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Medina and Buchler provide an introduction to chytrid fungi, an early diverging fungal lineage exhibiting characteristics found in both animals and fungi.Philip Donoghue introduces the fossil record of cells.How mitochondrial DNA mutations clonally expand in an individual cell is a question that has perplexed mitochondrial biologists for decades. A growing body of literature indicates that mitochondrial DNA mutations play a major role in ageing, metabolic diseases, neurodegenerative diseases, neuromuscular disorders and cancers. Importantly, this process of clonal expansion occurs for both inherited and somatic mitochondrial DNA mutations. To complicate matters further there are fundamental differences between mitochondrial DNA point mutations and deletions, and between mitotic and post-mitotic cells, that impact this pathogenic process. These differences, along with the challenges of investigating a longitudinal process occurring over decades in humans, have so far hindered progress towards understanding clonal expansion. Here we summarize our current understanding of the clonal expansion of mitochondrial DNA mutations in different tissues and highlight key unanswered questions. We then discuss the various existing biological models, along with their advantages and disadvantages. Finally, we explore what has been achieved with mathematical modelling so far and suggest future work to advance this important area of research.Duplication and divergence is a major mechanism by which new proteins and functions emerge in biology. Consequently, most organisms, in all domains of life, have genomes that encode large paralogous families of proteins. For recently duplicated pathways to acquire different, independent functions, the two paralogs must acquire mutations that effectively insulate them from one another. For instance, paralogous signaling proteins must acquire mutations that endow them with different interaction specificities such that they can participate in different signaling pathways without disruptive cross-talk. Although duplicated genes undoubtedly shape each other's evolution as they diverge and attain new functions, it is less clear how other paralogs impact or constrain gene duplication. Does the establishment of a new pathway by duplication and divergence require the system-wide optimization of all paralogs? The answer has profound implications for molecular evolution and our ability to engineer biological systems. Here, we discuss models, experiments, and approaches for tackling this question, and for understanding how new proteins and pathways are born.Background Medical decision-making is complex and involves a variety of decision criteria, many of which are universally recognised. However, decision-making analyses have demonstrated that certain decision criteria are not used uniformly among clinicians. Aim We describe decision criteria, which for various contexts are only used by a minority of decision makers. For these, we introduce and define the term "insular criteria". Methods 19 studies analysing clinical decision-making based on decision trees were included in our study. All studies were screened for decision-making criteria that were mentioned by less than three local decision makers in studies involving 8-26 participants. Results 14 out of the 19 included studies reported insular criteria. We identified 42 individual insular criteria. They could be intuitively allocated to seven major groups, these were comorbidities, treatment, patients' characteristics/preferences, caretaker, scores, laboratory and tumour properties/staging. Conclusion Insular criteria are commonly used in clinical decision-making, yet, the individual decision makers may not be aware of them. With this analysis, we demonstrate the existence of insular criteria and their variety. In daily practice and clinical studies, awareness of insular criteria is important.Objective Respiratory activity is an essential parameter to monitor healthy and disordered sleep, and unobtrusive measurement methods have important clinical applications in diagnostics of sleep-related breathing disorders. We propose a respiratory activity surrogate extracted from wrist-worn reflective photoplethysmography validated on a heterogeneous dataset of 389 sleep recordings. Approach The surrogate was extracted by interpolating the amplitude of the PPG pulses after evaluation of pulse morphological quality. Subsequent multistep post-processing was applied to remove parts of the surrogate with low quality and high motion levels. In addition to standard respiration rate performance, we evaluated the similarity between surrogate respiratory activity and reference inductance plethysmography of the thorax, using Spearman's correlations and spectral coherence, and assessed the influence of PPG signal quality, motion levels, sleep stages and obstructive sleep apnea. Main results Prior to post-processing, the surrogate already had a strong similarity with the reference (correlation=0.54, coherence=0.81), and reached respiration rate estimation performance in line with the literature (estimation error=0.76±2.11 breaths/min). Detrimental effects of low PPG quality, high motion levels and sleep stage-dependent physiological phenomena were significantly mitigated by the proposed post-processing steps (correlation=0.62, coherence=0.88, estimation error=0.53±1.98 breaths/min). selleck inhibitor Significance Wrist-worn PPG can be used to extract respiratory activity, thus allowing respiration monitoring in real-world sleep medicine applications using (consumer) wearable devices.Hydrogels are used in a wide range of biomedical applications, including three-dimensional (3D) cell culture, cell therapy and bioprinting. To enable processing using advanced additive fabrication techniques and to mimic the dynamic nature of the extracellular matrix (ECM), the properties of the hydrogels must be possible to tailor and change over time with high precision. The design of hydrogels that are both structurally and functionally dynamic, while providing necessary mechanical support is challenging using conventional synthesis techniques. Here, we show a modular and 3D printable hydrogel system that combines a robust but tunable covalent bioorthogonal cross-linking strategy with specific peptide-folding mediated interactions for dynamic modulation of cross-linking and functionalization. The hyaluronan-based hydrogels are covalently cross-linked using strain-promoted alkyne-azide cycloaddition using multi-arm poly(ethylene glycol). In addition, a de novo designed helix-loop-helix peptide was conjugated to the hyaluronan backbone to enable specific peptide-folding modulation of cross-linking density, cross-linking kinetics and functionality.
My Website: https://www.selleckchem.com/
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