Mutations of Key Functional Residues in CRM1/XPO1 Differently Alter Its Intranuclear Localization and the Nuclear Export of Endogenous Cargos.

CRM1 (XPO1) has been well-characterized as a shuttling receptor that mediates the export of protein and RNA cargos to the cytoplasm, and previous analyses have pinpointed several key residues (A541, F572, K568, S1055, and Q742) that modulate CRM1 export activity. CRM1 also has a less studied nuclear function in RNA biogenesis, which is reflected by its localization to the Cajal body and the nucleolus. Here, we have investigated how the mutation of these key residues affects the intranuclear localization of CRM1 and its ability to mediate export of endogenous cargos.

Mechanisms of recalcitrant fucoidan breakdown in marine Planctomycetota.

Marine brown algae produce the highly recalcitrant polysaccharide fucoidan, contributing to long-term oceanic carbon storage and climate regulation. Fucoidan is degraded by specialized heterotrophic bacteria, which promote ecosystem function and global carbon turnover using largely uncharacterized mechanisms. Here, we isolate and study two Planctomycetota strains from the microbiome associated with the alga Fucus spiralis, which grow efficiently on chemically diverse fucoidans.

Targeting CDK2 to circumvent treatment resistance in HR breast cancer.

Genetic and epigenetic defects of the p53 system have previously been associated with resistance to CDK4/6 inhibitors in women with HR breast cancer. Recent data from Kudo et al. demonstrate that CDK2-targeting agents may offer an effective strategy to circumvent such resistance by enforcing cellular senescence downstream of RBL2 dephosphorylation.

Preparation and Characterization of Novel Poly(Lactic Acid) Composites Reinforced with "Latxa" Sheep Wool Fibers: The Effect of Peroxide Surface Treatments and Fiber Content.

"Latxa" sheep wool is rough, and it is not used in the textile industry because the fiber diameter is high compared with other wool fibers. Nowadays, this wool is considered as disposal and, with the aim to give it value, new uses must be explored. In the current work, the "Latxa" sheep wool fiber was evaluated as poly(lactic acid) (PLA) polymer reinforcement.

Tumor slice culture system for ex vivo immunotherapy studies.

Personalized immunotherapy is emerging as a promising approach for cancer treatment, aiming to harness the patient's own immune system to target and eliminate tumor cells. One key aspect of developing effective personalized immunotherapies is the utilization of tumor slices derived from individual patient tumors. Tumor slice models retain the complexity and heterogeneity of the original tumor microenvironment, including interactions with immune cells, stromal elements, and vasculature.

The essential kinase TgGSK regulates centrosome division and endodyogeny in .

Intracellular replication is crucial for the success of apicomplexan parasites, including . Therefore, essential players in parasite replication present potential targets for drug development. In this study, we have characterized TgGSK, a glycogen synthase kinase homolog that plays an important role in endodyogeny.

Myosin A and F-Actin play a critical role in mitochondrial dynamics and inheritance in Toxoplasma gondii.

The single mitochondrion of the obligate intracellular parasite Toxoplasma gondii is highly dynamic. Toxoplasma's mitochondrion changes morphology as the parasite moves from the intracellular to the extracellular environment and during division. Toxoplasma's mitochondrial dynamic is dependent on an outer mitochondrion membrane-associated protein LMF1 and its interaction with IMC10, a protein localized at the inner membrane complex (IMC).

Genetic Sex and Origin Identification Suggests Differential Migration of Male and Female Atlantic Bluefin Tuna () in the Northeast Atlantic.

Knowledge about sex-specific difference in life-history traits-like growth, mortality, or behavior-is of key importance for management and conservation as these parameters are essential for predictive modeling of population sustainability. We applied a newly developed molecular sex identification method, in combination with a SNP (single nucleotide polymorphism) panel for inferring the population of origin, for more than 300 large Atlantic bluefin tuna (ABFT) collected over several years from newly reclaimed feeding grounds in the Northeast Atlantic. The vast majority (95%) of individuals were genetically assigned to the eastern Atlantic population, which migrates between spawning grounds in the Mediterranean and feeding grounds in the Northeast Atlantic.

Unveiling the multifaceted antitumor effects of interleukin 33.

Interleukin 33 (IL-33), once predominantly recognized for its pro-tumoral activities, has emerged as a multifunctional cytokine with antitumor properties. IL-33 pleiotropic activities include activation of Th1 CD4 T cells, CD8 T cells, NK cells, dendritic cells, eosinophils, as well as type 2 innate lymphoid cells. Regarding this immunomodulatory activity, IL-33 demonstrates synergistic interactions with various cancer therapies, including immune checkpoint blockade and chemotherapy.

Efficacy of LCMV-based cancer immunotherapies is unleashed by intratumoral injections of polyI:C.

Background: Lymphocytic choriomeningitis virus (LCMV) belongs to the Arenavirus family known for inducing strong cytotoxic T-cell responses in both mice and humans. LCMV has been engineered for the development of cancer immunotherapies, currently undergoing evaluation in phase I/II clinical trials. Initial findings have demonstrated safety and an exceptional ability to activate and expand tumor-specific T lymphocytes.

Myosin A and F-Actin play a critical role in mitochondrial dynamics and inheritance in .

The single mitochondrion of the obligate intracellular parasite is highly dynamic. Toxoplasma's mitochondrion changes morphology as the parasite moves from the intracellular to the extracellular environment and during division. Toxoplasma's mitochondrial dynamic is dependent on an outer mitochondrion membrane-associated protein LMF1 and its interaction with IMC10, a protein localized at the inner membrane complex (IMC).

Peritoneal carcinomatosis in mouse models.

Peritoneal carcinomatosis (PCa) represents a metastatic stage of a disease with unmet therapeutic options. Malignant cells from primary tumors (gastrointestinal or gynecologic malignancies) invade the peritoneal cavity and eventually seed onto peritoneal surfaces, with the omentum being the most common nest area. With a median survival of less than 6 months, PCa has a dismal prognosis that can be improved with treatments only available to a select few individuals with low tumor burden.

Near-Infrared Induced miR-34a Delivery from Nanoparticles in Esophageal Cancer Treatment.

Current nucleic acid delivery methods have not achieved efficient, non-toxic delivery of miRNAs with tumor-specific selectivity. In this study, a new delivery system based on light-inducible gold-silver-gold, core-shell-shell (CSS) nanoparticles is presented. This system delivers small nucleic acid therapeutics with precise spatiotemporal control, demonstrating the potential for achieving tumor-specific selectivity and efficient delivery of miRNA mimics.

Otolith-temperature estimates in Atlantic bluefin tuna (Thunnus thynnus) from the Mediterranean Sea: Insights from clumped isotope measurements.

The subpopulation and/or contingent structure of Atlantic bluefin tuna (Thunnus thynnus) within the Mediterranean Sea is undefined, leading to uncertainty regarding the best strategy for an effective assessment and management of this highly exploited stock. This study aimed to reconstruct temperatures experienced by Atlantic bluefin tuna during the early life period (<3.5 months) using clumped isotope temperature proxy, an innovative geothermometer for carbonates, that does not require previous knowledge of other environmental parameters such as water oxygen composition.

Thermal sensitivity of field metabolic rate predicts differential futures for bluefin tuna juveniles across the Atlantic Ocean.

Changing environmental temperatures impact the physiological performance of fishes, and consequently their distributions. A mechanistic understanding of the linkages between experienced temperature and the physiological response expressed within complex natural environments is often lacking, hampering efforts to project impacts especially when future conditions exceed previous experience. In this study, we use natural chemical tracers to determine the individual experienced temperatures and expressed field metabolic rates of Atlantic bluefin tuna (Thunnus thynnus) during their first year of life.

Unidirectional trans-Atlantic gene flow and a mixed spawning area shape the genetic connectivity of Atlantic bluefin tuna.

The commercially important Atlantic bluefin tuna (Thunnus thynnus), a large migratory fish, has experienced notable recovery aided by accurate resource assessment and effective fisheries management efforts. Traditionally, this species has been perceived as consisting of eastern and western populations, spawning respectively in the Mediterranean Sea and the Gulf of Mexico, with mixing occurring throughout the Atlantic. However, recent studies have challenged this assumption by revealing weak genetic differentiation and identifying a previously unknown spawning ground in the Slope Sea used by Atlantic bluefin tuna of uncertain origin.

Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis.

Background: Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.

Methods: MVA encoding scIL-12 (MVA.

The protein phosphatase PPKL is a key regulator of daughter parasite development in .

can cause severe disease in immunocompromised or immunosuppressed patients and during congenital infections. Treating toxoplasmosis presents enormous challenges since the parasite shares many biological processes with its mammalian hosts, which results in significant side effects with current therapies. Consequently, proteins that are essential and unique to the parasite represent favorable targets for drug development.

Lipid nanoparticles with PEG-variant surface modifications mediate genome editing in the mouse retina.

Ocular delivery of lipid nanoparticle (LNPs) packaged mRNA can enable efficient gene delivery and editing. We generated LNP variants through the inclusion of positively charged-amine-modified polyethylene glycol (PEG)-lipids (LNPa), negatively charged-carboxyl-(LNPz) and carboxy-ester (LNPx) modified PEG-lipids, and neutral unmodified PEG-lipids (LNP). Subretinal injections of LNPa containing Cre mRNA in the mouse show tdTomato signal in the retinal pigmented epithelium (RPE) like conventional LNPs.

Intratumoral injection of IL-12-encoding mRNA targeted to CSFR1 and PD-L1 exerts potent anti-tumor effects without substantial systemic exposure.

IL-12 is a potent cytokine for cancer immunotherapy. However, its systemic delivery as a recombinant protein has shown unacceptable toxicity in the clinic. Currently, the intratumoral injection of IL-12-encoding mRNA or DNA to avoid such side effects is being evaluated in clinical trials.

AliGater: a framework for the development of bioinformatic pipelines for large-scale, high-dimensional cytometry data.

Motivation: AliGater is an open-source framework to accelerate the development of bioinformatic pipelines for the analysis of large-scale, high-dimensional flow cytometry data. AliGater provides a Python package for automatic feature extraction workflows, as well as building blocks to construct analysis pipelines.

Results: We illustrate the use of AliGater in a high-resolution flow cytometry-based genome-wide association study on 46 immune cell populations in 14 288 individuals.

Controlled Degradation of Polycaprolactone Polymers through Ultrasound Stimulation.

This study describes the development of an ultrasound-responsive polymer system that provides on-demand degradation when exposed to high-intensity focused ultrasound (HIFU). Diels-Alder cycloadducts were used to crosslink polycaprolactone (PCL) polymers and underwent a retro Diels-Alder reaction when stimulated with HIFU. Two Diels-Alder polymer compositions were explored to evaluate the link between reverse reaction energy barriers and polymer degradation rates.

The protein phosphatase PPKL is a key regulator of daughter parasite development in .

Apicomplexan parasites, including , encode many plant-like proteins, which play significant roles and present attractive targets for drug development. In this study, we have characterized the plant-like protein phosphatase PPKL, which is unique to the parasite and absent in its mammalian host. We have shown that its localization changes as the parasite divides.