Establishing a neural marker for inhibitory control during balance recovery

Considerable evidence attests to a relationship between executive function and falls. Notable among cognitive elements related to fall risk is the ability to suppress a highly automatic but unwanted action – i.e., response inhibition. Although the ability to stop may seem an unlikely foundation for maintaining balance, there are many complex situations in daily life where we must adapt instinctual actions that could lead to further instability. Most of what we know about the role of response inhibition in balance control is based on correlations between cognitive test performance and self-reported falls, leaving a sizable gap in understanding the mechanisms linking inhibition and balance control. In the current study we expand from traditional balance assessments that accentuate reflexive action and instead impose a need to suppress a prepotent balance recovery step. We leverage recent techniques developed in cognitive neuroscience that can expose a chronology of neuromuscular events leading to successful inhibition. Specifically, we will measure neural markers shown to predict successful inhibition in seated voluntary reaction time tasks using focal hand responses, and apply this to a balance recovery stepping task. Given the link between executive function and falls, there is a strong reason to believe that research designs which incorporate a need for inhibition in balance recovery will offer new critical insights into this poorly understood risk factor leading to falls in vulnerable populations

Crystallization of the factor H-binding protein, FhbB, from the periopathogen Treponema denticola

Factor H-binding protein B from T. denticola was expressed, purified and crystallized. A native data set was collected to 1.8 Å resolution

Pharmacological and genomic profiling identifies NF-κB-targeted treatment strategies for mantle cell lymphoma

Mantle cell lymphoma (MCL) is an aggressive malignancy that is characterized by poor prognosis. Large-scale pharmacological profiling across more than 100 hematological cell line models identified a subset of MCL cell lines that are highly sensitive to the B cell receptor (BCR) signaling inhibitors ibrutinib and sotrastaurin. Sensitive MCL models exhibited chronic activation of the BCR-driven classical nuclear factor-{kappa}B (NF-{kappa}B) pathway, whereas insensitive cell lines displayed activation of the alternative NF-{kappa}B pathway. Transcriptome sequencing revealed genetic lesions in alternative NF-{kappa}B pathway signaling components in ibrutinib-insensitive cell lines, and sequencing of 165 samples from patients with MCL identified recurrent mutations in TRAF2 or BIRC3 in 15% of these individuals. Although they are associated with insensitivity to ibrutinib, lesions in the alternative NF-{kappa}B pathway conferred dependence on the protein kinase NIK (also called mitogen-activated protein 3 kinase 14 or MAP3K14) both in vitro and in vivo. Thus, NIK is a new therapeutic target for MCL treatment, particularly for lymphomas that are refractory to BCR pathway inhibitors. Our findings reveal a pattern of mutually exclusive activation of the BCR-NF-{kappa}B or NIK-NF-{kappa}B pathways in MCL and provide critical insights into patient stratification strategies for NF-{kappa}B pathway-targeted agents