We show that the unbounded derived category of a Grothendieck category with enough projective objects is the base category of a derivator whose category of diagrams is the full 2-category of small ...categories. With this structure, we give a description of the localization functor associated to a specialization closed subset of the spectrum of a commutative noetherian ring. In addition, using the derivator of modules, we prove some basic theorems of group cohomology for complexes of representations over an arbitrary base ring.
Research into seed germination classroom activities has been common in the last few decades. Didactic proposals have generally focused on the implementation of guided activities in a specific ...educational stage and context, and an evaluation of the results. However, it is not evident that students approach seed and germination concepts with a reasoned argument. In light of this, comparative research using an inquiry approach was undertaken with 59 primary school students and 82 trainee teachers at an education faculty in Spain, over two academic years. The results showed that it is necessary to give greater relevance to experimental activities to produce reasoned argumentation of seed and germination concepts. Activities should focus on variables that differ from those typical of common or historical agricultural knowledge. Variables derived from genetic information (size of the seed, latency period) are significant and helpful. It is also considered essential to work on the meaning and proper use of scientific terms, such as living and inert matter, sun-light-heat, or plant germination and growth processes. The search for explanations and the development of justifications, for example relating the excess of water to a lack of oxygen for the seeds, is also essential.
Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein ...effectors into host cells. The application of these “molecular syringes” for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells.
Salt harvesting through natural solar evaporation of salt brines is a practice notably abundant in the Iberian Peninsula. Such activity has been relevant for human consumption, food preservation, ...livestock feed, and various industries throughout history. The objective of this research is to analyze the productive history and conservation state of the salt evaporation ponds located in Naval and Peralta de la Sal (Huesca, Spain), as well as their didactic potential. These saltworks are associated with clay and gypsum levels from the Upper Triassic (Keuper). The earliest written records of salt production in the area date back to the 10th century, but they were exploited as early as the Bronze Age. Remains of most of the ponds and some buildings are still preserved and are easily accessed, which makes them very interesting from an educational perspective. Both on-site and off-site activities can be carried out to analyze their historical and current significance through modeling and argumentation practices. This can lead to a better understanding of how geology relates to everyday life and facilitate the development of positive attitudes among students towards geoheritage while raising awareness about its preservation and preventing its degradation.
Bone alterations have been observed in the course of HIV infection, characterized by a marked decrease in bone mineral density (BMD) and an increase in the frequency of fractures as a result of ...fragility. We aim to evaluate early changes in bone metabolic profile and the possible association with tenofovir and other nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) in treatment-naïve HIV patients.
We conducted a prospective study in naïve HIV-infected adults (under 50 years), separated into three groups according to NRTI therapy: tenofovir disoproxil fumarate (TDF); tenofovir alafenamide (TAF) and abacavir (ABC). BMD and epidemiological, immunological and metabolic bone parameters were evaluated. Bone markers were analyzed in plasma at baseline, 12 and 48 weeks after initiating treatment.
Average age of patients was 34.8 years (± 9.6). 92.4% of them with CD4 count > 200 cel/μL. At week 12 after starting treatment, both TDF increase in PN1P (31.7%, p = 0.004), TRAP (11.1%, p = 0.003), OPN (19.3%, p = 0.045) and OC (38.6%, p = 0.001); decrease in OPG (-23.4%, p = 0.003) and TAF increase in 42.6% for CTX (p = 0.011), 27.3% for OC (p = 0.001) and 21% for TRAP (p = 0.008); decrease in OPG (-28.8%, p = 0.049) presented a deep resorption profile compared to ABC, these differences in bone molecular markers, a tendency to equalize at week 48, where no significant differences were observed. Patients treated with TDF showed the greatest decrease in Z-score in both lumbar spine (LS) and femoral neck (FN) at week 48 without statistically significant differences.
Treatment-naïve HIV patients have a high prevalence of low bone density. Treatment with TDF is associated with greater bone deterioration at 12 and 48 weeks. TAF seems to present similar early bone deterioration at 12 weeks which disappears at 48 weeks.
Oncogene-negative, PDL1-negative metastatic non-small cell lung cancer (NSCLC) presents significant treatment challenges due to its complexity and resistance to conventional therapies. The case ...report presented addresses a 55-year-old male patient with oncogene-negative, PDL1-negative stage IV lung adenocarcinoma, showcasing an exceptional complete metabolic response to a multimodality treatment combining double immune checkpoint inhibition (ICI) and chemotherapy, followed by salvage stereotactic body radiotherapy (SBRT). The patient underwent a treatment regimen incorporating two cycles of carboplatin, pemetrexed, nivolumab, and ipilimumab followed by nivolumab, and ipilimumab maintenance. After a partial response, SBRT was applied to persistent lesions, achieving a complete metabolic response. This case highlights the potential of combining dual ICI with chemotherapy and SBRT in treating oncogene-negative, PDL1-negative NSCLC underscoring the importance of multimodality treatment strategies.
Targeting microtubules is the most effective wide-spectrum pharmacological strategy in antitumoral chemotherapy, and current research focuses on reducing main drawbacks: neurotoxicity and resistance. ...PM534 is a novel synthetic compound derived from the Structure–Activity-Relationship study on the natural molecule PM742, isolated from the sponge of the order Lithistida, family Theonellidae, genus Discodermia (du Bocage 1869). PM534 targets the entire colchicine binding domain of tubulin, covering four of the five centers of the pharmacophore model. Its nanomolar affinity and high retention time modulate a strikingly high antitumor activity that efficiently overrides two resistance mechanisms in cells (detoxification pumps and tubulin βIII isotype overexpression). Furthermore, PM534 induces significant inhibition of tumor growth in mouse xenograft models of human non-small cell lung cancer. Our results present PM534, a highly effective new compound in the preclinical evaluation that is currently in its first human Phase I clinical trial.
The objective of this study was to assess the risk of central line–associated bloodstream infection (CLABSI) of ultrasound (US)-guided cannulation of the brachiocephalic vein (BCV) compared to ...standard epicutaneous cava catheters (ECCs) in preterm infants. This was a retrospective cohort study in preterm infants with a birth weight of less than 1500 g. Each BCV catheter was matched 1:3 with ECCs according to sex, birth weight, and year of insertion. The main outcome was the CLABSI density rate per 1000 days. Secondary outcomes included CLABSI episodes, CLABSI episodes per infant, and CLABSI/death. A multivariate Cox regression analysis was performed to assess whether the type of catheter (ECC vs. BCV) was associated with CLABSI risk. Ninety-six catheters (21 BCVs and 75 ECCs) in 79 infants were included (993 catheter days). BCV catheters were associated with a reduced CLABSI density rate compared to ECCs (3.05/1000 days vs 21.1/1000 days;
p
< 0.001). ECCs were associated with increased CLABSI risk compared to BCV catheters in multivariate analysis (hazard ratio 36; (95% CI, 2.5–511);
p
= 0.008).
Conclusion
: US-guided supraclavicular cannulation of the BCV was associated with a reduced risk of CLABSI compared to ECCs. This finding deserves further multicenter research.
What is Known:
• An epicutaneous-cava catheter (ECC) is commonly used in preterm infants for routine care (eg. delivery of nutrition and antibiotics) but this device may not suffice in infants who need high-intensity care (multiple drugs, hemodynamic monitoring, fluid resuscitation etc.)
.
• Ultrasound-guided brachiocephalic vein (BCV) catheterization has shown a high success rate and few immediate complications in neonates and small infants but it has never been compared to standard ECCs.
What is New:
• When the operator in properly trained, US guided cannulation of the BCV in preterm infants is feasible, safe and may reduce the risk of CLABSI compared to standard ECCs
.
• This fact may expand the use of BCV catheters in selected high-risk preterm infants who need a large bore venous access.
Sweet Syndrome belongs to a group of diseases known as neutrophilic dermatoses. An uncommon variant named Histiocytoid Sweet Syndrome (HSS) can be associated with a variety of conditions, including ...cancer, infections, drug toxicity and others. Here we present an instance of HSS in an HIV-positive patient in an infectious disease setting.
Cocoa and cocoa-based products contain different compounds with beneficial properties for human health. Polyphenols are the most frequently studied, and display antioxidant properties. Moreover, ...protein content is a very interesting source of antioxidant bioactive peptides, which can be used therapeutically for the prevention of age-related diseases.
A bioactive peptide, 13L (DNYDNSAGKWWVT), was obtained from a hydrolyzed cocoa by-product by chromatography. The in vitro inhibition of prolyl endopeptidase (PEP) was used as screening method to select the suitable fraction for peptide identification. Functional analysis of 13L peptide was achieved using the transgenic Caenorhabditis elegans strain CL4176 expressing the human Aβ₁₋₄₂ peptide as a pre-clinical in vivo model for Alzheimer's disease. Among the peptides isolated, peptide 13L (1 µg/mL) showed the highest antioxidant activity (P≤0.001) in the wild-type strain (N2). Furthermore, 13L produced a significant delay in body paralysis in strain CL4176, especially in the 24-47 h period after Aβ₁₋₄₂ peptide induction (P≤0.0001). This observation is in accordance with the reduction of Aβ deposits in CL4176 by western blot. Finally, transcriptomic analysis in wild-type nematodes treated with 13L revealed modulation of the proteosomal and synaptic functions as the main metabolic targets of the peptide.
These findings suggest that the cocoa 13L peptide has antioxidant activity and may reduce Aβ deposition in a C. elegans model of Alzheimer's disease; and therefore has a putative therapeutic potential for prevention of age-related diseases. Further studies in murine models and humans will be essential to analyze the effectiveness of the 13L peptide in higher animals.
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