Norstictic Acid Is a Selective Allosteric Transcriptional Regulator.

Inhibitors of transcriptional protein-protein interactions (PPIs) have high value both as tools and for therapeutic applications. The PPI network mediated by the transcriptional coactivator Med25, for example, regulates stress-response and motility pathways, and dysregulation of the PPI networks contributes to oncogenesis and metastasis. The canonical transcription factor binding sites within Med25 are large (∼900 Å) and have little topology, and thus, they do not present an array of attractive small-molecule binding sites for inhibitor discovery.

Test-Retest Reliability and the Effects of Walking Speed on Stride Time Variability During Continuous, Overground Walking in Healthy Young Adults.

Studies have investigated the reliability and effect of walking speed on stride time variability during walking trials performed on a treadmill. The objective of this study was to investigate the reliability of stride time variability and the effect of walking speed on stride time variability, during continuous, overground walking in healthy young adults. Participants completed: (1) 2 walking trials at their preferred walking speed on 1 day and another trial 2 to 4 days later and (2) 1 trial at their preferred walking speed, 1 trial approximately 20% to 25% faster than their preferred walking speed, and 1 trial approximately 20% to 25% slower than their preferred walking speed on a separate day.

BET bromodomain ligands: Probing the WPF shelf to improve BRD4 bromodomain affinity and metabolic stability.

Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents for treating a range of cancers and inflammation. Here we report that our previously developed 3,5-dimethylisoxazole-based BET bromodomain ligand (OXFBD02) inhibits interactions of BRD4(1) with the RelA subunit of NF-κB, in addition to histone H4. This ligand shows a promising profile in a screen of the NCI-60 panel but was rapidly metabolised (t = 39.

A Synthetic Loop Replacement Peptide That Blocks Canonical NF-κB Signaling.

Aberrant canonical NF-κB signaling is implicated in diseases from autoimmune disorders to cancer. A major therapeutic challenge is the need for selective inhibition of the canonical pathway without impacting the many non-canonical NF-κB functions. Here we show that a selective peptide-based inhibitor of canonical NF-κB signaling, in which a hydrogen bond in the NBD peptide is synthetically replaced by a non-labile bond, shows an about 10-fold increased potency relative to the original inhibitor.

Students helping students: Evaluating a pilot program of peer teaching for an undergraduate course in human anatomy.

The educational literature generally suggests that supplemental instruction (SI) is effective in improving academic performance in traditionally difficult courses. A pilot program of peer teaching based on the SI model was implemented for an undergraduate course in human anatomy. Students in the course were stratified into three groups based on the number of peer teaching sessions they attended: nonattendees (0 sessions), infrequently attended (1-3 sessions), and frequently attended (≥ 4 sessions).

Patient-reported perception of difficulty as a clinical indicator of dysfunctional neuromuscular control during the prone hip extension test and active straight leg raise test.

Two clinical tests used to assess for neuromuscular control deficits in patients with low back pain (LBP) are the prone hip extension (PHE) test and active straight leg raise (ASLR) test. For these tests, it has been suggested that patients be classified as "positive" if they demonstrate specific "abnormal" lumbopelvic motion patterns. For the ASLR test, the use of patient-reported perception of difficulty is also used to assess neuromuscular control.

Inter-rater agreement, sensitivity, and specificity of the prone hip extension test and active straight leg raise test.

Background: Two clinical tests used to assess for neuromuscular control deficits in low back pain (LBP) patients are the prone hip extension (PHE) test and active straight leg raise (ASLR) test. For these tests, it has been suggested examiners classify patients as "positive" or "negative" based on the presence or absence (respectively) of specific "abnormal" lumbopelvic motion patterns. The inter-rater agreement of such a classification scheme has been reported for the PHE test, but not for the ASLR test.

Genetic and chemical targeting of epithelial-restricted with serine box reduces EGF receptor and potentiates the efficacy of afatinib.

EGF receptor (EGFR) is elevated in more than 90% of head and neck squamous cell carcinoma (HNSCC). However, a majority of patients with HNSCC do not respond to anti-EGFR therapeutics. Insensitivity to EGFR inhibitors may be due to kinase-independent actions of EGFR and/or activation of Her2.

Anatomically remote muscle contraction facilitates patellar tendon reflex reinforcement while mental activity does not: a within-participants experimental trial.

Background: The Jendrassik maneuver (JM) is a remote facilitation muscular contraction shown to affect amplitude and temporal components of the human stretch reflex. Conflicting theoretical models exist regarding the neurological mechanism related to its ability to reinforce reflex parameters. One mechanism involves the gamma motoneurons of the fusimotor system, which are subject to both physical and mental activity.

Use of the environmentally sensitive fluorophore 4-N,N-dimethylamino-1,8-naphthalimide to study peptoid helix structures.

Peptoids, oligomers of N-substituted glycine, have been valuable targets for study and diverse application as peptidomimetics and as nanomaterials. Their conformational heterogeneity has made the study of peptoid structures using high-resolution analyses challenging, limiting our understanding of the physiochemical features that mediate peptoid folding. Here, we introduce a new method for the study of peptoid structure that relies on the environmentally sensitive fluorescence properties of 4-N,N-dimethylamino-1,8-naphthalimide (4-DMN).

An investigation of neck muscle activity in asymptomatic participants who show different lumbar spine motion patterns during prone hip extension.

Objective: The objective of the current study was to investigate whether any differences exist in the activity of the cervical erector spinae and upper trapezius (TRA) muscles between asymptomatic participants who show "normal" and "abnormal" lumbar spine motion patterns during the prone hip extension (PHE) test.

Methods: Twenty-six asymptomatic participants recruited from a chiropractic college participated in the study. Surface electromyography was used to record the activity of the cervical erector spinae and upper TRA muscles as each participant performed a set of 4 repetitions of PHE for each leg.