Antibody blockade of the PSGL-1 immune checkpoint enhances T-cell responses to B-cell lymphoma.

Despite advancements in cancer immunotherapy, most lymphomas remain unresponsive to checkpoint inhibitors. P-selectin glycoprotein ligand-1 (PSGL-1), recently identified as a promoter of T-cell exhaustion in murine melanoma models, has emerged as a novel immune checkpoint protein and promising immunotherapeutic target. In this study, we investigated the potential of PSGL-1 antibody targeting in B-cell lymphoma. Using allogeneic co-culture systems, we demonstrated that targeted antibody interventions against human PSGL-1 enhanced T-cell activation and effector cytokine production in response to lymphoma cells. Moreover, in vitro treatment of primary lymphoma cell suspensions with PSGL-1 antibody resulted in increased activation of autologous lymphoma-infiltrating T cells. Using the A20 syngeneic B-cell lymphoma mouse model, we found that PSGL-1 antibody treatment significantly slowed tumor development and reduced the endpoint tumor burden. This antitumoral effect was accompanied by augmented tumor infiltration of CD4+ and CD8+ T cells and reduced infiltration of regulatory T cells. Finally, anti-PSGL-1 administration enhanced the expansion of CAR T cells previously transferred to mice bearing the aggressive Eµ-Myc lymphoma cells and improved disease control. These results demonstrate that PSGL-1 antibody blockade bolsters T-cell activity against B-cell lymphoma, suggesting a potential novel immunotherapeutic approach for treating these malignancies.

Molecular Screening and Characterization of Enteric Protozoan Parasites and Microsporidia in Wild Ducks from Portugal.

Enteric parasites pose significant threats to both human and veterinary health, ranking among the top causes of mortality worldwide. Wild migratory waterfowl, such as ducks, may serve as hosts and vectors for these parasites, facilitating their transmission across ecosystems. This study conducted a molecular screening of enteric parasites in three species of wild ducks of the genus Anas (A. acuta, A. platyrhynchos and A. crecca) from Portugal, targeting Blastocystis sp., Balantioides coli, Cryptosporidium spp., Encephalitozoon spp., and Enterocytozoon bieneusi. Fecal samples from 71 ducks were analyzed using PCR and sequencing techniques. The results revealed a 2.82% occurrence of Blastocystis sp. subtype 7 and Cryptosporidium baileyi, marking the first molecular detection of these pathogens in wild ducks in Portugal. While previous studies have documented these parasites in Anas spp. in other regions, this study contributes novel data specific to the Portuguese context. No evidence of Balantioides coli, Encephalitozoon spp. or Enterocytozoon bieneusi was found. These findings highlight the potential role of migratory ducks as vectors for zoonotic protozoa, emphasizing the need for enhanced surveillance of avian populations to mitigate cross-species transmission risks. Further research is warranted to understand the global public health implications associated with migratory waterfowl.

Performance of post-mortem diagnostic tests for tuberculosis in wild ungulates at low and high prevalence assessed using Bayesian latent class models.

Animal tuberculosis (TB) is often maintained by multi-host communities, including livestock and wildlife. Quantitative studies of such communities require estimating the true prevalence of TB, correcting the apparent prevalence by the diagnostic sensitivity (Se) and specificity (Sp) of the test. The goal of this study was to lay the foundations for estimating the true prevalence of TB in wild ungulate populations (wild boar and two cervids: red deer and fallow deer). We used Bayesian latent class models to assess the Se and Sp of gross pathology, IS6110 real-time PCR in tissues, bacteriological culture, and P22 indirect ELISA. We analyzed 308 harvested wild ungulates (211 wild boar and 97 cervids: 92 red deer and 5 fallow deer). The Se of bacteriological culture (80.4%, CI95 61.0-96.3%) and gross pathology (87.9%, CI95 69.5-99.9%) was reasonably good in wild boar. These tests showed lower Se in cervids: 60.2% (CI95 38.3-82.3%) for bacteriological culture and 81.5% (CI95 63.6-96.2%) for gross pathology. The Se of the real-time PCR was low (50.7% in wild boar and 53.0% in cervids). These tests showed Sp between 95.2 and 99.1% in both taxa. The P22 ELISA performed reasonably well in wild boar (Se = 71.9%, CI95 59.2-83.4%; Sp = 98.8%, CI95 96.9-99.9%) but lacked Sp in cervids (Se = 77.1%, CI95 62.9-89.7%; Sp = 74.5%, CI95 65.7-83.3%). The real-time PCR in wild boar and cervids and bacteriological culture in cervids tended to show higher Se in low-prevalence populations, possibly due to a higher proportion of early-stage TB lesions. In cervids, the parallel interpretation of gross pathology and bacteriological culture significantly improved the diagnostic performance (Se = 93.1%, CI95 84.7-98.9%; Sp = 92.9%, CI95 86.0-98.3%). Our results allow the estimation of true prevalence from the results of a single diagnostic test applied to harvested wild boar, red deer, and fallow deer, paving the way for more precise quantitative ecological studies of the multi-host TB maintenance community.

A small TAT-TrkB peptide prevents BDNF receptor cleavage and restores synaptic physiology in Alzheimer's disease.

In Alzheimer's disease (AD), amyloid ß (Aß)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission and plasticity. Using cerebrospinal fluid and postmortem human brain samples, we show that TrkB-FL cleavage occurs from the early stages of the disease and increases as a function of pathology severity. To explore the therapeutic potential of this disease mechanism, we designed small TAT-fused peptides and screened their ability to prevent TrkB-FL receptor cleavage. Among these, a TAT-TrkB peptide with a lysine-lysine linker prevented TrkB-FL cleavage both in vitro and in vivo and rescued synaptic deficits induced by oligomeric Aß in hippocampal slices. Furthermore, this TAT-TrkB peptide improved the cognitive performance, ameliorated synaptic plasticity deficits and prevented Tau pathology progression in vivo in the 5XFAD mouse model of AD. No evidence of liver or kidney toxicity was found. We provide proof-of-concept evidence for the efficacy and safety of this therapeutic strategy and anticipate that this TAT-TrkB peptide has the potential to be a disease-modifying drug that can prevent and/or reverse cognitive deficits in patients with AD.

Zika virus capsid protein closed structure modulates binding to host lipid systems.

Zika virus (ZIKV), a mosquito-borne Flavivirus of international concern, causes congenital microcephaly in newborns and Guillain-Barré syndrome in adults. ZIKV capsid (C) protein, one of three key structural proteins, is essential for viral assembly and encapsidation. In dengue virus, a closely related flavivirus, the homologous C protein interacts with host lipid systems, namely intracellular lipid droplets, for successful viral replication. Here, we investigate ZIKV C interaction with host lipid systems, showing that it binds host lipid droplets but, contrary to expected, in an unspecific manner. Contrasting with other flaviviruses, ZIKV C also does not bind very-low density-lipoproteins. Comparing with other Flavivirus, capsid proteins show that ZIKV C structure is particularly thermostable and seems to be locked into an auto-inhibitory conformation due to a disordered N-terminal, hence blocking specific interactions and supporting the experimental differences observed. Such distinct structural features must be considered when targeting capsid proteins in drug development.

An Unusual Case of Lynch Syndrome.

Lynch syndrome is the most common cause of hereditary colorectal cancer. It usually develops asymptomatically until symptoms related to colorectal carcinoma appear, such as gastrointestinal bleeding, abdominal pain, and changes in bowel habits and/or stool characteristics. Oftentime, when these clinical signs and symptoms are not present, the diagnosis becomes challenging. We present the clinical case of a 69-year-old woman, adopted, with no known previous history, who presented to the emergency department with low back pain, without irradiation, that had been going on for three days, associated with inflammatory signs in the right hip region. There were no urinary or sensory alterations and no recent trauma. She was initially discharged with antibiotherapy with the diagnosis of hip cellulitis. As the symptoms continued and the inflammation spread to the right lower limb, she returned to the emergency department. A CT scan revealed an abscess (17 cm) in the right buttock, complicated by necrotizing fasciitis due to fistulization from a tumor in the right colon. She underwent an exploratory laparotomy, which identified a neoplasm of the ascending colon, adherent to the abdominal wall, in the right lumbar region. Right hemicolectomy and drainage of the right buttock/thigh abscess were performed. The histology was compatible with invasive adenocarcinoma, with high-grade dysplasia but well differentiated, pT3G1N0. The immunohistochemistry was suggestive of Lynch syndrome.

Long-term in situ Eulerian Sea surface temperature records along the Portuguese Coast.

Monitoring ocean surface temperature is critical to infer the variability of the upper layers of the ocean, from short temporal scales to climatic change scales. Analysis of the climatological trends and anomalies is fundamental to comprehend the long-term effects of climate change on marine ecosystems and coastal regions. The original data for the dataset presented was collected by the Portuguese Hydrographic Institute (Instituto Hidrográfico) using seven Ondograph and Meteo-oceanography buoys anchored offshore along the Portuguese coast to acquire ocean surface temperatures. The original raw data was pre-processed to provide averages over 3-hour periods and daily averages, and this cleaned data constitutes the provided dataset. The 3-hour temperature averages were obtained mainly between 2011 and 2015, and the daily temperature averages were obtained in intervals that vary with the considered buoy, having an average interval of 14 years per buoy. The data gathered provides a considerable temporal window, enabling the creation of data series and the implementation of data mining algorithms to develop decision support systems. Collecting data in situ makes it possible to validate simulated results obtained using approximation models. This allows for more accurate temperature readings and facilitates testing and correcting created models.

Connexin43 promotes exocytosis of damaged lysosomes through actin remodelling.

A robust and efficient cellular response to lysosomal membrane damage prevents leakage from the lysosome lumen into the cytoplasm. This response is understood to happen through either lysosomal membrane repair or lysophagy. Here we report exocytosis as a third response mechanism to lysosomal damage, which is further potentiated when membrane repair or lysosomal degradation mechanisms are impaired. We show that Connexin43 (Cx43), a protein canonically associated with gap junctions, is recruited from the plasma membrane to damaged lysosomes, promoting their secretion and accelerating cell recovery. The effects of Cx43 on lysosome exocytosis are mediated by a reorganization of the actin cytoskeleton that increases plasma membrane fluidity and decreases cell stiffness. Furthermore, we demonstrate that Cx43 interacts with the actin nucleator Arp2, the activity of which was shown to be necessary for Cx43-mediated actin rearrangement and lysosomal exocytosis following damage. These results define a novel mechanism of lysosomal quality control whereby Cx43-mediated actin remodelling potentiates the secretion of damaged lysosomes.

Hepatitis E virus in wild and domestic rabbits from Portugal: a combined molecular and longitudinal serological study.

Hepatitis E virus (HEV), species Paslahepevirus balayani, poses a global public health threat, especially in developing countries, by causing acute enterically transmitted hepatitis. HEV infects various mammalian hosts and belongs to the genus Paslahepevirus in the family Hepeviridae. While swine are recognized as the main hosts of HEV, rabbits, which can also be affected by swine HEV-3 related strains, serve as the primary reservoir for the distinct emerging and zoonotic HEV-3ra subtype. In Portugal, where the European wild rabbit is abundant, their role in HEV epidemiology remains unclear. The primary aim of the present research was to evaluate the circulation and the potential for HEV infection within these species. This study employed a molecular and longitudinal serological approach to investigate HEV in Portuguese rabbits. Among the 205 wild rabbits tested, a seroprevalence of 2.44% (95% CI: 0.80-5.60) was found, with no significant associations with age, sex, localization, or sampling dates. Seropositive animals were found in the south and center regions of the country. HEV RNA was not detected in 120 fecal samples, suggesting a natural, low level, and widespread viral circulation. The study underscores the need for further research to comprehend HEV dynamics in these species, which is crucial for assessing potential transmission risks to humans.

Antiviral Activities of Mastoparan-L-Derived Peptides against Human Alphaherpesvirus 1.

Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective against HSV-1. This study aimed to demonstrate the antiviral properties of mastoparans, including mastoparan-L [I5, R8], mastoparan-MO, and [I5, R8] mastoparan, against HSV-1. Initially, Vero cell viability was assessed in the presence of these peptides, followed by the determination of antiviral activity, mechanism of action, and dose-response curves through plaque assays. Structural analyses via circular dichroism and nuclear magnetic resonance were conducted, along with evaluating membrane fluidity changes induced by [I5, R8] mastoparan using fluorescence-labeled lipid vesicles. Cytotoxic assays revealed high cell viability (>80%) at concentrations of 200 µg/mL for mastoparan-L and mastoparan-MO and 50 µg/mL for [I5, R8] mastoparan. Mastoparan-MO and [I5, R8] mastoparan exhibited over 80% HSV-1 inhibition, with up to 99% viral replication inhibition, particularly in the early infection stages. Structural analysis indicated an α-helical structure for [I5, R8] mastoparan, suggesting effective viral particle disruption before cell attachment. Mastoparans present promising prospects for HSV-1 infection control, although further investigation into their mechanisms is warranted.

Group Intervention Program to Facilitate Post-Traumatic Growth and Reduce Stigma in HIV.

Background: Research on post-traumatic growth (PTG) and HIV is scarce and the relationship between PTG and stigma is controversial. Group psychotherapeutic interventions to facilitate PTG in clinical samples are effective but none exist to simultaneously decrease stigma in the HIV population. The main objective was to evaluate the effectiveness of an intervention in increasing PTG and decreasing stigma in HIV, as well as to explore relationships between the variables. Methods: Quasi-experimental design with a sample of 42 HIV-positive adults (M = 46.26, SD = 11.90). The experimental group (EG) was subjected to a 9-week group intervention. Instruments: CBI, PTGI-X, PSS-10, HIV stigma, emotional expression, HIV stress indicators, HIV literacy, and skills. Multiple linear regression analysis was performed to assess the relationship between the variables. Results: There was an increase in PTG and a significant decrease in stigma in all domains and subscales in the EG. Compared to the control group, stigma (t(42) = -3.040, p = 0.004) and negative self-image (W = -2.937, p = 0.003) were significant, showing the efficacy of the intervention. Discussion: The intervention demonstrated success in facilitating PTG, attesting that in order to increase PTG, personal strength, and spiritual change, it is necessary to reduce stigma and negative self-image. The research provides more information on group interventions for PTG in HIV, relationships between variables, and population-specific knowledge for professionals.

Influence of antimicrobial peptides on the bacterial membrane curvature and vice versa.

Many factors contribute to bacterial membrane stabilization, including steric effects between lipids, membrane spontaneous curvature, and the difference in the number of neighboring molecules. This forum provides an overview of the physicochemical properties associated with membrane curvature and how this parameter can be tuned to design more effective antimicrobial peptides.

Optical fiber immunosensors based on surface plasmon resonance for the detection of Escherichia coli.

Every year, millions of people suffer some form of illness associated with the consumption of contaminated food. Escherichia coli (E. coli), found in the intestines of humans and other animals, is commonly associated with various diseases, due to the existence of pathogenic strains. Strict monitoring of food products for human consumption is essential to ensure public health, but traditional cell culture-based methods are associated with long waiting times and high costs. New approaches must be developed to achieve cheap, fast, and on-site monitoring. Thus, in this work, we developed optical fiber sensors based on surface plasmon resonance. Gold and cysteamine-coated fibers were functionalized with anti-E. coli antibody and tested using E. coli suspensions with concentrations ranging from 1 cell/mL to 105 cells/mL. An average logarithmic sensitivity of 0.21 ± 0.01 nm/log(cells/mL) was obtained for three independent assays. An additional assay revealed that including molybdenum disulfide resulted in an increase of approximately 50% in sensitivity. Specificity and selectivity were also evaluated, and the sensors were used to analyze contaminated water samples, which verified their promising applicability in the aquaculture field.

Fisheries Inspection in Portuguese Waters from 2015 to 2023.

As a coastal state, Portugal must ensure active surveillance over its maritime area, ensuring its proper control and inspection. One of the most critical inspection activities is the fishery inspection. To protect biodiversity, we must ensure that all the ships comply with the existing safety regulations and respect the current fishing quotas. This georeferenced dataset describes the fisheries inspections done in Portuguese waters between 2015 and 2023. Since we are dealing with occurrences that may have originated some legal process to the ship's owner, we have ensured data anonymization by pre-processing the dataset to maintain its accuracy while guaranteeing no unique identifiers exist. All the pre-processing performed to ensure data consistency and accuracy is described in detail to allow a quick analysis and implementation of new algorithms. The data containing the results of these inspections can be easily analyzed to implement data mining algorithms that can efficiently retrieve more knowledge and, e.g., suggest new areas of actuation or new strategies.

Enhancing Neuronal Cell Uptake of Therapeutic Nucleic Acids with Tetrahedral DNA Nanostructures.

The successful translation of therapeutic nucleic acids (NAs) for the treatment of neurological disorders depends on their safe and efficient delivery to neural cells, in particular neurons. DNA nanostructures can be a promising NAs delivery vehicle. Nonetheless, the potential of DNA nanostructures for neuronal cell delivery of therapeutic NAs is unexplored. Here, tetrahedral DNA nanostructures (TDN) as siRNA delivery scaffolds to neuronal cells, exploring the influence of functionalization with two different reported neuronal targeting ligands: C4-3 RNA aptamer and Tet1 peptide are investigated. Nanostructures are characterized in vitro, as well as in silico using molecular dynamic simulations to better understand the overall TDN structural stability. Enhancement of neuronal cell uptake of TDN functionalized with the C4-3 Aptamer (TDN-Apt), not only in neuronal cell lines but also in primary neuronal cell cultures is demonstrated. Additionally, TDN and TDN-Apt nanostructures carrying siRNA are shown to promote silencing in a process aided by chloroquine-induced endosomal disruption. This work presents a thorough workflow for the structural and functional characterization of the proposed TDN as a nano-scaffold for neuronal delivery of therapeutic NAs and for targeting ligands evaluation, contributing to the future development of new neuronal drug delivery systems based on DNA nanostructures.

Side-scan sonar imaging data of underwater vehicles for mine detection.

Unmanned vehicles have become increasingly popular in the underwater domain in the last decade, as they provide better operation reliability by minimizing human involvement in most tasks. Perception of the environment is crucial for safety and other tasks, such as guidance and trajectory control, mainly when operating underwater. Mine detection is one of the riskiest operations since it involves systems that can easily damage vehicles and endanger human lives if manned. Automating mine detection from side-scan sonar images enhances safety while reducing false negatives. The collected dataset contains 1170 real sonar images taken between 2010 and 2021 using a Teledyne Marine Gavia Autonomous Underwater Vehicle (AUV), which includes enough information to classify its content objects as NOn-Mine-like BOttom Objects (NOMBO) and MIne-Like COntacts (MILCO). The dataset is annotated and can be quickly deployed for object detection, classification, or image segmentation tasks. Collecting a dataset of this type requires a significant amount of time and cost, which increases its rarity and relevance to research and industrial development.

Antibody targeting of surface P-selectin glycoprotein ligand 1 leads to lymphoma apoptosis and tumorigenesis inhibition.

Lymphomas are a heterogeneous group of diseases that originate from T, B or natural killer cells. Lymphoma treatment is based on chemotherapy, radiotherapy, and monoclonal antibody (mAb) or other immunotherapies. The P-selectin glycoprotein ligand 1 (PSGL-1) is expressed at the surface of hematological malignant cells and has been shown to have a pro-oncogenic role in multiple myeloma and lymphoma. Here, we investigated the expression and therapeutic potential of PSGL-1 in T and B cell lymphomas. By flow cytometry analysis, we found that PSGL-1 was expressed in both T and B cell-derived lymphoma cell lines but generally at higher levels in T cell lymphoma cell lines. For most T and B cell-derived lymphoma cell lines, in vitro targeting with the PL1 mAb, which recognizes the PSGL-1 N-terminal extracellular region and blocks functional interactions with selectins, resulted in reduced cell viability. The PL1 mAb pro-apoptotic activity was shown to be dose-dependent, to be linked to increased ERK kinase phosphorylation, and to be dependent on the MAP kinase signaling pathway. Importantly, anti-PSGL-1 treatment of mice xenografted with the HUT-78 cutaneous T-cell lymphoma cell line resulted in decreased tumor growth, had no effect on in vivo proliferation, but increased the levels of apoptosis in tumors. Anti-PSGL-1 treatment of mice xenografted with a Burkitt lymphoma cell line that was resistant to anti-PSGL-1 treatment in vitro, had no impact on tumorigenesis. These findings show that PSGL-1 antibody targeting triggers lymphoma cell apoptosis and substantiates PSGL-1 as a potential target for lymphoma therapy.

State-of-the-Art Macromolecules in Portugal.

This Special Issue presents five contributions covering various topics, as it would be expected for an area as comprehensive and multidisciplinary as Macromolecules [...].