MAML3-fusions modulate vascular and immune tumour microenvironment and confer high metastatic risk in pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20-25 % of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a MAML3-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed.

Multiplexing LAMP Assays: A Methodological Review and Diagnostic Application.

The loop-mediated isothermal amplification (LAMP) technique is a great alternative to PCR-based methods, as it is fast, easy to use and works with high sensitivity and specificity without the need for expensive instruments. However, one of the limitations of LAMP is difficulty in achieving the simultaneous detection of several targets in a single tube, as the methodologies that allow this rely on fluorogenic probes containing specific target sequences, complicating their adaptation and the optimization of assays. Here, we summarize different methods for the development of multiplex LAMP assays based on sequence-specific detection, illustrated with a schematic representation of the technique, and evaluate their practical application based on the real-time detection and quantification of results, the possibility to visualize the results at a glance, the prior stabilization of reaction components, promoting the point-of-care use, the maximum number of specific targets amplified, and the validation of the technique in clinical samples.

Network switches and their role in circadian clocks.

Circadian rhythms are generated by complex interactions among genes and proteins. Self-sustained ∼24 h oscillations require negative feedback loops and sufficiently strong nonlinearities that are the product of molecular and network switches. Here, we review common mechanisms to obtain switch-like behavior, including cooperativity, antagonistic enzymes, multisite phosphorylation, positive feedback, and sequestration.

Coupling allows robust mammalian redox circadian rhythms despite heterogeneity and noise.

Circadian clocks are endogenous oscillators present in almost all cells that drive daily rhythms in physiology and behavior. There are two mechanisms that have been proposed to explain how circadian rhythms are generated in mammalian cells: through a transcription-translation feedback loop (TTFL) and based on oxidation/reduction reactions, both of which are intrinsically stochastic and heterogeneous at the single cell level. In order to explore the emerging properties of stochastic and heterogeneous redox oscillators, we simplify a recently developed kinetic model of redox oscillations to an amplitude-phase oscillator with 'twist' (period-amplitude correlation) and subject to Gaussian noise.

Antimicrobial Properties of New Polyamines Conjugated with Oxygen-Containing Aromatic Functional Groups.

Antibiotic resistance is now a first-order health problem, which makes the development of new families of antimicrobials imperative. These compounds should ideally be inexpensive, readily available, highly active, and non-toxic. Here, we present the results of our investigation regarding the antimicrobial activity of a series of natural and synthetic polyamines with different architectures (linear, tripodal, and macrocyclic) and their derivatives with the oxygen-containing aromatic functional groups 1,3-benzodioxol, ortho/para phenol, or 2,3-dihydrobenzofuran.

Are circadian amplitudes and periods correlated? A new twist in the story.

Three parameters are important to characterize a circadian and in general any biological clock: period, phase and amplitude. While circadian periods have been shown to correlate with entrainment phases, and clock amplitude influences the phase response of an oscillator to pulse-like zeitgeber signals, the co-modulations of amplitude and periods, which we term , have not been studied in detail. In this paper we define two concepts: refers to amplitude-period correlations arising in ensembles of self-sustained, limit cycle clocks in the absence of external inputs, and refers to the co-modulation of an individual clock's amplitude and period in response to external zeitgebers.

Biotechnological applications of biofilms formed by osmotolerant and halotolerant yeasts.

Many microorganisms are capable of developing biofilms under adverse conditions usually related to nutrient limitation. They are complex structures in which cells (in many cases of different species) are embedded in the material that they secrete, the extracellular matrix (ECM), which is composed of proteins, carbohydrates, lipids, and nucleic acids. The ECM has several functions including adhesion, cellular communication, nutrient distribution, and increased community resistance, this being the main drawback when these microorganisms are pathogenic.

Feasibility of Telemedicine in the Management Strategy of Patients With Lymphoma Amid the COVID-19 Pandemic in Spain: Prospective Observational Study.

Background: On March 14, 2020, a state of alarm was declared in Spain due to the spread of SARS-CoV-2. Beyond this date, COVID-19 in the country changed the practice of oncologic care.

Objective: Since recurrent hospital visits were a potential risk factor for contagion, the aim of this prospective observational study was to analyze the consequences of the COVID-19 pandemic in the health care of patients with lymphoma.

Inter-layer and inter-subject variability of diurnal gene expression in human skin.

The skin is the largest human organ with a circadian clock that regulates its function. Although circadian rhythms in specific functions are known, rhythms in the proximal clock output, gene expression, in human skin have not been thoroughly explored. This work reports 24 h gene expression rhythms in two skin layers, epidermis and dermis, in a cohort of young, healthy adults, who maintained natural, regular sleep-wake schedules.

Improvements in the genetic editing technologies: CRISPR-Cas and beyond.

Gene editing is a great hope not only for the scientific community, but also for society in general. This is due to its potential therapeutic applications that would allow curing diseases of genetic origin. The first realistic approach to achieve this goal was the development of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) tools.

The effects of aerobic exercise and transcranial direct current stimulation on cognitive function in older adults with and without cognitive impairment: A systematic review and meta-analysis.

Background: Aerobic exercise (AE) may slow age-related cognitive decline. However, such cognition-sparing effects are not uniform across cognitive domains and studies. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation and is also emerging as a potential alternative to pharmaceutical therapies.

Mathematical Modeling in Circadian Rhythmicity.

Circadian clocks are autonomous systems able to oscillate in a self-sustained manner in the absence of external cues, although such Zeitgebers are typically present. At the cellular level, the molecular clockwork consists of a complex network of interlocked feedback loops. This chapter discusses self-sustained circadian oscillators in the context of nonlinear dynamics theory.

Synergies of Multiple Zeitgebers Tune Entrainment.

Circadian rhythms are biological rhythms with a period close to 24 h. They become entrained to the Earth's solar day different periodic cues, so-called zeitgebers. The entrainment of circadian rhythms to a single zeitgeber was investigated in many mathematical clock models of different levels of complexity, ranging from the Poincaré oscillator and the Goodwin model to biologically more detailed models of multiple transcriptional translational feedback loops.

Recent developments in the biology and biotechnological applications of halotolerant yeasts.

Natural hypersaline environments are inhabited by an abundance of prokaryotic and eukaryotic microorganisms capable of thriving under extreme saline conditions. Yeasts represent a substantial fraction of halotolerant eukaryotic microbiomes and are frequently isolated as food contaminants and from solar salterns. During the last years, a handful of new species has been discovered in moderate saline environments, including estuarine and deep-sea waters.

Effect of a smartphone application (Perx) on medication adherence and clinical outcomes: a 12-month randomised controlled trial.

Objective: To determine whether the Perx app improves medication adherence and clinical outcomes over 12 months compared with standard care in patients requiring polypharmacy.

Design: Randomised controlled trial with 12-month follow-up.

Setting: Outpatient clinics in three tertiary hospitals in Sydney, Australia.

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.

Personality and Cognitive-Emotional Variables in Spanish Children and Adolescents With and Without Cleft Lip and/or Palate.

Objectives: To analyze personality (Big Five Model) and cognitive-emotional variables in children and adolescents with a cleft lip/palate (s) in comparison to an equivalent peer sample without an orofacial cleft.

Design: Cross-sectional study with data collected using self-reported questionnaires over 2 years.

Setting: Data were collected during visits to health center dental clinics.

The dilemma of choosing obstetrics and anesthesia techniques in a patient with cerebral cavernomatosis: a case report.

This report describes the case of a pregnant woman who arrived for preanesthetic assessment of External Cephalic Version (ECV) for fetus in breech presentation and cesarean section in case of ECV failure. Although the technique seems simple, attempts to rotate the fetus can result in elevated intracranial pressure, which might cause malformation bleeding. The most appropriate anesthetic technique in cases of arteriovenous malformations during C-sections has not been determined.

Linking functional traits with tree growth and forest productivity in Quercus ilex forests along a climatic gradient.

Plant functional traits are highly plastic to changes in climatic factors and nutrient availability. However, the intraspecific plant response to abiotic factors and the overall effect on tree growth and productivity is still under debate. We studied forest productivity for 30 Quercus ilex subsp.

Formation and characterization of biofilms formed by salt-tolerant yeast strains in seawater-based growth medium.

Yeast whole cells have been widely used in modern biotechnology as biocatalysts to generate numerous compounds of industrial, chemical, and pharmaceutical importance. Since many of the biocatalysis-utilizing manufactures have become more concerned about environmental issues, seawater is now considered a sustainable alternative to freshwater for biocatalytic processes. This approach plausibly commenced new research initiatives into exploration of salt-tolerant yeast strains.