What do you do when you get sick? In the UK you go to your GP unless it is an emergency. But what is a GP?

IMPD Chief Randal Taylor and Dreasjon Reed's family speak during emotional meeting, near where Reed was killed Wednesday in police-action shooting.

In a tense conversation, Indianapolis Police Chief Randal Taylor speaks with Dreasjon Reed's family near where he was fatally shot by police.

This Teacher Appreciation Week, IndyStar asked readers to help recognize some of the amazing teachers going above and beyond during these times.

The cousin of Grace Millane, who was murdered in New Zealand, says she would have been "so proud".

A family of four was able to safely get out of their house after a fire caused $200,000 of damage.

Photographer Barry Lewis captures the spirit of a Butlin's holiday camp in 1982.

1. Netizens swoon over Sunil Lahri's son's handsomeness; a look at rare and unseen pics of the cast of Ramayan's family members  Times of India
2. Ramayan actor Dipika Chikhlia would love to play Kaikeyi, Sunil Lahri wishes to play Raavan’s role if...  Hindustan Times
3. Throwback: Ramanand Sagar had THIS condition for roping in Arun Govil for Ram’s role in Ramayan  PINKVILLA
4. Buoyed by Ramayans record-breaking run, Kapil Sharmas episode with stars to air again - Republic World  Republic World
5. Ramayan's Sita Dipika Chikhlia and Lakshman Sunil Lahri on making of the show  Hindustan Times
6. View Full coverage on Google News

Review of 'A Good Provider Is One Who Leaves: One Family and Migration in the 21st Century' by Jason DeParle

Maybe it’s irony. Or maybe it’s her latest attempt to pinkwash her father’s anti-family agenda.

The body of an elderly woman, who died of Covid-19, has been lying at a funeral parlour since Monday because her family, who are in another province, cannot get the necessary documents from closed Home Affairs branches in order to travel.

The Duke of Sussex recently launched a fitness online program for the military community.

Around the World, Family Style

The Amateur Traveler talks to Nancy Sathre-Vogel from FamilyOnBikes.com about their odyssey – a bike ride with two young boys along the length of the Pan-American highway from Alaska to the southern end of South America. Learn why they did this trip, how they have managed it and what they have learned along the way.

TL;DR: Give a meaningful gift during these difficult times with a Tribute Video Montage for $64.99, a 34% saving as of May 9.

A Zoom happy hour only goes so far.

If you're looking for a way to celebrate and send affection to your loved ones, regardless of the reason, check out Tribute Video Montage as an alternative to those wonky (and sometimes awkward) video calls. 

Sending a Tribute might just be one of the best morale-boosting presents you can send during these trying times. It's a way for friends and family to share their love and appreciation for someone they want to celebrate, whether for a major milestone, like a 50th anniversary or 30th birthday or just because. The platform is super easy to use and breaks a 10-hour process down to just 10 minutes. Read more...

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.

David A. Mitchell
Jun 1, 2006; 47:1118-1127
Thematic Reviews

Michael Dean
Jul 1, 2001; 42:1007-1017
Thematic Reviews

Dawn L. Brasaemle
Dec 1, 2007; 48:2547-2559
Thematic Reviews

The DOCK-D (dedicator of cytokinesis D) family proteins are atypical guanine nucleotide exchange factors that regulate Rho GTPase activity. The family consists of Zizimin1 (DOCK9), Zizimin2 (DOCK11), and Zizimin3 (DOCK10). Functions of the DOCK-D family proteins are presently not well-explored, and the role of the DOCK-D family in neuroinflammation is unknown. In this study, we generated three mouse lines in which DOCK9 (DOCK9−/−), DOCK10 (DOCK10−/−), or DOCK11 (DOCK11−/−) had been deleted and examined the phenotypic effects of these gene deletions in MOG35–55 peptide-induced experimental autoimmune encephalomyelitis, an animal model of the neuroinflammatory disorder multiple sclerosis. We found that all the gene knockout lines were healthy and viable. The only phenotype observed under normal conditions was a slightly smaller proportion of B cells in splenocytes in DOCK10−/− mice than in the other mouse lines. We also found that the migration ability of macrophages is impaired in DOCK10−/− and DOCK11−/− mice and that the severity of experimental autoimmune encephalomyelitis was ameliorated only in DOCK10−/− mice. No apparent phenotype was observed for DOCK9−/− mice. Further investigations indicated that lipopolysaccharide stimulation up-regulates DOCK10 expression in microglia and that microglial migration is decreased in DOCK10−/− mice. Up-regulation of C–C motif chemokine ligand 2 (CCL2) expression induced by activation of Toll-like receptor 4 or 9 signaling was reduced in DOCK10−/− astrocytes compared with WT astrocytes. Taken together, our findings suggest that DOCK10 plays a role in innate immunity and neuroinflammation and might represent a potential therapeutic target for managing multiple sclerosis.

G. Alfelt
Theor. Probability and Math. Statist. 99 (2020), 5-17.
Abstract, references and article information

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.

Barbara J. Anderson
Jan 1, 2004; 17:
Articles

Gemma Cadby
Apr 1, 2020; 61:537-545
Patient-Oriented and Epidemiological Research

CVD is the leading cause of death worldwide, and genetic investigations into the human lipidome may provide insight into CVD risk. The aim of this study was to estimate the heritability of circulating lipid species and their genetic correlation with CVD traits. Targeted lipidomic profiling was performed on 4,492 participants from the Busselton Family Heart Study to quantify the major fatty acids of 596 lipid species from 33 classes. We estimated narrow-sense heritabilities of lipid species/classes and their genetic correlations with eight CVD traits: BMI, HDL-C, LDL-C, triglycerides, total cholesterol, waist-hip ratio, systolic blood pressure, and diastolic blood pressure. We report heritabilities and genetic correlations of new lipid species/subclasses, including acylcarnitine (AC), ubiquinone, sulfatide, and oxidized cholesteryl esters. Over 99% of lipid species were significantly heritable (h²: 0.06–0.50) and all lipid classes were significantly heritable (h²: 0.14–0.50). The monohexosylceramide and AC classes had the highest median heritabilities (h² = 0.43). The largest genetic correlation was between clinical triglycerides and total diacylglycerol (r_g = 0.88). We observed novel positive genetic correlations between clinical triglycerides and phosphatidylglycerol species (r_g: 0.64–0.82), and HDL-C and alkenylphosphatidylcholine species (r_g: 0.45–0.74). Overall, 51% of the 4,768 lipid species-CVD trait genetic correlations were statistically significant after correction for multiple comparisons. This is the largest lipidomic study to address the heritability of lipids and their genetic correlation with CVD traits. Future work includes identifying putative causal genetic variants for lipid species and CVD using genome-wide SNP and whole-genome sequencing data.

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.

BELMOPAN, Belize, CMC – Police Commissioner Chester Williams said there would be “absolutely no room for negotiation” after a family of four, including two minors, were arrested over the last weekend for illegally entering Belize...

bmj;369/may07_9/m1832/FAF1faYara/ReutersThe meeting in Rome of Domenico di Massa with his granddaughter Cecilia for the first time in two months was echoed across Italy as families emerged onto the...

As policymakers in a number of countries, the United States among them, debate limiting family-based immigration, this issue brief explores family-migration trends and policies in the United States, Australia, Canada, the United Kingdom, and several other European countries. Family admissions play a key role, even in countries that prioritize economic or other immigration streams.

Faced with a lack of employment opportunities and recurrent poverty, Albanian youth migrate to Italy alone in the hopes of improving their educational prospects or making money for their families. Yet upon arrival, they face many vulnerabilities. While some protections for unaccompanied minors exist in the Italy, the system is greatly fragmented and challenges, including how to return them to Albania, remain persistent.

This fact sheet uses U.S. and Mexican apprehensions data to trace the evolving trends in unaccompanied child and family migration from Central America through Mexico and to the United States, and discusses the push factors and pull factors responsible for the increase in flows seen in recent years, as well as the growing role of smuggling organizations.

This event marked the launch of New York Times reporter Jason DeParle's book tracing the arc of migration as a phenomenon, witnessed through three decades observing a particular Filipino family moving from Manila to Texas. The conversation explored both the human and policy aspects of migration and development.

Marking the launch of New York Times reporter Jason DeParle's book tracing the arc of migration and its impacts through the life of an extended family of Filipino migrants over a three-decade period, from Manila and through Dubai to the Houston area, this conversation with MPI's Andrew Selee and the World Bank's Dilip Ratha explores migration at both a global and very personal level.

Concerns about local school systems can pose recruitment and retention hurdles for the armed services as they seek to meet the needs of military families.

A young artist inherits her Grammy's home in The Vales and begins to remember the stories her Grammy once shared with her. Where they real or has Grammy already lost her marbles a wee bit? When some friends come to visit she regales them with the stories and gives them a tub of her Grammy's favourite chees - the Bless Family Vegan Parmesan Cheese that she had procured from the famous Blessed Cheese cafe run by the Bless family.