Premature aging in aneuploid yeast is caused in part by aneuploidy-induced defects in Ribosome Quality Control.

Premature aging is a hallmark of Down syndrome, caused by trisomy of human chromosome 21, but the reason is unclear and difficult to study in humans. We used an aneuploid model in wild yeast to show that chromosome amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, and healthy aging, across genetic backgrounds and amplified chromosomes. We discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC).

Fabrication and histological evaluation of a self-setting granular cement using calcium sulfate hemihydrate granules with different pore distribution.

Granular type of bone substitutes is currently used in the field of dentistry to restore alveolar bone defects. However, the migration of the granules from the implantation site is still an unresolved issue. In this study, the feasibility to fabricate self-setting calcium sulfate hemihydrate (CSH) granules using different ranges of loading pressure: CSH(0), CSH(50), CSH(100), and CSH(150) was investigated with the hypothesis that CSH granules with reduced microporosity can inhibit the rapid dissolution rate of the calcium sulfate dihydrate (CSD) set blocks and induce bone regeneration.

Mycetoma in Ecuador.

Background: Previous studies on the distribution of mycetoma globally have failed to identify Ecuador as an endemic country.

Methods: We present data on 35 cases of mycetoma in Ecuador between 1955 and 2021: 5 cases from our experience and 30 cases from the literature.

Results: Eight cases of eumycetoma (23%) and 27 cases of actinomycetoma (77%) were diagnosed.

Successful treatment of mucosal neuromas by radiofrequency ablation in a patient with multiple endocrine neoplasia type 2B.

This is the first report of mucosal neuromas being treated successfully with radiofrequency ablation in a patient with multiple endocrine neoplasia type 2B.

Nasal cartilage destruction associated to cutaneous histoplasmosis in AIDS.

Background: Systemic histoplasmosis is a disease of high morbidity and mortality in immunocompromised patients. Patients with AIDS get the infection through inhalation of spores, triggering a primary lung infection with a subsequent hematogenous spread to multiple organs, including the skin. Tissue necrosis have been documented in cutaneous histoplasmosis with multiple clinical manifestations that mimic other diseases.

The role of stress-activated RNA-protein granules in surviving adversity.

Severe environmental stress can trigger a plethora of physiological changes and, in the process, significant cytoplasmic reorganization. Stress-activated RNA-protein granules have been implicated in this cellular overhaul by sequestering pre-existing mRNAs and influencing their fates during and after stress acclimation. While the composition and dynamics of stress-activated granule formation has been well studied, their function and impact on RNA-cargo has remained murky.

The genetic basis of aneuploidy tolerance in wild yeast.

Aneuploidy is highly detrimental during development yet common in cancers and pathogenic fungi - what gives rise to differences in aneuploidy tolerance remains unclear. We previously showed that wild isolates of tolerate chromosome amplification while laboratory strains used as a model for aneuploid syndromes do not. Here, we mapped the genetic basis to Ssd1, an RNA-binding translational regulator that is functional in wild aneuploids but defective in laboratory strain W303.

Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.

Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models.

Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress.

From bacteria to humans, individual cells within isogenic populations can show significant variation in stress tolerance, but the nature of this heterogeneity is not clear. To investigate this, we used single-cell RNA sequencing to quantify transcript heterogeneity in single Saccharomyces cerevisiae cells treated with and without salt stress to explore population variation and identify cellular covariates that influence the stress-responsive transcriptome. Leveraging the extensive knowledge of yeast transcriptional regulation, we uncovered significant regulatory variation in individual yeast cells, both before and after stress.

Advances in Clinical Research in Ecuador.

Ecuador is undergoing a process of clinical research development and strengthening. At the turn of the century, Ecuador experienced a favorable transition period of economic stability, which enabled advances in the health system and improvements in population welfare indicators. During this period, Ecuador created an institutional infrastructure to support the implementation and development of research projects.

Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq.

Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation.

Multicomponent Assembly of the Kinesin Spindle Protein Inhibitor CPUYJ039 and Analogues as Antimitotic Agents.

The potent kinesin spindle protein inhibitor CPUYJ039 and a set of analogues were prepared by a target-oriented approach based on a Ugi reaction that uses 2-nitrophenyl isocyanides as key building blocks. The herein documented strategy provides straightforward and atom economical access to potent benzimidazole-based antimitotic agents by exploring the versatility and exploratory power of the Ugi reaction. The results of docking studies and biological activity evaluations of the benzimidazole compounds are also reported.

Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma.

Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures.

Discovery of Potent and Highly Selective A2B Adenosine Receptor Antagonist Chemotypes.

Three novel families of A2B adenosine receptor antagonists were identified in the context of the structural exploration of the 3,4-dihydropyrimidin-2(1H)-one chemotype. The most appealing series contain imidazole, 1,2,4-triazole, or benzimidazole rings fused to the 2,3-positions of the parent diazinone core. The optimization process enabled identification of a highly potent (3.

A massive expansion of effector genes underlies gall-formation in the wheat pest Mayetiola destructor.

Gall-forming arthropods are highly specialized herbivores that, in combination with their hosts, produce extended phenotypes with unique morphologies [1]. Many are economically important, and others have improved our understanding of ecology and adaptive radiation [2]. However, the mechanisms that these arthropods use to induce plant galls are poorly understood.

Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives.

Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG).

Comparison of breast and abdominal adipose tissue mesenchymal stromal/stem cells in support of proliferation of breast cancer cells.

In this study, we compared MSCs from breast and abdominal tissue in terms of their expression of genes deemed important in the support of breast cancer growth and their effect on gene profile of macrophages after coculture. In addition, we investigated the role of MSCs, alone or in combination with macrophages, on proliferation of breast cancer cell lines. Our results show that MSCs derived from breast and abdominal adipose tissues have a comparable gene expression profile, have similar effect on gene expression of macrophages, and are comparable in supporting breast cancer cell line proliferation.

Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells.

Multiple myeloma (MM) is characterized by almost exclusive tropism of malignant cells for the bone marrow (BM) milieu. The survival and proliferation of malignant plasma cells have been shown to rely on interactions with nonmalignant stromal cells, in particular mesenchymal stromal cells (MSCs), in the BM microenvironment. However, the BM microenvironment is composed of a diverse array of cell types.

Biologic and immunomodulatory properties of mesenchymal stromal cells derived from human pancreatic islets.

Background Aims: Mesenchymal stromal cells (MSC) have now been shown to reside in numerous tissues throughout the body, including the pancreas. Ex vivo culture-expanded MSC derived from many tissues display important interactions with different types of immune cells in vitro and potentially play a significant role in tissue homeostasis in vivo. In this study, we investigated the biologic and immunomodulatory properties of human pancreatic islet-derived MSC.

Gas phase elimination kinetics of methyl mandelate: experimental and DFT studies.

The gas phase elimination kinetics of racemic methyl mandelate was determined in a static system, and yielded on decomposition benzaldehyde, methanol, and carbon monoxide. The reaction was homogeneous, unimolecular, and follows a first-order law in the temperature range 379.5-440 degrees C and pressure range of 21.

Joint experimental and theoretical studies of the mechanism for the gas phase elimination kinetics of methyl 2,2-dimethyl-3-hydroxypropionate.

Methyl 2,2-dimethyl-3-hydroxypropionate was found to decompose, in a static system, mainly to methyl isobutyrate and formaldehyde. The reaction rates were affected in packed and unpacked clean Pyrex vessels, demonstrating little but significant surface effect. However, in vessels seasoned with allyl bromide this reaction was homogeneous and unimolecular and followed a first-order law.

Brønsted Acid-promoted intramolecular carbocyclization of alkynals leading to cyclic enones.

TFA-promoted exo carbocyclizations of nonterminal 7-alkynals gave good to excellent yields of seven-membered cycloalkenones, a medium-sized functionalized ring present in natural products with relevant pharmacological properties. Nonterminal 5- and 6-alkynals also gave very good yields of the corresponding exo cyclopentenones and cyclohexenones. On the other hand, terminal 5-alkynals gave endo carbocyclizations to cyclohexenones.

A single residue mutation abolishes attachment of the CBM26 starch-binding domain from Lactobacillus amylovorus alpha-amylase.

Starch is degraded by amylases that frequently have a modular structure composed of a catalytic domain and at least one non-catalytic domain that is involved in polysaccharide binding. The C-terminal domain from the Lactobacillus amylovorus alpha-amylase has an unusual architecture composed of five tandem starch-binding domains (SBDs). These domains belong to family 26 in the carbohydrate-binding modules (CBM) classification.