PMAP: databases for analyzing proteolytic events and pathways

The Proteolysis MAP (PMAP, http://www.proteolysis.org) is a user-friendly website intended to aid the scientific community in reasoning about proteolytic networks and pathways. PMAP is comprised of five databases, linked together in one environment. The foundation databases, ProteaseDB and SubstrateDB, are driven by an automated annotation pipeline that generates dynamic ‘Molecule Pages’, rich in molecular information. PMAP also contains two community annotated databases focused on function; CutDB has information on more than 5000 proteolytic events, and ProfileDB is dedicated to information of the substrate recognition specificity of proteases. Together, the content within these four databases will ultimately feed PathwayDB, which will be comprised of known pathways whose function can be dynamically modeled in a rule-based manner, and hypothetical pathways suggested by semi-automated culling of the literature. A Protease Toolkit is also available for the analysis of proteases and proteolysis. Here, we describe how the databases of PMAP can be used to foster understanding of proteolytic pathways, and equally as significant, to reason about proteolysis

The Importance of Central Pacific Meridional Heat Advection to the Development of ENSO

The relationship between the warm water volume (WWV) ENSO precursor and ENSO SST weakened substantially after similar to 2000, coinciding with a degradation in dynamical model ENSO prediction skill. It is important to understand the drivers of the equatorial thermocline temperature variations and their linkage to ENSO onsets. In this study, a set of ocean reanalyses is employed to assess factors responsible for the variation of the equatorial Pacific Ocean thermocline during 1982-2019. Off-equatorial thermocline temperature anomalies carried equatorward by the mean meridional currents associated with Pacific tropical cells are shown to play an important role in modulating the central equatorial thermocline variations, which is rarely discussed in the literature. Further, ENSO events are delineated into two groups based on precursor mechanisms: the western equatorial Pacific type (WEP) ENSO, when the central equatorial thermocline is mainly influenced by the zonal propagation of anomalies from the western Pacific, and the off-equatorial central Pacific (OCP) ENSO, when off-equatorial central thermocline anomalies play the primary role. WWV is found to precede all WEP ENSO events by 6-9 months, while the correlation is substantially lower for OCP ENSO events. In contrast, the central tropical Pacific (CTP) precursor, which includes off-equatorial thermocline signals, has a very robust lead correlation with the OCP ENSO. Most OCP ENSO events are found to follow the same ENSO conditions, and the number of OCP ENSO events increases substantially since the start of the twenty-first century. These results highlight the importance of monitoring off-equatorial subsurface preconditions for ENSO prediction and to understand multiyear ENSO

Towards harmonization of directly measured free 25-hydroxyvitamin D using an enzyme-linked immunosorbent assay.

The majority of circulating 25-hydroxyvitamin D (25(OH)D) is protein bound and perhaps less available than the free fraction of 25(OH)D; therefore, researchers have proposed that the measurement of free 25(OH)D in human serum may be a better indicator of vitamin D health status than total 25(OH)D. The availability of a new enzyme-linked immunosorbent assay (ELISA) for the determination of free 25(OH)D provides a method for direct measurement of the low levels of non-protein bound 25(OH)D. As an initial step towards harmonization of measurements of free 25(OH)D, the ELISA was used to measure free 25(OH)D in three existing Standard Reference Materials (SRMs): SRM 972a Vitamin D Metabolites in Frozen Human Serum, SRM 2973 Vitamin D Metabolites in Frozen Human Serum (High Level), and SRM 1949 Frozen Prenatal Human Serum. Target values for free 25(OH)D in the nine SRM serum pools, obtained by combining the results from two laboratories, ranged from 3.76 ± 0.36 to 10.0 ± 0.58 pg/mL. Of particular significance is the assignment of free 25(OH)D target values to SRM 1949, which consists of four serum pools from non-pregnant female donors of reproductive age and pregnant women in each of the three trimesters and which also has values assigned for vitamin D binding protein, which increases during pregnancy. The availability of target values for free 25(OH)D in these SRMs will allow researchers to validate new analytical methods and to compare their results with other researchers as an initial step towards harmonization of measurements among different studies and laboratories

PMAP: databases for analyzing proteolytic events and pathways.

The Proteolysis MAP (PMAP, http://www.proteolysis.org) is a user-friendly website intended to aid the scientific community in reasoning about proteolytic networks and pathways. PMAP is comprised of five databases, linked together in one environment. The foundation databases, ProteaseDB and SubstrateDB, are driven by an automated annotation pipeline that generates dynamic 'Molecule Pages', rich in molecular information. PMAP also contains two community annotated databases focused on function; CutDB has information on more than 5000 proteolytic events, and ProfileDB is dedicated to information of the substrate recognition specificity of proteases. Together, the content within these four databases will ultimately feed PathwayDB, which will be comprised of known pathways whose function can be dynamically modeled in a rule-based manner, and hypothetical pathways suggested by semi-automated culling of the literature. A Protease Toolkit is also available for the analysis of proteases and proteolysis. Here, we describe how the databases of PMAP can be used to foster understanding of proteolytic pathways, and equally as significant, to reason about proteolysis