Single cell dynamics of tumor specificity vs bystander activity in CD8 T cells define the diverse immune landscapes in colorectal cancer.

CD8 T cell activation via immune checkpoint blockade (ICB) is successful in microsatellite instable (MSI) colorectal cancer (CRC) patients. By comparison, the success of immunotherapy against microsatellite stable (MSS) CRC is limited. Little is known about the most critical features of CRC CD8 T cells that together determine the diverse immune landscapes and contrasting ICB responses.

Trial watch: chemotherapy-induced immunogenic cell death in oncology.

Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated cell death that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency of ICD is dependent on the immunogenicity of dying cells as defined by the antigenicity of these cells and their ability to expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) and cytokines like type I interferons (IFNs).

Multiomics and spatial mapping characterizes human CD8 T cell states in cancer.

Clinically relevant immunological biomarkers that discriminate between diverse hypofunctional states of tumor-associated CD8 T cells remain disputed. Using multiomics analysis of CD8 T cell features across multiple patient cohorts and tumor types, we identified tumor niche-dependent exhausted and other types of hypofunctional CD8 T cell states. CD8 T cells in "supportive" niches, like melanoma or lung cancer, exhibited features of tumor reactivity-driven exhaustion (CD8 T).

Evaluation of Control Strategies for in the Balearic Islands.

The emergence of (Xf) in the Balearic Islands in October 2016 was a major phytosanitary challenge with international implications. Immediately after its detection, eradication and containment measures included in Decision 2015/789 were implemented. Surveys intensified during 2017, which soon revealed that the pathogen was widely distributed on the islands and eradication measures were no longer feasible.

The Interface of Tumour-Associated Macrophages with Dying Cancer Cells in Immuno-Oncology.

Tumour-associated macrophages (TAMs) are essential players in the tumour microenvironment (TME) and modulate various pro-tumorigenic functions such as immunosuppression, angiogenesis, cancer cell proliferation, invasion and metastasis, along with resistance to anti-cancer therapies. TAMs also mediate important anti-tumour functions and can clear dying cancer cells via efferocytosis. Thus, not surprisingly, TAMs exhibit heterogeneous activities and functional plasticity depending on the type and context of cancer cell death that they are faced with.

CRISPR Activation Screening Identifies VGLL3-TEAD1-RUNX1/3 as a Transcriptional Complex for PD-L1 Expression.

The PD-L1/2-PD-1 immune checkpoint is essential for the proper induction of peripheral tolerance and limits autoimmunity, whereas tumor cells exploit their expression to promote immune evasion. Many different cell types express PD-L1/2, either constitutively or upon stimulation, but the factors driving this expression are often poorly defined. In this study, using genome-wide CRISPR activation screening, we identified three factors that upregulate PD-L1 expression: GATA2, MBD6, and transcription cofactor vestigial-like protein 3 (VGLL3).

Trial watch: Dendritic cell (DC)-based immunotherapy for cancer.

Dendritic cell (DC)-based vaccination for cancer treatment has seen considerable development over recent decades. However, this field is currently in a state of flux toward niche-applications, owing to recent paradigm-shifts in immuno-oncology mobilized by T cell-targeting immunotherapies. DC vaccines are typically generated using autologous (patient-derived) DCs exposed to tumor-associated or -specific antigens (TAAs or TSAs), in the presence of immunostimulatory molecules to induce DC maturation, followed by reinfusion into patients.

Peripherally-driven myeloid NFkB and IFN/ISG responses predict malignancy risk, survival, and immunotherapy regime in ovarian cancer.

Background: Tumors can influence peripheral immune macroenvironment, thereby creating opportunities for non-invasive serum/plasma immunobiomarkers for immunostratification and immunotherapy designing. However, current approaches for immunobiomarkers' detection are largely quantitative, which is unreliable for assessing functional peripheral immunodynamics of patients with cancer. Hence, we aimed to design a functional biomarker modality for capturing peripheral immune signaling in patients with cancer for reliable immunostratification.

Transcriptome-Based Identification and Functional Characterization of NAC Transcription Factors Responsive to Drought Stress in L.

L. is one of the most cultivated Solanaceae species, and in the open field, water limitation leading to drought stress affects its fruit quality, fruit setting, fruit size and ultimately yield. We identified stage-specific and a common core set of differentially expressed genes, following RNA-seq transcriptome analyses of a breeding line subjected to acute drought stress followed by recovery (rewatering), at three stages of plant development.

Early memory differentiation and cell death resistance in T cells predicts melanoma response to sequential anti-CTLA4 and anti-PD1 immunotherapy.

Immune checkpoint blockers (ICBs)-based immunotherapy has revolutionised oncology. However, the benefits of ICBs are limited to only a subset of patients. Herein, the biomarkers-driven application of ICBs promises to increase their efficacy.

High dimensional profiling identifies specific immune types along the recovery trajectories of critically ill COVID19 patients.

The COVID-19 pandemic poses a major burden on healthcare and economic systems across the globe. Even though a majority of the population develops only minor symptoms upon SARS-CoV-2 infection, a significant number are hospitalized at intensive care units (ICU) requiring critical care. While insights into the early stages of the disease are rapidly expanding, the dynamic immunological processes occurring in critically ill patients throughout their recovery at ICU are far less understood.

The influence of acute water stresses on the biochemical composition of bell pepper (Capsicum annuum L.) berries.

Background: Crops are exposed to recurrent and acute drought stress episodes during their vegetative and reproductive cycles, and these episodes are increasingly frequent due to ongoing climate change. Sweet pepper (Capsicum annuum), alias bell pepper, is one of the most widely cultivated vegetables and is grown in open fields worldwide. Here we assessed the effect of acute water stress, applied to a breeding line of sweet pepper at three stages of plant development: five true-leaves (Stage 1), production of the third flower (Stage 2) and setting of the first fruit (Stage 3), on the production and biochemical composition of its ripe fruits.

Phylogenetic inference enables reconstruction of a long-overlooked outbreak of almond leaf scorch disease (Xylella fastidiosa) in Europe.

The recent introductions of the bacterium Xylella fastidiosa (Xf) into Europe are linked to the international plant trade. However, both how and when these entries occurred remains poorly understood. Here, we show how almond scorch leaf disease, which affects ~79% of almond trees in Majorca (Spain) and was previously attributed to fungal pathogens, was in fact triggered by the introduction of Xf around 1993 and subsequently spread to grapevines (Pierce's disease).

Uncoupling DNA damage from chromatin damage to detoxify doxorubicin.

The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility.

Comprehensive diagnostics of acute myeloid leukemia by whole transcriptome RNA sequencing.

Acute myeloid leukemia (AML) is caused by genetic aberrations that also govern the prognosis of patients and guide risk-adapted and targeted therapy. Genetic aberrations in AML are structurally diverse and currently detected by different diagnostic assays. This study sought to establish whole transcriptome RNA sequencing as single, comprehensive, and flexible platform for AML diagnostics.

Physiological Responses to Swimming-Induced Exercise in the Adult Zebrafish Regenerating Heart.

Exercise promotes a set of physiological responses known to provide long-term health benefits and it can play an important role in cardioprotection. In the present study, we examined cardiac responses to exercise training in the adult zebrafish and in the context of cardiac regeneration. We found that swimming-induced exercise increased cardiomyocyte proliferation and that this response was also found under regenerating conditions, when exercise was performed either prior to and after ventricular cryoinjury (CI).

Water associated with residential areas and tourist resorts is the key predictor of Asian tiger mosquito presence on a Mediterranean island.

The Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae), is a highly invasive species and a vector of several viruses of serious concern to public health. Investigating the habitat selection of this species at small to medium scales is essential to the planning of effective prevention and control campaigns. The present group considered detailed data for this species' presence/absence collected at 228 sites on Mallorca Island (Spain) in autumn 2015, 3 years after the first detection of the species on the island.

Modelling the range expansion of the Tiger mosquito in a Mediterranean Island accounting for imperfect detection.

Backgrounds: (Diptera; Culicidae) is a highly invasive mosquito species and a competent vector of several arboviral diseases that have spread rapidly throughout the world. Prevalence and patterns of dispersal of the mosquito are of central importance for an effective control of the species. We used site-occupancy models accounting for false negative detections to estimate the prevalence, the turnover, the movement pattern and the growth rate in the number of sites occupied by the mosquito in 17 localities throughout Mallorca Island.

Detecting PKD1 variants in polycystic kidney disease patients by single-molecule long-read sequencing.

A genetic diagnosis of autosomal-dominant polycystic kidney disease (ADPKD) is challenging due to allelic heterogeneity, high GC content, and homology of the PKD1 gene with six pseudogenes. Short-read next-generation sequencing approaches, such as whole-genome sequencing and whole-exome sequencing, often fail at reliably characterizing complex regions such as PKD1. However, long-read single-molecule sequencing has been shown to be an alternative strategy that could overcome PKD1 complexities and discriminate between homologous regions of PKD1 and its pseudogenes.

Silencing of Profilin-1 suppresses cell adhesion and tumor growth via predicted alterations in integrin and Ca2+ signaling in T24M-based bladder cancer models.

Bladder cancer (BC) is the second most common malignancy of the genitourinary system, characterized by the highest recurrence rate of all cancers. Treatment options are limited; thus a thorough understanding of the underlying molecular mechanisms is needed to guide the discovery of novel therapeutic targets. Profilins are actin binding proteins with attributed pleiotropic functions to cytoskeletal remodeling, cell adhesion, motility, even transcriptional regulation, not fully characterized yet.

Use of Embryos Extracted from Individual Cannabis sativa Seeds for Genetic Studies and Forensic Applications.

Legal limits on the psychoactive tetrahydrocannabinol (THC) content in Cannabis sativa plants have complicated genetic and forensic studies in this species. However, Cannabis seeds present very low THC levels. We developed a method for embryo extraction from seeds and an improved protocol for DNA extraction and tested this method in four hemp and six marijuana varieties.

Integrative analysis of extracellular and intracellular bladder cancer cell line proteome with transcriptome: improving coverage and validity of -omics findings.

Characterization of disease-associated proteins improves our understanding of disease pathophysiology. Obtaining a comprehensive coverage of the proteome is challenging, mainly due to limited statistical power and an inability to verify hundreds of putative biomarkers. In an effort to address these issues, we investigated the value of parallel analysis of compartment-specific proteomes with an assessment of findings by cross-strategy and cross-omics (proteomics-transcriptomics) agreement.

Characterization of composition traits related to organoleptic and functional quality for the differentiation, selection and enhancement of local varieties of tomato from different cultivar groups.

Tomato (Solanum lycopersicum) local varieties are having an increasing demand. We characterized 69 local tomato accessions from eight cultivar groups for proximate composition traits, major sugars, acids and antioxidants. A large diversity was found, with differences among accessions of almost tenfold for lycopene.