Mohamed Jleli, Bessem Samet and Philippe Souplet
Proc. Amer. Math. Soc. 148 (2020), 2579-2593.
Abstract, references and article information

Guest of Honour at Film Mayo launch on 1st December

Caryl Ann O'Reilly
Jul 1, 2005; 18:162-166
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Priscilla Hollander
Jul 1, 2007; 20:159-165
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W. Guyton Hornsby
Apr 1, 2005; 18:102-107
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Ji Chun
May 1, 2019; 32:104-111
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Peggy Yarborough
Jan 1, 2003; 16:
Case Studies

Geralyn Spollett
Jan 1, 2003; 16:
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(Fundação de Amparo à Pesquisa do Estado de São Paulo) Thanks to its magnetic properties, the material -- zinc-doped manganese chromite -- can be used in a range of products, from gas sensors to data storage devices.

"In his new book--The Math of Life & Death: 7 Mathematical Principles that Shape Our Lives--mathematician Kit Yates makes complex mathematical concepts easily accessible to anyone, and which can improve decision making in an increasingly quantitative society. In this Q&A, Yates discusses why math is relevant to everyday life." See "Mathematician Kit Yates on Anti Vaxxer Movement, Air Travel Germs and Samoa's Measles Outbreak," by Meredith Wold Schizer, Newsweek, December 23, 2019.

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.

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.

VOLUME 292 (2017) PAGES 3531–3540This article has been withdrawn by Shuofeng Hu, Xiaomin Ying, Xiangming Zhang, and Ya Wang. Baocheng Hu, Xiang Wang, Ping Wang, Jian Wang, and Hongyan Wang could not be reached. In Fig. 1C, the DAPI and merged images for the no IR control were switched. The DNA-PKcs and actin immunoblots on the left appear to have been spliced. In Fig. 4C, the DNA-PKcs immunoblot appears to have been spliced. In Fig. 4D, lanes 1 and 5; lanes 2, 6, and 8; and lanes 3 and 7 of the DNA-PKcs immunoblot are the same. In the p-DNA-PKcs immunoblot, lanes 1 and 8, lanes 2 and 6, and lanes 3 and 7 are the same. In the CRY2 immunoblot, lanes 5 and 7 are the same. In the CDC25A immunoblot, lanes 3 and 8 are the same. In the GSK3B immunoblot, lanes 1 and 5 and lanes 3 and 7 are the same. Also in the GSK3B immunoblot, the upper GSK3B bands in lanes 6 and 8 are the same. Lanes 4 and 8 of the cyclin D1 immunoblot are the same. In Fig. 5A, the CDC25A immunoblot appears to have been spliced. Also in Fig. 5A, lanes 2–4 and lanes 6–8 of the CDC25A immunoblot are the same. Lanes 4–6 and 7–9 of the actin immunoblot are the same. In Fig. 5C, lane 1 of the CDC25A immunoblot was reused in lane 5, and lanes 3 and 4 were reused in lanes 7 and 8. In the...

VOLUME 289 (2014) PAGES 30635–30644This article has been withdrawn by Guangnan Chen, Dongkyoo Park, Francis A. Cucinotta, David S. Yu, Xingming Deng, William S. Dynan, Paul W. Doetsch, and Ya Wang. Hongyan Wang, Xiang Wang, Xiangming Zhang, and Xiaobing Tang could not be reached. The last two lanes of the actin immunoblot in Fig. 1A were reused in the last two lanes of the actin immunoblot in Fig. 1C. In Fig. 2A, the γ-H2AX and the merge with DAPI images for no IR treatment do not match. In Fig. 3A, lanes 3 and 4 of the γ-H2AX immunoblot were reused in lanes 7 and 8, and lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3B, lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3C, lanes 5 and 6 of the γ-H2AX immunoblot were reused in lanes 7 and 8. Additionally, lanes 1 and 2 of the H2A immunoblot were reused in lanes 3 and 4. In Fig. 3D, lanes 1 and 2 of the Mre11 immunoblot from lysates were reused in lanes 4 and 5. In the γ-H2AX immunoblot, lane 3 was reused in lane 7, and lane 4 was reused in lanes 6 and 8. Also in the H2A immunoblot, lanes 1 and 2 were reused in lanes 3 and 4. In Fig. 4B, lanes 2 and 6 of the Mre11 immunoblot from Ogg1−/− cells are the same. In the Ape1...

In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB.

Nucleoside analogues are a valuable experimental tool. Incorporation of these molecules into newly synthesized DNA (i.e. pulse-labeling) is used to monitor cell proliferation or to isolate nascent DNA. Some of the most common nucleoside analogues used for pulse-labeling of DNA in cells are the deoxypyrimidine analogues 5-ethynyl-2'-deoxyuridine (EdU) and 5-ethynyl-2'-deoxycytidine (EdC). Click chemistry enables conjugation of an azide molecule tagged with a fluorescent dye or biotin to the alkyne of the analog, which can then be used to detect incorporation of EdU and EdC into DNA. The use of EdC is often recommended because of the potential cytotoxicity associated with EdU during longer incubations. Here, by comparing the relative incorporation efficiencies of EdU and EdC during short 30-min pulses, we demonstrate significantly lower incorporation of EdC than of EdU in noninfected human fibroblast cells or in cells infected with either human cytomegalovirus or Kaposi's sarcoma-associated herpesvirus. Interestingly, cells infected with herpes simplex virus type-1 (HSV-1) incorporated EdC and EdU at similar levels during short pulses. Of note, exogenous expression of HSV-1 thymidine kinase increased the incorporation efficiency of EdC. These results highlight the limitations when using substituted pyrimidine analogues in pulse-labeling and suggest that EdU is the preferable nucleoside analogue for short pulse-labeling experiments, resulting in increased recovery and sensitivity for downstream applications. This is an important discovery that may help to better characterize the biochemical properties of different nucleoside analogues with a given kinase, ultimately leading to significant differences in labeling efficiency of nascent DNA.

(University of Cambridge) Parents should not feel pressured to make their young children undertake structured learning or achieve specific tasks, particularly during lockdown. A new study of children under the age of two has found that parents who take a more flexible approach to their child's learning can - for children who were easy babies - minimise behavioural problems during toddlerhood.

(Arizona State University) Gary Moore, assistant professor in ASU's School of Molecular Sciences and the Biodesign Institute's Center for Applied Structural Discovery has just been named one of 14 young faculty nationwide to be honored with a 2020 Camille Dreyfus Teacher-Scholar Award by the Camille and Henry Dreyfus Foundation.

Seventy-year-old Theresa Chan suffers from joint degeneration, which is why she needs a walking stick.

“My joints are severely abraded. They are painful when I walk or stand. My doctor suggested I replace some joints with implants, but I don't want surgery,” she said.

Smart seniors

Interested in how gerontechnology can help improve the quality of life for older adults, Ms Chan joined the Gerontechnology Practitioner Training Course under Lingnan University’s Gerontechnology & Smart Ageing Project.

The course targets elderly people and caregivers. It introduces them to devices that help seniors get around with ease and live more independent lives.

Ms Chan was impressed by a smart walking stick that is equipped with senior-worthy features like a flashlight with an adjustable safety light, a siren for emergency use and a radio.

“I am grateful for the course because I can learn more about gerontechnology in my free time. After class, I can share my knowledge with others who have no idea about this new technology. It is modern and I want to keep up with the times and progress,” she said.

Youth opportunities

Gerontechnology has also opened up career opportunities for young people.

Cecilia Auyeung recently graduated from Lingnan University with a major in marketing. Last year she set up a social enterprise called Gatherly. It provides a platform for the elderly to teach other people handicraft skills and helps them to sell their products online.

Ms Auyeung joined the Socialpreneur Incubation Course under the Lingnan University project. It encourages the development of social enterprises in Hong Kong, gerontechnology and marketing. She quickly drew inspiration from other socialpreneurs.

“I discovered that my social enterprise has to change every two years according to market demands. For example, fabric bags are popular among youngsters. While the elderly at Gatherly are equipped with blue-dye techniques, I make use of their skills to create products that match the market situation.”

University contribution

According to the Census & Statistics Department, in 2036, the proportion of the population aged 65 and over is projected to be 31%. To meet the needs of an ageing population, the Government is promoting gerontechnology, which combines gerontology and technology. It focuses on providing effective solutions to increase vitality and quality of life.

The Lingnan University’s three-year project aims to enhance public understanding of gerontechnology and support smart ageing socialpreneurship development. The project also covers studies with the goal of building a database for gerontech products and services as well as social innovation and startups. The overall vision is to offer policy recommendations to the industry and Government.

Lingnan University Asia-Pacific Institute of Ageing Studies Project Manager Chloe Siu said: “Most of the participating students are willing to think out-of-the-box, using their creativity and knowledge learnt from their courses and to echo the needs of the society. We are trying to facilitate different stakeholders and community partners to create a co-working atmosphere.”

The university has also built a 2,000 sq ft Gerontech-X Lab to display over 40 gerontech products catered to healthcare, dining, living and transport. Anyone interested can book an appointment for a free visit from November 28.

The modern day phenomenon of fast fashion has completely changed consumer and retailer behaviour.

The latest trends fresh off the catwalk are now available off the rack in record time and for a fraction of the price. But these garments are usually made of cheap, low quality materials that fall apart after a few wears and end up in the landfill.

Fast fashion’s impact on the environment is huge. This is where environmental non-governmental organisation Redress plays a role.

Drawing board

Launched in 2007, Redress works to reduce waste in the fashion industry. It promotes sustainability through organising fashion shows, seminars and exhibitions in Hong Kong and abroad.

In 2011, the EcoChic Design Award was born. Relaunched as the Redress Design Award in 2018, it is open to emerging fashion designers and design students all over the world. The award aims to inspire designers to create mainstream clothing with minimal textile waste.

Redress Circular Fashion Programme Director Kay Liu explained the motivation behind setting up the award came from discovering that 80% of a product’s environmental impact is determined during the design stage.

“That means designers have a lot of influence on how their product is going to impact the environment, so we really want to spread the message for fashion designers to understand the power they have and to positively impact the industry,” Ms Liu added.

The competition works to educate emerging fashion designers around the world about sustainable design theories and techniques to drive growth towards a circular fashion system.

In the space of a decade, the award has evolved from a local competition to the largest global platform for talented fashion game changers to transform the fashion industry worldwide.

Fashion muse

Keith Chan is one of those young design talents. His collection, inspired by Hong Kong’s signature neon signs, won him the Hong Kong Best Prize for 2019.

Mr Chan said his fellow competitors inspired him to try out different sustainable design techniques. A designer from Spain used natural plant dyes to colour her garments and changed his perspective on the industry’s dyeing methods.

“This is not only about design, you also need to consider our society, really think about the materials you use and how to make your outfit better,” Mr Chan noted.

Fashion design students like Jasmine Leung were also inspired through joining the competition.

Each competition cycle takes participants on an educational journey lasting several theory and design-packed months to educate designers about fashion’s negative environmental impacts.

By attending seminars and completing various tasks for her collection, Ms Leung gained a better understanding of eco-fashion.

“The award gave me an opportunity to acquire practical fashion knowledge beyond the classroom. I have learnt about circular design strategy, like applying the concept of zero waste, recycling and upcycling.”

Major milestone

The Redress Design Award marks its 10th cycle this year. Many of its alumni have gone on to establish more than 40 sustainable brands globally, with some already receiving international recognition.

A new addition to this year’s contest is the Redress All-Star design competition which is open to alumni from past cycles to mark the milestone birthday. Applications for the Redress Design Award 2020 officially opened on January 8.

To celebrate the 10th cycle, a retrospective exhibition is also being held at The Mills until January 19, where visitors can get a close-up look at all the winners’ creations.

(Cleveland Clinic) A new Cleveland Clinic study demonstrates the importance of genetics evaluation and genetic testing for children, adolescents and young adults with solid tumor cancers. The study was published today in Nature Communications.

(Wiley) A recent Psycho-Oncology analysis of published studies found that few cancer survivors received financial information support from healthcare facilities during their initial treatment, even though cancer-related financial toxicity has multiple impacts on survivors' health and quality of life.

(Memorial Sloan Kettering Cancer Center) Scientists at the Sloan Kettering Institute have solved the puzzle of how small chromosomes ensure that they aren't skipped over during meiosis, the process that makes sperm and egg.

(Impact Journals LLC) Oncotarget Volume 11, Issue 12 reported that the p16 tumor suppressor is coded by CDKN2A and plays an important role during carcinogenesis and tumor progression in numerous tumor entities.

(JAMA Network) The considerations and challenges affecting the palliative care specialty and delivery of palliative care in the COVID-19 era, as well as potential solutions, are discussed in this Viewpoint.

(University of Houston) A University of Houston biomedical researcher is developing a new device to treat babies with blood disorders, because current technology is designed for adults. The ability to perform lifesaving leukapheresis safely and effectively in these most vulnerable pediatric patients will significantly increase their access to highly effective cell-based therapies.

(Purdue University) Researchers at Purdue University have discovered that male treefrogs reduce their attractiveness to predators and parasites by overlapping their mating calls with their neighbors.

(Marine Biological Laboratory) Microbial life is bubbling up to the ocean floor along with fluids from deeply buried petroleum reservoirs, reports a team of scientists from the University of Calgary and the Marine Biological Laboratory, Woods Hole.

The presumptive Democratic presidential nominee Joe Biden campaigns virtually in his Delaware home; Fox News correspondent Peter Doocy reports.

SAVANNAH—Gregory and Travis McMichael have been arrested and charged with murder and aggravated assault in connection with the February killing of Ahmaud Arbery, the Georgia Bureau of Investigation announced Thursday. According to police, the white father and son, 64 and 34, chased Arbery, a 25-year-old black man, after he ran by Travis McMichael’s home in the Satilla Shores neighborhood of Brunswick on Feb. 23. He was unarmed and jogging at the time. “This is a start towards victory,” Thea Brooks, Arbery’s aunt, told The Daily Beast on Thursday. “This only the beginning though, but this is what we were all hoping for.”The McMichaels said they believed Arbery was a burglar responsible for a series of break-ins in their neighborhood and that they pursued him in their pickup truck while armed with a shotgun and a .357 magnum. The GBI alleges the McMichaels confronted Arbery, and that Travis shot him. A local prosecutor previously indicated a third man, William Bryan, took part in the chase and filmed the incident.‘It’s Murder’: This Shooting of an Unarmed Black Man Is Roiling GeorgiaAt least two shots hit the 25-year-old, the Glynn County Coroner’s Office told The Daily Beast last week.Video that Brooks said depicted her nephew’s death elicited a furious reaction nationwide, and residents of the area protested the initial failure to prosecute a case on Tuesday.“It’s murder. It’s heartbreaking to even look at. The whole city has seen it,” Brooks told The Daily Beast after the video was released this week.The Georgia NAACP echoed her words in a Thursday response to the McMichaels’ arrest: “The murderers of Ahmaud Arbery have been arrested.”Gregory McMichael, a former cop and investigator with a local prosecutor’s office, previously told The Daily Beast he “never would have gone after someone for their color.” He also said the “closest version of the truth” about the incident was captured in a letter effectively clearing him and his son that was written by a prosecutor who recused himself from the case, George Barnhill. McMichael also admitted he had no direct evidence that Arbery was a thief. “But he’s the guy who’s there without permission,” he said from behind the closed front door of his son’s home.The owner of an unfinished home just down the street from Travis McMichael's home, Larry English, told The Daily Beast earlier this week that he had surveillance footage that appeared to show Arbery stopping to look at the foundation of his still-under-construction home. While Gregory McMichael claimed to police that Arbery had been caught on surveillance video, it was not immediately clear what video he was referring to. English told The Daily Beast he had no knowledge of the McMichaels seeing his surveillance footage. McMichael’s ties to law enforcement helped fuel a haze of suspicion around the killing from the beginning. Barnhill was one of two area prosecutors who looked into the incident before recusing themselves. A third prosecutor—District Attorney Tom Durden—sought a GBI probe ahead of the arrests this week.Read more at The Daily Beast.Got a tip? Send it to The Daily Beast hereGet our top stories in your inbox every day. Sign up now!Daily Beast Membership: Beast Inside goes deeper on the stories that matter to you. Learn more.

(American Geriatrics Society) The American Geriatrics Society (AGS) and the AGS Health in Aging Foundation today conferred one of their newest honors, the Arti Hurria Memorial Award for Emerging Investigators in Internal Medicine Focused on the Care of Older Adults, on two experts: Rasheeda Hall, MD, a board-certified nephrologist and assistant professor of medicine at Duke University; and Kah Poh (Melissa) Loh, MBBCh, BAO, a board-certified internist, hematologist, and oncologist at the University of Rochester Medical Center.

(Kessler Foundation) Andrew Houtenville, Ph.D., research director of the University of New Hampshire's Institute on Disability: 'Unlike the Great Recession and the Great Depression, many workers in the COVID Recession may be 'on temporary layoff' (aka furloughed) and may be recalled, rather than losing their jobs completely. To further investigate this issue, we plan to release a Special nTIDE Report on May 15.'

(American Geriatrics Society) The American Geriatrics Society (AGS) will this year honor past AGS President Todd Semla, PharmD, MS, AGSF, with the prestigious Nascher/Manning Award, given biannually at the AGS Annual Scientific Meeting (#AGS21, to be held next year May 13-15 in Chicago, Ill., following the cancellation of the AGS 2020 Annual Scientific Meeting due to COVID-19).

(University of Tsukuba) Researchers from the University of Tsukuba discovered that fish schools showed a significant change in behavior with varying school sizes. Using integrated information theory, they showed that a significant change in the interaction between the fish and the overall collective behavior occurred between three- and four-fish schools, including the emergence of leadership within the group. These findings help understand the dynamics of collective behavior.

Andrea López
Feb 1, 2012; 25:14-18
From Research to Practice

Norma Van Walleghem
Feb 1, 2011; 24:9-13
From Research to Practice/Transitions in Young Adults with Type 1 Diabetes

Gregory A. Maynard
Oct 1, 2008; 21:241-247
Articles

Korey Capozza
May 1, 2015; 28:83-91
Feature Articles

Chester B. Good
Oct 1, 2002; 15:
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Carol Rees Parrish
Oct 1, 2007; 20:231-234
Nutrition FYI

Daren Anderson
Jan 1, 2007; 20:10-16
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