MEROPS: the peptidase database

Peptidases (proteolytic enzymes) and their natural, protein inhibitors are of great relevance to biology, medicine and biotechnology. The MEROPS database () aims to fulfil the need for an integrated source of information about these proteins. The organizational principle of the database is a hierarchical classification in which homologous sets of proteins of interest are grouped into families and the homologous families are grouped in clans. The most important addition to the database has been newly written, concise text annotations for each peptidase family. Other forms of information recently added include highlighting of active site residues (or the replacements that render some homologues inactive) in the sequence displays and BlastP search results, dynamically generated alignments and trees at the peptidase or inhibitor level, and a curated list of human and mouse homologues that have been experimentally characterized as active. A new way to display information at taxonomic levels higher than species has been devised. In the Literature pages, references have been flagged to draw attention to particularly ‘hot’ topics

Rhino poaching: supply and demand uncertain

IN THEIR POLICY FORUM “LEGAL TRADE OF AFRICA’S RHINO HORNS” (1 MARCH, P. 1038), D. Biggs et al. point out that the trade ban on rhino horn has not been successful in reducing rhino poaching, which reached a record high of 668 in 2012. They argue that trade bans support illegal organizations, whereas a regulated legal market could reduce poaching effort and provide much-needed income for conservation. In making their case, Biggs et al. overlook a few important points

Expressiveness of real-time motion captured avatars influences perceived animation realism and perceived quality of social interaction in virtual reality

Using motion capture to enhance the realism of social interaction in virtual reality (VR) is growing in popularity. However, the impact of different levels of avatar expressiveness on the user experience is not well understood. In the present study we manipulated levels of face and body expressiveness of avatars while investigating participant perceptions of animation realism and interaction quality when disclosing positive and negative experiences in VR. Moderate positive associations were observed between perceptions of animation realism and interaction quality. Post-experiment questions revealed that many of our participants (approximately 40 %) indicated the avatar with the highest face and body expressiveness as having the most realistic face and body expressions. The same proportion also indicated the avatar with the highest face and body expressiveness as being the most comforting and enjoyable avatar to interact with. Our results suggest that higher levels of face and body expressiveness are important for enhancing perceptions of realism and interaction quality within a social interaction in VR using motion capture

Col-OSSOS: Colors of the Interstellar Planetesimal 1I/`Oumuamua

The recent discovery by Pan-STARRS1 of 1I/2017 U1 (`Oumuamua), on an unbound and hyperbolic orbit, offers a rare opportunity to explore the planetary formation processes of other stars, and the effect of the interstellar environment on a planetesimal surface. 1I/`Oumuamua's close encounter with the inner Solar System in 2017 October was a unique chance to make observations matching those used to characterize the small-body populations of our own Solar System. We present near-simultaneous g$^\prime$, r$^\prime$, and J photometry and colors of 1I/`Oumuamua from the 8.1-m Frederick C. Gillett Gemini North Telescope, and $gri$ photometry from the 4.2 m William Herschel Telescope. Our g$^\prime$r$^\prime$J observations are directly comparable to those from the high-precision Colours of the Outer Solar System Origins Survey (Col-OSSOS), which offer unique diagnostic information for distinguishing between outer Solar System surfaces. The J-band data also provide the highest signal-to-noise measurements made of 1I/`Oumuamua in the near-infrared. Substantial, correlated near-infrared and optical variability is present, with the same trend in both near-infrared and optical. Our observations are consistent with 1I/`Oumuamua rotating with a double-peaked period of $8.10 \pm 0.42$ hours and being a highly elongated body with an axial ratio of at least 5.3:1, implying that it has significant internal cohesion. The color of the first interstellar planetesimal is at the neutral end of the range of Solar System $g-r$ and $r-J$ solar-reflectance colors: it is like that of some dynamically excited objects in the Kuiper belt and the less-red Jupiter Trojans.Comment: Accepted to ApJ

Low-Dose Sodium Nitrite Attenuates Myocardial Ischemia and Vascular Ischemia-Reperfusion Injury in Human Models

ObjectivesThe aim of this study was to assess the potential benefits of inorganic nitrite in 2 clinical models: stress-induced myocardial ischemia and whole-arm ischemia-reperfusion.BackgroundInorganic nitrite, traditionally considered a relatively inert metabolite of nitric oxide, may exert vasomodulatory and vasoprotective effects. Despite promising results from animal models, few have shown effectiveness in human model systems, and none have fully translated to the clinical setting.MethodsIn 10 patients with inducible myocardial ischemia, saline and low-dose sodium nitrite (NaNO2) (1.5 μmol/min for 20 min) were administered in a double-blind fashion during dobutamine stress echocardiography, at separate visits and in a random order; long-axis myocardial function was quantified by peak systolic velocity (Vs) and strain rate (SR) responses. In 19 healthy subjects, flow-mediated dilation was assessed before and after whole-arm ischemia-reperfusion; nitrite was given before ischemia or during reperfusion.ResultsComparing saline and nitrite infusions, Vs and SR at peak dobutamine increased in regions exhibiting ischemia (Vs from 9.5 ± 0.5 cm/s to 12.4 ± 0.6 cm/s, SR from −2.0 ± 0.2 s−1 to −2.8 ± 0.3 s−1), whereas they did not change in normally functioning regions (Vs from 12.6 ± 0.4 cm/s to 12.6 ± 0.6 cm/s, SR from −2.6 ± 0.3 s−1 to −2.3 ± 0.1 s−1) (p < 0.001, analysis of variance). With NaNO2, the increment of Vs (normalized for increase in heart rate) increased only in poorly functioning myocardial regions (+122%, p < 0.001). Peak flow-mediated dilation decreased by 43% after ischemia-reperfusion when subjects received only saline (6.8 ± 0.7% vs. 3.9 ± 0.7%, p < 0.01); administration of NaNO2 before ischemia prevented this decrease in flow-mediated dilation (5.9 ± 0.7% vs. 5.2 ± 0.5%, p = NS), whereas administration during reperfusion did not.ConclusionsLow-dose NaNO2 improves functional responses in ischemic myocardium but has no effect on normal regions. Low-dose NaNO2 protects against vascular ischemia-reperfusion injury only when it is given before the onset of ischemia

Insights into the molecular basis of the palmitoylation and depalmitoylation of NCX1

Catalyzed by zDHHC-PAT enzymes and reversed by thioesterases, protein palmitoylation is the only post-translational modification recognized to regulate the sodium/calcium exchanger NCX1. NCX1 palmitoylation occurs at a single site at position 739 in its large regulatory intracellular loop. An amphipathic ɑ-helix between residues 740-756 is a critical for NCX1 palmitoylation. Given the rich background of the structural elements involving in NCX1 palmitoylation, the molecular basis of NCX1 palmitoylation is still relatively poorly understood. Here we found that (1) the identity of palmitoylation machinery of NCX1 controls its spatial organization within the cell, (2) the NCX1 amphipathic ɑ-helix directly interacts with zDHHC-PATs, (3) NCX1 is still palmitoylated when it is arrested in either Golgi or ER, indicating that NCX1 is a substrate for multiple zDHHC-PATs, (4) the thioesterase APT1 but not APT2 as a part of NCX1-depalmitoylation machinery governs subcellular organization of NCX1, (5) APT1 catalyzes NCX1 depalmitoylation in the Golgi but not in the ER. We also report that NCX2 and NCX3 are dually palmitoylated, with important implications for substrate recognition and enzyme catalysis by zDHHC-PATs. Our results could support new molecular or pharmacological strategies targeting the NCX1 palmitoylation and depalmitoylation machinery

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer

BackgroundReduced testosterone levels can influence immune system function, particularly T cells. Exercise during cancer reduces treatment-related side effects and provide a stimulus to mobilize and redistribute immune cells. However, it is unclear how conventional and unconventional T cells (UTC) respond to acute exercise in prostate cancer survivors compared to healthy controls.MethodsAge-matched prostate cancer survivors on androgen deprivation therapy (ADT) and those without ADT (PCa) along with non-cancer controls (CON) completed ∼45 min of intermittent cycling with 3 min at 60% of peak power interspersed by 1.5 min of rest. Fresh, unstimulated immune cell populations and intracellular perforin were assessed before (baseline), immediately following (0 h), 2 h, and 24 h post-exercise.ResultsAt 0 h, conventional T cell counts increased by 45%–64% with no differences between groups. T cell frequency decreased by −3.5% for CD3+ and −4.5% for CD4+ cells relative to base at 0 h with CD8+ cells experiencing a delayed decrease of −4.5% at 2 h with no group differences. Compared to CON, the frequency of CD8+CD57+ cells was −18.1% lower in ADT. Despite a potential decrease in maturity, ADT increased CD8+perforin+ GMFI. CD3+Vα7.2+CD161+ counts, but not frequencies, increased by 69% post-exercise while CD3+CD56+ cell counts increased by 127% and were preferentially mobilized (+1.7%) immediately following the acute cycling bout. There were no UTC group differences. Cell counts and frequencies returned to baseline by 24 h.ConclusionFollowing acute exercise, prostate cancer survivors demonstrate normal T cell and UTC responses that were comparable to CON. Independent of exercise, ADT is associated with lower CD8+ cell maturity (CD57) and perforin frequency that suggests a less mature phenotype. However, higher perforin GMFI may attenuate these changes, with the functional implications of this yet to be determined

Improving communication between postgraduate researchers and the university library: a case study at De Montfort University Library and Learning Services

A well-established postgraduate researcher development program has existed at De Montfort University for many years. Library and Learning Services include modules on literature searching skills and critical appraisal. However, we recognized that researchers seemed to be disengaged with the services on offer. This concern informed a research project that considered the ways we could communicate better with researchers based on their needs. This paper explores the essential components of successful communication, such as context, timeliness and communication channels. An action-research approach was taken including focus groups and online surveys. The outcomes highlighted three significant crisis points, emphasizing the key times when researchers might need some intervention. The findings of this research identified the distinct needs of Postgraduate Researchers (PGRs) and how relevant and timely communication from the library can meet these needs. It also considers the impact of how communication has improved with researchers as a result of some of our interventions

Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies

The analysis of less common variants in genome-wide association studies promises to elucidate complex trait genetics but is hampered by low power to reliably detect association. We show that addition of population-specific exome sequence data to global reference data allows more accurate imputation, particularly of less common SNPs (minor allele frequency 1–10%) in two very different European populations. The imputation improvement corresponds to an increase in effective sample size of 28–38%, for SNPs with a minor allele frequency in the range 1–3%