Experiences at every stage of life contribute to cognitive abilities in old age

Early life experiences, such as childhood socioeconomic status and literacy, may have greater influence on the risk of cognitive impairment late in life than such demographic characteristics as race and ethnicity, a large study by researchers with the UC Davis Alzheimer’s Disease Center and the University of Victoria, Canada, has found.”Declining cognitive function in older adults is a major personal and public health concern,” said Bruce Reed professor of neurology and associate director of the UC Davis Alzheimer’s Disease Center.”But not all people lose cognitive function, and understanding the remarkable variability in cognitive trajectories as people age is of critical importance for prevention, treatment and planning to promote successful cognitive aging and minimize problems associated with cognitive decline.”The study, “Life Experiences and Demographic Influences on Cognitive Function in Older Adults,” is published online in Neuropsychology, a journal of the American Psychological Association. It is one of the first comprehensive examinations of the multiple influences of varied demographic factors early in life and their relationship to cognitive aging.The research was conducted in a group of over 300 diverse men and women who spoke either English or Spanish. They were recruited from senior citizen social, recreational and residential centers, as well as churches and health-care settings. At the time of recruitment, all study participants were 60 or older, and had no major psychiatric illnesses or life threatening medical illnesses. Participants were Caucasian, African-American or Hispanic.The extensive testing included multidisciplinary diagnostic evaluations through the UC Davis Alzheimer’s Disease Center in either English or Spanish, which permitted comparisons across a diverse cohort of participants.Consistent with previous research, the study found that non-Latino Caucasians scored 20 to 25 percent higher on tests of semantic memory (general knowledge) and 13 to 15 percent higher on tests of executive functioning compared to the other ethnic groups. However, ethnic differences in executive functioning disappeared and differences in semantic memory were reduced by 20 to 30 percent when group differences in childhood socioeconomic status, adult literacy and extent of physical activity during adulthood were considered.”This study is unusual in that it examines how many different life experiences affect cognitive decline in late life,” said Dan Mungas, professor of neurology and associate director of the UC Davis Alzheimer’s Disease Research Center.”It shows that variables like ethnicity and years of education that influence cognitive test scores in a single evaluation are not associated with rate of cognitive decline, but that specific life experiences like level of reading attainment and intellectually stimulating activities are predictive of the rate of late-life cognitive decline. This suggests that intellectual stimulation throughout the life span can reduce cognitive decline in old age.”Regardless of ethnicity, advanced age and apolipoprotein-E (APOE genotype) were associated with increased cognitive decline over an average of four years that participants were followed. APOE is the largest known genetic risk factor for late-onset Alzheimer’s. Less decline was experienced by persons who reported more engagement in recreational activities in late life and who maintained their levels of activity engagement from middle age to old age. Single-word reading — the ability to decode a word on sight, which often is considered an indication of quality of educational experience — was also associated with less cognitive decline, a finding that was true for both English and Spanish readers, irrespective of their race or ethnicity. …

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Scientists solve the riddle of zebras’ stripes: Those pesky bugs

Why zebras have black and white stripes is a question that has intrigued scientists and spectators for centuries. A research team led by the University of California, Davis, has now examined this riddle systematically. Their answer is published April 1 in the online journal Nature Communications.The scientists found that biting flies, including horseflies and tsetse flies, are the evolutionary driver for zebra’s stripes. Experimental work had previously shown that such flies tend to avoid black-and-white striped surfaces, but many other hypotheses for zebra stripes have been proposed since Alfred Russel Wallace and Charles Darwin debated the problem 120 years ago.These include:A form of camouflage Disrupting predatory attack by visually confusing carnivores A mechanism of heat management Having a social function Avoiding ectoparasite attack, such as from biting flies The team mapped the geographic distributions of the seven different species of zebras, horses and asses, and of their subspecies, noting the thickness, locations, and intensity of their stripes on several parts of their bodies. Their next step was to compare these animals’ geographic ranges with different variables, including woodland areas, ranges of large predators, temperature, and the geographic distribution of glossinid (tsetse flies) and tabanid (horseflies) biting flies. They then examined where the striped animals and these variables overlapped.After analyzing the five hypotheses, the scientists ruled out all but one: avoiding blood-sucking flies.”I was amazed by our results,” said lead author Tim Caro, a UC Davis professor of wildlife biology. “Again and again, there was greater striping on areas of the body in those parts of the world where there was more annoyance from biting flies.”While the distribution of tsetse flies in Africa is well known, the researchers did not have maps of tabanids (horseflies, deer flies). Instead, they mapped locations of the best breeding conditions for tabanids, creating an environmental proxy for their distributions. They found that striping is highly associated with several consecutive months of ideal conditions for tabanid reproduction.Why would zebras evolve to have stripes whereas other hooved mammals did not? The study found that, unlike other African hooved mammals living in the same areas as zebras, zebra hair is shorter than the mouthpart length of biting flies, so zebras may be particularly susceptible to annoyance by biting flies.”No one knew why zebras have such striking coloration,” Caro said. …

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In-hospital formula use deters breastfeeding

When mothers feed their newborns formula in the hospital, they are less likely to fully breastfeed their babies in the second month of life and more likely to quit breastfeeding early, even if they had hoped to breastfeed longer, UC Davis researchers have found.”We are a step closer to showing that giving formula in the hospital can cause problems by reducing how much women breastfeed later,” says Caroline Chantry, lead author and professor of clinical pediatrics at UC Davis Medical Center. “Despite being highly motivated to breastfeed their babies, in-hospital formula use limits this important practice. Given the benefits of breastfeeding for both mother and baby, this is a public health issue.””In-Hospital Formula Use Shortens Breastfeeding Duration” was published online in The Journal of Pediatrics today. The study only included women who intended to exclusively breastfeed their babies for at least a week, meaning they did not plan to use formula in the hospital.While previous studies have examined the relationship between formula use and breastfeeding, some have questioned the results, wondering if mothers using formula were simply less committed to breastfeeding. To examine this objection, the UC Davis team surveyed expectant mothers to determine their intentions toward breastfeeding and then followed them closely after delivery to see how they fared.In the study, 210 babies were exclusively breastfed in the hospital (UC Davis Medical Center), while 183 received at least some formula. Over the next two months, breastfeeding dropped dramatically in the formula group. Between the first and second month, 68 percent of the babies receiving in-hospital formula were not fully breastfed, compared to 37 percent of babies who were exclusively breastfed in the hospital. After two months, 33 percent of the formula babies were not being breastfed at all. By contrast, only 10 percent of the hospital breastfed group had stopped breastfeeding.Perhaps most significant, in-hospital formula feeding dramatically reduced the likelihood of later fully breastfeeding as well as any breastfeeding, even after adjusting for the strength of the mothers’ intention to continue these practices. Early formula use nearly doubled the risk of formula use from the first to the second month and nearly tripled the risk of ending all breastfeeding by the end of the second month.The study also found that breastfeeding deterrence was dose dependent. …

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Water supply availability ‘to dominate U.S. natural resource management’

Water supply is the most pressing environmental issue facing the United States according to a survey of policy makers and scientists revealed in a new publication in BioScience by researchers at the University of York and the University of California, Davis.A question on the water supply necessary to sustain human populations and ecosystem resilience was ranked as having the greatest potential, if it was answered, to increase the effectiveness of policies related to natural resource management in the United States. The publication comes as California suffers its worst drought in nearly half a century.The question emerged from a previous collaboration among decision makers and scientists that yielded 40 research questions that most reflected the needs of those with jurisdiction over natural resources. That research also was published in BioScience.The survey, by Dr Murray Rudd of the Environment Department at York and Dr Erica Fleishman, of the John Muir Institute of the Environment at UC Davis, asked managers, policymakers and their advisers, and scientists to rank the questions on the basis of their applicability to policy.The 602 respondents included 194 policymakers, 70 government scientists, and 228 academic scientists.Other questions that were ranked as of high importance to policy included those on methods for measuring the benefits humans receive from ecosystems; the effects of sea-level rise, storm surge, erosion and variable precipitation on coastal ecosystems and human communities; and the effect on carbon storage and ecosystem resilience of different management strategies for forests, grasslands, and agricultural systems .Dr Rudd said, “We found a significant difference in research priorities between respondents. Importantly, there was no evidence of a simple science-policy divide. Priorities did not differ between academics and government employees or between scientists (academic and government) and policymakers.”Our results suggest that participatory exercises such as this are a robust way of establishing priorities to guide funders of research and researchers who aim to inform policy.”Dr Fleishman added, “The consensus in priorities is even more striking as California’s current drought leads to unprecedented reductions in water supply and delivery.”Story Source:The above story is based on materials provided by University of York. Note: Materials may be edited for content and length.

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Patient embraces personalized approach to lung cancer diagnosis

Sep. 10, 2013 — As a woman in her mid-forties who didn’t smoke, Elizabeth Lacasia never expected to be diagnosed with lung cancer. But in 2006, after she developed a persistent and serious cough, a chest X-ray and CT scan revealed several tumors in her lower left lung.She was eventually diagnosed with stage IV lung cancer, a rare subtype called “bronchioalveolar carcinoma.” Over the next 18 months, she underwent two surgeries followed by a tough combination of a targeted drug treatment and two chemotherapies. Yet the cancer continued to spread. As it turned out, the chemotherapy she was taking was later found to be ineffective against her cancer, although it caused significant side effects.Lacasia, who was an avid rollerblader, a snow skier and had a successful career with a biotech oncology company, was not a woman who gave up easily. She contacted David Gandara, a nationally recognized lung cancer expert and senior advisor for clinical research at the UC Davis Comprehensive Cancer Center.Gandara is known for his emphasis on “personalized treatment” using information available through genetic testing of a patient’s tumor to find the most effective therapies. Lacasia underwent a battery of molecular and genetic tests to help identify whether her cancer would respond to drugs designed to target specific genetic mutations in her cancer. These tests can also reveal which chemotherapies might be most effective in fighting a patient’s tumor.”The genetic testing panel I underwent at UC Davis was very cutting-edge, and it provided important information about how to effectively treat my cancer,” Lacasia now says.In Lacasia’s case, the molecular and genetic tests revealed that her cancer was a “wild type,” meaning it did not have the mutations that can cause some lung cancers to take hold and spread, and which can be effectively targeted by new state-of-the-art medications. So Gandara recommended a clinical trial that used an approach now proven effective for people with Lacasia’s “wild type” cancer.Instead of just one medication, patients like Lacasia in the clinical trial received two drugs, usually considered ineffective when used together. Yet in the clinical trial, Lacasia took the two drugs — erlotinib (Tarceva) and pemetrexed (Alimta) — in a novel alternating schedule that Gandara knew from experience could help treat Lacasia’s cancer. …

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Brain circuitry loss may be an early sign of cognitive decline

Sep. 9, 2013 — The degeneration of a small, wishbone-shaped structure deep inside the brain may provide the earliest clues to future cognitive decline, long before healthy older people exhibit clinical symptoms of memory loss or dementia, a study by researchers with the UC Davis Alzheimer’s Disease Center has found.The longitudinal study found that the only discernible brain differences between normal people who later developed cognitive impairment and those who did not were changes in their fornix, an organ that carries messages to and from the hippocampus, and that has long been known to play a role in memory.”This could be a very early and useful marker for future incipient decline,” said Evan Fletcher, the study’s lead author and a project scientist with the UC Davis Alzheimer’s Disease Center.”Our results suggest that fornix variables are measurable brain factors that precede the earliest clinically relevant deterioration of cognitive function among cognitively normal elderly individuals,” Fletcher said.The research is published online today in JAMA Neurology.Hippocampal atrophy occurs in the later stages of cognitive decline and is one of the most studied changes associated with the Alzheimer’s disease process. However, changes to the fornix and other regions of the brain structurally connected to the hippocampus have not been as closely examined. The study found that degeneration of the fornix in relation to cognition was detectable even earlier than changes in the hippocampus.”Although hippocampal measures have been studied much more deeply in relation to cognitive decline, our direct comparison between fornix and hippocampus measures suggests that fornix properties have a superior ability to identify incipient cognitive decline among healthy individuals,” Fletcher said.The study was conducted over five years in a group of 102 diverse, cognitively normal people with an average age of 73 who were recruited through community outreach at the Alzheimer’s Disease Center. The researchers conducted magnetic resonance imaging (MRI) studies of the participants’ brains that described their volumes and integrity. A different type of MRI was used to determine the integrity of the myelin, the fatty coating that sheaths and protects the axons. The axons are analogous to the copper wiring of the brain’s circuitry and the myelin is like the wiring’s plastic insulation.Either one of those things being lost will “degrade the signal transmission” in the brain, Fletcher said.The researchers also conducted psychological tests and cognitive evaluations of the study participants to gauge their level of cognitive functioning. The participants returned for updated MRIs and cognitive testing at approximately one-year intervals. At the outset, none of the study participants exhibited symptoms of cognitive decline. Over time about 20 percent began to show symptoms that led to diagnoses with either mild cognitive impairment (MCI) and, in a minority of cases, Alzheimer’s disease.”We found that if you looked at various brain factors there was one — and only one — that seemed to be predictive of whether a person would have cognitive decline, and that was the degradation of the fornix,” Fletcher said.The study measured two relevant fornix characteristics predicting future cognitive impairment — low fornix white matter volume and reduced axonal integrity. …

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Clearest new pictures of immune cells

July 23, 2013 — Scientists from The University of Manchester have revealed new images which provide the clearest picture yet of how white blood immune cells attack viral infections and tumours.They show how the cells, which are responsible for fighting infections and cancer in the human body, change the organisation of their surface molecules, when activated by a type of protein found on viral-infected or tumour cells.Professor Daniel Davis, who has been leading the investigation into the immune cells, known as natural killers, said the work could provide important clues for tackling disease.The research reveals the proteins at the surface of immune cells are not evenly spaced but grouped in clusters — a bit like stars bunched together in galaxies.Professor Davis, Director of Research at the Manchester Collaborative Centre for Inflammation Research (MCCIR), a partnership between the University and two pharmaceutical companies GlaxoSmithKline and Astra Zeneca, said: “This is the first time scientists have looked at how these immune cells work at such a high resolution. The surprising thing was that these new pictures revealed that immune cell surfaces alter at this scale — the nano scale — which could perhaps change their ability to be activated in a subsequent encounter with a diseased cell.”We have shown that immune cells are not evenly distributed as once thought, but instead they are grouped in very small clumps — a bit like if you were an astronomer looking at clusters of stars in the Universe and you would notice that they were grouped in clusters. “We studied how these clusters or proteins change when the immune cells are switched on — to kill diseased cells. Looking at our cells in this much detail gives us a greater understanding about how the immune system works and could provide useful clues for developing drugs to target disease in the future.”Until now the limitations of light microscopy have prevented a clear understanding of how immune cells detect other cells as being diseased or healthy.The team used high quality, super-resolution fluorescence microscopy to view the cells in blood samples in their laboratory to create the still images published in the journal Science Signalling this week.

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Gene mutation in dogs offers clues for neural tube defects in humans

July 19, 2013 — A gene related to neural tube defects in dogs has for the first time been identified by researchers at the University of California, Davis, and University of Iowa.The researchers also found evidence that the gene may be an important risk factor for human neural tube defects, which affect more than 300,000 babies born each year around the world, according to the U.S. Centers for Disease Control and Prevention. Neural tube defects, including anencephaly and spina bifida, are caused by the incomplete closure or development of the spine and skull.The new findings appear this week in the journal PLOS Genetics.”The cause of neural tube defects is poorly understood but has long been thought to be associated with genetic, nutritional and environmental factors,” said Noa Safra, lead author on the study and a postdoctoral fellow in the laboratory of Professor Danika Bannasch in the UC Davis School of Veterinary Medicine.She noted that dogs provide an excellent biomedical model because they receive medical care comparable to what humans receive, share in a home environment and develop naturally occurring diseases that are similar to those found in humans. More specifically, several conditions associated with neural-tube defects are known to occur naturally in dogs. All DNA samples used in the study were taken from household pets, rather than laboratory animals, Safra said.She and colleagues carried out genome mapping in four Weimaraner dogs affected by spinal dysraphism, a naturally occurring spinal-cord disorder, and in 96 such dogs that had no neural tube defects. Spinal dysraphism, previously reported in the Weimaraner breed, causes symptoms that include impaired motor coordination or partial paralysis in the legs, abnormal gait, a crouched stance and abnormal leg or paw reflexes.Analysis of a specific region on canine chromosome eight led the researchers to a mutation in a gene called NKX2-8, one of a group of genes known as “homeobox genes,” known to be involved with regulating patterns of anatomical development in the embryo.The researchers determined that the NKX2-8 mutation occurred in the Weimaraner breed with a frequency of 1.4 percent — 14 mutations in every 1,000 dogs.Additionally, they tested nearly 500 other dogs from six different breeds that had been reported to be clinically affected by neural tube defects, but did not find copies of the NKX2-8 gene mutation among the non-Weimaraner dogs.”The data indicate that this mutation does not appear as a benign mutation in some breeds, while causing defects in other breeds,” Safra said. “Our results suggest that the NKX2-8 mutation is a ‘private’ mutation in Weimaraners that is not shared with other breeds.”The researchers say that identification of such a breed-specific gene may help veterinarians diagnose spinal dysraphism in dogs and enable Weimaraner breeders to use DNA screening to select against the mutation when developing their breeding plans.In an effort to investigate a potential role for the NKX2-8 mutation in cases of neural tube defects in people, the researchers also sequenced 149 unrelated samples from human patients with spina bifida. They found six cases in which the patients carried mutations of the NKX2-8 gene but stress that further studies are needed to confirm whether these mutations are responsible for the diagnosed neural tube defects.Collaborating with Safra were Danika Bannasch, Miriam Aguilar, Rochelle L. Coulson, Nicholas Thomas, Peta L. Hitchens, Peter J. …

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Cattle flatulence doesn’t stink with biotechnology: Farmers could improve air quality by using hormones

July 1, 2013 — The agriculture industry is researching new technologies to help feed the growing population. But feeding the world without harming air quality is a challenge.According to a new article in Animal Frontiers, biotechnologies increase food production and reduce harmful gas output from cattle.”We are increasing the amount of product with same input,” said Clayton Neumeier, PhD student at University of California, Davis, in an interview.In the Animal Frontiers paper, Neumeier describes a recent experiment using biotechnologies. In the experiment, a test group of cattle were treated with biotechnologies. Different groups of cattle received implants, Ionophores and Beta-adrenergic agonists. These biotechnologies help cattle grow more efficiently. A control group of cattle were not treated with any of these biotechnologies.Researchers measured gas output by placing finishing steers in a special corral that traps emissions. Each treatment group was tested four times to ensure accurate results.The researchers also tested a dairy biotechnology called rBST. This biotechnology is a synthetic version of a cattle hormone that does not affect humans. Many producers inject cows with rBST to help them produce more milk.In their experiment, the researchers gave rBST to a test group of cows and gave no rBST to a control group of cows. They discovered that the rBST group produced more milk per cow. …

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Comparing genomes of wild and domestic tomato

June 26, 2013 — You say tomato, I say comparative transcriptomics. Researchers in the U.S., Europe and Japan have produced the first comparison of both the DNA sequences and which genes are active, or being transcribed, between the domestic tomato and its wild cousins.The results give insight into the genetic changes involved in domestication and may help with future efforts to breed new traits into tomato or other crops, said Julin Maloof, professor of plant biology in the College of Biological Sciences at the University of California, Davis. Maloof is senior author on the study, published June 24 in the journal Proceedings of the National Academy of Sciences.For example, breeding new traits into tomatoes often involves crossing them with wild relatives. The new study shows that a large block of genes from one species of wild tomato is present in domestic tomato, and has widespread, unexpected effects across the whole genome.Maloof and colleagues studied the domestic tomato, Solanum lycopersicum, and wild relatives S. pennellii, S. habrochaites and S. pimpinellifolium. Comparison of the plants’ genomes shows the effects of evolutionary bottlenecks, Maloof noted — for example at the original domestication in South America, and later when tomatoes were brought to Europe for cultivation.Among other findings, genes associated with fruit color showed rapid evolution among domesticated, red-fruited tomatoes and green-fruited wild relatives. And S. pennellii, which lives in desert habitats, had accelerated evolution in genes related to drought tolerance, heat and salinity.New technology is giving biologists the unprecedented ability to look at all the genes in an organism, not just a select handful. …

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Cellular basis for how anti-aging cosmetics work identified

Aug. 13, 2012 — A team of investigators from UC Davis and Peking University have discovered a mechanism that may explain how alpha hydroxyl acids (AHAs) ― the key ingredient in cosmetic chemical peels and wrinkle-reducing creams ― work to enhance skin appearance. An understanding of the underlying process may lead to better cosmetic formulations as well as have medical applications.

The findings were published in the Journal of Biological Chemistry in an article entitled “Intracellular proton-mediated activation of TRPV3 channels accounts for exfoliation effect of alpha hydroxyl acids on keratinocytes.”

AHAs are a group of weak acids typically derived from natural sources such as sugar cane, sour milk, apples and citrus that are well known in the cosmetics industry for their ability to enhance the appearance and texture of skin. Before this research, little was known about how AHAs actually caused skin to flake off and expose fresh, underlying skin.

The cellular pathway the research team studied focuses on an ion channel ― known as transient receptor potential vanilloid 3 (TRPV3) ― located in the cell membrane of keratinocytes, the predominant cell type in the outer layer of skin. The channel is known from other studies to play an important role in normal skin physiology and temperature sensitivity.

In a series of experiments that involved recording electrical currents across cultured cells exposed to AHAs, the investigators developed a model that describes how glycolic acid (the smallest and most biologically available AHA) enters into keratinocytes and generates free protons, creating acidic conditions within the cell. The low pH strongly activates the TRPV3 ion channel, opening it and allowing calcium ions to flow into the cell. Because more protons also enter through the open TRPV3 channel, the process feeds on itself. The resulting calcium ion overload in the cell leads to its death and skin exfoliation.

“Our experiments are the first to show that the TRPV3 ion channel is likely to be the target of the most effective skin enhancer in the cosmetics industry,” said Jie Zheng, professor of physiology and membrane biology at UC Davis and one of the principal investigators of the study. “Although AHAs have been used for years, no one until now understood their likely mechanism of action.”

Besides being found in skin cells, TRPV3 also is found in cells in many areas of the nervous system and is sensitive to temperature as well as acidity. The authors speculate that the channel may have a variety of important physiological functions, including pain control.

Lead author Xu Cao, who conducted the study with UC Davis scientists as a visiting student from Peking University Health Science Center, focuses on TRPV3 channel research. With a team of researchers in China, he recently contributed to the discovery that a mutation in TRPV3 leads to Olmsted syndrome, a rare congenital disorder characterized by severe itching and horny skin development over the palms of the hands and soles of the feet. While in the UC Davis Department of Physiology and Membrane Biology, Cao discovered that AHAs also utilize the TRPV3 channel.

“Calcium channels are becoming increasingly recognized as having vital functions in skin physiology,” said Cao. “TRPV3 has the potential to become an important target not only for the cosmetics industry but for analgesia and treating skin disease.”

The other study author and co-principal investigator is KeWei Wang of Peking University School of Pharmaceutical Sciences, where the research was conducted.

The research was funded with grants to KeWei Wang from the National Science Foundation of China and the Ministry of Education in China, the China Scholarship Council, and to Zheng from the National Institutes of Health.

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