The PWWP domain was first identified in the HDGF protein family and named after the conserved Proline-Tryptophan-Tryptophan-Proline motif in WHSC1. The PWWP domain-containing proteins play important roles in different biological processes, such as DNA replication, transcription, DNA repair, pre-mRNA processing by recognizing methylated histone and dsDNA simultaneously. Recently, how the HDGF family of PWWP domains recognize histone H3K36me3-modified nucleosome has been reported. In order to better understand the interactions between the PWWP domain and dsDNA, we carried out family-wide characterization of dsDNA binding abilities of human PWWP domains. Our binding assays confirmed that PWWP domains bind to dsDNA without sequence selectivity. Our crystal structure of the BRPF2 PWWP domain in complex with a 12-mer dsDNA reveals that the PWWP domain interacts with dsDNA by binding to its major groove, instead of the minor groove observed in the HDGF family of PWWP domains. Our study indicates that PWWP domains could bind to dsDNA in different modes.A holistic understanding of a physiological system can be accomplished through the use of multiple methods. Our current understanding of the fish gastrointestinal tract (GIT) and its role in both nutrient handling and osmoregulation is the result of the examination of the GIT using multiple reductionist methods. This review summarizes the following methods in vivo mass balance studies, and in vitro gut sac preparations, intestinal perfusions, and Ussing chambers. From Homer Smith's initial findings of marine fish intestinal osmoregulation in the 1930s through to today's research, we discuss the methods, their advantages and pitfalls, and ultimately how they have each contributed to our understanding of fish GIT physiology. Although in vivo studies provide substantial information on the intact animal, segment specific functions of the GIT cannot be easily elucidated. Instead, in vitro gut sac preparations, intestinal perfusions, or Ussing chamber experiments can provide considerable information on the function of a specific tissue and permit the delineation of specific transport pathways through the use of pharmacological agents; however, integrative inputs (e.g. hormonal and neuronal) are removed and only a fraction of the organ system can be studied.  https://www.selleckchem.com/products/vt103.html  We conclude with two case studies, i) divalent cation transport in teleosts and ii) nitrogen handling in the elasmobranch GIT, to highlight how the use of multiple reductionist methods contributes to a greater understanding of the organ system as a whole.The study of transbranchial ion and gas transport of water-breathing animals has long been a useful means of modeling transport processes of higher vertebrate organs through comparative physiology. The molecular era of biological research has brought forward valuable information detailing shifts in gene expression related to environmental stress and the sub-cellular localization of transporters; however, purely molecular studies can cause hypothetical transport mechanisms and hypotheses to be accepted without any direct physiological proof. Isolated perfused gill experiments are useful for testing most of these hypotheses and can sometimes be used outright to develop a well-supported working model for transport processes relating to an animal's osmoregulation, acid-base balance, nitrogen excretion, and respiratory gas exchange as well as their sensitivity to pollutants and environmental stress. The technique allows full control of internal hemolymph-like saline as well as the ambient environmental fluid compositions and can measure the electrophysiological properties of the gill as well as the transport rates of ions and gases as they traverse the gill epithelium. Additives such as pharmaceuticals or peptides as well as the exclusion of ions from the media are commonly used to identify the importance of specific transporters to transport mechanisms. The technique can also be used to identify the penetrance, retention, and localization of pollutants within the gill epithelium or to explore the uptake and metabolism of nutrients directly from the ambient environment. While this technique can be applied to virtually any isolatable organ, the anatomy and rigidity of the decapod crustacean gill make it an ideal candidate for most experimental designs.
  An implanted device for brain-responsive neurostimulation (RNS® System) is approved as an effective treatment to reduce seizures in adults with medically-refractory focal epilepsy. Clinical trials of the RNS System demonstrate population-level reduction in average seizure frequency, but therapeutic response is highly variable.
 
  Recent evidence links seizures to cyclical fluctuations in underlying risk. We tested the hypothesis that effectiveness of responsive neurostimulation varies based on current state within cyclical risk fluctuations.
 
  We analyzed retrospective data from 25 adults with medically-refractory focal epilepsy implanted with the RNS System. Chronic electrocorticography was used to record electrographic seizures, and hidden Markov models decoded seizures into fluctuations in underlying risk. State-dependent associations of RNS System stimulation parameters with changes in risk were estimated.
 
  Higher charge density was associated with improved outcomes, both for remaining in a low seizure ective in another. These findings represent conceptual advances in understanding the therapeutic mechanism of RNS, and directly inform current practices of RNS tuning and the development of next-generation neurostimulation systems.Erosive pustular dermatosis of the scalp (EPDS) is a chronic inflammatory condition with an unclear etiology that typically occurs on sun-damaged skin of older individuals. Clinically it is characterized by sterile pustules, erosions, and crusting that can lead to scarring alopecia and skin atrophy (Yang et al., 2016; Broussard et al., 2012; Cunha et al., 2019). EPDS is a therapeutic challenge and often resistant to numerous treatments. Herein, we describe a case of erosive pustular dermatosis of the scalp in a patient with lichen planopilaris successfully treated with curettage followed by aminolevulinic acid photodynamic therapy.