More Than 1,001 Problems with Protein Domain Databases: Transmembrane Regions, Signal Peptides and the Issue of Sequence Homology

Large-scale genome sequencing gained general importance for life science because functional annotation of otherwise experimentally uncharacterized sequences is made possible by the theory of biomolecular sequence homology. Historically, the paradigm of similarity of protein sequences implying common structure, function and ancestry was generalized based on studies of globular domains. Having the same fold imposes strict conditions over the packing in the hydrophobic core requiring similarity of hydrophobic patterns. The implications of sequence similarity among non-globular protein segments have not been studied to the same extent; nevertheless, homology considerations are silently extended for them. This appears especially detrimental in the case of transmembrane helices (TMs) and signal peptides (SPs) where sequence similarity is necessarily a consequence of physical requirements rather than common ancestry. Thus, matching of SPs/TMs creates the illusion of matching hydrophobic cores. Therefore, inclusion of SPs/TMs into domain models can give rise to wrong annotations. More than 1001 domains among the 10,340 models of Pfam release 23 and 18 domains of SMART version 6 (out of 809) contain SP/TM regions. As expected, fragment-mode HMM searches generate promiscuous hits limited to solely the SP/TM part among clearly unrelated proteins. More worryingly, we show explicit examples that the scores of clearly false-positive hits, even in global-mode searches, can be elevated into the significance range just by matching the hydrophobic runs. In the PIR iProClass database v3.74 using conservative criteria, we find that at least between 2.1% and 13.6% of its annotated Pfam hits appear unjustified for a set of validated domain models. Thus, false-positive domain hits enforced by SP/TM regions can lead to dramatic annotation errors where the hit has nothing in common with the problematic domain model except the SP/TM region itself. We suggest a workflow of flagging problematic hits arising from SP/TM-containing models for critical reconsideration by annotation users

The Development and Validation of the Empathy Components Questionnaire (ECQ)

Key research suggests that empathy is a multidimensional construct comprising of both cognitive and affective components. More recent theories and research suggest even further factors within these components of empathy, including the ability to empathize with others versus the drive towards empathizing with others. While numerous self-report measures have been developed to examine empathy, none of them currently index all of these wider components together. The aim of the present research was to develop and validate the Empathy Components Questionnaire (ECQ) to measure cognitive and affective components, as well as ability and drive components within each. Study one utilized items measuring cognitive and affective empathy taken from various established questionnaires to create an initial version of the ECQ. Principal component analysis (PCA) was used to examine the underlying components of empathy within the ECQ in a sample of 101 typical adults. Results revealed a five-component model consisting of cognitive ability, cognitive drive, affective ability, affective drive, and a fifth factor assessing affective reactivity. This five-component structure was then validated and confirmed using confirmatory factor analysis (CFA) in an independent sample of 211 typical adults. Results also showed that females scored higher than males overall on the ECQ, and on specific components, which is consistent with previous findings of a female advantage on self-reported empathy. Findings also showed certain components predicted scores on an independent measure of social behavior, which provided good convergent validity of the ECQ. Together, these findings validate the newly developed ECQ as a multidimensional measure of empathy more in-line with current theories of empathy. The ECQ provides a useful new tool for quick and easy measurement of empathy and its components for research with both healthy and clinical populations

Endarterectomy of the Aneurysm Sac in Open Abdominal Aortic Aneurysm Repair Reduces Perigraft Seroma and Improves Graft Incorporation

Fluid around the graft in the original aneurysm sac after open abdominal aortic aneurysm (AAA) repair is a poorly researched phenomenon. If large, such perigraft seroma can cause symptoms of compression, and cases of rupture have even been described. We assessed whether endarterectomy of the aneurysm sac reduces the incidence of perigraft fluid and improves graft incorporation

Clinical significance of recurrent venous thromboembolism Significância clínica de tromboembolismo venoso recorrente

Recurrent venous thromboembolism is a significant problem leading to increased morbidity and mortality. It has a high impact on patients' quality of life and imposes a great financial burden on society. Cumulative recurrence has been reported as 40% at 10 years, while the chance of developing postthrombotic signs and symptoms in the lower extremities almost quadruples when ipsilateral. There is also a higher chance of developing pulmonary hypertension. Important factors for recurrence are unprovoked episodes of deep vein thrombosis, malignancy and older age. The evidence for other factors is controversial. Accurate diagnosis and treatment tailored to the patients' history, thrombotic events and risk factors are necessary to optimize management and prevent recurrence.<br>O tromboembolismo venoso recorrente é um problema importante que leva ao aumento da morbimortalidade. Impõe forte impacto à qualidade de vida dos pacientes e grande carga financeira para a sociedade. Acredita-se que a recorrência cumulativa atinja 40% em 10 anos, enquanto que a chance de desenvolver sinais e sintomas pós-trombóticos nas extremidades inferiores quase quadruplica no caso de trombose ipsilateral. Há também uma maior chance do desenvolvimento de hipertensão pulmonar. Fatores importantes para a recorrência são: episódios não provocados de trombose venosa profunda, malignidade e idade avançada. As evidências relacionadas a outros fatores são controversas. Diagnóstico preciso e tratamento adaptado ao histórico dos pacientes, aos eventos trombóticos e aos fatores de risco são necessários para otimizar o manejo e prevenir a recorrência