D. V. Gusak and E. V. Karnaukh
Theor. Probability and Math. Statist. 99 (2020), 77-89.
Abstract, references and article information

All the details on Uber's biggest announcements as well as updates on the controversial company's trials and tribulations

Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable, with T50 values of ∼30–40 °C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared with related extant forms, but they also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. Whereas extant human CYP1B1 has one molecule of α-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17β-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to its thermostability.

In this blog by Julianne Vega, graduate student at University of Kentucky, Julianne tells us how to make the most of attending math conferences. If you are heading to a conference, challenge yourself! Your first conference may not be the … Continue reading →

Kotaro Hama
Apr 1, 2020; 61:523-536
Patient-Oriented and Epidemiological Research

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder caused by deleterious mutations in the ABCD1 gene. The ABCD1 protein transports very long-chain FAs (VLCFAs) from the cytosol into the peroxisome where the VLCFAs are degraded through β-oxidation. ABCD1 dysfunction leads to VLCFA accumulation in individuals with X-ALD. FAs are activated by esterification to CoA before metabolic utilization. However, the intracellular pools and metabolic profiles of individual acyl-CoA esters have not been fully analyzed. In this study, we profiled the acyl-CoA species in fibroblasts from X-ALD patients and in ABCD1-deficient HeLa cells. We found that hexacosenoyl (26:1)-CoA, but not hexacosanoyl (26:0)-CoA, was the most abundantly concentrated among the VLCFA-CoA species in these cells. We also show that 26:1-CoA is mainly synthesized from oleoyl-CoA, and the metabolic turnover rate of 26:1-CoA was almost identical to that of oleoyl-CoA in both WT and ABCD1-deficient HeLa cells. The findings of our study provide precise quantitative and metabolic information of each acyl-CoA species in living cells. Our results suggest that VLCFA is endogenously synthesized as VLCFA-CoA through a FA elongation pathway and is then efficiently converted to other metabolites, such as phospholipids, in the absence of ABCD1.

Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable, with T50 values of ∼30–40 °C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared with related extant forms, but they also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. Whereas extant human CYP1B1 has one molecule of α-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17β-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to its thermostability.

We are looking at the players on each active roster who are making history for their franchises every time they step on the field. We're looking at the player who has compiled the highest WAR (per Baseball Reference) for his current team so far in his career.

With immigration increasingly visible in the news and the political space in the United States and internationally, getting access to accurate, high-quality data is essential to understand immigration’s demographic effects and impacts on the economy, education and labor systems, and communities. This event marks the release of the Immigration Data Matters guide.

In exchange for resolving the status of DREAMers, the White House and its congressional allies are demanding billions of dollars for a border wall and additional enforcement, sharp limits on asylum, cuts to legal immigration, and more. But what would the two bills expected to be voted on by the House do in terms of extending temporary or permanent status to DREAMers? This commentary offers estimates.

At this release of an updated version of the popular Immigration Data Matters guide, presenters discuss how to navigate and access the increasing number of data sources on immigration and immigrants in the United States and internationally. 

The United Nations more than tripled its humanitarian aid appeal on Thursday from $2 billion to $6.7 billion to accommodate its updated global plan to help the poorest nations fight the coronavirus pandemic.

On the frontlines of responding to the COVID-19 pandemic yet also more disproportionately affected by the virus and with reduced health care access, immigrants in the United States have largely found themselves blocked from federal economic relief. As states and philanthropic groups seek to plug the gap, this article examines conditions and changing policies around immigration and the coronavirus response.

For years, economists have taught their students a simple maxim: As employers hunt for workers, they want to get the best talent at the lowest price.

The perjury trial of I. Lewis "Scooter" Libby goes to the jury this week. The case speaks to several issues -- how the Bush administration deals with critics of the war in Iraq, and the games that Washington's reporters and politicians play with each other. As far as the jury is concerned, however,...

So, you wanted to follow this nice website for new content, but it doesn’t have an RSS feed yet? Don’t…

For decades, researchers have been studying the effectiveness of different kinds of pick-up lines in order to better understand the psychology of attraction. What they’ve found is that certain types of lines definitely seem to work better than others—and the results have been surprisingly consistent over the years.

What do people want to know about sex? Here's are the ten most read question-and-answer features of all time on the blog. These questions (all submitted by readers of Sex and Psychology) span a wide range of topics. Many of them fall under the category of “What’s normal when it comes to sex?” However, others reflect curiosity about diverse sexual practices, as well as interest in better understanding what's safe when it comes to sex.

Massachusetts ranks high in laying the groundwork for moving through its educational system, but officials are keenly aware that children in poverty, those with special needs, and English-learners can fall short.

Ohio Gov. John Kasich is expected to sign a bill into law that would ban suspensions and expulsions for children in prekindergarten through 3rd grade for minor offenses.

Lawmakers in Michigan, Mississippi, North Dakota, and Utah have all gave previews this to their 2018 fiscal year budget proposals.

When Scott Gann learned his son Dustin had dyslexia, he was shocked at the school's reaction. No one there wanted to use the word.

A federal judge dismissed most claims in a lawsuit challenging Connecticut's restrictions on magnet schools, charter schools, and school choice programs, saying there is no fundamental right to equal education opportunity under the U.S. Constitution.

Charter schools in Washington state can continue to receive public funding, the state's high court ruled last week.

Kansas' auditor found that more than $400 million of state aid intended for poor, black, Latino and ELL students was being spent ineffectively, including on items such as food service supplies and an after-prom party.

London : Chemist and Druggist, 1898.

London : Bailliere, Tindall, & Cox, 1879.

Bath : And sold by Underwood, London, 1825.

In remote regions of rural Alaska, both schools and the students themselves have to work harder to put together an education that meets students' needs.

Led by Hecht’s two goals and Briere’s three assists, the Sabres emerged with a 5-4 victory to claim what remains their most recent playoff series win.

Gregory Cox.

Source: The Annals of Statistics, Volume 48, Number 1, 584--606.

Abstract:
This paper establishes the argmin of a random objective function to be unique almost surely. This paper first formulates a general result that proves almost sure uniqueness without convexity of the objective function. The general result is then applied to a variety of applications in statistics. Four applications are discussed, including uniqueness of M-estimators, both classical likelihood and penalized likelihood estimators, and two applications of the argmin theorem, threshold regression and weak identification.

For millions of Americans, working at home isn't an option. NBC News identified seven occupations in which employees are at especially high risk of COVID-19.

The infections and deaths are spread across roughly two farms and 189 meat and processed food factories.

Basic facts The world contains an estimated 1 400 million cubic km of water. Only 0.003% of this vast amount, about 45 000 cubic km, are what is called “fresh water resources” - water that theoretically can be used for drinking, hygiene, agriculture and industry. But not all of this water is accessible. For example, seasonal flooding makes water extremely difficult [...]