6 February 2014 , Volume 70, Number 1

From the point of view of a Saudi policy-maker, the country, the region and the world look to be increasingly complex places

John M. Dietschy
Aug 1, 2004; 45:1375-1397
Thematic Reviews

Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies.

Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity.

28 April 2020

Invitation Only Research Event

Invitation Only Research Event

Expert

Van Wedeen talks about the geometry of the brain's communication pathways.

Researcher: John A. Adam, Old Dominion University. John A. Adam explains the math and physics behind rainbows.

Tropical rainforests are the world's richest land habitats for biodiversity, harbouring stunning numbers of plant and animal species. The Amazon and the Congo basins, together with Asian rainforests, represent only 6 per cent of earth's land surface, and yet more than 50 per cent of global biodiversity can be found under their shade.

While coordinated action is urgently needed, should we be racing to download everything that promises a solution?

Burt Totaro
Trans. Amer. Math. Soc. 373 (2020), 3609-3626.
Abstract, references and article information

Boris Adamczewski, Julien Cassaigne and Marion Le Gonidec
Trans. Amer. Math. Soc. 373 (2020), 3085-3115.
Abstract, references and article information

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The coach and rail journey app has launched a new AI voice app for automated disruption alerts

The UK-based digital identity specialist managed to raise a bumper round during the peak of the COVID-19 pandemic, and is looking at ways to apply its technology to help combat the global crisis

The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function.

β-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate β-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. Liquid chromatography–tandem MS revealed that β-GlcChol and β-GalChol are present throughout development from embryo to adult in the mouse brain. We found that β-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of β-GalChol biosynthesis appeared to be during myelination. We also found that β-GlcChol and β-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form β-GalChol. This is the first report of the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain.

(Institute for Operations Research and the Management Sciences) Job performance has long been understood to be the primary equalizing factor affecting promotions for men and women in the workplace, but research shows, women don't gain as much from the same performance improvements as men do. New research in the INFORMS journal Information Systems Research shows training plays an important part in promotions for women in the field of information technology.

Vladimir Dragović and Irina Goryuchkina
Bull. Amer. Math. Soc. 57 (2020), 293-299.
Abstract, references and article information

Stretching from Sai Kung on the east coast to Tuen Mun in the west, the whopping 100 km-long MacLehose Trail is the longest and first long-distance hiking trail in Hong Kong.

The trail is divided into 10 sections and traverses eight country parks which embrace magnificent natural scenery, interesting historical relics and a wide range of wild fauna and flora, winding past the coastline, rugged mountains, valleys and reservoirs to provide a diverse outdoor experience for hikers.

It was even named as one of the world's 20 dream trails by National Geographic.

A lot of hard work went into building the trail, with Agriculture, Fisheries & Conservation Department workers out in the elements without much shelter, often carrying heavy equipment uphill and downhill over varied terrain.

Building bonds

Wan Keung and Lai Hing joined the department around 40 years ago. They both took part in the MacLehose Trail project which was started in 1979 to promote hiking activities in Hong Kong.

The project was named after the then-Governor Sir Murray MacLehose - who was himself a keen walker - for his significant efforts to conserve Hong Kong’s countryside.

“I have contributed a lot to the trail. I am happy as it is packed with people now,” said Mr Wan.

While Mr Lai added: “We are going to retire, but the trail will be here for a long time.”

Despite working on the same project, the pair - now in their 60s - only met for the first time recently because they were assigned to different work stations back then. However, they became firm friends instantly.

From setting up the many signposts along the way, to hand-building the heavy stone steps, the two men eagerly shared all the skills and techniques they learnt on the project.

Listening to their conversations now it is hard to imagine that when they first started work, both had little practical knowledge about constructing a trail. They acquired welding, plastering and woodwork skills through hands-on experience and with the support of their seniors. But that was not the biggest challenge they encountered.

“Building the trail was really difficult, as there were so many sections. We were either drowned in sweat or drenched by rain while working,” Mr Lai explained.

One poignant memory for Mr Wan was of working during wildfires that raged through the countryside.

“There was only one thing for it: we stayed until the fire was extinguished. That was really hard.”

Lasting legacy

After nine months’ hard work the MacLehose Trail was finally opened on October 26, 1979.

These days Mr Wan and Mr Lai enjoy the trail for leisure instead of work.

Both said receiving compliments from family and friends or witnessing the sheer enjoyment of hikers on the trail made their hard work worthwhile.

They now hope to pass on their skills to the younger workers, so that a new generation of Hong Kong people can take care of the trail and ensure it lasts for decades to come.

The recent economic downturn has dealt a severe blow to many employees. However, for Shiu Yin-ming and Poon Man-kit, the crisis has brought them skill-upgrading opportunities.

Miss Shiu has over 30 years’ experience in the retail industry. Her last job was a salesperson at a lighting store. Struck by the competition with online stores and a series of protests, the shop closed in October last year and left her unemployed.

“I have got no choice. Many people in Hong Kong have mortgage burdens. It is the most worrying part. And it is frightening to see my account balance drop,” she said.

Miss Shiu spent several months trying to get a job but failed.

“Of course I was frustrated. Perhaps the employers think that young people are more hard-working. It is difficult for middle-aged people like me to get a job. It hurt my confidence and I hesitated to keep going."

Seeing the demand in the healthcare industry, Miss Shiu decided to swap careers. She joined the Love Upgrading Special Scheme and enrolled in the Foundation Certificate in Care-related Support Worker Training.

The course covered basic pathology and healthcare skills. It also arranged recruitment from the Hospital Authority in class. Miss Shiu said the special course helped her to find a job and she will soon work at a nursing home.

“It is like an admission ticket. During an interview at a nursing home, the interviewer asked how I would change a nappy for an elderly person. I answered what I had learnt from the course. Moreover, as I have not participated in an interview after so many years of work, the interview skills that I have learnt from the course have geared me up,” she said.

Better prospects

Young newcomers to the job market are also affected by the economic downturn.

Mr Poon has been engaged in casual work in the catering industry. The 19-year-old said there used to be plenty of casual job opportunities on career websites, but that is no longer the case. He has been underemployed in recent months and feels his family just see him as someone who is not in education, employment, or training.

“The full-time waiters have not got much work to do, and each of them is assigned to be responsible for a few positions. So, the restaurant does not need extra casual manpower. My relatives look down on me like I am a neet,” he said.

Mr Poon has enrolled in the Foundation Certificate in Barista Training to gain experience in different positions in the industry.

"Many coffee shops and hotels need people to make latte art. I think the course will help me get a job more easily. I plan to further enroll in other courses relating to pastry-making," he added.

Skills upgrade

The Love Upgrading Special Scheme, launched in last October, provides free training to employees affected by the recent economic downturn to upgrade their skills. The courses are conducted in full-time or part-time mode and offer special allowances.

According to the Employees Retraining Board, as of the end of March, more than 12,200 people have applied for the scheme. About one-third of them are aged between 50 to 59.

The applicants mainly come from the catering, retail, social and personal services industries.

The most popular course is the Foundation Certificate in Care-related Support Worker Training, followed by courses related to baker and pastry cook, barista and security training.

Employees Retraining Board Executive Director Byron Ng said the 66 courses under the scheme were specially selected.

“We want to help those employees in the hard-hit industries like tourism, catering, retail, hotel, construction, etc. Also, we want to provide courses in industries which demand heavy labour during this period, such as healthcare and innovative technology.”

The scheme does not impose any restrictions on the trainees’ industry and educational attainment.

“We hope to encourage all unemployed or underemployed employees, including those who are highly educated, and take these chances to upgrade their own skills so they can re-enter the market smoothly,” Mr Ng said.

He added that those who have completed a full-time vocational skills course will get a follow-up service that includes three months of employment.

The second phase of the scheme will be launched in July, and the monthly maximum allowance is expected to increase from $4,000 to $5,800.