Miracle-dz/UniFAR-FTUs huggingface dataset:
The Importance of Time and Place: Nutrient Composition and Utilization of Seasonal Pollens by European Honey Bees (Apis mellifera L.)

Simple Summary Honey bees rely on pollen and nectar to provide nutrients to support their yearly colony cycle. Specifics of the cycle differ among geographic regions as do the species of flowering plants and the nutrients they provide. We examined responses of honey bees from two different queen lines fed pollens from locations that differed in floral species composition and yearly colony cycles. We detected differences between the queen lines in the amount of pollen they consumed and the size of their hypopharyngeal glands (HPG). There were also seasonal differences between the nutrient composition of pollens. Spring pollens collected from colonies in both locations had higher amino and fatty acid concentrations than fall pollens. There also were seasonal differences in responses to the pollens consumed by bees from both queen lines. Bees consumed more spring than fall pollen, but digested less of it so that bees consumed more protein from fall pollens. Though protein consumption was higher with fall pollen, HPG were larger in spring bees. Abstract Honey bee colonies have a yearly cycle that is supported nutritionally by the seasonal progression of flowering plants. In the spring, colonies grow by rearing brood, but in the fall, brood rearing declines in preparation for overwintering. Depending on where colonies are located, the yearly cycle can differ especially in overwintering activities. In temperate climates of Europe and North America, colonies reduce or end brood rearing in the fall while in warmer climates bees can rear brood and forage throughout the year. To test the hypothesis that nutrients available in seasonal pollens and honey bee responses to them can differ we analyzed pollen in the spring and fall collected by colonies in environments where brood rearing either stops in the fall (Iowa) or continues through the winter (Arizona). We fed both types of pollen to worker offspring of queens that emerged and open mated in each type of environment. We measured physiological responses to test if they differed depending on the location and season when the pollen was collected and the queen line of the workers that consumed it. Specifically, we measured pollen and protein consumption, gene expression levels (hex 70, hex 110, and vg) and hypopharyngeal gland (HPG) development. We found differences in macronutrient content and amino and fatty acids between spring and fall pollens from the same location and differences in nutrient content between locations during the same season. We also detected queen type and seasonal effects in HPG size and differences in gene expression between bees consuming spring vs. fall pollen with larger HPG and higher gene expression levels in those consuming spring pollen. The effects might have emerged from the seasonal differences in nutritional content of the pollens and genetic factors associated with the queen lines we used.
Review and Evaluation of the Potential Health Effects of Oxidic Nickel Nanoparticles

The exceptional physical and chemical properties of nickel nanomaterials have been exploited in a range of applications such as electrical conductors, batteries, and biomaterials. However, it has been suggested that these unique properties may allow for increased bioavailability, bio-reactivity, and potential adverse health effects. Thus, the purpose of this review was to critically evaluate data regarding the toxicity of oxidic nickel nanoparticles (nickel oxide (NiO) and nickel hydroxide (Ni(OH)2) nanoparticles) with respect to: (1) physico-chemistry properties; (2) nanomaterial characterization in the defined delivery media; (3) appropriateness of model system and translation to potential human effects; (4) biodistribution, retention, and clearance; (5) routes and relevance of exposure; and (6) current research data gaps and likely directions of future research. Inhalation studies were prioritized for review as this represents a potential exposure route in humans. Oxidic nickel particle size ranged from 5 to 100 nm in the 60 studies that were identified. Inflammatory responses induced by exposure of oxidic nickel nanoparticles via inhalation in rodent studies was characterized as acute in nature and only displayed chronic effects after relatively large (high concentration and long duration) exposures. Furthermore, there is no evidence, thus far, to suggest that the effects induced by oxidic nickel nanoparticles are related to preneoplastic events. There are some data to suggest that nano- and micron-sized NiO particles follow a similar dose response when normalized to surface area. However, future experiments need to be conducted to better characterize the exposure–dose–response relationship according to specific surface area and reactivity as a dose metric, which drives particle dissolution and potential biological responses.
The Effect of Maternal Immune Activation on Social Play-Induced Ultrasonic Vocalization in Rats

Prenatal maternal infection is associated with an increased risk of various neurodevelopmental disorders, including autism spectrum disorders (ASD). Maternal immune activation (MIA) can be experimentally induced by prenatal administration of polyinosinic:polycytidylic acid (poly I:C), a synthetic viral-like double-stranded RNA. Although this MIA model is adopted in many studies, social and communicative deficits, included in the first diagnostic criterion of ASD, are poorly described in the offspring of poly(I:C)-exposed dams. This study aimed to characterize the impact of prenatal poly(I:C) exposure on socio-communicative behaviors in adolescent rats. For this purpose, social play behavior was assessed in both males and females. We also analyzed quantitative and structural changes in ultrasonic vocalizations (USVs) emitted by rats during the play test. Deficits of social play behaviors were evident only in male rats. Males also emitted a significantly decreased number of USVs during social encounters. Prenatal poly(I:C) exposure also affected acoustic call parameters, as reflected by the increased peak frequencies. Additionally, repetitive behaviors were demonstrated in autistic-like animals regardless of sex. This study demonstrates that prenatal poly(I:C) exposure impairs socio-communicative functioning in adolescent rats. USVs may be a useful tool for identifying early autistic-like abnormalities.
Collagen Assembly at the Cell Surface: Dogmas Revisited

With the increased awareness about the importance of the composition, organization, and stiffness of the extracellular matrix (ECM) for tissue homeostasis, there is a renewed need to understand the details of how cells recognize, assemble and remodel the ECM during dynamic tissue reorganization events. Fibronectin (FN) and fibrillar collagens are major proteins in the ECM of interstitial matrices. Whereas FN is abundant in cell culture studies, it is often only transiently expressed in the acute phase of wound healing and tissue regeneration, by contrast fibrillar collagens form a persistent robust scaffold in healing and regenerating tissues. Historically fibrillar collagens in interstitial matrices were seen merely as structural building blocks. Cell anchorage to the collagen matrix was thought to be indirect and occurring via proteins like FN and cell surface-mediated collagen fibrillogenesis was believed to require a FN matrix. The isolation of four collagen-binding integrins have challenged this dogma, and we now know that cells anchor directly to monomeric forms of fibrillar collagens via the α1β1, α2β1, α10β1 and α11β1 integrins. The binding of these integrins to the mature fibrous collagen matrices is more controversial and depends on availability of integrin-binding sites. With increased awareness about the importance of characterizing the total integrin repertoire on cells, including the integrin collagen receptors, the idea of an absolute dependence on FN for cell-mediated collagen fibrillogenesis needs to be re-evaluated. We will summarize data suggesting that collagen-binding integrins in vitro and in vivo are perfectly well suited for nucleating and supporting collagen fibrillogenesis, independent of FN.
Redirecting the Immune Microenvironment in Acute Myeloid Leukemia

Simple Summary Despite remarkable progress in the outcome of childhood acute myeloid leukemia (AML), risk of relapse and refractory diseases remains high. Treatment of the chemo-refractory disease is restricted by dose-limiting therapy-related toxicities which necessitate alternative tolerable efficient therapeutic modalities. By disrupting its immune environment, leukemic blasts are known to gain the ability to evade immune surveillance and promote disease progression; therefore, many efforts have been made to redirect the immune system against malignant blasts. Deeper knowledge about immunologic alterations has paved the way to the discovery and development of novel targeted therapeutic concepts, which specifically override the immune evasion mechanisms to eradicate leukemic blasts. Herein, we review innovative immunotherapeutic strategies and their mechanisms of action in pediatric AML. Abstract Acute myeloid leukemia is a life-threatening malignant disorder arising in a complex and dysregulated microenvironment that, in part, promotes the leukemogenesis. Treatment of relapsed and refractory AML, despite the current overall success rates in management of pediatric AML, remains a challenge with limited options considering the heavy but unsuccessful pretreatments in these patients. For relapsed/refractory (R/R) patients, hematopoietic stem cell transplantation (HSCT) following ablative chemotherapy presents the only opportunity to cure AML. Even though in some cases immune-mediated graft-versus-leukemia (GvL) effect has been proven to efficiently eradicate leukemic blasts, the immune- and chemotherapy-related toxicities and adverse effects considerably restrict the feasibility and therapeutic power. Thus, immunotherapy presents a potent tool against acute leukemia but needs to be engineered to function more specifically and with decreased toxicity. To identify innovative immunotherapeutic approaches, sound knowledge concerning immune-evasive strategies of AML blasts and the clinical impact of an immune-privileged microenvironment is indispensable. Based on our knowledge to date, several promising immunotherapies are under clinical evaluation and further innovative approaches are on their way. In this review, we first focus on immunological dysregulations contributing to leukemogenesis and progression in AML. Second, we highlight the most promising therapeutic targets for redirecting the leukemic immunosuppressive microenvironment into a highly immunogenic environment again capable of anti-leukemic immune surveillance.
Performance, Correlation and Kinetic Profile of Circulating Serum Fungal Biomarkers of Invasive Aspergillosis in High-Risk Patients with Hematologic Malignancies

As conventional microbiological documentation of invasive aspergillosis (IA) is difficult to obtain, serum fungal biomarkers are important adjunctive diagnostic tools. Positivity rates and the kinetic profiles of galactomannan (GM), 1,3-β-D-glucan (BDG) and Aspergillus DNA (PCR) were studied in high-risk patients with hematologic malignancies. GM, BDG and PCR data from serial serum specimens (n = 240) from 93 adult hematology patients with probable (n = 8), possible (n = 25) and no (n = 60) IA were retrospectively analyzed. Positivity rates and sensitivity/specificity/positive/negative predictive values (NPV) of each fungal biomarker alone and in combination were estimated. The three markers were compared head-to-head and correlated with various biochemical, demographic and patient characteristics. The positivity rates for patients with probable/possible/no IA were 88%/8%/0% for GM (X2 = 55, p < 0.001), 62%/46%/35% for BDG (X2 = 2.5, p = 0.29), 62%/33%/27% for PCR (X2 = 3.9, p = 0.15), 50%/4%/0% for GM + BDG and GM + PCR (X2 = 31, p < 0.001), 50%/8%/22% for BDG + PCR (X2 = 6.5, p = 0.038) and 38%/4%/0% for GM + BDG + PCR (X2 = 21, p < 0.001). Higher agreement (76%) and negative correlation (rs = −0.47, p = 0.0017) was found between GM index and PCR Ct values. The sensitivity and NPV was 45–55% and 90–92% when biomarkers assessed alone and increased to 75–90% and 93–97%, respectively when combined. Weak significant correlations were found between GM, PCR and BDG results with renal/liver function markers (r = 0.11–0.57) with most GM+ and PCR+ samples found in the first and second week of clinical assessment, respectively and BDG later on. Different positivity rates, time profiles and performances were found for the three biomarkers advocating the combination of GM with PCR for the early diagnosis of IA, whereas the high NPV of combined biomarkerscould help excluding IA.
The Independent Role of Body Mass Index (BMI) and Severity of Depressive Symptoms on Biological Changes of Women Affected by Overweight/Obesity

Background: Both obesity and depression are medical conditions associated with severe disability and biological abnormalities. Our aim was to study associations between Body Mass Index (BMI), depression and biological changes in women affected by overweight or obesity. Methods: Depressive symptoms were evaluated by the Beck Depression Inventory II (BDI-II) questionnaire in 200 women affected by overweight/obesity (mean age of the sample 52.7 ± 12.9 years, BMI 33.8 ± 5.5 kg/m2). A blood sample was obtained for evaluation of biochemical (oxytocin and vitamin D), inflammatory and epigenetic (methylation of clock genes) parameters. Multivariable linear regression models were used to study the association between BMI or severity of depressive symptoms (BDI-II scores) with different biomarkers. Results: BMI was found to be associated with severity of depressive symptoms (p = 0.050). Severity of obesity resulted to be associated with lower plasma levels of oxytocin (p = 0.053), vitamin D deficiency (p = 0.006) and higher plasma levels of IFN-γ (p = 0.004), IL-6 (p = 0.013), IL-7 (p = 0.013), TNF-alpha (p = 0.036) and chemokine ligand 3 (CCL3) (p = 0.013, R2 = 0.03). Severity of depression was significantly associated with more methylation of clock genes CRY1 (p = 0.034, R2 = 0.16) and CRY2 (p = 0.019, R2 = 0.47). More severe depression together with higher levels of IL-8 strongly predicted lower methylation of CLOCK gene (p = 0.009); Conclusions: Different biological abnormalities have been found to be independently associated with BMI and severity of depressive symptoms in women affected by overweight/obesity. The complex interplay between overweight, depression and biological changes will have to be better clarified by future studies.
Novel Carbon Dots Derived from Glycyrrhizae Radix et Rhizoma and Their Anti-Gastric Ulcer Effect

Glycyrrhizae Radix et Rhizoma (GRR) is one of the commonly used traditional Chinese medicines in clinical practice, which has been applied to treat digestive system diseases for hundreds of years. GRR is preferred for anti-gastric ulcer, however, the main active compounds are still unknown. In this study, GRR was used as precursor to synthesize carbon dots (CDs) by a environment-friendly one-step pyrolysis process. GRR-CDs were characterized by using transmission electron microscopy, high-resolution TEM, fourier transform infrared, ultraviolet-visible and fluorescence spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction and high-performance liquid chromatography. In addition, cellular toxicity of GRR-CDs was studied by using CCK-8 in RAW264.7 cells, and the anti-gastric ulcer activity was evaluated and confirmed using mice model of acute alcoholic gastric ulcer. The experiment confirmed that GRR-CDs were the spherical structure with a large number of active groups on the surface and their particle size ranged from 2 to 10 nm. GRR-CDs had no toxicity to RAW264.7 cells at concentration of 19.5 to 5000 μg/mL and could reduce the oxidative damage of gastric mucosa and tissues caused by alcohol, as demonstrated by restoring expression of malondialdehyde, superoxide dismutase and nitric oxide in serum and tissue of mice. The results indicated the explicit anti-ulcer activity of GRR-CDs, which provided a new insights for the research on effective material basis of GRR.
Effect of inhibitory compounds on the anaerobic digestion performance of diluted wastewaters from the alimentary industry.

BACKGROUND: Up to now the effect of inhibitory compounds on the anaerobic digestion performance of urban and industrial wastewaters has been mostly studied in fluidized bed and upflowing anaerobic sludge blanket (UASB) bioreactors but not in upflow packed-bed biodigesters. RESULTS: In this paper, response surface methodology (RSM) was used to quantify the effect of various inhibitory compounds (olive oil, ethanol and phenol) on chemical oxygen demand (COD) removal and biogas production rate from synthetic solutions and real industrial wastewaters by anaerobic digestion. The synthetic solutions possessed the same composition in these inhibitory compounds as diluted effluents from olive oil mill and winery industries. The process was performed in a laboratory scale digester containing anaerobic sludge from the Urban Reclamation Station of Toledo (Spain). The comparison of both individual factors and interactions between factors showed that the addition of olive oil at moderate concentrations (up to 0.5% w/w) did not change the performance of the process in comparison with that observed when feeding to the system a model solution (51.5% COD removal, 0.65 L biogas day−1). However, low concentrations of ethanol or phenol (250 and 150 mg L−1, respectively) almost completely inhibited the methanogenic phase. Moreover, a strong interaction between ethanol and phenol concentrations on COD removal was observed. CONCLUSION: The experimental results showed quantitatively the importance of some inhibitory compounds on anaerobic treatment of both synthetic solutions and real wastewaters from olive oil mill and winery industries. Inhibitory effects are closely related to both the organic loads and the anaerobic bioreactor used. Copyright © 2009 Society of Chemical Industry
Pleiotropic Effects of PCSK-9 Inhibitors

Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a group of drugs whose main mechanism of action is binding to the PCSK-9 molecule, which reduces the degradation of the low-density lipoprotein receptor (LDL-R) and, hence, increases the uptake of low-density lipoprotein cholesterol (LDLc) from the bloodstream as well as reducing its concentration. The effectiveness of three monoclonal antibodies, namely, alirocumab (human IgG1/κ monoclonal antibody, genetically engineered in Chinese hamster ovary cells), evolocumab (the first fully human monoclonal antibody), and bococizumab (humanized mouse antibody), in inhibiting the action of PCSK-9 and reducing LDLc levels has been confirmed. The first two, after clinical trials, were approved by the Food and Drug Administration (FDA) and are used primarily in the treatment of autosomal familial hypercholesterolemia and in cases of statin intolerance. They are currently used both as monotherapy and in combination with statins and ezetimibe to intensify therapy and achieve therapeutic goals following the American Heart Association (AHA) and European Society of Cardiology (ESC) guidelines. However, the lipid-lowering effect is not the only effect of action described by researchers that PCSK-9 inhibitors have. This paper is a review of the literature describing the pleiotropic effects of PCSK-9 inhibitors, which belong to a group of drugs that are being increasingly used, especially when standard lipid-lowering therapy fails. The article focuses on activities other than lipid-lowering, such as the anti-atherosclerotic effect and stabilization of atherosclerotic plaque, the anti-aggregation effect, the anticoagulant effect, the antineoplastic effect, and the ability to influence the course of bacterial infections. In this publication, we try to systematically review the current scientific data, both from our own scientific work and knowledge from international publications.
Age and Sex-Related Changes in Human First-Trimester Placenta Transcriptome and Insights into Adaptative Responses to Increased Oxygen

Physiological oxygen tension rises dramatically in the placenta between 8 and 14 weeks of gestation. Abnormalities in this period can lead to gestational diseases, whose underlying mechanisms remain unclear. We explored the changes at mRNA level by comparing the transcriptomes of human placentas at 8–10 gestational weeks and 12–14 gestational weeks. A total of 20 samples were collected and divided equally into four groups based on sex and age. Cytotrophoblasts were isolated and sequenced using RNAseq. Key genes were identified using two different methods: DESeq2 and weighted gene co-expression network analysis (WGCNA). We also constructed a local database of known targets of hypoxia-inducible factor (HIF) subunits, alpha and beta, to investigate expression patterns likely linked with changes in oxygen. Patterns of gene enrichment in and among the four groups were analyzed based on annotations of gene ontology (GO) and KEGG pathways. We characterized the similarities and differences between the enrichment patterns revealed by the two methods and the two conditions (age and sex), as well as those associated with HIF targets. Our results provide a broad perspective of the processes that are active in cytotrophoblasts during the rise in physiological oxygen, which should benefit efforts to discover possible drug-targeted genes or pathways in the human placenta.
Comparison of the Genetic Features Involved in Bacillus subtilis Biofilm Formation Using Multi-Culturing Approaches

Surface-associated multicellular assemblage is an important bacterial trait to withstand harsh environmental conditions. Bacillus subtilis is one of the most studied Gram-positive bacteria, serving as a model for the study of genetic pathways involved in the different steps of 3D biofilm formation. B. subtilis biofilm studies have mainly focused on pellicle formation at the air-liquid interface or complex macrocolonies formed on nutritive agar. However, only few studies focus on the genetic features of B. subtilis submerged biofilm formation and their link with other multicellular models at the air interface. NDmed, an undomesticated B. subtilis strain isolated from a hospital, has demonstrated the ability to produce highly structured immersed biofilms when compared to strains classically used for studying B. subtilis biofilms. In this contribution, we have conducted a multi-culturing comparison (between macrocolony, swarming, pellicle, and submerged biofilm) of B. subtilis multicellular communities using the NDmed strain and mutated derivatives for genes shown to be required for motility and biofilm formation in pellicle and macrocolony models. For the 15 mutated NDmed strains studied, all showed an altered phenotype for at least one of the different culture laboratory assays. Mutation of genes involved in matrix production (i.e., tasA, epsA-O, cap, ypqP) caused a negative impact on all biofilm phenotypes but favored swarming motility on semi-solid surfaces. Mutation of bslA, a gene coding for an amphiphilic protein, affected the stability of the pellicle at the air-liquid interface with no impact on the submerged biofilm model. Moreover, mutation of lytF, an autolysin gene required for cell separation, had a greater effect on the submerged biofilm model than that formed at aerial level, opposite to the observation for lytABC mutant. In addition, B. subtilis NDmed with sinR mutation formed wrinkled macrocolony, less than that formed by the wild type, but was unable to form neither thick pellicle nor structured submerged biofilm. The results are discussed in terms of the relevancy to determine whether genes involved in colony and pellicle formation also govern submerged biofilm formation, by regarding the specificities in each model.