Maytansinoids are a successful class of natural and semisynthetic tubulin binders, known for their potent cytotoxic activity. Their wider application as cytotoxins and chemical probes to study ...tubulin dynamics has been held back by the complexity of natural product chemistry. Here we report the synthesis of long‐chain derivatives and maytansinoid conjugates. We confirmed that bulky substituents do not impact their high activity or the scaffold's binding mode. These encouraging results open new avenues for the design of new maytansine‐based probes.
The design and synthesis as well as biochemical and structural characterization of long‐chain maytansinoids and maytansinoid conjugates is reported. The results show the prospects of maytansinoids as probes to study microtubule dynamics and lead towards the design of new maytansine‐based derivatives.
Gestational Diabetes Mellitus (GDM) and obesity affect the functioning of multiple maternal systems and influence colonization of the newborn gastrointestinal through the breastmilk microbiota (BMM). ...It is currently unclear how GDM and obesity affect the human BMM composition. Here, we applied 16S-rRNA high-throughput sequencing to human colostrum milk to characterize BMM taxonomic changes in a cohort of 43 individuals classified in six subgroups according to mothers patho-physiological conditions (healthy control (n = 18), GDM (n = 13), or obesity (n = 12)) and newborn gender. Using various diversity indicators, including Shannon/Faith phylogenetic index and UniFrac/robust Aitchison distances, we evidenced that BMM composition was influenced by the infant gender in the obesity subgroup. In addition, the GDM group presented higher microbial diversity compared to the control group. Staphylococcus, Corynebacterium 1, Anaerococcus and Prevotella were overrepresented in colostrum from women with either obesity or GDM, compared to control samples. Finally, Rhodobacteraceae was distinct for GDM and 5 families (Bdellovibrionaceae, Halomonadaceae, Shewanellaceae, Saccharimonadales and Vibrionaceae) were distinct for obesity subgroups with an absolute effect size greater than 1 and a q-value ≤ 0.05. This study represents the first effort to describe the impact of maternal GDM and obesity on BMM.
Invited for the cover of this issue are the groups of Professors Passarella and Pieraccini at the University of Milan, in collaboration with some of the members of TubInTrain consortium. The image ...depicts work with the elements of nature, in particular the destabilising effect of maytansinol (the constellation) on microtubules (the trees). Read the full text of the article at 10.1002/chem.202203431.
A two‐decade evolution nodule on the upper lip Capusan, T. M.; Herrero‐Moyano, M.; Llamas‐Velasco, M. ...
Clinical and experimental dermatology,
June 2021, 2021-Jun, 2021-06-00, 20210601, Letnik:
46, Številka:
4
Journal Article
Recenzirano
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Concentrated solar power (CSP) is one of the growing technologies that is leading the process of change from fossil fuels to renewable energies for electricity production. The sophistication and size ...of the systems require an increase in maintenance tasks to ensure reliability, availability, maintainability, and safety. Currently, automatic detection of broken glass envelopes of receiver tubes in CSP plants using parabolic trough collector systems has two main drawbacks: 1) the devices in use need to be manually placed near the receiver tube, 2) the machine learning–based solutions have only been tested in constrained environments. We address both gaps by combining the data collected by an unmanned aerial vehicle with data provided by sensors placed within 7 real CSP plants. The resulting dataset is the first of this type and can help standardize research activities for the problem of fault detection in this type of power plant. Our work proposes supervised machine-learning algorithms for detecting broken envelopes of the receiver tubes in CSP plants. The proposed solution takes the class imbalance problem into account, boosting the accuracy of the algorithms for the minority class without harming the overall performance of the models. For a deep residual network, we solve an imbalance and a balance problem at the same time, which increases the recall of the minority class by 5% with no harm to the F1 score. Additionally, the random under-sampling technique boosts the performance of traditional machine learning models. The histogram gradient boost classifier was found to be the algorithm with the highest increase (3%) in the F1 score. To the best of our knowledge, this paper is the first to provide an automated solution to this problem using data from operating plants, drones, and highly unbalanced datasets.
Control of gene expression and induction of cellular protection mechanisms are two important processes that plants employ to protect themselves against abiotic stresses. ABA-, stress, and ...ripening-induced (ASR) proteins have been identified to participate in such responses. Previous studies have proposed that these proteins can act as transcription factors and as molecular chaperones protecting transgenic plants against stresses; however a gene network regulated by ASRs has not been explored. To expand our knowledge on the function of these proteins in cereals, we present the functional characterization of a barley ASR gene. Expression of HvASR5 was almost ubiquitous in different organs and responded to ABA and to different stress treatments. When expressed ectopically, HvASR5 was able to confer drought and salt stress tolerance to Arabidopsis thaliana and to improve growth performance of rice plants under stress conditions. A transcriptomic analysis with two transgenic rice lines overexpressing HvASR5 helped to identify potential downstream targets and understand ASR-regulated cellular processes. HvASR5 up-regulated the expression of a distinct set of genes associated with stress responses, metabolic processes (particularly carbohydrate metabolism), as well as reproduction and development. These data, together with the confirmed nuclear and cytoplasmic localization of HvASR5, further support the hypothesis that HvASR5 can also carry out roles as molecular protector and transcriptional regulator.
Here, a measurement with high statistics of the differential energy spectrum of light elements in cosmic rays, in particular, of primary H plus He nuclei, is reported. The spectrum is presented in ...the energy range from 6 to 158 TeV per nucleus. Data was collected with the High Altitude Water Cherenkov (HAWC) Observatory between June 2015 and June 2019. The analysis was based on a Bayesian unfolding procedure, which was applied on a subsample of vertical HAWC data that was enriched to 82% of events induced by light nuclei. To achieve the mass separation, a cut on the lateral age of air shower data was set guided by predictions of CORSIKA/QGSJET-II-04 simulations. The measured spectrum is consistent with a broken power-law spectrum and shows a kneelike feature at around E = 24.0$^{+3.6}_{-3.1}$ TeV , with a spectral index γ = -2.51 ± 0.02 before the break and with γ = -2.83 ± 0.02 above it. The feature has a statistical significance of 4.1σ. Within systematic uncertainties, the significance of the spectral break is 0.8σ.
Hyperoxia−hypoxia exposure is a proposed cause of alveolar developmental arrest in bronchopulmonary dysplasia in preterm infants, where mitochondrial reactive oxygen species and oxidative stress ...vulnerability are increased. The aryl hydrocarbon receptor (AhR) is one of the main activators of the antioxidant enzyme system that protects tissues and systems from damage. The present study aimed to determine if the activation of the AhR signaling pathway by prenatal administration of indole-3-carbinol (I3C) protects rat pups from hyperoxia–hypoxia-induced lung injury. To assess the activation of protein-encoding genes related to the AhR signaling pathway (Cyp1a1, Cyp1b1, Ugt1a6, Nqo1, and Gsta1), pup lungs were excised at 0, 24, and 72 h after birth, and mRNA expression levels were quantified by reverse transcription-quantitative polymerase chain reaction assays (RT-qPCR). An adapted Ratner's method was used in rats to evaluate radial alveolar counts (RACs) and the degree of fibrosis. The results reveal that the relative expression of AhR-related genes in rat pups of prenatally I3C-treated dams was significantly different from that of untreated dams. The RAC was significantly lower in the hyperoxia–hypoxia group (4.0 ± 1.0) than that in the unexposed control group (8.0 ± 2.0; P < 0.01). When rat pups of prenatally I3C-treated dams were exposed to hyperoxia–hypoxia, an RAC recovery was observed, and the fibrosis index was similar to that of the unexposed control group. A cytokine antibody array revealed an increase in the NF-κB signaling cascade in I3C-treated pups, suggesting that the pathway could regulate the inflammatory process under the stimulus of this compound. In conclusion, the present study demonstrates that I3C prenatal treatment activates AhR-responsive genes in pup’s lungs and hence attenuates lung damage caused by hyperoxia–hypoxia exposure in newborns.
•The most consistent finding was the detection of Lihan virus (Family Phenuiviridae, genus Uukuvirus, specie Lihan uukuvirus), identifying in Amblyomma patinoi and A. cajennense.•Sequences of ...Quaranjavirus were detected in Amblyomma patinoi and A. cajennense.•Sequences of Mivirus were detected in Amblyomma patinoi and A. cajennense, this was close Changping Tick Virus 2 (ChTV-2).•“Flavi-like” viruses detected in Rhipicephalus microplus was close Bole Tick Virus.
Tick-borne viruses (TBV) have gained public health relevance in recent years due to the recognition of human-associated fatal cases and the increase in tick-borne disease and transmission. However, many tick species have not been studied for their potential to transmit pathogenic viruses, especially those found in Latin America. To gain better understanding of the tick virome, we conducted targeted amplification using broadly-reactive consensus-degenerate pan-viral targeting viruses from the genera Flavivirus, Bandavirus, Uukuvirus, and Orthonairovirus genus. Additionally, we conducted unbiased metagenomic analyses to investigate the presence of viral RNA sequences in Amblyomma cajennense, A. patinoi and Rhipicephalus microplus ticks collected from a horse slaughter plant in Medellín, Colombia. While no viral products were detected by PCR, results of the metagenomic analyses revealed the presence of viral genomes belonging to the genera Phlebovirus, Bandavirus, and Uukuvirus, including Lihan Tick Virus (LTV), which was previously reported in Rhipicephalus microplus from Colombia. Overall, the results emphasized the enormous utility of the next-generation sequencing in identifying virus genetic diversity presents in ticks and other species of vectors and reservoirs.
Single-neutron and single-proton removal cross sections have been measured for medium-mass neutron-rich nuclei around Z=50 and energies around 1000A MeV using the FRagment Separator (FRS) at GSI. The ...measured cross sections confirm the relative low values of the proton-removal cross sections, observed since a long time ago and not yet understood. Model calculations considering the knock-out process together with initial- and final-state interactions describe the measured neutron-removal cross sections. Proton-removal cross sections are, however, significantly over-predicted by the same calculations. The observed difference can be explained to a large extent by the knock-out of short-range correlated nucleons from dominant neutron-proton pairs in neutron-rich nuclei.
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