Hypersecretion of glucagon from pancreatic α-cells strongly contributes to diabetic hyperglycemia. Moreover, failure of α-cells to increase glucagon secretion in response to falling blood glucose concentrations compromises the defense against hypoglycemia, a common complication in diabetes therapy. However, the mechanisms underlying glucose regulation of glucagon secretion are poorly understood and likely involve both α-cell–intrinsic and intraislet paracrine signaling. Among paracrine factors, glucose-stimulated release of the GABA metabolite γ-hydroxybutyric acid (GHB) from pancreatic β-cells might mediate glucose suppression of glucagon release via GHB receptors on α-cells. However, the direct effects of GHB on α-cell signaling and glucagon release have not been investigated. Here, we found that GHB (4–10 μm) lacked effects on the cytoplasmic concentrations of the secretion-regulating messengers Ca2+ and cAMP in mouse α-cells. Glucagon secretion from perifused mouse islets was also unaffected by GHB at both 1 and 7 mm glucose. The GHB receptor agonist 3-chloropropanoic acid and the antagonist NCS-382 had no effects on glucagon secretion and did not affect stimulation of secretion induced by a drop in glucose from 7 to 1 mm. Inhibition of endogenous GHB formation with the GABA transaminase inhibitor vigabatrin also failed to influence glucagon secretion at 1 mm glucose and did not prevent the suppressive effect of 7 mm glucose. In human islets, GHB tended to stimulate glucagon secretion at 1 mm glucose, an effect mimicked by 3-chloropropanoic acid. We conclude that GHB does not mediate the inhibitory effect of glucose on glucagon secretion.

VOLUME 294 (2019) PAGES 2555–2568Due to publisher error, “150 l/mm” was changed to “150 liters/mm” in the second paragraph of the “Vibrational spectroscopy of samples” section under “Experimental Procedures.” The correct phrase should be “150 l/mm.”

In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena.

Lens proteins become increasingly cross-linked through nondisulfide linkages during aging and cataract formation. One mechanism that has been implicated in this cross-linking is glycation through formation of advanced glycation end products (AGEs). Here, we found an age-associated increase in stiffness in human lenses that was directly correlated with levels of protein–cross-linking AGEs. α-Crystallin in the lens binds to other proteins and prevents their denaturation and aggregation through its chaperone-like activity. Using a FRET-based assay, we examined the stability of the αA-crystallin–γD-crystallin complex for up to 12 days and observed that this complex is stable in PBS and upon incubation with human lens–epithelial cell lysate or lens homogenate. Addition of 2 mm ATP to the lysate or homogenate did not decrease the stability of the complex. We also generated complexes of human αA-crystallin or αB-crystallin with alcohol dehydrogenase or citrate synthase by applying thermal stress. Upon glycation under physiological conditions, the chaperone–client complexes underwent greater extents of cross-linking than did uncomplexed protein mixtures. LC-MS/MS analyses revealed that the levels of cross-linking AGEs were significantly higher in the glycated chaperone–client complexes than in glycated but uncomplexed protein mixtures. Mouse lenses subjected to thermal stress followed by glycation lost resilience more extensively than lenses subjected to thermal stress or glycation alone, and this loss was accompanied by higher protein cross-linking and higher cross-linking AGE levels. These results uncover a protein cross-linking mechanism in the lens and suggest that AGE-mediated cross-linking of α-crystallin–client complexes could contribute to lens aging and presbyopia.

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion of autophagy-related 5 (ATG5), results in accumulation of intracellular VEGFA, indicating that VEGFA is a basal autophagic substrate. Mechanistically, decorin increased the VEGFA clearance rate by augmenting autophagic flux, a process that required RAB24 member RAS oncogene family (RAB24), a small GTPase that facilitates the disposal of autophagic compartments. We validated these findings by demonstrating the physiological relevance of this process in vivo. Mice starved for 48 h exhibited a sharp decrease in overall cardiac and aortic VEGFA that could be blocked by systemic chloroquine treatment. Thus, our findings reveal a unified mechanism for the metabolic control of endothelial VEGFA for autophagic clearance in response to decorin and canonical pro-autophagic stimuli. We posit that the VEGFR2/AMPK/PEG3 axis integrates the anti-angiogenic and pro-autophagic bioactivities of decorin as the molecular basis for tumorigenic suppression. These results support future therapeutic use of decorin as a next-generation protein therapy to combat cancer.

(Florida Atlantic University) Despite PPE use, reports show that many health care workers contracted COVID-19. A novel training technique reinforces the importance of using proper procedures to put on and take off PPE when caring for patients during the pandemic. Researchers vividly demonstrate how aerosol-generating procedures can lead to exposure of the contagion with improper PPE use. The most common error made by the health care workers was contaminating the face or forearms during PPE removal.

(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.

Carlos Gustavo T. Moreira, Maria José Pacifico and Sergio Romaña Ibarra
Bull. Amer. Math. Soc. 57 (2018), 269-292.
Abstract, references and article information

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.

After you submit a stored process from the SAS Stored Process Web Application, the generated URL is placed into a cell in a Microsoft Excel worksheet. When you click this URL, you expect that the stored process is sub

(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.

(Moscow Research and Practical Clinical Center for Diagnostics and Telemedicine Technologies) Researchers of the Moscow Diagnostics and Telemedicine Center collected a dataset that includes more than a thousand sets of chest CT scans of patients with imaging finding of COVID-19. As of today, it is the largest completely anonymized database of CT studies, which has no analogues in Russia or in the world. It is available for download and can be used for developing services based on artificial intelligence technologies.

(University of Massachusetts Amherst) As physicians and families know too well, though Alzheimer's disease has been intensely studied for decades, too much is still not known about molecular processes in the brain that cause it. Now researchers at the University of Massachusetts Amherst say new insights from analytic theory and molecular simulation techniques offer a better understanding of amyloid fibril growth and brain pathology.

(U.S. Army Research Laboratory) A US Army-funded project is identifying how officials at different levels of government can work together to encourage protective behaviors to prevent the spread of COVID-19.

(Uppsala University) Artificial intelligence (AI) may be an aid to interpreting ECG results, helping healthcare staff to diagnose diseases that affect the heart. Researchers at Uppsala University and heart specialists in Brazil have developed an AI that automatically diagnoses atrial fibrillation and five other common ECG abnormalities just as well as a cardiologist. The study has been published in Nature Communications.

(University of British Columbia) Mars had a global magnetic field much earlier -- and much later -- than previously known. Analysis of new satellite data found clear evidence of a magnetic field coming from a lava flow that formed less than 3.7 billion years ago, half a billion years after many people thought the Martian dynamo had ceased. The researchers also detected low-intensity magnetic fields over the Borealis Basin, believed to be one of the oldest features on Mars.

(Kazan Federal University) Senior Research Associate Margarita Sharina (Special Astrophysical Observatory) and Associate Professor Vladislav Shimansky (Kazan Federal University) studied the globular cluster NGC 6652.4.05957 and found out that its age is close to 13.6 billion years, which makes it one of the oldest objects in the Milky Way.

(JAMA Network) This randomized clinical trial looked at the effect of a face-aging mobile app on daily sunscreen use and other skin protection among teens in Brazil. Selfies of students were altered to show UV effects on their future faces and shown to their class, accompanied by information about sun protection. Reducing UV exposure in children and adolescents is important because of the increased risk of skin cancer with cumulative UV exposure and sunburns early in life.

(American Chemical Society) Modern society relies on polymers, such as polypropylene or polyethylene plastic, for a wide range of applications, from food containers to automobile parts to medical devices. However, like people, polymers age, and when they do, the materials become prone to cracking or breaking. Now, researchers reporting in ACS Central Science have developed a method to visualize variations in polymers that arise with age.

(Stony Brook University) In evolutionary terms, islands are the stuff of weirdness. It is on islands where animals evolve in isolation, often for millions of years, with different food sources, competitors, predators, and parasites...indeed, different everything compared to mainland species. As a result, they develop into different shapes and sizes and evolve into new species that, given enough time, spawn yet more new species.

(University of Maryland) Many historians have claimed the Justinianic Plague (c. 541-750 CE) killed half of the population of Byzantine (Eastern Roman) Empire. New historical research and mathematical modeling challenge the death rate and severity of this first plague pandemic, named for Emperor Justinian I.

(Perot Museum of Nature and Science) Published in PLOS ONE today, a study by an international team from the Perot Museum of Nature and Science in Dallas and Hokkaido University in Japan further explores the proliferation of the most commonly occurring duck-billed dinosaur of the ancient Arctic as the genus Edmontosaurus. The findings reinforce that the hadrosaurs -- dubbed 'caribou of the Cretaceous' -- had a geographical distribution of approximately 60 degrees of latitude, spanning the North American West from Alaska to Colorado.

(American Society of Agronomy) Researchers develop soil-gas diffusivity model based on two agricultural soils.

(NOAA Headquarters) While the global average number of tropical cyclones each year has not budged from 86 over the last four decades, climate change has been influencing the locations of where these deadly storms occur, according to new NOAA-led research published in Proceedings of the National Academy of Science.

(ETH Zurich) Global warming has affected the entire planet's surface, except for one particular area of the ocean, which has bucked the trend. A research team comprising scientists from ETH Zurich and Princeton University has unravelled the causes of this conundrum.

The streets of Chicago may be largely empty as residents hunker down from coronavirus but some of the city's most deprived neighborhoods are still echoing to the sound of deadly gunfire and raucous partying. While significant falls in crime have been one of the few positive side effects of lockdowns in much of the United States and elsewhere, they have barely made a dent in the homicide rate in Chicago, a city that has long recorded the most murders in the country. Chicago police say 56 murders were committed in April despite statewide stay-at-home orders -- only a fraction lower than the 61 for the same month in 2019 -- while last weekend, the first of the new month, four people were killed and 46 others shot and wounded.

(American Geriatrics Society) The American Geriatrics Society (AGS) annually honors researchers, clinicians, educators, and emerging health professionals who have made outstanding contributions to high-quality, person-centered care for older people. This year's award recipients include more than 20 leaders representing the breadth of disciplines championing care for us all as we age.

(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.

(American Geriatrics Society) The American Geriatrics Society (AGS) and the AGS Health in Aging Foundation today announced that two expert researchers--Kavita Dharmarajan, MD, MSc, an assistant professor in the Department of Radiation Oncology and the Brookdale Department of Geriatrics and Palliative Medicine at the Icahn School of Medicine at Mount Sinai in N.Y.; and Nazema Siddiqui, MD, MHSc, an associate professor of obstetrics and gynecology at Duke University Medical Center in Durham, N.C.--will receive the 2020 Jeffrey H. Silverstein Memorial Award.

(American Geriatrics Society) The American Geriatrics Society (AGS) today announced that John B. Murphy, MD, a clinician, educator, and administrator working to embed geriatrics education in the fabric of medical curricula and clinical operations will be honored with the 2020 Dennis W. Jahnigen Award celebrating work to train health professionals in the care we all need as we age.

(American Geriatrics Society) The American Geriatrics Society (AGS) today named James Lin, DO, MS, MHSA, president of the Lake Erie College of Osteopathic Medicine (LECOM) Institute for Successful Aging in Erie, Pa., its 2020 Clinician of the Year. Lin will be honored at the AGS 2021 Annual Scientific Meeting (#AGS21), May 13-15, 2021, in Chicago, Ill., following the cancellation of the AGS 2020 Annual Scientific Meeting due to COVID-19.

(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 Huddersfield) A team of researchers received funding of almost £130,000 to work with a group of women in Zambia and create songs that warn against the dangers of the coronavirus -- and now New York wants to hear them.

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

Linda J. Piccinino
May 1, 2017; 30:95-100
From Research to Practice

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

Jan Pearson
Apr 1, 2001; 14:
Articles

Carol Rees Parrish
Oct 1, 2007; 20:231-234
Nutrition FYI

Belinda S. O’Connell
Aug 1, 2001; 14:
Articles

Martha Mitchell Funnell
Oct 1, 2007; 20:221-226
Articles

Ruban Dhaliwal
Feb 1, 2014; 27:9-20
Research to Practice

Russell E. Glasgow
Jan 1, 2001; 14:
Articles

Emmy Suhl
Oct 1, 2006; 19:234-240
Articles