Photoswitch dissociation from a G protein-coupled receptor resolved by time-resolved serial crystallography.

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in humans. The binding and dissociation of ligands tunes the inherent conformational flexibility of these important drug targets towards distinct functional states. Here we show how to trigger and resolve protein-ligand interaction dynamics within the human adenosine A receptor.

FastAd: A versatile toolkit for rapid generation of single adenoviruses or diverse adenoviral vector libraries.

Adenoviruses (Ads) are potent gene delivery vectors for and applications. However, current methods for their construction are time-consuming and inefficient, limiting their rapid production and utility in generating complex genetic libraries. Here, we introduce FastAd, a rapid and easy-to-use technology for inserting recombinant "donor" DNA directly into infectious "receiver" Ads in mammalian cells by the concerted action of two efficient recombinases: Cre and Bxb1.

Structure-derived insights from blood factors binding to the surfaces of different adenoviruses.

The tropism of adenoviruses (Ads) is significantly influenced by the binding of various blood factors. To investigate differences in their binding, we conducted cryo-EM analysis on complexes of several human adenoviruses with human platelet factor-4 (PF4), coagulation factors FII (Prothrombin), and FX. While we observed EM densities for FII and FX bound to all the species-C adenoviruses examined, no densities were seen for PF4, even though PF4 can co-pellet with various Ads.

Longitudinal assessment of SNPs rs72552763 and rs622342 in over HbA1c control among Mexican-Mestizo diabetic type 2 patients.

In Mexico, 75% of diabetes mellitus type 2 (DMT2) patients are not in glycaemic control criteria (HbA1c<7%); this entails a significantly variable drug response. Amongst the factors influencing such variability, are genetics, more specifically, single nucleotide polymorphisms (SNPs). Three genes implied in metformin pharmacokinetics are , , and , which are polymorphic.

Relationships between media influence, body image and sociocultural appearance ideals in Latin America: A systematic literature review.

The rapidly growing body of research investigating media influence on body image in Latin America has not been previously comprehensively synthesised. We systematically reviewed studies of the relationships between media use/influence, body image, and sociocultural appearance ideals in Latin America (CRD42021254607). We searched PsycINFO/Medline, Pubmed, Web of Science, ERIC, Scopus, ProQuest Dissertations, SciElo, and LILACS for quantitative and qualitative peer-reviewed articles and doctoral theses in English, Spanish, and Portuguese.

Impact of variants rs622342 and rs72552763 on HbA1c and metformin plasmatic concentration levels in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a major global health problem. Response to first-line therapy is variable. This is partially due to interindividual variability across those genes codifying transport, metabolising, and drug activation proteins involved in first-line pharmacological treatment.

Molecular Analysis of Copy-Back Defective Interfering RNAs of Morbilliviruses.

Copy-back defective interfering RNAs are major contaminants of viral stock preparations of morbilliviruses and other negative strand RNA viruses. They are hybrid molecules of positive sense antigenome and negative sense genome. They possess perfectly complementary ends allowing the formation of extremely stable double-stranded RNA panhandle structures.

Implications of analytical nanoscience in pharmaceutical and biomedical fields: A critical view.

This review summarizes recent progress performed in the design and application of analytical tools and methodologies using nanomaterials for pharmaceutical analysis, and specifically new nanomedicines at distinct phases of development and translation from preclinical to clinical stages. Over the last 10-15 years, a growing number of studies have utilized various nanomaterials, including carbon-based, metallic nanoparticles, polymeric nanomaterials, materials based on biological molecules, and composite nanomaterials as tools for improving the analysis of pharmaceutical products. New and more complex nanomaterials are currently being explored to influence different stages of the analytical process.

Target enrichment sequencing coupled with GWAS identifies as a candidate gene in the control of budbreak in apple.

The timing of floral budbreak in apple has a significant effect on fruit production and quality. Budbreak occurs as a result of a complex molecular mechanism that relies on accurate integration of external environmental cues, principally temperature. In the pursuit of understanding this mechanism, especially with respect to aiding adaptation to climate change, a QTL at the top of linkage group (LG) 9 has been identified by many studies on budbreak, but the genes underlying it remain elusive.

Pharmacogenomic biomarker information on drug labels of the Spanish Agency of Medicines and Sanitary products: evaluation and comparison with other regulatory agencies.

This work aimed to analyse the pharmacogenetic information in the Spanish Drug Regulatory Agency (AEMPS) Summary of Products Characteristics (SmPC), evaluating the presence of pharmacogenetic biomarkers, as well as the associated recommendations. A total of 55.4% of the 1891 drug labels reviewed included information on pharmacogenetic biomarker(s).

A perspective on the role of physiological stresses in cancer, diabetes and cognitive disease as environmental diseases.

With rapid industrialization, urbanization, and climate change, the impact of environmental factors on human health is becoming increasingly evident and understanding the complex mechanisms involved is vital from a healthcare perspective. Nevertheless, the relationship between physiological stress resulting from environmental stressors and environmental disease is complex and not well understood. Chronic exposure to environmental stressors, such as air and water contaminants, pesticides, and toxic metals, has been recognized as a potent elicitor of physiological responses ranging from systemic inflammation to immune system dysregulation causing or progressing environmental diseases.

"Look straight ahead"-A new test to diagnose spatial neglect by computed tomography.

Spatial neglect is the dominant behavioral disorder after right hemisphere brain lesions. Reliabel diagnosis by formal neuropsychological testing is often achieved only later during hospitalization, leading to delays in targeted therapies. We propose a way to diagnose spatial neglect right at admission.

Endothelial protein C receptor is increased in preterm preeclampsia and fetal growth restriction.

Placental dysfunction is the leading cause of both preeclampsia and fetal growth restriction. This study aimed to characterize endothelial protein C receptor (EPCR) in preterm preeclampsia, term preeclampsia, and fetal growth restriction (defined by delivery of a small for gestational age [SGA] infant [<10% birthweight centile]) and examine its regulation in primary syncytiotrophoblast. Placental EPCR mRNA and protein were significantly increased in patients with preterm preeclampsia (<34 weeks gestation) compared to gestation-matched controls (p < .

Current perspectives on interethnic variability in multiple myeloma: Single cell technology, population pharmacogenetics and molecular signal transduction.

Multiple myeloma (MM) is an aggressive cancer characterised by malignancy of the plasma cells and a rising global incidence. The gold standard for optimum response is aggressive chemotherapy followed by autologous stem cell transplantation (ASCT). However, majority of the patients are above 60 years and this presents the clinician with complications such as ineligibility for ASCT, frailty, drug-induced toxicity and differential/partial response to treatment.

Pharmacogenetics of Metformin Transporters Suggests No Association with Therapeutic Inefficacy among Diabetes Type 2 Mexican Patients.

Mexico has been under official epidemiological alert due to diabetes since 2016. This study presents new information on the frequency and variants of metformin transporters OCT1, OCT2, OCT3, ABCB1, and CYP2C9 variants as well. It also reports the association with HbA1c control on 103 DMT2 patients.

The Identification of Small RNAs Differentially Expressed in Apple Buds Reveals a Potential Role of the Mir159-MYB Regulatory Module during Dormancy.

Winter dormancy is an adaptative mechanism that temperate and boreal trees have developed to protect their meristems against low temperatures. In apple trees (), cold temperatures induce bud dormancy at the end of summer/beginning of the fall. Apple buds stay dormant during winter until they are exposed to a period of cold, after which they can resume growth (budbreak) and initiate flowering in response to warmer temperatures in spring.

Circulating Activin A is elevated at 36 weeks' gestation preceding a diagnosis of preeclampsia.

Activin A is aberrantly expressed by the preeclamptic placenta and circulating levels have been investigated as a potential biomarker for the disease. In a nested case-control study we measured Activin A levels in maternal plasma at 28- and 36-weeks' gestation preceding term preeclampsia diagnosis. At 28 weeks Activin A was not significantly altered (n = 73 destined to develop preeclampsia vs n = 191 controls).

A disintegrin and metalloproteinase 12 (ADAM12) is reduced at 36 weeks' gestation in pregnancies destined to deliver small for gestational age infants.

First trimester circulating ADAM12 is reduced in fetal growth restriction (FGR) and preeclampsia. We measured plasma ADAM12 at 36 weeks' gestation preceding diagnosis of term preeclampsia or delivery of a small for gestational age (SGA; birthweight <10th centile) infant in two independent cohorts (Cohort 1 90 SGA, 41 preeclampsia, 862 controls; Cohort 2121 SGA 23 preeclampsia; 190 controls). ADAM12 was reduced with SGA in both cohorts (p = 0.

Treatment-Relevant Findings in Transesophageal Echocardiography After Stroke: A Prospective Multicenter Cohort Study.

Background And Purpose: Cardiac ultrasound to identify sources of cardioembolism is part of the diagnostic workup of acute ischemic stroke. Recommendations on whether transesophageal echocardiography (TEE) should be performed in addition to transthoracic echocardiography (TTE) are controversial. We aimed to determine the incremental diagnostic yield of TEE in addition to TTE in patients with acute ischemic stroke with undetermined cause.

Unraveling the role of MADS transcription factor complexes in apple tree dormancy.

A group of MADS transcription factors (TFs) are believed to control temperature-mediated bud dormancy. These TFs, called DORMANCY-ASSOCIATED MADS-BOX (DAM), are encoded by genes similar to SHORT VEGETATIVE PHASE (SVP) from Arabidopsis. MADS proteins form transcriptional complexes whose combinatory composition defines their molecular function.

waveRAPID-A Robust Assay for High-Throughput Kinetic Screens with the Creoptix WAVEsystem.

Surface-based biophysical methods for measuring binding kinetics of molecular interactions, such as surface plasmon resonance (SPR) or grating-coupled interferometry (GCI), are now well established and widely used in drug discovery. Increasing throughput is an often-cited need in the drug discovery process and this has been achieved with new instrument generations where multiple interactions are measured in parallel, shortening the total measurement times and enabling new application areas within the field. Here, we present the development of a novel technology called waveRAPID for a further-up to 10-fold-increase in throughput, consisting of an injection method using a single sample.