Massague

The head domain of the hemagglutinin of influenza viruses plays a dominant role in the antibody response due to the presence of immunodominant antigenic sites that are the main targets of host neutralizing antibodies. For the H1 hemagglutinin, five major antigenic sites defined as Sa, Sb, Ca1, Ca2, and Cb have been described. Although previous studies have focused on defining the hierarchy of the antigenic sites of the hemagglutinin in different human cohorts, it is still unclear if the immunodominance profile of the antigenic sites might change with the antibody levels of individuals or if other demographic factors (such as exposure history, sex, or age) could also influence the importance of the antigenic sites...

Driver gene mutations can increase the metastatic potential of the primary tumor 1-3 , but their role in sustaining tumor growth at metastatic sites is poorly understood. A paradigm of such mutations is inactivation of SMAD4 - a transcriptional effector of TGFβ signaling - which is a hallmark of multiple gastrointestinal malignancies 4,5 . SMAD4 inactivation mediates TGFβ's remarkable anti-to pro-tumorigenic switch during cancer progression and can thus influence both tumor initiation and metastasis 6-14 ...

Macrophage activation is controlled by a balance between activating and inhibitory receptors1-7 , which protect normal tissues from excessive damage during infection8,9 but promote tumour growth and metastasis in cancer7,10 . Here we report that the Kupffer cell lineage-determining factor ID3 controls this balance and selectively endows Kupffer cells with the ability to phagocytose live tumour cells and orchestrate the recruitment, proliferation and activation of natural killer and CD8 T lymphoid effector cells in the liver to restrict the growth of a variety of tumours...

One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes in order to facilitate the generation of 1 O2 . We have obtained derivatives of formulas [Cp*Ir(C∧ N)Cl] and [Cp*Ir(C∧ N)L]BF4 with different degrees of π-expansion in the C∧ N ligands...

Shortly after the beginning of the SARS-CoV-2 pandemic, many countries implemented sewage sentinel systems to monitor the circulation of the virus in the population. A fundamental part of these surveillance programs is the variant tracking through sequencing approaches to monitor and identify new variants or mutations that may be of importance. Two of the main sequencing platforms are Illumina and Oxford Nanopore Technologies. Here, we compare the performance of MiSeq (Illumina) and MinION (Oxford Nanopore Technologies), as well as two different data processing pipelines, to determine the effect they may have on the results...

Improved broad-spectrum influenza virus vaccines are desperately needed to provide protection against both drifted seasonal and emerging pandemic influenza A viruses (IAVs). Antibody-based protection from influenza A virus-induced morbidity and mortality is traditionally associated with neutralizing antibodies. As such, vaccine efforts have solely focused on the hemagglutinin (HA) as a vaccine target; however, the HA is mutation prone resulting in the need for annual vaccine reformulation. Broad-spectrum vaccines could be achieved through non-neutralizing antibodies that target conserved influenza virus antigens...

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The TGF-β regulatory system plays crucial roles in the preservation of organismal integrity. TGF-β signaling controls metazoan embryo development, tissue homeostasis, and injury repair through coordinated effects on cell proliferation, phenotypic plasticity, migration, metabolic adaptation, and immune surveillance of multiple cell types in shared ecosystems. Defects of TGF-β signaling, particularly in epithelial cells, tissue fibroblasts, and immune cells, disrupt immune tolerance, promote inflammation, underlie the pathogenesis of fibrosis and cancer, and contribute to the resistance of these diseases to treatment...

Seasonal influenza virus vaccines are effective when they are well matched to circulating strains. Because of antigenic drift/change in the immunodominant hemagglutinin (HA) head domain, annual vaccine reformulations are necessary to maintain a match with circulating strains. In addition, seasonal vaccines provide little to no protection against newly emerging pandemic strains. Sequential vaccination with chimeric HA (cHA) constructs has been proven to direct the immune response toward the immunosubdominant but more conserved HA stalk domain...

Cognitive alterations are a common feature associated with many neurodegenerative diseases and are considered a major health concern worldwide. Cognitive alterations are triggered by microglia activation and oxidative/inflammatory processes in specific areas of the central nervous system. Consumption of bioactive compounds with antioxidative and anti-inflammatory effects, such as astaxanthin and spirulina, can help in preventing the development of these pathologies. In this study, we have investigated the potential beneficial neuroprotective effects of a low dose of astaxanthin (ASX) microencapsulated within spirulina (ASXSP) in female rats to prevent the cognitive deficits associated with the administration of LPS...

Tropospheric ozone (O3 ) is a secondary air pollutant that affects human health, vegetation and climate, especially in Mediterranean countries such as Spain. In order to tackle this long-standing issue, the Spanish government recently started to design the Spanish O3 Mitigation Plan. To support this initiative and ultimately provide recommendations, we performed a first ambitious emission and air quality modeling exercise. This study presents the development of different emission scenarios - aligned with or beyond the measures planned for 2030 in Spain - and the modeling of their respective impact on the O3 pollution across Spain (in July 2019) with both MONARCH and WRF-CMAQ air quality models...

The water-soluble ruthenium complex cis-[Ru(dcbpyH)2 (PTAH)2 ]Cl2 ·3H2 O (1) (dcbpy = 4,4'-dicarboxy-2,2'-bipyridine; PTA = 1,3,5-triaza-7-phosphaadamantane) has been synthesized and characterised by NMR, IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction. The optical properties of 1 were studied, including photoactivation under visible light, as well as its biological properties, together with those of the previously published Ru complexes cis-[Ru(bpy)2 (PTA)2 ]Cl2 (2), trans-[Ru(bpy)2 (PTA)2 ](CF3 SO3 )2 (3) and cis-[Ru(bpy)2 (H2 O)(PTA)](CF3 SO3 )2 (4) (bpy = 2,2'-bipyridine)...

Seasonal influenza viruses account for 1 billion infections worldwide every year, including 3-5 million cases of severe illness and up to 650,000 deaths. The effectiveness of current influenza virus vaccines is variable and relies on the immunodominant hemagglutinin (HA) and to a lesser extent on the neuraminidase (NA), the viral surface glycoproteins. Efficient vaccines that refocus the immune response to conserved epitopes on the HA are needed to tackle infections by influenza virus variants. Sequential vaccination with chimeric HA (cHA) and mosaic HA (mHA) constructs has proven to induce immune responses to the HA stalk domain and conserved epitopes on the HA head...

OBJECTIVE: This study aimed to determine whether being overweight during childhood is a risk factor for torsion of the appendix testis (TAT). METHODS: We conducted a paired case-control study with all boys surgically treated for TAT, paired by age and sex with patients who were seen in the emergency department for a reason other than acute scrotum. Age and weight were registered, and weight percentile (WP) by age was calculated and compared between groups. Weight percentile was classified into 4 groups (<25, 25-50, 50-75, >75), and a conditional logistic regression analysis was performed to establish the risk of TAT related to the WP...

Mutation research is crucial for detecting and treating SARS-CoV-2 and developing vaccines. Using over 5,300,000 sequences from SARS-CoV-2 genomes and custom Python programs, we analyzed the mutational landscape of SARS-CoV-2. Although almost every nucleotide in the SARS-CoV-2 genome has mutated at some time, the substantial differences in the frequency and regularity of mutations warrant further examination. C>U mutations are the most common. They are found in the largest number of variants, pangolin lineages, and countries, which indicates that they are a driving force behind the evolution of SARS-CoV-2...

This study aims to support the development of Spain's Ozone Mitigation Plan by evaluating the present-day spatial variation (2015-2019) and trends (2008-2019) for seven ground-level ozone (O3 ) metrics relevant for human/ecosystems exposure and regulatory purposes. Results indicate that the spatial variation of O3 depends on the part of the O3 distribution being analyzed. Metrics associated with moderate O3 concentrations depict an increasing O3 gradient between the northern and Mediterranean coasts due to climatic factors, while for metrics considering the upper end of the O3 distribution, this climatic gradient tends to attenuate in favor of hotspot regions pointing to relevant local/regional O3 formation...

The human gut microbiome plays an important role in health, and its initial development is conditioned by many factors, such as feeding. It has also been claimed that this colonization is guided by bacterial populations, the dynamic virome, and transkingdom interactions between host and microbial cells, partially mediated by epigenetic signaling. In this article, we characterized the bacteriome, virome, and smallRNome and their interaction in the meconium and stool samples from infants. Bacterial and viral DNA and RNA were extracted from the meconium and stool samples of 2- to 4-month-old milk-fed infants...

Ethylene propylene diene monomer (EPDM) is one of the most used polymers in the world. It is an elastomer, which means that the existing cross-linking between the main chains of the polymer created during the vulcanization process makes its recycling difficult. In this paper, a possible solution to this issue is studied. The devulcanization of EPDM is achieved by a thermomechanical process followed by microwave irradiation. These combined treatments suppress the cross-linking, yielding a material (EPDMd) that can be successfully blended to form composites...

Brain metastasis is a dismal cancer complication, hinging on the initial survival and outgrowth of disseminated cancer cells. To understand these crucial early stages of colonization, we investigated two prevalent sources of cerebral relapse, triple-negative (TNBC) and HER2+ breast cancer (HER2BC). We show that these tumor types colonize the brain aggressively, yet with distinct tumor architectures, stromal interfaces, and autocrine growth programs. TNBC forms perivascular sheaths with diffusive contact with astrocytes and microglia...

Metastasis frequently develops from disseminated cancer cells that remain dormant after the apparently successful treatment of a primary tumour. These cells fluctuate between an immune-evasive quiescent state and a proliferative state liable to immune-mediated elimination1-6 . Little is known about the clearing of reawakened metastatic cells and how this process could be therapeutically activated to eliminate residual disease in patients. Here we use models of indolent lung adenocarcinoma metastasis to identify cancer cell-intrinsic determinants of immune reactivity during exit from dormancy...