First ever UK based language tool to decode baby talk

A tool which could radically improve the diagnosis of language delays in infants in the UK is being developed by psychologists.

A £358,000 grant to develop the first standardised UK speech and language development tool means that for the first time, researchers will be able to establish language development norms for UK children aged eight months to 18 months.

The tool will plug an important gap which has left UK researchers, education and health professionals at a disadvantage.

Until now, UK language experts have been forced to rely upon more complicated methods of testing child language development, or on methods designed for American English speakers which can lead to UK babies being misdiagnosed as being delayed in language development.

The two-and-a-half year project funded by the ESRC will also look into the impact of family income and education on UK children’s language development, as well as examining differences between children learning UK English, and other languages and English dialects.

The project is expected to make a major contribution to language development research as well as to the effectiveness of speech and language therapy and improved policy making.

Research helps explain early-onset puberty in females

New research from Oregon Health & Science University has provided significant insight into the reasons why early-onset puberty occurs in females. The research, which was conducted at OHSU’s Oregon National Primate Research Center, is published in the current early online edition of the journal Nature Neuroscience.

The paper explains how OHSU scientists are investigating the role of epigenetics in the control of puberty. Epigenetics refers to changes in gene activity linked to external factors that do not involve changes to the genetic code itself. The OHSU scientists believe improved understanding of these complex protein/gene interactions will lead to greater understanding of both early-onset (precocious) puberty and delayed puberty, and highlight new therapy avenues.

To conduct this research, scientists studied female rats, which like their human counterparts, go through puberty as part of their early aging process. These studies revealed that a group of proteins, called PcG proteins, regulate the activity of a gene called the Kiss1 gene, which is required for puberty to occur. When these PcG proteins diminish, Kiss1 is activated and puberty begins.

PcG proteins are produced by another set of genes that act as a biological switch during the embryonic stage of life. The role of these proteins is to turn off specific downstream genes at key developmental stages.

OHSU scientists found that both the activity of these “master” genes and their ability to turn off puberty are impacted by two forms of epigenetic control: a chemical modification of DNA known as DNA methylation, and changes in the composition of histones, a specialized set of proteins that modify gene activity by interacting with DNA.

Using this new information, researchers were then able to delay puberty in female rats. They accomplished this by increasing PcG protein levels in the hypothalamus of the brain using a targeted gene therapy approach so that Kiss1 activation failed to occur at the normal time in life. The hypothalamus is a region of the brain that controls reproductive development.

"While it was always understood that an organism’s genes determine the timing of puberty, the role of epigenetics in this process has never been recorded until now," said Alejandro Lomniczi, Ph.D., a scientist in the Division of Neuroscience at the OHSU Oregon National Primate Research Center.

"Because epigenetic changes are driven by environmental, metabolic and cell-to-cell influences, these findings raise the possibility that a significant percentage of precocious and delayed puberty cases occurring in humans may be the result of environmental factors and other alterations in epigenetic control," said Sergio Ojeda, D.V.M, who is also a scientist in the Division of Neuroscience at the OHSU ONPRC.

"There is also much more to be learned about the way that epigenetic factors may link environmental factors such as nutrition, man-made chemicals, social interactions and other day-today influences to the timing and completion of normal puberty."

Researcher Advancing Motor Neuron Studies

Supported by the commitment of the University of Connecticut and the state to stem cell research, a UConn Health Center researcher is advancing the understanding of the devastating inherited condition known as spinal muscular atrophy.

Xue-Jun Li, assistant professor in the Department of Neuroscience, is corresponding author of a paper published in the prestigious journal Cell Research in December 2012 entitled “Recapitulation of spinal motor neuron-specific disease phenotypes in a human cell model of spinal muscular atrophy.” The paper’s other authors are UConn Health Center researcher Zhi-Bo Wang and Xiaoqing Zhang of the Tongji University School of Medicine in Shanghai.

Spinal muscular atrophy (SMA) is a group of inherited diseases that cause muscle damage and debilitation, which progress over time and eventually lead to death. To be affected, a person must inherit the defective gene from both parents. About 1 in 10,000 people have SMA, and most do not survive childhood due to respiratory problems, heart failure and infections.

“There is no effective treatment for spinal muscular atrophy, and one of the roadblocks is not knowing why the spinal motor neuron degenerates,” Li explains. “One of the aspects of our research is to understand how specific types of neurons are specified and degenerated. We are trying to model neurological disorders by using human motor neurons derived from stem cells.”

Establishing human cell models of SMA to mimic motor neuron-specific phenotypes holds the key to understanding this destructive disease, she says. The model described in the journal article provides a unique paradigm for studying how motor neurons degenerate. It also highlights the potential importance of antioxidants for the treatment of SMA.

Understanding how motor neurons are specifically degenerated can lead to effective interventions in the future. “It can help us find some way to rescue the motor neuron degeneration in this disease,” Li points out. “Understanding the role of antioxidants can provide potential clues to finding a treatment.”

A step towards repairing the central nervous system

Despite recent advances in understanding the mechanisms of nerve injury, tissue-engineering solutions for repairing damage in the central nervous system (CNS) remain elusive, owing to the crucial and complex role played by the neural stem cell (NSC) niche. This zone, in which stem cells are retained after embryonic development for the production of new cells, exerts a tight control over many crucial tasks such as growth promotion and the recreation of essential biochemical and physical cues for neural cell differentiation.

According to the first author of the paper, Zaida Álvarez, from the Group on Biomaterials for Regenerative Therapies of the Institute for Bioengineering of Catalonia (IBEC), “in order to develop tissue-engineering strategies to repair damage to the CNS, it is essential to design biomaterials that closely mimic the NSC niche and its physical and biochemical characteristics”.

In the study headed by Soledad Alcántara of the Department of Pathology and Experimental Therapeutics, the team tested types of polylactic acid (PLA) with different proportions of isomers L and D/L, a biodegradable material allowing neural cell adhesion and growth, as materials for nerve regeneration. They found that one type, PLA with a proportion of isomers of 70/30, maintained the important pools of neuronal and glial progenitor cells in vitro. PLA 70/30 was more amorphous, degraded faster and, crucially, released significant amounts of L-lactate, which is essential for the maintenance and differentiation of neural progenitor cells. “The aim of the research was to find a biomaterial able to sustain the population of neural stem cells and to generate new differentiated cells in order to start the development of an implant that allows brain regeneration,” explains Dr Alcántara.

“The mechanical and surface properties of PLA70/30, which we used here in the form of microthin films, make it a good substrate for neural cell adhesion, proliferation and differentiation,” adds Álvarez. “The physical properties of this material and the release of L-lactate when it degrades, which provides an alternative oxidative substrate for neural cells, act synergistically to modulate progenitor phenotypes”, concludes the researcher.

The results suggest that the introduction of 3D patterns mimicking the architecture of the embryonic NSC niches on PLA70/30-based scaffolds may be a good starting point for the design of brain-implantable devices. “These will be able to induce or activate existing neural progenitor cells to self-renew and produce new neurons, boosting the CNS regenerative response in situ,” states Álvarez.

Enabling the CNS to regenerate could open doors to promising new strategies to tackle accidental damage as well as numerous diseases like stroke and degenerative disorders such as Parkinson’s and Alzheimer’s diseases.

A better way to culture central nervous cells

A protein associated with neuron damage in people with Alzheimer’s disease is surprisingly useful in promoting neuron growth in the lab, according to a new study by engineering researchers at Brown University. The findings, in press at the journal Biomaterials, suggest a better method of growing neurons outside the body that might then be implanted to treat people with neurodegenerative diseases.

The research compared the effects of two proteins that can be used as an artificial scaffold for growing neurons (nerve cells) from the central nervous system. The study found that central nervous system neurons from rats cultured in apolipoprotein E-4 (apoE4) grew better than neurons cultured in laminin, which had been considered the gold standard for growing mammalian neurons in the lab.

“Most scientists assumed that laminin was the best protein for growing CNS (central nervous system),” said Kwang-Min Kim, a biomedical engineering graduate student at Brown University and lead author of the study, “but we demonstrated that apoE4 has substantially better performance for mammalian CNS neurons.”

Kim performed the research under the direction of Tayhas Palmore, professor of engineering and medical science and Kim’s Ph.D. adviser. Also involved in the project was Janice Vicenty, an undergraduate from the University of Puerto Rico, who was working in the Palmore lab as a summer research fellow through the Leadership Alliance.

The results are surprising partly because of the association of apoE4 with Alzheimer’s. Apolipoproteins are responsible for distributing and depositing cholesterols and other lipids in the brain. They come in three varieties: apoE2, apoE3 and apoE4. People with the gene that produces apoE4 are at higher risk for amyloid plaques and neurofibrillary tangles, the hallmarks of Alzheimer’s. But exactly how the protein itself contributes to Alzheimer’s is not known.

This study suggests that outside the body, where the protein can be separated from the cholesterols it normally carries, apoE4 is actually beneficial in promoting neuron growth.

In-brain monitoring shows memory network

Working with patients with electrodes implanted in their brains, researchers at the University of California, Davis, and The University of Texas Health Science Center at Houston (UTHealth) have shown for the first time that areas of the brain work together at the same time to recall memories. The unique approach promises new insights into how we remember details of time and place.

"Previous work has focused on one region of the brain at a time," said Arne Ekstrom, assistant professor at the UC Davis Center for Neuroscience. "Our results show that memory recall involves simultaneous activity across brain regions." Ekstrom is senior author of a paper describing the work published Jan. 27 in the journal Nature Neuroscience.

Ekstrom and UC Davis graduate student Andrew Watrous worked with patients being treated for a severe seizure condition by neurosurgeon Dr. Nitin Tandon and his UTHealth colleagues.

To pinpoint the origin of the seizures in these patients, Tandon and his team place electrodes on the patient’s brain inside the skull. The electrodes remain in place for one to two weeks for monitoring.

Six such patients volunteered for Ekstrom and Watrous’ study while the electrodes were in place. Using a laptop computer, the patients learned to navigate a route through a virtual streetscape, picking up passengers and taking them to specific places. Later, they were asked to recall the routes from memory.

Correct memory recall was associated with increased activity across multiple connected brain regions at the same time, Ekstrom said, rather than activity in one region followed by another.

However, the analysis did show that the medial temporal lobe is an important hub of the memory network, confirming earlier studies, he said.

Intriguingly, memories of time and of place were associated with different frequencies of brain activity across the network. For example, recalling, “What shop is next to the donut shop?” set off a different frequency of activity from recalling “Where was I at 11 a.m.?”

Using different frequencies could explain how the brain codes and recalls elements of past events such as time and location at the same time, Ekstrom said.

"Just as cell phones and wireless devices work at different radio frequencies for different information, the brain resonates at different frequencies for spatial and temporal information," he said.

The researchers hope to explore further how the brain codes information in future work.

The neuroscientists analyzed their results with graph theory, a new technique that is being used for studying networks, ranging from social media connections to airline schedules.

"Previously, we didn’t have enough data from different brain regions to use graph theory. This combination of multiple readings during memory retrieval and graph theory is unique," Ekstrom said.

Placing electrodes inside the skull provides clearer resolution of electrical signals than external electrodes, making the data invaluable for the study of cognitive functions, Tandon said. “This work has yielded important insights into the normal mechanisms underpinning recall, and provides us with a framework for the study of memory dysfunction in the future.”

Previously unknown sleep pattern revealed in University of Sydney research

There’s no need to panic if you didn’t get a solid eight hours of beauty sleep last night. According to new University of Sydney research, sleep duration naturally waxes and wanes over a period of days regardless of individual lifestyle, timing of sleep or waking, and social and environmental influences.

With further research, the discovery could have important implications for predicting work performance, managing fatigue-related accidents after shift work, and treatment recovery in clinical populations.

"Sleep requirements vary in a cyclical fashion and between individuals. If you incur a sleep debt, your body will signal a need to catch up on extra sleep," says Dr Chin Moi Chow, principal investigator of the article published in Nature and Science of Sleep.

"As you increase your sleep duration to recover from the debt, your ability to prolong wakefulness increases. Then, as prior wakefulness increases, sleepiness is inevitable, and a need for further sleep develops again."

Dr Chow and colleagues Shi Wong and Dr Mark Halaki, from the University’s Faculty of Health Sciences, monitored a group of healthy young males over a fortnight using an actigraph - a small activity recording device worn like a wristwatch on the non-dominant arm - designed to measure sleep patterns.

To the researchers’ fascination, the actigraph data showed participants’ sleep duration oscillated in a sine wave pattern - a phenomenon that had not previously been observed. Clear periodic patterns were found in the majority of the participants, varying from periods of between two and 18 days.

The cyclic pattern observed in the research suggests that the sleep balance mechanism operates on an ongoing basis in daily life, with changes in sleep duration constantly accompanied by compensatory adjustments.

Interestingly, despite the fact that participants in the study habitually slept below the recommended seven to eight hours a night, they still maintained a cyclic sleep duration pattern.

"Our sleep quantity and quality vary according to a range of factors," Dr Chow says. "Some individuals have a slower accumulation or faster dissipation of sleep pressure, which may define their pattern of total sleep time."

Variations in daily sleep duration may also arise from differences such as slight variations in the body clock or external factors like temperature, daylight, exercise, or eating and drinking patterns.

"Changing your sleep patterns on weekends, or resetting the pattern through shift work, could alter your sleep duration cycle and could put the body under significant strain," says Dr Chow.

This research is part of Dr Chow’s broader interest in the lifestyle factors influencing sleep. The team hopes to follow the research by examining the cyclical phenomenon in special groups such as long or short sleepers and people with insomnia.

Research Institute Study Shows How Brain Cells Shape Temperature Preferences

While the wooly musk ox may like it cold, fruit flies definitely do not. They like it hot, or at least warm. In fact, their preferred optimum temperature is very similar to that of humans—76 degrees F.

Scientists have known that a type of brain cell circuit helps regulate a variety of innate and learned behavior in animals, including their temperature preferences. What has been a mystery is whether or not this behavior stems from a specific set of neurons (brain cells) or overlapping sets.

Now, a new study from The Scripps Research Institute (TSRI) shows that a complex set of overlapping neuronal circuits work in concert to drive temperature preferences in the fruit fly Drosophila by affecting a single target, a heavy bundle of neurons within the fly brain known as the mushroom body. These nerve bundles, which get their name from their bulbous shape, play critical roles in learning and memory.

The study, published in the January 30, 2013 edition of the Journal of Neuroscience, shows that dopaminergic circuits—brain cells that synthesize dopamine, a common neurotransmitter—within the mushroom body do not encode a single signal, but rather perform a more complex computation of environmental conditions.

“We found that dopamine neurons process multiple inputs to generate multiple outputs—the same set of nerves process sensory information and reward-avoidance learning,” said TSRI Assistant Professor Seth Tomchik. “This discovery helps lay the groundwork to better understand how information is processed in the brain. A similar set of neurons is involved in behavior preferences in humans—from basic rewards to more complex learning and memory.”

Using imaging techniques that allow scientists to visualize neuron activity in real time, the study illuminated the response of dopaminergic neurons to changes in temperature. The behavioral roles were then examined by silencing various subsets of these neurons. Flies were tested using a temperature gradient plate; the flies moved from one place to another to express their temperature preferences.

As it turns out, genetic silencing of dopaminergic neurons innervating the mushroom body substantially reduces cold avoidance behavior. “If you give the fly a choice, it will pick San Diego weather every time,” Tomchik said, “but if you shut down those nerves, they suddenly don’t mind being in Minnesota.”

The study also showed dopaminergic neurons respond to cooling with sudden a burst of activity at the onset of a drop in temperature, before settling down to a lower steady-state level. This initial burst of dopamine could function to increase neuronal plasticity—the ability to adapt—during periods of environmental change when the organism needs to acquire new associative memories or update previous associations with temperature changes.

(Image: ALAMY)

Scientists build the One Million Dollar man

Discovering the Missing “LINC” to Deafness

Because half of all instances of hearing loss are linked to genetic mutations, advanced gene research is an invaluable tool for uncovering causes of deafness — and one of the biggest hopes for the development of new therapies. Now Prof. Karen Avraham of the Sackler Faculty of Medicine at Tel Aviv University has discovered a significant mutation in a LINC family protein — part of the cells of the inner ear — that could lead to new treatments for hearing disorders.

Her team of researchers, including Dr. Henning Horn and Profs. Colin Stewart and Brian Burke of the Institute of Medical Biology at A*STAR in Singapore, discovered that the mutation causes chaos in a cell’s anatomy. The cell nucleus, which contains our entire DNA, moves to the top of the cell rather than being anchored to the bottom, its normal place. Though this has little impact on the functioning of most of the body’s cells, it’s devastating for the cells responsible for hearing, explains Prof. Avraham. “The position of the nucleus is important for receiving the electrical signals that determine proper hearing,” she explains. “Without the ability to receive these signals correctly, the entire cascade of hearing fails.”

This discovery, recently reported in the Journal of Clinical Investigation, may be a starting point for the development of new therapies. In the meantime, the research could lead towards work on a drug that is able to mimic the mutated protein’s anchoring function, and restore hearing in some cases, she suggests.