DAS Writeback: A Collaborative Annotation System

<p>Abstract</p> <p>Background</p> <p>Centralised resources such as GenBank and UniProt are perfect examples of the major international efforts that have been made to integrate and share biological information. However, additional data that adds value to these resources needs a simple and rapid route to public access. The Distributed Annotation System (DAS) provides an adequate environment to integrate genomic and proteomic information from multiple sources, making this information accessible to the community. DAS offers a way to distribute and access information but it does not provide domain experts with the mechanisms to participate in the curation process of the available biological entities and their annotations.</p> <p>Results</p> <p>We designed and developed a Collaborative Annotation System for proteins called DAS Writeback. DAS writeback is a protocol extension of DAS to provide the functionalities of adding, editing and deleting annotations. We implemented this new specification as extensions of both a DAS server and a DAS client. The architecture was designed with the involvement of the DAS community and it was improved after performing usability experiments emulating a real annotation task.</p> <p>Conclusions</p> <p>We demonstrate that DAS Writeback is effective, usable and will provide the appropriate environment for the creation and evolution of community protein annotation.</p

The impact of bed rest on human skeletal muscle metabolism

Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest

Imaging aspects of cardiovascular disease at the cell and molecular level

Cell and molecular imaging has a long and distinguished history. Erythrocytes were visualized microscopically by van Leeuwenhoek in 1674, and microscope technology has evolved mightily since the first single-lens instruments, and now incorporates many types that do not use photons of light for image formation. The combination of these instruments with preparations stained with histochemical and immunohistochemical markers has revolutionized imaging by allowing the biochemical identification of components at subcellular resolution. The field of cardiovascular disease has benefited greatly from these advances for the characterization of disease etiologies. In this review, we will highlight and summarize the use of microscopy imaging systems, including light microscopy, electron microscopy, confocal scanning laser microscopy, laser scanning cytometry, laser microdissection, and atomic force microscopy in conjunction with a variety of histochemical techniques in studies aimed at understanding mechanisms underlying cardiovascular diseases at the cell and molecular level

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants

Effects of an artificial gravity countermeasure on orthostatic tolerance, blood volumes and aerobic power after short-term bed rest

Exposure to artificial gravity (AG) in a short-arm centrifuge has potential benefits for maintaining human performance during long-term space missions. Eleven subjects were investigated during three campaigns of 5 days head-down bed rest: 1) bed rest without countermeasures (control), 2) bed rest and 30 min of AG (AG1) daily, and 3) bed rest and six periods of 5 min AG (AG2) daily. During centrifugation, the supine subjects were exposed to AG in the head-to-feet direction with 1 G at the center of mass. Subjects participated in the three campaigns in random order. The cardiovascular effects of bed rest and countermeasures were determined from changes in tolerance to a head-up tilt test with superimposed lower body negative pressure (HUT), from changes in plasma volume (PV) and from changes in maximum aerobic power (VO2 peak) during upright work on a cycle ergometer. Complete data sets were obtained in eight subjects. After bed rest, HUT tolerance times were 36, 64, and 78% of pre-bed rest baseline during control, AG1 and AG2, respectively, with a significant difference between AG2 and control. PV and V̇o2 peak decreased to 85 and 95% of pre-bed rest baseline, respectively, with no differences between the treatments. It was concluded that the AG2 countermeasure should be further investigated during future long-term bed rest studies, especially as it was better tolerated than AG1. The superior effect of AG2 on orthostatic tolerance could not be related to concomitant changes in PV or aerobic power

Artificial gravity during a spaceflight analog alters brain sensory connectivity

Spaceflight has numerous untoward effects on human physiology. Various countermeasures are under investigation including artificial gravity (AG). Here, we investigated whether AG alters resting-state brain functional connectivity changes during head-down tilt bed rest (HDBR), a spaceflight analog. Participants underwent 60 days of HDBR. Two groups received daily AG administered either continuously (cAG) or intermittently (iAG). A control group received no AG. We assessed resting-state functional connectivity before, during, and after HDBR. We also measured balance and mobility changes from pre- to post-HDBR. We examined how functional connectivity changes throughout HDBR and whether AG is associated with differential effects. We found differential connectivity changes by group between posterior parietal cortex and multiple somatosensory regions. The control group exhibited increased functional connectivity between these regions throughout HDBR whereas the cAG group showed decreased functional connectivity. This finding suggests that AG alters somatosensory reweighting during HDBR. We also observed brain-behavioral correlations that differed significantly by group. Control group participants who showed increased connectivity between the putamen and somatosensory cortex exhibited greater mobility declines post-HDBR. For the cAG group, increased connectivity between these regions was associated with little to no mobility declines post-HDBR. This suggests that when somatosensory stimulation is provided via AG, functional connectivity increases between the putamen and somatosensory cortex are compensatory in nature, resulting in reduced mobility declines. Given these findings, AG may be an effective countermeasure for the reduced somatosensory stimulation that occurs in both microgravity and HDBR

Age-Related Decline in Vertical Jumping Performance in Masters Track and Field Athletes: Concomitant Influence of Body Composition

Vertical jumping power declines with advancing age, which is theoretically explicable by loss of muscle mass and increases in body fat. However, the results of previous cross-sectional studies remain inconsistent on these relationships. The present study included 256 masters athletes who competed at the 2018 track and field world championships in Malaga, Spain. We assessed body composition with bioelectrical impedance (Inbody S10) and vertical jumping power with a Leonardo ground reaction force platform. Relationships between age, jumping power, and body composition were analyzed by correlation and regression analyses. Hierarchical multiple regression analysis was used to evaluate effects of each factor on vertical jumping power. Age-related rates of decreases in maximal power and jump height were similar between male and female athletes. Percent fat-free mass and percent body fat were negatively and positively, respectively, associated with age in masters athletes and were comparable to those previously observed in the general population. Moreover, these effects in body composition can, to a great extent, explain the age-related decline in jumping power, an effect that seems at least partly independent of age. Finally, the multiple regression model to determine independent predictors of vertical jump performance yielded an overall R-2 value of 0.75 with the inclusion of (1) athletic specialization in power events, (2) percent fat-free mass, and (3) phase angle. However, partial regression yielded significant effects of age, but not gender, on peak power, even when adjusting for athletic specialization, percent fat-free mass, and phase angle. We concluded that loss of skeletal muscle mass and changes in bio-impedance phase angle are important contributors to the age-related reduction in anaerobic power, even in adults who maintain high levels of physical activity into old age. However, age per se remains a significant predictor of vertical jump performance, further demonstrating deteriorated muscle quality at old age (sarcosthenia)

MARS 520: Ambulante Blutdrucküberwachung während Isolation

Wie und durch welche physiologischen Wege Isolation das Verhalten von Blutdruck beeinflusst, war unsere Fragestellung für MARS 520. Nach gegenwärtigem Wissenstand wird langfristige Blutdruckregulation hauptsächlich durch den Wasser-Elektrolyt-Haushalt betrieben, aber auch Umwelt-, psychosoziale und stressbedingte Einflüsse modulieren das Blutdruckverhalten. Langzeit-Isolationsstudien bieten dank des Wegfalls äußerlicher Reize eine außerordentliche Gelegenheit, das Zusammenspiel physiologischer Blutdruckdeterminanten unter kontrollierten Bedingungen zu untersuchen. Bei den sechs Probanden [Mittelwert (SD): 31.8 (4.5) Jahre; 80.3 (7.8) kg KG] der MARS520-Studie wurden insgesamt sechzehn 24h–Blutdruckmessungen durchgeführt (Ambulante Blutdruck (ABD) – Überwachungsmonitore, Spacelabs GmbH): einmal vor, 11 Mal während und 4 Mal nach 520 Tagen Isolation in der MARS 500 Anlage, IBMP, Moskau. Während der ersten 250 Tage wurde die diätetische Kochsalzzufuhr auf 12g, 9g, und 6g für jeweils 6 Wochen konstant gehalten, zwei weitere Perioden mit 12g und 9g folgten. Während der übrigen Zeit wurde die Salzzufuhr nicht kontrolliert. Mittelwerte systolischen und diastolischen Blutdrucks und der Herzfrequenz wurden für jede Messung berechnet. Die parallel zu 13 der 16 Blutdruckmessungen entnommenen Blut- und Urinproben wurden auf Elektrolytgehalt und Steroide untersucht. Der Blutdruck [Systolisch (p=0,0483) und Diastolisch (p=0,0215)] und die Herzfrequenz (p=0,0141) waren während Isolation niedriger als in Vor- und Nachisolation zusammengenommen –auch unter Berücksichtigung einer beachtlichen ‚between-subjects‘ Variabilität. Die Natriumausscheidung hing mit der diätetischen Zufuhr und mit einem entsprechenden Aldosteron und Reninprofil zusammen. Es bestand nur eine schwache (diastolisch) bzw. keine (systolisch) Korrelation zwischen 24h-Natriumexkretion und ABD. Glucocorticoide und Androgene zeigten selten ein deutlich erkennbares Muster während der Isolation, auch wenn die 24h-Urinwerte von Cortisol (p=0,0060) und Cortison (p=0,0095) niedriger innerhalb als außerhalb der Isolationsanlage ausfielen. Multiple Regressionsanalysen zeigten, dass 71% der systolischen ABD-Varianz durch eine Kombination aus einer begrenzten Anzahl von Glucocorticoiden und Androgenen zum größten Teil erklärbar war (multiple R = 0.8428). Der Wegfall alltäglicher Reize trug zur Abnahme des Blutdrucks bei, wie die niedrigeren Cortisol- und Cortisonwerte als Ausdruck verminderten Stresses während der Isolation nahe legen. Eine schwache oder gar abwesende Korrelation zwischen diätetischer Natriumzufuhr und ABD ist nicht überraschend, insofern als schon während der Phase kontrollierter Natriumzufuhr festgestellt wurde, dass der Salzeffekt auf den täglich gemessenen Blutdruck bescheiden und unbeständig ist und zeitlich verzögert einsetzt (cf. Cell Metab. 17: 125–131). Die bemerkenswerte Assoziation zwischen Glucocorticoide und Androgene und ABD-Verhalten lenkt die Aufmerksamkeit auf einen bis heute weitgehend vernachlässigten Aspekt: die physiologische Rolle, die insbesondere den Androgenen bei der Blutdruckregulation zukommt