Importantly, the treatment with Senexin A stabilizes MED13, and in combination with alkylating agents significantly reduces viability of cancer cells. In summary, our findings identify novel alkylation stress response mechanism dependent on MED13 and cyclin D1 that can serve as basis for development of innovative therapeutic strategies.In vivo phage display is widely used for identification of organ- or disease-specific homing peptides. However, the current in vivo phage biopanning approaches fail to assess biodistribution of specific peptide phages across tissues during the screen, thus necessitating laborious and time-consuming post-screening validation studies on individual peptide phages. Here, we adopted bioinformatics tools used for RNA sequencing for analysis of high-throughput sequencing (HTS) data to estimate the representation of individual peptides during biopanning in vivo. The data from in vivo phage screen were analyzed using differential binding-relative representation of each peptide in the target organ versus in a panel of control organs. Application of this approach in a model study using low-diversity peptide T7 phage library with spiked-in brain homing phage demonstrated brain-specific differential binding of brain homing phage and resulted in identification of novel lung- and brain-specific homing peptides. Our study provides a broadly applicable approach to streamline in vivo peptide phage biopanning and to increase its reproducibility and success rate.
  Parkinson disease (PD) is the second-most common neurodegenerative condition worldwide. Approximately 50% of people with PD experience freezing of gait, a motor symptom associated with falls, disability, and poorer quality of life. Accurate assessment of freezing of gait severity is important for guiding management. The aim of this systematic review was to determine the measurement properties of subjective and objective clinical assessments of freezing of gait severity using the COSMIN methodology to facilitate better outcome measure selection.
 
  Three databases (MEDLINE, EMBASE, and CINAHL) were searched. The COSMIN Risk of Bias checklist was used for evaluating quality of included studies. Data on measurement properties were extracted. Where possible, meta-analysis was performed.
 
  Nineteen studies investigating measurement properties of 7 outcome measures (patient-reported outcome measures, n=3; objective assessment tools, n=4) were included. Ten studies evaluated the Freezing of Gait Questionnaire. Basewhether it can be applied in populations different to the original study's population.
 
  Accurately assessing freezing of gait severity is important for guiding management of this disabling symptom. The best clinical assessment currently available is one that relies on the self-report of patients.
 Accurately assessing freezing of gait severity is important for guiding management of this disabling symptom. The best clinical assessment currently available is one that relies on the self-report of patients.Argonaute (Ago) proteins are conserved nucleic acid-guided proteins present in all domains of life. Eukaryotic Argonaute proteins (eAgos) are key players in RNA interference pathways and function as RNA-guided RNA endonucleases at physiological temperatures.  https://www.selleckchem.com/products/ABT-888.html  Although eAgos are considered to evolve from prokaryotic Argonaute proteins (pAgos), previously studied pAgos were unable to catalyze RNA-guided RNA cleavage at physiological temperatures. Here, we describe a distinctive pAgo from mesophilic bacteria Kurthia massiliensis (KmAgo). KmAgo utilizes DNA guides to cleave single-stranded DNA (ssDNA) and RNA targets with high activity. KmAgo also utilizes RNA guides to cleave ssDNA and RNA targets at moderate temperatures. We show that KmAgo can use 5' phosphorylated DNA guides as small as 9-mers to cut ssDNA and RNA, like Clostridium butyricum Ago. Small DNA binding confers remarkable thermostability on KmAgo, and we can suppress the guide-independent plasmid processing activity of empty KmAgo by elevating the DNA guide loaded temperature. Moreover, KmAgo performs programmable cleavage of double-stranded DNA and highly structured RNA at 37°C. Therefore, KmAgo can be regarded as a DNA-guided programmable omnipotent nuclease for cleaving most types of nucleic acids efficiently. This study broadens our understanding of Ago proteins and could expand the pAgo-based DNA and RNA manipulation toolbox.
  This study demonstrated the use of computerized motion analysis to assist in evidence-based clinical decision-making.
 
  A 15-year-old girl who had right hemiparesis after a stroke was referred for 3-dimensional computerized motion analysis to determine the effect of 3 devices intended to control her dropfoot and to assist in developing a treatment plan. Four conditions were tested and compared barefoot, lateral support ankle brace, functional electrical stimulation (FES) device, and dropfoot cuff.
 
  Kinematics showed the right ankle had significant dropfoot during swing phase (32.7degrees of plantarflexion at terminal swing) in barefoot. The lateral support ankle brace, FES device, and dropfoot cuff reduced terminal swing plantarflexion to 27.2degrees, 17.6degrees, and 15.3degrees, respectively, though ankle kinematics remained abnormal because of inadequate dorsiflexion. Improvements in gait variable score with FES (-8.2degrees) or dropfoot cuff (-8.7degrees) were significantly more than that with the lateendations were made as a result of evidence-based practice.
 Computerized motion analysis provides quantitative evaluation of subtle differences in the effect of braces with different designs, which are hard for the human eye to discern. The objective data inform and validate treatment decision-making. The recommendations were made as a result of evidence-based practice.
  Exercise programs to improve upper extremity function following stroke in the community setting are needed as the length of hospital stay continues to decrease. However, little has been done to increase understanding of how to translate an evidence-based rehabilitation intervention to real-world programs. The purpose of this case report was to describe a process evaluation of the implementation of an evidence-based upper extremity rehabilitation intervention for stroke, the Graded Repetitive Arm Supplementary Program, in a community setting.
 
  A partnership between a nonprofit support organization and a local community center was established to deliver the program in the community. The Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework with mixed methods was used to evaluate the implementation.
 
  Reach Twenty people were screened, 14 people met eligibility requirements, and 13 consented to participate. The program reached approximately 1.25% of the potential target population. Effectiveness Participants with stroke demonstrated significant improvement in upper extremity function and quality of life as measured by the Fugl-Meyer Assessment for upper extremity, Action Research Arm Test, Rating of Everyday Arm-use in the Community and Home Scale, and Stroke Impact Scale.