MICAL is an oxidoreductase that participates in cytoskeleton reorganization via actin disassembly in the presence of NADPH. Although three MICALs (MICAL1, MICAL2 and MICAL3) have been identified in mammals, only the structure of mouse MICAL1 has been reported. Here, the first crystal structure of human MICAL3, which contains the flavin-containing monooxygenase (FMO) and calponin-homology (CH) domains, is reported. MICAL3 has an FAD/NADP-binding Rossmann-fold domain for mono­oxygenase activity like MICAL1. The FMO and CH domains of both MICAL3 and MICAL1 are highly similar in structure, but superimposition of the two structures shows a different relative position of the CH domain in the asymmetric unit. Based on kinetic analyses, the catalytic efficiency of MICAL3 dramatically increased on adding F-actin only when the CH domain was available. However, this did not occur when two residues, Glu213 and Arg530, were mutated in the FMO and CH domains, respectively. Overall, MICAL3 is structurally highly similar to MICAL1, which suggests that they may adopt the same catalytic mechanism, but the difference in the relative position of the CH domain produces a difference in F-actin substrate specificity.

Transforming growth factor β-1 (TGFβ-1) is a secreted signalling protein that directs many cellular processes and is an attractive target for the treatment of several diseases. The primary endogenous activity regulatory mechanism for TGFβ-1 is sequestration by its pro-peptide, latency-associated peptide (LAP), which sterically prohibits receptor binding by caging TGFβ-1. As such, recombinant LAP is promising as a protein-based therapeutic for modulating TGFβ-1 activity; however, the mechanism of binding is incompletely understood. Comparison of the crystal structure of unbound LAP (solved here to 3.5 Å resolution) with that of the bound complex shows that LAP is in a more open and extended conformation when unbound to TGFβ-1. Analysis suggests a mechanism of binding TGFβ-1 through a large-scale conformational change that includes contraction of the inter-monomer interface and caging by the `straight-jacket' domain that may occur in partnership through a loop-to-helix transition in the core jelly-roll fold. This conformational change does not appear to include a repositioning of the integrin-binding motif as previously proposed. X-ray scattering-based modelling supports this mechanism and reveals possible orientations and ensembles in solution. Although native LAP is heavily glycosylated, solution scattering experiments show that the overall folding and flexibility of unbound LAP are not influenced by glycan modification. The combination of crystallography, solution scattering and biochemical experiments reported here provide insight into the mechanism of LAP sequestration of TGFβ-1 that is of fundamental importance for therapeutic development.

Mitochondrial calcium uptake proteins 1 and 2 (MICU1 and MICU2) mediate mitochondrial Ca2+ influx via the mitochondrial calcium uniporter (MCU). Its molecular action for Ca2+ uptake is tightly controlled by the MICU1–MICU2 heterodimer, which comprises Ca2+ sensing proteins which act as gatekeepers at low [Ca2+] or facilitators at high [Ca2+]. However, the mechanism underlying the regulation of the Ca2+ gatekeeping threshold for mitochondrial Ca2+ uptake through the MCU by the MICU1–MICU2 heterodimer remains unclear. In this study, we determined the crystal structure of the apo form of the human MICU1–MICU2 heterodimer that functions as the MCU gatekeeper. MICU1 and MICU2 assemble in the face-to-face heterodimer with salt bridges and me­thio­nine knobs stabilizing the heterodimer in an apo state. Structural analysis suggests how the heterodimer sets a higher Ca2+ threshold than the MICU1 homodimer. The structure of the heterodimer in the apo state provides a framework for understanding the gatekeeping role of the MICU1–MICU2 heterodimer.

As one of the most important phenomena in crystallization, the crystal nucleation process has always been the focus of research. In this work, influences of pre-assembly species and the desolvation process on the crystal nucleation process were studied. p-Nitro­benzoic acid (PNBA) was taken as a model compound to investigate the relationship between solution chemistry and nucleation kinetics in seven different solvents. One unsolvated form and four solvates of PNBA were obtained and one of the solvates was newly discovered. The nucleation behaviours and nucleation kinetics of PNBA in the seven solvents were studied and analyzed. Density functional theory (DFT) and solvation energy calculation were adopted to evaluate the strength of solute–solvent interactions. Vibrational spectroscopy combined with molecular simulation was applied to reveal the pre-assembly species in the solution. Based on these results, a comprehensive understanding of the relationship between molecular structure, crystal structure, solution chemistry and nucleation dynamics was proposed and discussed. It was found that the structural similarity between solution chemistry and crystal structure, the interaction between specific sites and the overall strength of solvation will jointly affect the nucleation process.

Ba excess in LaBaGaO4 triggers ionic conductivity together with structural disorder. A direct correlation is found between the density functional theory model energy and the pair distribution function fit residual.

New observations by the Smithsonian’s Submillimeter Array, a radio telescope atop Mauna Kea in Hawaii, are shedding light on planet formation. The array provides sharp views by combining eight antennas into the equivalent of a single, large telescope. It can resolve details as small as a dime seen from seven miles away.

The post Cosmic “baby photos” of distant solar systems lend insight as to how planets form appeared first on Smithsonian Insider.

Kandula, an 8-year-old male Asian elephant at the Smithsonian’s National Zoo, recently demonstrated to researchers for the first time that elephants are capable of insightful problem solving.

The post A first: National Zoo elephant shows insightful problem solving appeared first on Smithsonian Insider.

NASA’s InSight probe, scheduled to land on the surface of Mars in November 2018, will be boring. Boring a hole, that is. It will drill […]

The post ISO: a boring Martian landing spot for NASA’s InSight probe appeared first on Smithsonian Insider.

The Open Banking Report 2019 clarifies the role of key key-players in a post-September 14th world and assesses how the landscape has shifted within Europe and beyond.

Yaya Wang
Apr 7, 2020; 133:jcs228072-jcs228072
REVIEW

A new study indicates that ‘commitment’ interventions are effective in encouraging environmentally-friendly behaviour, both in the short- and long-term. However, to increase the effectiveness of such interventions, whereby people promise or pledge to perform certain behaviours, more research is needed on the psychological processes behind their effects.

A new study indicates that ‘commitment’ interventions are effective in encouraging environmentally-friendly behaviour, both in the short- and long-term. However, to increase the effectiveness of such interventions, whereby people promise or pledge to perform certain behaviours, more research is needed on the psychological processes behind their effects.

Comprehensive flood risk management should include household measures, such as improving a home’s stability and relocating heating systems to safe places within the house. According to new research, better communication with householders by authorities on the effectiveness of such measures, and how to implement them, could increase their uptake.

Controlling pests using their natural enemies can be an environmentally sound alternative to pesticides. However, the complex interactions between different pest control species and the landscape itself can affect the efficiency of such biological pest control, research suggests.

Phytoplankton are essential to marine food webs and fisheries. However, a new study indicates that their levels have declined in the North Atlantic since the beginning of the 19th century. This coincides with weakening ocean-circulation patterns, partly caused by melting ice caps. If the melting continues, the study warns of a dramatic fall in North Atlantic plankton levels that could have cascading effects across marine food webs, reducing the ocean’s ability to absorb carbon and threatening the supply of seafood for humans.

The impacts of drought on European trees are of high concern, especially under a changing climate. New research has indicated that, if summers become continually drier, sensitive species, such as larch and spruce, will suffer reduced growth in some Alpine areas. This could potentially compromise ecosystem services provided by forests in these areas.

It can take six to seven years before the financial benefits of brownfield regeneration projects are realised, according to a new study which focused on redevelopment in Michigan, USA. The study examines liability issues, regulatory concerns, clean-up standards and funding mechanisms, and introduces a new model that informs debate on brownfield redevelopment policies and funding mechanisms.

Constructed wetlands serve as a cost-effective and multi-purpose option for storm-water treatment in urban landscapes, offering flood protection as well as wildlife habitat. However, a new study shows that when nearby land use includes industry, wetlands can accumulate high levels of pollution and potentially become toxic to wildlife. This new piece of research offers important insights for the planning and management of wetlands.

Rare earth elements (REE) are used to make many low-carbon technologies, including electric vehicles and wind turbines. Mining and processing of REE, which mostly takes place in China, has a reputation for causing environmental damage. A new study presents a method for evaluating the environmental impacts of REE production based on life-cycle assessment (LCA: a way of determining a product's overall impact during some or all of its journey from extraction to end-of-life). The researchers applied the method to a prospective REE mine in Malawi, south-east Africa, to reveal the most environmentally impactful stages of production, and the greenest source of energy.

A mixture of fine particles in air leads to harmful effects on human health. Currently, particulate matter (PM) is defined in policy by particle size, but according to a new study, focusing on air pollutants and their toxic effects on cells may provide an effective way to legislate for PM.

A study on the transport of radioactive isotopes from Fukushima in the two months after the nuclear incident suggests that they were at official levels of contamination for 34,000 km2 of Japan, and that 2.8% of iodine radionuclides from the event were calculated to have reached the EU.

Makower, one of the most respected voices in green business, talks about greener corporations, what the government could be doing to foster more environmentally

Humans have detected and confirmed seismic event son another planet. Here's what you need to know about "marsquakes" and what they mean.

Scott, who founded Aston Scott Group, has invested in the start-up which was launched by former Aviva broker distribution director Fraser Edmond.

Last week iuvo Technologies, Boston's premier white-glove IT services and Managed Services Provider, attended the 2019 Channel Partner Insight MSP Innovation Awards at the Harmonie Club in New York.

New research on streaming data systems will identify trends in analytics and data management

New research on engaging candidates effectively will guide HR teams and business leaders in this critical arena

Source One Director Jennifer Ulrich will discuss end-to-end supplier engagement in a webinar sponsored by ISM-New Jersey.

Healthcare industry to reach $372 billion by 2022

South Africa currently runs a two-tiered healthcare system, comprising of the public and the smaller, rapidly -growing private sector.

The South Africa medical device market will register a 9.1% CAGR between 2017-2018 according to a recent Fitch Solutions report. This significant growth will raise the market to USD 1.27 bn by 2018.

According to Fitch Solutions, the Middle East and North Africa (MENA) region's US$182.9 billion healthcare market is forecast to expand to US$261.1 billion with a 13.6% compound annual growth rate (CAGR) at constant exchange rates through to 2023.

Corcentric's Source-to-Pay Team will Discuss Mapping a Procurement Transformation at Sourcing Outlook 2019.

Corcentric Analyst to discuss Procurement's recession-proofing powers in ISM-NJ webinar.

She Rules Gives Readers the Opportunity to Open up to Private Situations and Explains the Hidden Intricacies of the Dating World

Annual listing profiles 10 companies at the forefront of providing cloud communications consulting services and impacting the marketplace

E-Book Edition

Procuring SeamlessDocs just got even easier

Brittany Melville Discussed Using Funds from Existing Workplace Retirement Plans or IRAs to Fund a New Self-Directed IRA, Take Advantage of Opportunities to Invest in Alternative Assets

"Controversy" over COVID-19 and fertility treatment reveals investor-led interest pushing for more control in the IVF field

Latest research aims to understand advances in natural language capabilities and its impact on business

Malcolm Salter, Harvard Business School professor.

Scott Berinato and Andy O'Connell, editors of the Idea Watch section of Harvard Business Review.

Dr. Oliver Sacks, neurologist and author of "The Mind's Eye."

As a source of information and guidance for businesses and individuals since 1965, Anders is here for you during this time of uncertainty. We’re researching and dissecting the latest legislation, local news and relevant updates around COVID-19 and sharing them… Read More

The post COVID-19 Resource Center Offers Insights and Guidance for Individuals and Businesses appeared first on Anders CPAs.

Enterprise search projects start with intentions to provide ?Google for our organization' but too often fail to deliver on that promise. In our experience, these projects fail due to a lack of sustained effort and governance. The commercialization of next-generation search technologies allows you to fulfill this promise if you take a systematic approach to implementation.

Increases analytics ROI by closing the gap between insights and action

DALLAS, April 3, 2020 —As physicians, scientists and researchers worldwide struggle to understand the coronavirus (COVID-19) pandemic, the American Heart Association is developing a novel registry to aggregate data and aid research on the disease,...

Chance to watch programme from dance company.