p53 and p21 dynamics encode single-cell DNA damage levels, fine-tuning proliferation and shaping population heterogeneity.

Cells must accurately and quickly detect DNA damage through a set of checkpoint mechanisms that enable repair and control proliferation. Heterogeneous levels of cellular stress and noisy signaling processes can lead to phenotypic variability but little is known about their role in underlying proliferation heterogeneity. Here we study two previously published single cell datasets and find that cells encode heterogeneous levels of endogenous and exogenous DNA damage to shape proliferation heterogeneity at the population level.

Analysis of Complex Circadian Time Series Data Using Wavelets.

Experiments that compare rhythmic properties across different genetic alterations and entrainment conditions underlie some of the most important breakthroughs in circadian biology. A robust estimation of the rhythmic properties of the circadian signals goes hand in hand with these discoveries. Widely applied traditional signal analysis methods such as fitting cosine functions or Fourier transformations rely on the assumption that oscillation periods do not change over time.

Intercellular coupling between peripheral circadian oscillators by TGF-β signaling.

Coupling between cell-autonomous circadian oscillators is crucial to prevent desynchronization of cellular networks and disruption of circadian tissue functions. While neuronal oscillators within the mammalian central clock, the suprachiasmatic nucleus, couple intercellularly, coupling among peripheral oscillators is controversial and the molecular mechanisms are unknown. Using two- and three-dimensional mammalian culture models in vitro (mainly human U-2 OS cells) and ex vivo, we show that peripheral oscillators couple via paracrine pathways.

Live-cell imaging of circadian clock protein dynamics in CRISPR-generated knock-in cells.

The cell biology of circadian clocks is still in its infancy. Here, we describe an efficient strategy for generating knock-in reporter cell lines using CRISPR technology that is particularly useful for genes expressed transiently or at low levels, such as those coding for circadian clock proteins. We generated single and double knock-in cells with endogenously expressed PER2 and CRY1 fused to fluorescent proteins allowing us to simultaneously monitor the dynamics of CRY1 and PER2 proteins in live single cells.

The effects of proliferation status and cell cycle phase on the responses of single cells to chemotherapy.

DNA-damaging chemotherapeutics are widely used in cancer treatments, but for solid tumors they often leave a residual tumor-cell population. Here we investigated how cellular states might affect the response of individual cells in a clonal population to cisplatin, a DNA-damaging chemotherapeutic agent. Using a live-cell reporter of cell cycle phase and long-term imaging, we monitored single-cell proliferation before, at the time of, and after treatment.

Incidence of antiretroviral drug-related problems in the treatment of HIV among hospitalized patients in the Hospital Santa Clara, Bogotá.

Introduction: The antiretroviral therapy for the treatment of the human immunodeficiency virus (HIV) is a therapeutic strategy linked to drug-related problems that cause or can cause the appearance of negative results associated with the medication. It is important, therefore, to identify their incidence, characterize them, and classify them to design strategies to minimize their impact. Objective: To estimate the overall incidence and the incidence of each one of the antiretroviral drugs-related problems in the treatment of the HIV infection in a cohort of hospitalized patients in Bogotá, Colombia.

[Prevalence and risk factors associated to tuberculosis and non-tuberculous mycobacterial infections in HIV-positive patients in Bogotá].

Introduction: Tuberculosis is one of the most widely distributed infectious diseases worldwide. It is the most common cause of mortality among AIDS patients. In Colombia, 12,918 tuberculosis cases were notified, and 926 deaths were reported in 2015.

Tuning the phase of circadian entrainment.

The circadian clock coordinates daily physiological, metabolic and behavioural rhythms. These endogenous oscillations are synchronized with external cues ('zeitgebers'), such as daily light and temperature cycles. When the circadian clock is entrained by a zeitgeber, the phase difference ψ between the phase of a clock-controlled rhythm and the phase of the zeitgeber is of fundamental importance for the fitness of the organism.

Chitosan-decorated polystyrene-b-poly(acrylic acid) polymersomes as novel carriers for topical delivery of finasteride.

In view of the fact that the oral administration of finasteride (FIN) has resulted in various undesirable systemic side effects, the topical application of polystyrene and poly(acrylic acid)-based polymersomes (underexplored system) was investigated. Undecorated PS139-b-PAA17 and PS404-b-PAA63 vesicles (C3 and C7, respectively) or vesicles decorated with chitosan samples of different molecular weight (C3/CS-oligo, C7/CS-oligo, C3/CS-37 and C7/CS-37) were prepared by the co-solvent self-assembly method and characterized by small-angle X-ray scattering,transmission electron microscopy and dynamic light scattering techniques. In vitro release experiments and ex vivo permeation using Franz diffusion cells were carried out (through comparison with hydroethanolic finasteride solution).

Nifedipine-loaded polymeric nanocapsules: validation of a stability-indicating HPLC method to evaluate the drug entrapment efficiency and in vitro release profiles.

A simple stability-indicating analytical method was developed and validated to quantify nifedipine in polymeric nanocapsule suspensions; an in vitro drug release study was then carried out. The analysis was performed using an RP C18 column, UV-Vis detection at 262 nm, and methanol-water (70 + 30, v/v) mobile phase at a flow rate of 1.2 mL/min.

Genetic redundancy strengthens the circadian clock leading to a narrow entrainment range.

Circadian clocks are internal timekeepers present in almost all organisms. Driven by a genetic network of highly conserved structure, they generate self-sustained oscillations that entrain to periodic external signals such as the 24 h light-dark cycle. Vertebrates possess multiple, functionally overlapping homologues of the core clock genes.

Human chronotypes from a theoretical perspective.

The endogenous circadian timing system has evolved to synchronize an organism to periodically recurring environmental conditions. Those external time cues are called Zeitgebers. When entrained by a Zeitgeber, the intrinsic oscillator adopts a fixed phase relation ψ to the Zeitgeber.

Circadian desynchronization.

The suprachiasmatic nucleus (SCN) coordinates via multiple outputs physiological and behavioural circadian rhythms. The SCN is composed of a heterogeneous network of coupled oscillators that entrain to the daily light-dark cycles. Outside the physiological entrainment range, rich locomotor patterns of desynchronized rhythms are observed.

Coupling governs entrainment range of circadian clocks.

Circadian clocks are endogenous oscillators driving daily rhythms in physiology and behavior. Synchronization of these timers to environmental light-dark cycles ('entrainment') is crucial for an organism's fitness. Little is known about which oscillator qualities determine entrainment, i.

Organochlorine pesticides in umbilical cord blood serum of women from Southern Spain and adherence to the Mediterranean diet.

Exposure of pregnant women to organochlorine (OC) pesticides largely derives from contaminated food, but environmental, occupational, and domestic factors have also been implicated. We investigated the presence of nine OC residues in the umbilical cord blood of newborns in Southern Spain and analyzed the relationship of this exposure with maternal and pregnancy variables, including maternal adherence to the Mediterranean Diet (MD). OCs were detected in 95% of umbilical cord blood samples from the 318 mothers, who had a mean degree of adherence to the MD of 56.

How to achieve fast entrainment? The timescale to synchronization.

Entrainment, where oscillators synchronize to an external signal, is ubiquitous in nature. The transient time leading to entrainment plays a major role in many biological processes. Our goal is to unveil the specific dynamics that leads to fast entrainment.

Assessment of the total effective xenoestrogen burden in extracts of human placentas.

We have standardized a method to assess the total effective xenoestrogen burden (TEXB) in human placentas by the extraction and separation by high-performance liquid chromatography of two fractions containing lipophilic xenoestrogens (alpha) and endogenous hormones (beta), followed by assessing their estrogenicity in MCF-7 breast cancer cell-based E-Screen and Yeast Estrogen Screen (YES) bioassays. The means of TEXB alpha concentrations (in estradiol equivalent (Eeq) units) were 1.32 and 0.

Proposal of a Mediterranean diet index for pregnant women.

Numerous studies have addressed the nutritional needs of pregnant women. The nutritional status of the woman before and during gestation affects the growth of the fetus and the course of the pregnancy and influences the risk of obesity for mother and infant. The aim of this study was to propose a diet quality index for pregnancy based on a Mediterranean-type diet (MDS-P), evaluating the diet of a group of pregnant women by applying the Mediterranean Diet Score (MDS) and evaluating their intake of micronutrients required in optimal amounts during pregnancy, such as Fe, folic acid and Ca.

Phase response curves elucidating the dynamics of coupled oscillators.

Phase response curves (PRCs) are widely used in circadian clocks, neuroscience, and heart physiology. They quantify the response of an oscillator to pulse-like perturbations. Phase response curves provide valuable information on the properties of oscillators and their synchronization.

Dietary exposure assessment of pregnant women to bisphenol-A from cans and microwave containers in Southern Spain.

Bisphenol-A (BPA), material for polycarbonate and epoxy resin synthesis, has been detected in canned food, among other food containers. In mammal studies, BPA transferred from mother to fetus, caused abnormality of reproductive organs, and advanced female puberty. BPA from canned food and microwave containers was analyzed using high performance liquid chromatography and gas chromatography-mass spectrometry.

Development and validation of an HPLC method to quantify camptothecin in polymeric nanocapsule suspensions.

A simple, rapid, and sensitive reversed-phase column high-performance liquid chromatographic method was developed and validated to quantify camptothecin (CPT) in polymeric nanocapsule suspensions. The chromatographic separation was performed on a Supelcosil LC-18 column (15 cm x 4.6 mm id, 5 microm) using a mobile phase consisting of methanol-10 mM KH2PO4 (60 + 40, v/v; pH 2.

Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study.

Background: Exposure to xenoestrogens during pregnancy may disturb the development and function of male sexual organs.

Objective: In this study we aimed to determine whether the combined effect of environmental estrogens measured as total effective xenoestrogen burden (TEXB) is a risk factor for male urogenital malformations.

Methods: In a case-control study, nested in a mother-child cohort (n = 702) established at Granada University Hospital, we compared 50 newborns with diagnosis of cryptorchidism and/or hypospadias with 114 boys without malformations matched by gestational age, date of birth, and parity.

Pesticide exposure of two age groups of women and its relationship with their diet.

The widespread presence of organochlorine (OC) pesticides in human samples may be explained by the environmental exposure of the population. Foods are considered a constant source of exposure, despite compliance with maximum permitted residue levels. This study aimed to examine the relationship between nutritional habits of women in Southeast Spain and their serum concentrations of OCs.