Project description:The temporary storage and re-use of tools can significantly enhance foraging efficiency. New Caledonian crows in one of our study populations use two types of stick tools - hooked and non-hooked - which differ in raw material, manufacture costs, and foraging performance. Using a large sample of wild-caught, temporarily captive New Caledonian crows, we investigated experimentally whether individuals prefer one tool type over the other when given a choice and whether they take better care of their preferred tools between successive episodes of use, safely storing them underfoot or in nearby holes. Crows strongly preferred hooked stick tools made from Desmanthus virgatus stems over non-hooked stick tools. Importantly, this preference was also reflected in subsequent tool-handling behaviour, with subjects keeping hooked stick tools safe more often than non-hooked stick tools sourced from leaf litter. These results suggest that crows 'value' hooked stick tools, which are both costlier to procure and more efficient to use, more than non-hooked stick tools. Results from a series of control treatments suggested that crows altered their tool 'safekeeping' behaviour in response to a combination of factors, including tool type and raw material. To our knowledge, our study is the first to use safekeeping behaviour as a proxy for assessing how non-human animals value different tool types, establishing a novel paradigm for productive cross-taxonomic comparisons.
Project description:The corpus callosum (CC) connects the left and right cerebral hemispheres in mammals and its development requires intercellular communication at the telencephalic midline mediated by signaling proteins. Heparan sulfate (HS) is a sulfated polysaccharide that decorates cell surface and extracellular matrix proteins and regulates the biological activity of numerous signaling proteins via sugar-protein interactions. HS is subject to regulated enzymatic sulfation and desulfation and an attractive, although not proven, hypothesis is that the biological activity of HS is regulated by a sugar sulfate code. Mutant mouse embryos lacking the heparan sulfotransferases Hs2st or Hs6st1 have severe CC phenotypes and form Probst bundles of noncrossing axons flanking large tangles of midline glial processes. Here, we identify a precocious accumulation of Sox9-expressing glial cells in the indusium griseum region and a corresponding depletion at the glial wedge associated with the formation of Probst bundles along the rostrocaudal axis in both mutants. Molecularly, we found a surprising hyperactivation of Erk signaling in Hs2st(-/-) (2-fold) and Hs6st1(-/-) (6-fold) embryonic telencephalon that was most striking at the midline, where Erk signaling is lowest in wild-types, and a 2-fold increase in Fgf8 protein levels in Hs6st1(-/-) embryos that could underpin Erk hyperactivation and excessive glial movement to the indusium griseum. The tightly linked Hs6st1(-/-) CC glial and axonal phenotypes can be rescued by genetic or pharmacological suppression of Fgf8/Erk axis components. Overall, our data fit a model in which Hs2st and Hs6st1 normally generate conditions conducive to CC development by generating an HS-containing environment that keeps Erk signaling in check.
Project description:We report a case of a type A aortic dissection with extension into the main pulmonary artery through a sinus of Valsalva fistula. Echocardiography and computed tomographic angiography of the chest were performed and bicuspid aortic valve, hemopericardium, and dilatation of the aortic root were found. A Stanford type A dissection was seen, extending to the distal transverse thoracic aorta, and there was a communication between the dissection at the left sinus of Valsalva and the main pulmonary artery, where a dissection flap was detected at computed tomographic angiography. This case report reviews the rare diagnosis of pulmonary artery dissection, multimodality imaging findings, and a brief review of etiology and management.
Project description:Bax is kept inactive in the cytosol by refolding its C-terminal transmembrane domain into the hydrophobic binding pocket. Although energetic calculations predicted this conformation to be stable, numerous Bax binding proteins were reported and suggested to further stabilize inactive Bax. Unfortunately, most of them have not been validated in a physiological context on the endogenous level. Here we use gel filtration analysis of the cytosol of primary and established cells to show that endogenous, inactive Bax runs 20-30 kDa higher than recombinant Bax, suggesting Bax dimerization or the binding of a small protein. Dimerization was excluded by a lack of interaction of differentially tagged Bax proteins and by comparing the sizes of dimerized recombinant Bax with cytosolic Bax on blue native gels. Surprisingly, when analyzing cytosolic Bax complexes by high sensitivity mass spectrometry after anti-Bax immunoprecipitation or consecutive purification by gel filtration and blue native gel electrophoresis, we detected only one protein, called p23 hsp90 co-chaperone, which consistently and specifically co-purified with Bax. However, this protein could not be validated as a crucial inhibitory Bax binding partner as its over- or underexpression did not show any apoptosis defects. By contrast, cytosolic Bax exhibits a slight molecular mass shift on SDS-PAGE as compared with recombinant Bax, which suggests a posttranslational modification and/or a structural difference between the two proteins. We propose that in most healthy cells, cytosolic endogenous Bax is a monomeric protein that does not necessarily need a binding partner to keep its pro-apoptotic activity in check.
Project description:BackgroundWorse outcomes have been reported for women with type A acute aortic dissection (TAAD). We sought to determine sex-specific operative approaches and outcomes for TAAD in the current era.MethodsThe Interventional Cohort (IVC) of the International Registry of Acute Aortic Dissection (IRAD) database was queried to explore sex differences in presentation, operative approach, and outcomes. Multivariable logistic regression was performed to identify adjusted outcomes in relation to sex.ResultsWomen constituted approximately one-third (34.3%) of the 2823 patients and were significantly older than men (65.4 vs 58.6 years, P < .001). Women were more likely to present with intramural hematoma, periaortic hematoma, or complete or partial false lumen thrombosis (all P < .05) and more commonly had hypotension or coma (P = .001). Men underwent a greater proportion of Bentall, complete arch, and elephant trunk procedures (all P < .01). In-hospital mortality during the study period was higher in women (16.7% vs 13.8%, P = .039). After adjustment, female sex trended towards higher in-hospital mortality overall (odds ratio, 1.40; P = .053) but not in the last decade of enrollment (odds ratio, 0.93; P = .807). Five-year mortality and reintervention rates were not significantly different between the sexes.ConclusionsIn-hospital mortality remains higher among women with TAAD but demonstrates improvement in the last decade. Significant differences in presentation were noted in women, including older age, distinct imaging findings, and greater evidence of malperfusion. Although no distinctions in 5-year mortality or reintervention were observed, a tailored surgical approach should be considered to reduce sex disparities in early mortality rates for TAAD.
Project description:Recently, microRNAs (miRNAs) have emerged as important elements of gene regulatory networks. MiRNAs are endogenous single-stranded non-coding RNAs (~22-nt long) that regulate gene expression at the post-transcriptional level. Through pairing with mRNA, miRNAs can down-regulate gene expression by inhibiting translation or stimulating mRNA degradation. In some cases they can also up-regulate the expression of a target gene. MiRNAs influence a variety of cellular pathways that range from development to carcinogenesis. The involvement of miRNAs in several human diseases, particularly cancer, makes them potential diagnostic and prognostic biomarkers. Recent technological advances, especially high-throughput sequencing, have led to an exponential growth in the generation of miRNA-related data. A number of bioinformatic tools and databases have been devised to manage this growing body of data. We analyze 129 miRNA tools that are being used in diverse areas of miRNA research, to assist investigators in choosing the most appropriate tools for their needs.
Project description:Although uncommon, acute aortic dissections are a life-threatening, cannot miss diagnosis for the emergency medicine clinician. Point of care ultrasound can play an integral role in the initial work up of the undifferentiated patient. While not initially utilized to make the diagnosis of aortic dissection, the ultrasound images obtained in this case describe key findings on ultrasound vital for an emergency clinician to recognize. It is essential for emergency medicine clinicians to differentiate an aortic dissection from other causes of chest pain and abdominal pain because the quick mobilization of resources plays a key role in the management and outcome of such patients.TopicsAortic dissection, vascular, dissection flap, back pain, point of care ultrasound, POCUS.
Project description:A 37-year-old male presented to the Emergency Department with acute worsening of back pain and new onset dyspnea. Transthoracic echocardiography revealed moderate left ventricular dysfunction and a bicuspid aortic valve (BAV). In addition, he was noted to have a dilated thoracic aorta concerning for a dissection, severe aortic insufficiency (AI), and both a pericardial and pleural effusion. Magnetic resonance imaging revealed a Type A ascending aortic dissection. He was taken emergently to the operating room for repair. An intraoperative transesophageal echocardiography examination was performed which revealed a normal trileaflet AV with a Type A aortic dissection flap masquerading as a BAV. The dissection flap interfered with both the valve's function, causing severe AI, as well as the valve's appearance, causing it to look bicuspid on echocardiography.