Customizable gene sensing and response without altering endogenous coding sequences.

Synthetic biology aims to modify cellular behaviors by implementing genetic circuits that respond to changes in cell state. Integrating genetic biosensors into endogenous gene coding sequences using clustered regularly interspaced short palindromic repeats and Cas9 enables interrogation of gene expression dynamics in the appropriate chromosomal context. However, embedding a biosensor into a gene coding sequence may unpredictably alter endogenous gene regulation.

Geometric cohesion in two-dimensional systems composed of star-shaped particles.

Using a discrete element method, we investigate the phenomenon of geometric cohesion in granular systems composed of star-shaped particles with 3 to 13 arms. This was done by analyzing the stability of columns built with these particles and by studying the microstructure of these columns in terms of density and connectivity. We find that systems composed of star-shaped particles can exhibit geometric cohesion (i.

Unswitched memory B cell deficiency in children with sickle cell disease and response to pneumococcal polysaccharide vaccine.

Early mortality in sickle cell disease (SCD) is attributed to increased infections due to loss of splenic function. Marginal zone B cells are important for initial opsonization of pathogens and can be absent in spleen histopathology in SCD. The frequency of unswitched memory B cells (UMBC), the circulating correlate of marginal zone B cells, reflects the immunologic function of the spleen.

Dynamics of clonal hematopoiesis under DNA-damaging treatment in patients with ovarian cancer.

Clonal hematopoiesis (CH) driven by mutations in the DNA damage response (DDR) pathway is frequent in patients with cancer and is associated with a higher risk of therapy-related myeloid neoplasms (t-MNs). Here, we analyzed 423 serial whole blood and plasma samples from 103 patients with relapsed high-grade ovarian cancer receiving carboplatin, poly(ADP-ribose) polymerase inhibitor (PARPi) and heat shock protein 90 inhibitor (HSP90i) treatment within the phase II EUDARIO trial using error-corrected sequencing of 72 genes. DDR-driven CH was detected in 35% of patients and was associated with longer duration of prior PARPi treatment.

Growth and paralytic shellfish poisoning toxin production by a Mexican dinoflagellate strain of Alexandrium tamiyavanichii Balech (1994) under different nutrient conditions.

Alexandrium tamiyavanichii is a marine dinoflagellate known to produce Paralytic Shellfish Poisoning (PSP) toxin. Thus, a strain was isolated from La Paz Bay, Baja California Sur, Mexico and used to explore whether stress conditions, such as phosphorus limitation (PL) and nitrogen enrichment (NE) modulate population growth and PSP toxin production in the GSe medium. Growth kinetics showed that the PL treatment produced a 3.

Grain size distribution does not affect the residual shear strength of granular materials: An experimental proof.

Granular materials are used in several fields and in a wide variety of processes. An important feature of these materials is the diversity of grain sizes, commonly referred to as polydispersity. When granular materials are sheared, they exhibit a predominant small elastic range.

Production of New Biopesticides from for the Control of Coffee Rust () under Laboratory and Field Conditions.

One of the diseases with the greatest economic impact on coffee cultivation worldwide and particularly in Peru is coffee rust (). The search for sustainable control methods as disease management strategies in coffee cultivation is necessary. The objective of this research was to determine the effectiveness of five biopesticides based on lemon verbena () for the control of rust applied in laboratory and field conditions to allow the recovery of coffee ( L.

Association between Germline Single-Nucleotide Variants in ADME Genes and Major Molecular Response to Imatinib in Chronic Myeloid Leukemia Patients.

Imatinib is the most common first-line tyrosine kinase inhibitor (TKI) used to treat chronic-phase chronic myeloid leukemia (CP-CML). However, only a proportion of patients achieve major molecular response (MMR), so there is a need to find biological factors that aid the selection of the optimal therapeutic strategy (imatinib vs. more potent second-generation TKIs).

Finding the grain size distribution that produces the densest arrangement in frictional sphere packings: Revisiting and rediscovering the century-old Fuller and Thompson distribution.

By means of discrete-element methods, we investigate the joint effects of the grain size distribution (GSD) and contact friction on the structure of three-dimensional samples composed of spherical grains. Specifically, we compress these systems isotropically until jamming and then analyze their structure in terms of density, connectivity, coefficients of uniformity and curvature, and parameters of grading entropy. Our study focuses on power-law GSDs and particularly on the Fuller and Thompson distribution, proposed over a century ago.

Impact of Individual Comorbidities on Survival of Patients with Myelofibrosis.

The comorbidity burden is an important risk factor for overall survival (OS) in several hematological malignancies. This observational prospective study was conducted to evaluate the impact of individual comorbidities on survival in a multicenter series of 668 patients with primary myelofibrosis (PMF) or MF secondary to polycythemia vera (PPV-MF) or essential thrombocythemia (PET-MF). Hypertension (hazard ratio (HR) = 4.

Natural killer cell receptors and ligand variants modulate response to tyrosine kinase inhibitors in patients with chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm treated with tyrosine kinase inhibitors (TKIs). Although survival rates have improved, response to these treatments is highly heterogeneous. Variations in response rates may be due to different causes such as, treatment adherence, mutations in the BCR-ABL1 gene, clonal evolution and amplification of the BCR-ABL1 gene, but innate immune response is also considered to play a very important role and, specifically, NK cell activity through their receptors and ligands, could be determinant.

Influence of Telomere Length on the Achievement of Deep Molecular Response With Imatinib in Chronic Myeloid Leukemia Patients.

Tyrosine kinase inhibitors have dramatically changed the outcome of chronic myeloid leukemia (CML), and nowadays, one of the main treatment goals is the achievement of deep molecular responses (DMRs), which can eventually lead to therapy discontinuation approaches. Few biological factors at diagnosis have been associated with this level of response. Telomere length (TL) in peripheral blood cells of patients with CML has been related to disease stage, response to therapy and disease progression, but little is known about its role on DMR.

Impact of BCR-ABL1 Transcript Type on Response, Treatment-Free Remission Rate and Survival in Chronic Myeloid Leukemia Patients Treated with Imatinib.

The most frequent -p210 transcripts in chronic myeloid leukemia (CML) are e14a2 and e13a2. Imatinib (IM) is the most common first-line tyrosine-kinase inhibitor (TKI) used to treat CML. Some studies suggest that transcript types confer different responses to IM.

High Throughput Profiling of Flavonoid Abundance in Residue-Valorizing under Explored Mexican Plant.

waste biomass () is an undervalued abundant plant material with natural active compounds such as flavonoids. Hence, the search and conservation of flavonoids through the different productive areas have to be studied to promote the use of this agro-residue for industrial purposes. In this work, we compared the proportion of total flavonoid content (TFC) among the total polyphenolics (TPC) and described the variation of specific flavonoid profiles (HPLC-UV-MS/MS) of from three locations.

Evaluation of Programmed Cell Death in the Immune System of Pacific Oyster by the Effect of Marine Toxins.

Programmed cell death (PCD) is an essential process for the immune system's development and homeostasis, enabling the remotion of infected or unnecessary cells. There are several PCD's types, depending on the molecular mechanisms, such as non-inflammatory or pro-inflammatory. Hemocytes are the main component of cellular immunity in bivalve mollusks.

Psychometry and estimation of cutoff points of Jefferson Scale of empathy in dental students.

Objective: The objective of this study was to determine the psychometric properties of the 3-dimensional latent model of empathy on the Jefferson Scale of Physician Empathy instrument (version S), and to verify the existence of cutoff points capable of differentiating empathy measures classified as: "high," "medium," and "low" using data collected from observations of students from 11 dental faculties of 5 Central American and Caribbean countries (n = 3082) between 2015 and 2019.

Methods: This is an exploratory, "a posteriori," and non-experimental study. Factor structure and factor invariance by country and gender were analyzed.

Combined effects of contact friction and particle shape on strength properties and microstructure of sheared granular media.

We present a systematic numerical investigation concerning the combined effects of sliding friction and particle shape (i.e., angularity) parameters on the shear strength and microstructure of granular packings.

miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk.

Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis.