A 221-entry NESdb database produces data sets of true- and false-positive nuclear export signals (NES). Analysis of these data sets leads to identification of a set of sequence and structural properties that distinguishes true NESs from peptides without export capability that merely conform to the NES consensus sequences.
BackgroundThe increase in the quantities of central nervous system (CNS)-acting medications prescribed has coincided with increases in overdose mortality, suicide-related behaviors, and unintentional deaths in military personnel deployed in support of the wars in Iraq and Afghanistan. Data on the extent and impact of prescribing multiple CNS drugs among Iraq and Afghanistan Veterans (IAVs) are sparse.ObjectivesWe sought to identify the characteristics of IAVs with CNS polypharmacy and examine the association of CNS polypharmacy with drug overdose and suicide-related behaviors controlling for known risk factors.MethodsThis cross-sectional cohort study examined national data of Iraq and Afghanistan Veterans (N = 311,400) who used the Veterans Health Administration (VHA) during the fiscal year 2011. CNS polypharmacy was defined as five or more CNS-acting medications; drug/alcohol overdose and suicide-related behaviors were identified using ICD-9-CM codes. Demographic and clinical characteristics associated with CNS polypharmacy were identified using a multivariable logistic regression model.ResultsWe found that 25,546 (8.4 %) of Iraq and Afghanistan Veterans had CNS polypharmacy. Those with only post-traumatic stress disorder (PTSD) (adjusted odds ratio (AOR) 6.50, 99 % confidence interval (CI) 5.96–7.10), only depression (AOR 6.42, 99 % CI 5.86–7.04), co-morbid PTSD and depression (AOR 12.98, 99 % CI 11.97–14.07), and co-morbid traumatic brain injury (TBI), PTSD, and depression (AOR 15.30, 99 % CI 14.00–16.73) had the highest odds of CNS polypharmacy. After controlling for these co-morbid conditions, CNS polypharmacy was significantly associated with drug/alcohol overdose and suicide-related behavior.ConclusionCNS polypharmacy was most strongly associated with PTSD, depression, and TBI, and independently associated with overdose and suicide-related behavior after controlling for known risk factors. These findings suggest that CNS polypharmacy may be used as an indicator of risk for adverse outcomes. Further research should evaluate whether CNS polypharmacy may be used as a trigger for evaluation of the current care provided to these individuals.Electronic supplementary materialThe online version of this article (doi:10.1007/s40801-015-0055-0) contains supplementary material, which is available to authorized users.
Import-Karyopherin or Importin proteins bind nuclear localization signals (NLSs) to mediate the import of proteins into the cell nucleus. Karyopherin β2 or Kapβ2, also known as Transportin, is a member of this transporter family responsible for the import of numerous RNA binding proteins. Kapβ2 recognizes a targeting signal termed the PY-NLS that lies within its cargos to target them through the nuclear pore complex. The recognition of PY-NLS by Kapβ2 is conserved throughout eukaryotes. Kap104, the Kapβ2 homolog in Saccharomyces cerevisiae, recognizes PY-NLSs in cargos Nab2, Hrp1, and Tfg2. We have determined the crystal structure of Kapβ2 bound to the PY-NLS of the mRNA processing protein Nab2 at 3.05-Å resolution. A seven-residue segment of the PY-NLS of Nab2 is observed to bind Kapβ2 in an extended conformation and occupies the same PY-NLS binding site observed in other Kapβ2•PY-NLS structures.
Background Successful healing of the subscapularis during anatomic total shoulder arthroplasty surgery is critical to optimize functional outcomes and avoid complications. The purpose of this study was to examine the upper and lower subscapularis nerve insertion in relation to the musculotendinous junction to estimate the risk of nerve injury. Our hypothesis was that arm position changes the risks to these nerves when exposing the anterior glenoid. Methods Twenty cadaveric shoulders were dissected, and the subscapular nerves were identified from the posterior cord of the brachial plexus to the muscle insertion. The nerve length from the origin to the muscle insertion and the distance to the myotendinous junction were measured in various shoulder positions including neutral, external, and internal rotation. Results The mean length of the upper subscapular nerve was 51.4 ± 12.8 mm; that of the lower subscapular nerve was 50.5 ± 14 mm. The mean distance from the insertion of the upper subscapular nerve to the myotendinous junction 53.0 ± 14.7 mm with external rotation, 38.5 ± 9.7 mm with neutral rotation, and 30.0 ± 9.2 mm with internal rotation. The mean distance from the lower subscapular nerve to the myotendinous junction was 44.5 ± 13.8 mm with external rotation, 31.9 ± 9.3 mm with neutral rotation, and 25.4 ± 8.8 mm with internal rotation. The internally rotated position placed these nerves closest to the glenohumeral joint. Conclusion The upper and lower subscapular nerves insert in the muscle belly close to the myotendinous junction, putting them at risk of iatrogenic injury. Care must be taken to avoid damage with retractor placement in the anterior glenoid neck as these nerves are at risk of compression or torsional injury.
Background The purpose of this study was to define the relationship of the axillary and radial nerves, particularly how these are affected with changing arm position. Methods Twenty cadaveric shoulders were dissected, identifying the axillary and radial nerves. Distances between the latissimus dorsi tendon and these nerves were recorded in different shoulder positions. Positions included adduction/neutral rotation, abduction/neutral rotation for the axillary nerve, adduction/internal rotation, adduction/neutral rotation, adduction/external rotation, and abduction/external rotation for the radial nerve. Results Width of the latissimus tendon at its humeral insertion was 29.3 ± 5.7 mm. Mean distance from the latissimus insertion to the axillary nerve in adduction/neutral rotation was 24.2 ± 7.1 mm, the distance increased to 41.1 ± 9.8 mm in abduction/neutral rotation. Mean distance from the latissimus insertion to the radial nerve was 15.3 ± 5.5 mm with adduction/internal rotation, 25.8 ± 6.9 mm in adduction/neutral rotation, and 39.5 ± 6.8 mm in adduction/external rotation. Mean distance increased with abduction/external rotated 51.1 ± 7.4 mm. Conclusions Knowing the axillary and radial nerve locations relative to the latissimus dorsi tendon decreases the risk of iatrogenic nerve injury. Understanding the dynamic nature of these nerves related to different shoulder positions is critical to avoid complications.
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