Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A pragmatic comparison of oncological outcomes in synchronous versus metachronous disease.

Background: disease burden (PCI), completeness of cytoreduction or histological features, are known to influence survival after CRS-HIPEC for colorectal peritoneal metastases (CPM). However, there is still debate about influence of CPM onset. The aim of this study is to determine the impact of CPM onset on oncological outcomes after CRS-HIPEC.

Human senescent fibroblasts trigger progressive lung fibrosis in mice.

Cell senescence has recently emerged as a potentially relevant pathogenic mechanism in fibrosing interstitial lung diseases (f-ILDs), particularly in idiopathic pulmonary fibrosis. We hypothesized that senescent human fibroblasts may suffice to trigger a progressive fibrogenic reaction in the lung. To address this, senescent human lung fibroblasts, or their secretome (SASP), were instilled into the lungs of immunodeficient mice.

Lithic cyanobacterial communities in the polyextreme Sahara Desert: implications for the search for the limits of life.

The hyperarid Sahara Desert presents extreme and persistent dry conditions with a limited number of hours during which the moisture availability, temperature and light allow phototrophic growth. Some cyanobacteria can live in these hostile conditions by seeking refuge under (hypolithic) or inside (endolithic) rocks, by colonizing porous spaces (cryptoendoliths) or fissures in stones (chasmoendoliths). Chroococcidiopsis spp.

Microenvironmental Conditions Drive the Differential Cyanobacterial Community Composition of Biocrusts from the Sahara Desert.

The Sahara Desert is characterized by extreme environmental conditions, which are a unique challenge for life. Cyanobacteria are key players in the colonization of bare soils and form assemblages with other microorganisms in the top millimetres, establishing biological soil crusts (biocrusts) that cover most soil surfaces in deserts, which have important roles in the functioning of drylands. However, knowledge of biocrusts from these extreme environments is limited.

Clear cell clusters in the kidney: a rare finding that should not be misdiagnosed as renal cell carcinoma.

Clear cytoplasm is a major characteristic feature of most malignant renal neoplasms. Benign clear cells in the renal parenchyma, usually histiocytes, can occasionally be found, but they are infrequently of an epithelial nature. We report histological, immunohistochemical, ultrastructural, and cytogenomic features of clear epithelial cell clusters incidentally found in four kidney specimens.

Analysis of molecular diversity within single cyanobacterial colonies from environmental samples.

Attached or floating macroscopic cyanobacteria can be found in shallow waters and can be easily hand-collected, but their identification is often challenging due to their high morphological variability. In addition, many members of environmental samples lose their morphological adaptations under controlled conditions, making the integration of analyses of field populations and derived isolated cultures necessary in order to evaluate phenotypic plasticity for identification purposes. Therefore, in this study, twenty-nine macroscopic field samples were analyzed by Illumina sequencing and parallel optical microscopy.

Metaplastic carcinomas of the breast without evidence of epithelial differentiation: a diagnostic approach for management.

Aims: Although rare, malignant sarcomatoid breast tumours without evidence of epithelial differentiation comprise a diagnostic challenge with management implications. Earlier studies have generally considered these to be primary breast sarcomas; however, supporting evidence is lacking and management remains variable. This study aimed to provide an evidence-based approach to improve the consistency of diagnosis and management for such cases.

Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases.

Pluripotent stem cells (PSCs) transition between cell states in vitro, reflecting developmental changes in the early embryo. PSCs can be stabilized in the naive state by blocking extracellular differentiation stimuli, particularly FGF-MEK signalling. Here, we report that multiple features of the naive state in human and mouse PSCs can be recapitulated without affecting FGF-MEK signalling or global DNA methylation.

Differences in the Cyanobacterial Community Composition of Biocrusts From the Drylands of Central Mexico. Are There Endemic Species?

In drylands worldwide, biocrusts, topsoil microbial communities, are prevalent, contributing to the biostabilization of soils and allowing the subsequent establishment and growth of vascular plants. In early successional biocrusts, cyanobacteria are the first dominant colonizers of bare ground, largely determining their functioning. However, there are large gaps in our knowledge of the cyanobacterial diversity in biocrusts, particularly in understudied geographic regions, such as the tropical latitudes.

Polyphasic evaluation of key cyanobacteria in biocrusts from the most arid region in Europe.

Cyanobacteria are key microbes in topsoil communities that have important roles in preventing soil erosion, carbon and nitrogen fixation, and influencing soil hydrology. However, little is known regarding the identity and distribution of the microbial components in the photosynthetic assemblages that form a cohesive biological soil crust (biocrust) in drylands of Europe. In this study, we investigated the cyanobacterial species colonizing biocrusts in three representative dryland ecosystems from the most arid region in Europe (SE Spain) that are characterized by different soil conditions.

Cyanobacterial biocrust diversity in Mediterranean ecosystems along a latitudinal and climatic gradient.

Cyanobacteria are a key biotic component as primary producers in biocrusts, topsoil communities that have important roles in the functioning of drylands. Yet, major knowledge gaps exist regarding the composition of biocrust cyanobacterial diversity and distribution in Mediterranean ecosystems. We describe cyanobacterial diversity in Mediterranean semiarid soil crusts along an aridity gradient by using next-generation sequencing and bioinformatics analyses, and detect clear shifts along it in cyanobacterial dominance.

Diversity of biocrust-forming cyanobacteria in a semiarid gypsiferous site from Central Spain.

Cyanobacteria are a key constituent of biocrusts, communities dominated by lichens, mosses and associated microorganisms, which are prevalent in drylands worldwide and that largely determine their functioning. Despite their importance, there are large gaps in our knowledge of the composition and diversity of cyanobacteria associated with biocrusts, particularly in areas such as the Mediterranean Basin. We studied the diversity of these cyanobacteria in a gypsiferous grassland from Central Spain using both morphological identification after cultivation and genetic analyses with the 16S rRNA gene.

A versatile drug delivery system targeting senescent cells.

Senescent cells accumulate in multiple aging-associated diseases, and eliminating these cells has recently emerged as a promising therapeutic approach. Here, we take advantage of the high lysosomal β-galactosidase activity of senescent cells to design a drug delivery system based on the encapsulation of drugs with galacto-oligosaccharides. We show that gal-encapsulated fluorophores are preferentially released within senescent cells in mice.

Modeling Dynamics and Function of Bone Marrow Cells in Mouse Liver Regeneration.

In rodents and humans, the liver can efficiently restore its mass after hepatectomy. This is largely attributed to the proliferation and cell cycle re-entry of hepatocytes. On the other hand, bone marrow cells (BMCs) migrate into the liver after resection.

Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.

Reprogramming of differentiated cells into pluripotent cells can occur in vivo, but the mechanisms involved remain to be elucidated. Senescence is a cellular response to damage, characterized by abundant production of cytokines and other secreted factors that, together with the recruitment of inflammatory cells, result in tissue remodeling. Here, we show that in vivo expression of the reprogramming factors OCT4, SOX2, KLF4, and cMYC (OSKM) in mice leads to senescence and reprogramming, both coexisting in close proximity.

PI3Kα inhibition reduces obesity in mice.

Partial inhibition of PI3K is one of the best-validated and evolutionary conserved manipulations to extend longevity. The best known health beneficial effects of reduced PI3K are related to metabolism and include increased energy expenditure, reduced nutrient storage, and protection from obesity. We have previously shown that a dual chemical inhibitor of the alpha and delta PI3K isoforms (CNIO-PI3Ki) reduces obesity in mice and monkeys, without evident toxic effects after long-term treatment.

p21 plays a critical role in the physiological adaptation to fasting through activation of PPARα.

Fasting is a physiological stress that elicits well-known metabolic adaptations, however, little is known about the role of stress-responsive tumor suppressors in fasting. Here, we have examined the expression of several tumor suppressors upon fasting in mice. Interestingly, p21 mRNA is uniquely induced in all the tissues tested, particularly in liver and muscle (>10 fold), and this upregulation is independent of p53.

Re-Evaluating Simpson Grade I, II, and III Resections in Neurosurgical Treatment of World Health Organization Grade I Meningiomas.

Background: Since 1957, the Simpson grading system has been considered a predictive system for meningioma recurrence. However, since then, surgical equipment and neurosurgical technique have developed extensively, so this grading system should be re-evaluated. This study aims to assess if the recurrence rate and recurrence-free survival (RFS) are different after Simpson grade I, II, and III resections in World Health Organization (WHO) grade I meningiomas.

Nitrogen fixation in a non-heterocystous cyanobacterial mat from a mountain river.

In situ nitrogen fixation was investigated in a cyanobacterial mat growing on the bed of rocks of the Muga River, Spain. The filamentous non-heterocystous cyanobacterium Schizothrix dominated the mat, showing nitrogenase activity in the light at similar rates to those found in nearby heterocystous Rivularia colonies. N2 fixation in the light was significantly increased by an inhibitor of PSII and oxygen evolution, DCMU (3-[3,4-dichlorophenyl]-1,1-dimethylurea), and anaerobic conditions.

Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells.

Parkinson's disease is a common neurodegenerative disorder, which is due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and for which no definitive cure is currently available. Cellular functions in mouse and human tissues can be restored after fusion of bone marrow (BM)-derived cells with a variety of somatic cells. Here, after transplantation of hematopoietic stem and progenitor cells (HSPCs) in the SNpc of two different mouse models of Parkinson's disease, we significantly ameliorated the dopaminergic neuron loss and function.

Pharmacological inhibition of PI3K reduces adiposity and metabolic syndrome in obese mice and rhesus monkeys.

Genetic inhibition of PI3K signaling increases energy expenditure, protects from obesity and metabolic syndrome, and extends longevity. Here, we show that two pharmacological inhibitors of PI3K, CNIO-PI3Ki and GDC-0941, decrease the adiposity of obese mice without affecting their lean mass. Long-term treatment of obese mice with low doses of CNIO-PI3Ki reduces body weight until reaching a balance that is stable for months as long as the treatment continues.

Construction of a self-luminescent cyanobacterial bioreporter that detects a broad range of bioavailable heavy metals in aquatic environments.

A self-luminescent bioreporter strain of the unicellular cyanobacterium Synechococcus sp. PCC 7942 was constructed by fusing the promoter region of the smt locus (encoding the transcriptional repressor SmtB and the metallothionein SmtA) to luxCDABE from Photorhabdus luminescens; the sensor smtB gene controlling the expression of smtA was cloned in the same vector. The bioreporter performance was tested with a range of heavy metals and was shown to respond linearly to divalent Zn, Cd, Cu, Co, Hg, and monovalent Ag.

NOTCH pathway inactivation promotes bladder cancer progression.

NOTCH signaling suppresses tumor growth and proliferation in several types of stratified epithelia. Here, we show that missense mutations in NOTCH1 and NOTCH2 found in human bladder cancers result in loss of function. In murine models, genetic ablation of the NOTCH pathway accelerated bladder tumorigenesis and promoted the formation of squamous cell carcinomas, with areas of mesenchymal features.