Progression through the cell cycle is driven by cyclin-dependent kinases that control gene expression, orchestration of mitotic spindle, and cell division. To identify new regulators of the cell cycle, we performed transcriptomic analysis of human non-transformed cells expressing a fluorescent ubiquitination-based cell cycle indicator and identified 701 transcripts differentially expressed in G1 and G2 cells. Family with sequence similarity 110 member A (FAM110A) protein is highly expressed in G2 cells and localized at mitotic spindle and spindle poles during mitosis. Depletion of FAM110A impairs chromosomal alignment, delays metaphase-to-anaphase transition, and affects spindle positioning. Using mass spectrometry and immunoprecipitation, we identified casein kinase I (CK1) in complex with FAM110A during mitosis. CK1 phosphorylates the C-terminal domain of FAM110A in vitro, and inhibition of CK1 reduces phosphorylation of mitotic FAM110A. Niraparib Wild-type FAM110A, but not the FAM110A-S252-S255A mutant deficient in CK1 phosphorylation, rescues the chromosomal alignment, duration of mitosis, and orientation of the mitotic spindle after depletion of endogenous FAM110A. We propose that CK1 regulates chromosomal alignment by phosphorylating FAM110A and promoting its interaction with mitotic spindle.Diethynyl phosphinates were developed as bisfunctional electrophiles for the site-selective modification of peptides, proteins and antibodies. One of their electron-deficient triple bonds reacts selectively with a thiol and positions an electrophilic moiety for a subsequent intra- or intermolecular reaction with another thiol. The obtained conjugates were found to be stable in human plasma and in the presence of small thiols. We further demonstrate that this method is suitable for the generation of functional protein conjugates for intracellular delivery. Finally, this reagent class was used to generate functional homogeneously rebridged antibodies that remain specific for their target. Their modular synthesis, thiol selectivity and conjugate stability make diethynyl phosphinates ideal candidates for protein conjugation for biological and pharmaceutical applications.We explore, from the perspective of primary care health professionals, the motivations that lead patients to not initiate prescribed treatments, by developing a qualitative study in Spanish primary care. Six focus groups (N = 46) were conducted with general practitioners, nurse practitioners, social workers and community pharmacists and carried out in primary care (PC) of Barcelona Province, from April to July of 2018. The 46 participants were identified by three general practitioners and two pharmacists. In the interviews, the reasons for non-initiation of PC patients' medication were explored. Triangulated content analysis was performed. Patients' perspective, analysed in a previous study, and professionals' perspective agree on most of the factors that affect non-initiation. New factors were categorized into existent categories, confirming, and supplementing the model developed with patients. Health professionals identified some new factors which were not present in the patients' discourse, such as stigma related to the drug, hidden reasons for consultation, the role of nurses in prescription and support, the role of the pharmacy technician, illiteracy and lack of social support. The professionals confirm and expand on the Theoretical Model of Medication Non-Initiation. Primary care professionals should consider the factors described when prescribing a new medication. Knowledge contributed by the model should guide the design of interventions to improve initiation. Finger skin thermometry is one of the most commonly used methods for evaluating the response of the digital vessels to cold stimulation. The aim of this study was to evaluate the applicability of a novel finger skin temperature device for performing cold-stimulation test (CST) in subjects with primary and secondary Raynaud's phenomenon (RP). A total of 155 consecutive subjects were studied. They were divided into three groups 73 patients with primary RP (8 males, 65 females, mean age 38.5±16.2), 42 patients with secondary RP (4 males, 38 females, mean age 49.6±13.1, connected with lupus erythematosus and systemic scleroderma), and 40 healthy controls (5 males, 35 females, mean age 38.8±16.6). Standardized CST consisting of exposure of both hands to water with a temperature of 10℃ for 5minutes was performed. Changes in skin temperature of both wrists and 2-5 fingers were measured using a novel finger temperature device (Courage & Khazaka). Measurements were made before and 5, 10, 15, 20, 25, and 30minule contrast analysis (LASCA) at different skin areas of hands and found that it was significantly lower in primary RP than in secondary RP related to systemic sclerosis. The new finger temperature device used could be considered useful for performing cold-stimulation test in patients with Raynaud's phenomenon.The new finger temperature device used could be considered useful for performing cold-stimulation test in patients with Raynaud's phenomenon. To demonstrate and validate electric field (E-field) calculation and peripheral nerve stimulation (PNS) prediction methods that are accurate, computationally efficient, and that could be used to inform regulatory standards. We describe a simplified method for calculating the spatial distribution of induced E-field over the volume of a body model given a gradient coil vector potential field. The method is easily programmed without finite element or finite difference software, allowing for straightforward and computationally efficient E-field evaluation. Using these E-field calculations and a range of body models, population-weighted PNS thresholds are determined using established methods and compared against published experimental PNS data for two head gradient coils and one body gradient coil. A head-gradient-appropriate chronaxie value of 669 µs was determined by meta-analysis. Prediction errors between our calculated PNS parameters and the corresponding experimentally measured values were ~5% for the body gradient and ~20% for the symmetric head gradient.

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