Publications by authors named "Jose A Guerra-Assuncao"
Article Synopsis
- Virulence studies on the one-carbon metabolism pathway and proline synthesis indicate their importance in the infection process, particularly in Δ and Δ mutant strains of capsular serotype 6B BHN418.* -
- These mutant strains showed significantly reduced virulence in models of mouse sepsis and pneumonia despite being able to colonize the nasopharynx and grow normally in nutrient-rich environments.* -
- Differences in metabolic profiles and gene transcription under various stress conditions revealed strain-specific effects on virulence and metabolism, underscoring the need for rapid adaptation to host physiological conditions.*
Article Synopsis
- Cancer-associated fibroblasts (CAFs) in B-cell precursor acute lymphoblastic leukemia (B-ALL) originate from bone marrow-derived mesenchymal stromal cells (MSCs) and are influenced by reactive oxygen species from chemotherapy.
- The study shows that exposure of MSCs to B-ALL cells or their secretions initiates the CAF formation, marked by a strong interferon pathway response.
- A key finding is that leukemia cell-derived mitochondrial double-stranded RNA (dsRNA) stimulates MSCs to transition into CAFs, and disrupting dsRNA can block this process, revealing a new way cancer cells interact with their environment.
Mutagenic antiviral drugs have shown promise against multiple viruses, but concerns have been raised about whether their use might promote the emergence of new and harmful viral variants. Recently, genetic signatures associated with molnupiravir use have been identified in the global SARS-COV-2 population. Here, we examine the consequences of using favipiravir and molnupiravir to treat SARS-CoV-2 infection in a hamster model, comparing viral genome sequence data collected from (1) untreated hamsters, and (2) from hamsters receiving effective and suboptimal doses of treatment.
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- The study investigates the effects of molnupiravir on viral clearance, antibody response, and mutagenesis in non-hospitalized individuals within 5 days of experiencing COVID-19 symptoms, comparing it to usual care.
- Results show that while molnupiravir accelerates the decline of viral load, many participants still test positive for the virus 5 days later, and significantly lower antiviral antibodies are observed after 14 days compared to those receiving usual care.
- Serial sequencing suggests that treatment with molnupiravir leads to increased mutations of the virus, raising concerns about the emergence of potentially transmissible variants, indicating that the current treatment duration may be insufficient.
Article Synopsis
- The study focused on the long-term health outcomes of immunocompromised patients infected with COVID-19, specifically evaluating the effectiveness of various antiviral treatments on achieving sustained viral clearance.
- Among the 103 patients treated, 71 achieved sustained viral clearance, while 32 did not, with a notable number of these patients experiencing poor health outcomes, including deaths.
- The research highlighted that those with persistent PCR positivity had significantly lower B cell counts and immunoglobulin levels, indicating a potential link between immune function and the ability to clear the virus.
Article Synopsis
- Over 1,000 unexplained pediatric hepatitis cases have been identified globally, with a study focusing on 38 cases and various control groups to understand potential viral causes.
- High levels of adeno-associated virus 2 (AAV2) DNA were found in most cases, while low levels of adenovirus and human herpesvirus 6B were also detected; however, AAV2 appeared infrequently in healthy controls even when they were immunocompromised.
- The study suggests that abnormal replication of AAV2, potentially influenced by other viruses like HAdV and HHV-6B, may be responsible for immune-related liver disease in susceptible children.
The advent of pneumococcal conjugate vaccines led to the near disappearance of most of the included serotypes in high-income settings but also the rise of nonvaccine-type colonization and disease. Alternative strategies, using genetically conserved proteins as antigens, have been evaluated preclinically and clinically for years, so far unsuccessfully. One possible explanation for the failure of these efforts is that the choice of antigens may not have been sufficiently guided by an understanding of the gene expression pattern in the context of infection.
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- The study investigates immune responses to SARS-CoV-2 during primary exposure to identify factors that contribute to protective immunity against future variants.
- It utilizes advanced techniques like blood transcriptomics and T cell receptor sequencing to observe rapid immune responses, particularly type 1 interferon and CD8 T cell proliferation, that occur at or before virus detection.
- Findings suggest that early immune responses play a protective role and highlight potential strategies for developing universal T cell vaccines.
Article Synopsis
- HIV-1 infects CD4 T cells, which leads to AIDS, and understanding how it creates a favorable environment for replication is crucial for finding treatments and potential cures.
- A major challenge in studying HIV-T cell interactions is that activating T cells in labs alters their natural behavior, complicating infection studies.
- This research reveals that HIV-1 can efficiently infect resting memory T cells without activation, transforming them to behave like tissue-resident memory T cells, driven by the viral protein Vpr and affecting specific signaling pathways.
Article Synopsis
- - The study examines genetic differences within childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) during and after chemotherapy, suggesting that rather than significantly reducing genetic diversity, chemotherapy mainly affects cell behavior and characteristics.
- - Researchers transplanted individual leukemias into multiple hosts to analyze how chemotherapy impacts these tumors at a single-cell level, finding that the treatment decreases the variety of cell states without greatly altering the genetic makeup of the cancer cells.
- - The findings indicate that the reduction of different cell states during chemotherapy leads to a more uniform population of cancer cells, suggesting that this "canalization" of cell states is a key factor in how certain cell types dominate after treatment and may influence outcomes in cancer relapse. *
Article Synopsis
- Recent SARS-CoV-2 variants have raised concerns about increased transmission within communities, prompting an investigation into their impact on hospital settings.
- A study analyzed viral sequences and epidemiological data from patients in nine UK hospitals to assess the likelihood of healthcare-associated infections being caused by the Alpha variant versus community-acquired infections.
- The results indicated no significant difference in the transmission of the Alpha variant compared to other lineages, suggesting existing infection control measures in UK hospitals are effective at containing the spread of emergent variants.
Article Synopsis
- The study investigated the impact of the SARS-CoV-2 B.1.1.7 variant on hospitalised patients, focusing on transmission rates and disease severity.
- Analysis included data from 2,341 inpatients, and results indicated no overall increase in mortality or intensive therapy unit (ITU) admissions associated with B.1.1.7 compared to other variants.
- However, female patients infected with B.1.1.7 demonstrated a higher risk for ITU admission and a modestly increased risk of mortality.
Article Synopsis
- DMEK is a newer, preferred procedure for treating corneal endothelial issues, but its risks of infectious complications, particularly from HSV-1, are not well understood.
- Two patients developed atypical HSV-1 infections shortly after receiving DMEK transplants from different donors on the same day, raising concerns about the source of the virus.
- Genetic analysis revealed that the HSV-1 strains in both patients' eyes were highly similar to those found in one of the donor corneas, suggesting a possible link between the donor tissue and the infections.
A recent surge in human mastadenovirus (HAdV) cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. We compared sequences from 37 patients collected over a 20-month period with sequences from GenBank and our own database of HAdVs. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships, paired with the epidemiological data from routine infection prevention and control (IPC) records and hospital activity data.
View Article and Find Full Text PDFBackground: We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.
Methods: We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew's Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work.
Article Synopsis
- Researchers explored using live, weakened strains of bacteria given through the nose as a new way to prevent infections, focusing on strains without a protective capsule.
- In mouse models, these weakened strains showed reduced ability to colonize the nasal area and triggered weaker immune responses compared to the normal strain, but still provided some protection against severe pneumonia.
- The study concluded that targeting the bacterial capsule for vaccine development might not be the best approach, as it did not effectively prevent future infections compared to other methods.
Article Synopsis
- Checkpoint inhibitors (CPIs) enhance the body's immune response against tumors by analyzing both tumor characteristics and surrounding tissue features, which can help identify how well patients may respond to treatment.
- In a study involving over 1,000 patients with different tumor types, researchers found that clonal tumor mutation burden (TMB) was the strongest predictor of response to CPIs, followed by total TMB and specific gene expressions like CXCL9.
- Additional factors influencing CPI responses were identified, including genetic alterations such as TRAF2 loss linked to better outcomes and CCND1 amplification associated with resistance, as well as specific immune markers found in tumor-infiltrating lymphocytes.
Article Synopsis
- Follicular lymphoma (FL) is a type of slow-growing B-cell lymphoma that can turn into a more aggressive form known as transformed FL (tFL), but the mechanisms behind this transformation are not well understood.
- Researchers investigated mutations in microRNA (miRNA)-binding sites within the genomes of FL and tFL patients, identifying 544 mutations linked to these regions.
- Out of a targeted sequencing study of 55 FL patients, they found 16 recurrent mutations and 69 additional variants, leading to the identification of 21 mutated genes associated with B-cell functions, with over 40% of these mutations present only in tFL patients.
Article Synopsis
- There has been a surge in whole genome sequencing data from research projects and consumer services, but a gap exists for free tools that simplify data interpretation for users.
- GenomeChronicler was created by the Personal Genome Project UK to fill this gap, generating reports on genetic variants, ancestry, and traits based on open-access genomic data.
- Reports can highlight beneficial and harmful variants using data from sources like SNPedia and ClinVar, and the tool can operate offline, ensuring privacy while offering flexible use for individual or batch sample analysis.
Article Synopsis
- - Tumour mutational burden (TMB) can predict how well patients with non-small cell lung cancer (NSCLC) will respond to immunotherapy, but persistent exposure to antigens can harm T cell function.
- - Research found that higher TMB led to changes in T cell differentiation in untreated NSCLC, such as fewer progenitor-like CD4 T cells and more dysfunctional CD8 and CD4 T cells that resemble those activated by neoantigens.
- - A gene signature indicating the shift from healthy to dysfunctional T cell states was linked to poorer survival rates, highlighting the need for new therapeutic strategies to improve outcomes in NSCLC patients.
Article Synopsis
- An amendment to the original paper has been published.
- You can find the amendment by following the link located at the top of the paper.
- This provides updated or additional information relevant to the original content.
Article Synopsis
- Loss-of-function mutations in PRC2's EZH2 component are linked to poor outcomes and chemotherapy resistance in T-cell acute lymphoblastic leukemia (T-ALL).
- A study using edited T-ALL cells showed that EZH2-deficient cells are more sensitive to CHK1 inhibitors, which can delay tumor growth in models with EZH2 mutations.
- This research suggests that EZH2 loss leads to immature T-ALL characteristics and increased reliance on CHK1 for survival, revealing a potential therapeutic target for treating high-risk T-ALL cases.
Article Synopsis
- Integrative analysis of multi-omics data helps to understand biological processes, but accessing raw sequencing data is often challenging due to restricted availability.* -
- The Personal Genome Project UK (PGP-UK) offers openly accessible multi-omics data from ten different types of biological samples, ensuring participant consent and data integrity through strict quality control.* -
- The PGP-UK dataset can be easily downloaded via a REST API and is hosted on cloud platforms, making it a valuable resource for researchers in personal and medical genomics.*
Article Synopsis
- Somatic mutations and immunoediting contribute to significant diversity within non-small-cell lung cancer (NSCLC), particularly in the T cell antigen receptor (TCR) repertoire.
- The study finds that the number of expanded TCR sequences in tumors varies among and within tumors, correlating with nonsynonymous mutations, and categorizes these TCRs as either ubiquitous (found in all tumor regions) or regional (found in specific areas).
- Ubiquitous TCRs, which show functional impairment in CD8 lymphocytes and are more frequently detected in the blood during tumor resection, offer a promising noninvasive approach to track tumor-reactive TCRs for immunotherapy applications.
Article Synopsis
- In cancer immunotherapy, it's crucial for agents targeting immune responses to be specifically expressed on cancer cells and to provoke a strong immune reaction.
- Cancer Testis Antigens, normally found in the germ-line, are mistakenly expressed in various cancers and could be targeted for immune therapy due to this aberration.
- The study demonstrates the creation of an mCherry reporter cell line in HCT116 colorectal cancer cells, intended to help identify new regulators of CTA expression, potentially enhancing the effectiveness of cancer immunotherapy.