark smoothness, bud size, petiole shape, leaf inflorescence, male anther length and male anther tip.
Vaccine Strategies to Improve Anti-cancer Cellular Immune Responses

More than many other fields in medicine, cancer vaccine development has been plagued by a wide gap between the massive amounts of highly encouraging preclinical data on one hand, and the disappointing clinical results on the other. It is clear now that traditional approaches from the infectious diseases' vaccine field cannot be borrowed as such to treat cancer. This review highlights some of the strategies developed to improve vaccine formulations for oncology, including research into more powerful or “smarter” adjuvants to elicit anti-tumoral cellular immune responses. As an illustration of the difficulties in translating smart preclinical strategies into real benefit for the cancer patient, the difficult road of vaccine development in lung cancer is given as example. Finally, an outline is provided of the combinatorial strategies that leverage the increasing knowledge on tumor-associated immune suppressive networks. Indeed, combining with drugs that target the dominant immunosuppressive pathway in a given tumor promises to unlock the true power of cancer vaccines and potentially offer long-term protection from disease relapse.
Loss of Neurofascin-186 Disrupts Alignment of AnkyrinG Relative to Its Binding Partners in the Axon Initial Segment

The axon initial segment (AIS) is a specialized region within the proximal portion of the axon that initiates action potentials thanks in large part to an enrichment of sodium channels. The scaffolding protein ankyrinG (AnkG) is essential for the recruitment of sodium channels as well as several other intracellular and extracellular proteins to the AIS. In the present study, we explore the role of the cell adhesion molecule (CAM) neurofascin-186 (NF-186) in arranging the individual molecular components of the AIS in cultured rat hippocampal neurons. Using a CRISPR depletion strategy to ablate NF expression, we found that the loss of NF selectively perturbed AnkG accumulation and its relative proximal distribution within the AIS. We found that the overexpression of sodium channels could restore AnkG accumulation, but not its altered distribution within the AIS without NF present. We go on to show that although the loss of NF altered AnkG distribution, sodium channel function within the AIS remained normal. Taken together, these results demonstrate that the regulation of AnkG and sodium channel accumulation within the AIS can occur independently of one another, potentially mediated by other binding partners such as NF.
Hemorrhagic Bullous Henoch-Schönlein Purpura: Case Report and Review of the Literature

Henoch-Schönlein Purpura (HSP) or IgA vasculitis is the most common systemic vasculitis of childhood and may affect skin, joints, gastrointestinal tract, and kidneys. Skin manifestations of HSP are characteristic and include a non-thrombocytopenic palpable purpura of the lower extremities and buttocks. Rarely, HSP may initially present as or evolve into hemorrhagic vesicles and bullae. We present an otherwise healthy 5-year-old boy with an acute papulovesicular rash of both legs and intermittent abdominal pain. After a few days the skin lesions rapidly evolved into palpable purpura and hemorrhagic bullous lesions of variable size and severe hemorrhagic HSP was suspected. A histological examination of a skin biopsy showed signs of a small vessel leukocytoclastic vasculitis limited to the upper dermis and direct immunofluorescence analysis revealed IgA deposits in vessel walls, compatible with HSP. To further characterize the clinical picture and treatment options of bullous HSP we performed an extensive literature research and identified 41 additional pediatric patients with bullous HSP. Two thirds of the reported patients were treated with systemic corticosteroids, however, up to 25% of the reported patients developed skin sequelae such as hyperpigmentation and/or scarring. The early use of systemic corticosteroids has been discussed controversially and suggested in some case series to be beneficial by reducing the extent of lesions and minimizing sequelae of disease. Our patient was treated with systemic corticosteroids tapered over 5 weeks. Fading of inflammation resulted in healing of most erosions, however, a deep necrosis developing from a large blister at the dorsum of the right foot persisted so that autologous skin transplantation was performed. Re-examination 11 months after disease onset showed complete clinical remission with re-epithelialization but also scarring of some affected areas.
The Contribution of Iron to Protein Aggregation Disorders in the Central Nervous System

The homeostasis of iron is of fundamental importance in the central nervous system (CNS) to ensure biological processes such as oxygen transport, mitochondrial respiration or myelin synthesis. Dyshomeostasis and accumulation of iron can be observed during aging and both are shared characteristics of several neurodegenerative diseases. Iron-mediated generation of reactive oxygen species (ROS) may lead to protein aggregation and cellular toxicity. The process of misfolding and aggregation of neuronal proteins such as α-synuclein, Tau, amyloid beta (Aβ), TDP-43 or SOD1 is a common hallmark of many neurodegenerative disorders and iron has been shown to facilitate protein aggregation. Thus, both, iron and aggregating proteins are proposed to amplify their detrimental effects in the disease state. In this review, we give an overview on effects of iron on aggregation of different proteins involved in neurodegeneration. Furthermore, we discuss the proposed mechanisms of iron-mediated toxicity and protein aggregation emphasizing the red-ox chemistry and protein-binding properties of iron. Finally, we address current therapeutic approaches harnessing iron chelation as a disease-modifying intervention in neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis.
Cytokines and Soluble Receptors in Breast Milk as Enhancers of Oral Tolerance Development

The postpartum period is an important window during which environmental factors can shape the life-long health of the infant. This time period often coincides with substantial milk consumption either in the form of breast milk or from cow's milk sources, such as infant formulas. Although breast milk is the most beneficial source of nutrients for infants during the first 6 months after birth, its role in regulating food allergy development, through regulation of oral tolerance, is still controversial. Breast milk contains several factors that can impact mucosal immune function, including immune cells, antibodies, microbiota, oligosaccharides, cytokines, and soluble receptors. However, there is considerable variation in the assessed levels of cytokines and soluble receptors between studies and across the lactation period. Most of these cytokines and soluble receptors are absent, or only found in limited quantities, in commercial baby formulas. Differences in content of these pluripotent factors, which impact on both the mother and the neonate, could contribute to the controversy surrounding the role of breast milk regulating oral tolerance. This review highlights current knowledge about the importance of cytokines and soluble receptors in breast milk on the development of oral tolerance and tolerance-relateddisorders. Understanding the mechanisms by which such milk components might promote oral tolerance could aid in the development of improved strategies for allergy prevention.
COMTVal158Met Genotype Affects Complex Emotion Recognition in Healthy Men and Women

The catechol-o-methyltransferase (COMT) gene has repeatedly been shown to change amygdala activity and amygdala-prefrontal connectivity during face processing. Although the COMT gene appears to induce a negativity bias during the neural processing of faces, it is currently unclear whether a similar negativity bias emerges during the behavioral processing of faces. To address this issue, we investigated differences in complex emotion recognition between participants (n = 181) that had been a priori genotyped for functional polymorphisms of the COMT (Val158Met) and serotonin transporter (5-HTTLPR) gene. We were, thus, able to analyze differences in face processing on basis of participants’ COMT genotype while controlling for participants’ 5-HTTLPR genotype. Variations of participants’ COMT but not 5-HTTLPR genotype accounted for differences in participants’ emotion recognition performance: Met/Met carriers and Met/Val carriers were more accurate in the recognition of negative, but not neutral or positive, expressions than Val/Val carriers. We, therefore, revealed a similar negativity bias during the behavioral processing of faces that has already been demonstrated during the neural processing of faces, indicating that genotype-dependent changes in catecholamine metabolism may affect face processing on the behavioral and neural level.
Platelet-Derived Microparticles From Obese Individuals: Characterization of Number, Size, Proteomics, and Crosstalk With Cancer and Endothelial Cells

Rationale: Obesity is a risk factor for atherothrombosis and various cancers. However, the mechanisms are not yet completely clarified. Objectives: We aimed to verify whether the microparticles (MPs) released from thrombin-activated platelets differed in obese and non-obese women for number, size, and proteomics cargo and the capacity to modulate in vitro the expression of (i) genes related to the epithelial to mesenchymal transition (EMT) and the endothelial to mesenchymal transition (EndMT), and (ii) cyclooxygenase (COX)-2 involved in the production of angiogenic and inflammatory mediators. Methods and Results: MPs were obtained from thrombin activated platelets of four obese and their matched non-obese women. MPs were analyzed by cytofluorimeter and protein content by liquid chromatography-mass spectrometry. MPs from obese women were not different in number but showed increased heterogeneity in size. In obese individuals, MPs containing mitochondria (mitoMPs) expressed lower CD41 levels and increased phosphatidylserine associated with enhanced Factor V representing a signature of a prothrombotic state. Proteomics analysis identified 44 proteins downregulated and three upregulated in MPs obtained from obese vs. non-obese women. A reduction in the proteins of the α-granular membrane and those involved in mitophagy and antioxidant defenses-granular membrane was detected in the MPs of obese individuals. MPs released from platelets of obese individuals were more prone to induce the expression of marker genes of EMT and EndMT when incubated with human colorectal cancer cells (HT29) and human cardiac microvascular endothelial cells (HCMEC), respectively. A protein, highly enhanced in obese MPs, was the pro-platelet basic protein with pro-inflammatory and tumorigenic actions. Exclusively MPs from obese women induced COX-2 in HCMEC. Conclusion: Platelet-derived MPs of obese women showed higher heterogeneity in size and contained different levels of proteins relevant to thrombosis and tumorigenesis. MPs from obese individuals presented enhanced capacity to cause changes in the expression of EMT and EndMT marker genes and to induce COX-2. These effects might contribute to the increased risk for the development of thrombosis and multiple malignancies in obesity. Clinical Trial Registration: www.ClinicalTrials. gov, identifier NCT01581801.
Sex-Specific Associations Between Inter-Individual Differences in Heart Rate Variability and Inter-Individual Differences in Emotion Regulation

Neurobiological theories suggest that inter-individual differences in vagally mediated heart rate variability (vmHRV) have the potential to serve as a biomarker for inter-individual differences in emotion regulation that are due to inter-individual differences regarding the engagement of prefrontal and (para-)limbic brain regions during emotion processing. To test these theories, we investigated whether inter-individual differences in vmHRV would be associated with inter-individual differences in emotion regulation. We determined resting state vmHRV in a sample of 176 individuals that had also completed a short self-report measure of reappraisal and suppression use. Resting state vmHRV was derived from short-term (300 s) and ultra-short-term (120 s, 60 s) recordings of participants’ heart rate to determine the robustness of possible findings. Irrespective of recording length, we found that an increase in resting state vmHRV was associated with an increase in self-reported reappraisal but not suppression use. However, this association was only evident among male but not female participants, indicating a sex-specific association between inter-individual differences in resting state vmHRV and inter-individual differences in self-reported emotion regulation. These findings, which are consistent with previous ones, support theoretical claims that inter-individual differences in vmHRV serve as a biomarker for inter-individual differences in emotion regulation. Combing (ultra-)short-term measures of resting state vmHRV with short self-report measures of emotion regulation may, thus, be useful for researchers who have to investigate the neurobiological mechanisms of emotion regulation in a time- and resource-efficient manner.
The Effects of Universal Preschool on Grade Retention

Nationwide, the percentage of four-year-olds enrolled in state-supported preschool programs has more than doubled since the early 2000s as states dramatically increased their investments in early childhood education. Florida's Voluntary Pre-kindergarten Program (VPK), which began in 2005, has been a national leader with respect to preschool access. This paper provides the first evidence of the program's impacts. We measure the effect of VPK participation on the likelihood that children are retained at any point between kindergarten and third grade. Using an instrumental variables approach, we leverage local program expansion and detailed student-level data on eight cohorts of children, four of which were of preschool age in the years before VPK was implemented and four of which had access to VPK programs. The results indicate that VPK did not lead to changes in the likelihood that children complete the third grade without ever being retained. We do find, however, that VPK led to a change in the timing of retention. Specifically, the program led to a drop in the likelihood that children were retained during the kindergarten year, but this drop was counteracted by increases in retention in subsequent school years. Implications for policy are discussed.
Effect of Greening Vacant Land on Mental Health of Community-Dwelling Adults

Key Points Question Does the greening of vacant urban land reduce self-reported poor mental health in community-dwelling adults? Findings In this cluster randomized trial of urban greening and mental health, 110 randomly sampled vacant lot clusters were randomly assigned to 3 study groups. Among 342 participants included in the analysis, feeling depressed significantly decreased by 41.5% and self-reported poor mental health showed a reduction of 62.8% for those living near greened vacant lots compared with control participants. Meaning The remediation of vacant and dilapidated physical environments, particularly in resource-limited urban settings, can be an important tool for communities to address mental health problems, alongside other patient-level treatments.
Association of Hemoglobin A1c Levels With Use of Sulfonylureas, Dipeptidyl Peptidase 4 Inhibitors, and Thiazolidinediones in Patients With Type 2 Diabetes Treated With Metformin

Key Points Question Can the effectiveness of second-line treatment of type 2 diabetes after initial therapy with metformin be characterized via an open collaborative research network? Findings In this analysis of data from more than 246 million patients in multiple cohorts, treatment with dipeptidyl peptidase 4 inhibitors compared with sulfonylureas and thiazolidinediones did not differ in reducing hemoglobin A1c levels or hazard of kidney disorders. In a meta-analysis, sulfonylureas compared with dipeptidyl peptidase 4 inhibitors were associated with a small increased hazard of myocardial infarction and eye disorders in patients with type 2 diabetes. Meaning Large-scale characterization of the effectiveness of type 2 diabetes therapy across nations through an open collaborative research network aligns with the 2017 recommendation of the American Association of Clinical Endocrinologists and American College of Endocrinology in type 2 diabetes management recommending dipeptidyl peptidase 4 inhibitors over sulfonylureas in patients with diabetes for whom metformin was the first-line treatment.
Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites

Background Developing new methods to deliver cells to the injured tissue is a critical factor in translating cell therapeutics research into clinical use; therefore, there is a need for improved cell homing capabilities. Materials and methods In this study, we demonstrated the effects of labeling rat bone marrow-derived mesenchymal stem cells (MSCs) with fabricated polydopamine (PDA)-capped Fe3O4 (Fe3O4@PDA) superparticles employing preassembled Fe3O4 nanoparticles as the cores. Results We found that the Fe3O4@PDA composite superparticles exhibited no adverse effects on MSC characteristics. Moreover, iron oxide nanoparticles increased the number of MSCs in the S-phase, their proliferation index and migration ability, and their secretion of vascular endothelial growth factor relative to unlabeled MSCs. Interestingly, nanoparticles not only promoted the expression of C-X-C chemokine receptor 4 but also increased the expression of the migration-related proteins c-Met and C-C motif chemokine receptor 1, which has not been reported previously. Furthermore, the MSC-loaded nanoparticles exhibited improved homing and anti-inflammatory abilities in the absence of external magnetic fields in vivo. Conclusion These results indicated that iron oxide nanoparticles rendered MSCs more favorable for use in injury treatment with no negative effects on MSC properties, suggesting their potential clinical efficacy.
Phenotypic and Functional Diversities of Myeloid-Derived Suppressor Cells in Autoimmune Diseases

Myeloid-derived suppressor cells (MDSCs) are identified as a heterogeneous population of cells with the function to suppress innate as well as adaptive immune responses. The initial studies of MDSCs were primarily focused on the field of animal tumor models or cancer patients. In cancer, MDSCs play the deleterious role to inhibit tumor immunity and to promote tumor development. Over the past few years, an increasing number of studies have investigated the role of MDSCs in autoimmune diseases. The beneficial effects of MDSCs in autoimmunity have been reported by some studies, and thus, immunosuppressive MDSCs may be a novel therapeutic target in autoimmune diseases. There are some controversial findings as well. Many questions such as the activation, differentiation, and suppressive functions of MDSCs and their roles in autoimmune diseases remain unclear. In this review, we have discussed the current understanding of MDSCs in autoimmune diseases.
Homicide clearance in Western Europe

This study provides an overview of homicide clearance in four West European countries: Finland, the Netherlands, Sweden and Switzerland. Using data from the European Homicide Monitor, employing similar definitions and uniform coding schemes, this study allowed for unique cross-country comparisons in factors influencing differences in homicide clearance rates. Findings based on homicides occurring in the period 2009–14 revealed overall low homicide rates in all countries, with a wide variety in homicide clearance rates, ranging from 77 percent in the Netherlands to 98 percent in Finland. Results further showed that both event-based as well as victim-based characteristics significantly influenced the likelihood of homicide clearance, suggesting that homicide clearance rates can, for a large part, be attributed to the prevalent types of homicide in each of these European countries.
Epithelial Membrane Protein-2 (EMP2) Antibody Blockade Reduces Corneal Neovascularization in an In Vivo Model

Purpose Pathologic corneal neovascularization is a major cause of blindness worldwide, and treatment options are currently limited. VEGF is one of the critical mediators of corneal neovascularization but current anti-VEGF therapies have produced limited results in the cornea. Thus, additional therapeutic agents are needed to enhance the antiangiogenic arsenal. Our group previously demonstrated epithelial membrane protein-2 (EMP2) involvement in pathologic angiogenesis in multiple cancer models including breast cancer and glioblastoma. In this paper, we investigate the efficacy of anti-EMP2 immunotherapy in the prevention of corneal neovascularization. Methods An in vivo murine cornea alkali burn model was used to study pathologic neovascularization. A unilateral corneal burn was induced using NaOH, and subconjunctival injection of either anti-EMP2 antibody, control antibody, or sterile saline was performed after corneal burn. Neovascularization was clinically scored at 7 days postalkali burn, and eyes were enucleated for histologic analysis and immunostaining including VEGF, CD31, and CD34 expression. Results Anti-EMP2 antibody, compared to control antibody or vehicle, significantly reduced neovascularization as measured by clinical score and central cornea thickness, as well as by histologic reduction of neovascularization, decreased CD34 staining, and decreased CD31 staining. Incubation of corneal limbal cells in vitro with anti-EMP2 blocking antibody significantly decreased EMP2 expression, VEGF expression and secretion, and cell migration. Conclusions This work demonstrates the effectiveness of EMP2 as a novel target in pathologic corneal neovascularization in an animal model and supports additional investigation into EMP2 antibody blockade as a potential new therapeutic option.