Clinical Research Organisation Chennai
We’re usually told that the left side of the brain controls the right side of the body, and vice versa, but new research shows there’s a lot more to it than that.
For decades, scientists have been finding evidence in both animals and humans to suggest that it’s not just the contralateral (opposing side) brain hemisphere that plays a role in body movement, but also the ipsilateral (same side) hemisphere.
As it stands, though, the extent to which the ipsilateral brain hemisphere helps regulate movement in limbs and digits on the same, shared side of the body has never been well understood. Now researchers have broken new ground in identifying the relationship between cortical activity and ipsilateral movement.
For the first time, researchers at Washington University in St. Louis have demonstrated that 3D arm movement kinematics – encompassing limb speed, velocity, and position – can be decoded from human electrocorticographic (ECoG) signals ipsilateral to the moving limb.
“These results clarify our understanding that the ipsilateral hemisphere robustly contributes to motor execution and supports that the information of complex movements is more bihemispherically represented in humans than has been previously understood,” the authors write in their paper.
Before now, evidence of movement kinematics decoded from the ipsilateral hemisphere was relatively limited.
To go deeper, lead researcher and neuroscientists Eric C. Leuthardt recruited four epilepsy patients (three male, one female) undergoing a separate ECoG procedure to pinpoint the source of their condition.
With their brains implanted with ECoG electrodes – which could register their neural activity in both the left and right hemispheres of the brain – Leuthardt wanted to measure both contralateral and ipsilateral activity as the participants moved their arms around in a three-dimensional reaching exercise.
Using a machine learning algorithm to decode the neural signals, the researchers found that movement kinematics are distributed bilaterally across cortical hemispheres, with evidence of ipsilateral arm reaches being decoded with comparable accuracy to contralateral reaches.
The researchers say this doesn’t necessarily mean that the ipsilateral hemisphere is the dominant cause of physical movement in limbs closest to it, but the fact that so much information is parsed by the ipsilateral hemisphere is in itself significant.
“While the ability to decode ipsilateral limb kinematics does not establish a causal role of the ipsilateral hemisphere for movement execution, a representation of specific movement features, such as kinematics, is a necessary condition for the ipsilateral hemisphere to play a causal role in movement execution,” the authors explain.
“This is the first study to show that specific kinematics of arm movements are bihemispherically represented on a time-point by time-point basis.”
Obviously, we need to keep our expectations in check, because the current study involved only four patients (with intractable epilepsy), and there’s a lot more research to be done before we understand what exactly is going on here between both sides of the brain (and body).
But the researchers say their findings provide an important advancement that could one day point to new potential treatments for stroke patients, whose condition may affect one side of their brain, but not the other.
“The ability to use ECoG to decode kinematics of the same-sided hand also underscores the possibility for a stroke survivor to use signals from their unaffected hemisphere to control a brain-computer interface (BCI),” the researchers explain.
Beyond that, it’s possible that given both hemispheres of the brain appear to register the same cortical representation of movement kinematic information, one days these findings might help patients re-learn to control their bodies as a part of an ipsilateral-based rehabilitation treatment.
It’s early days, but it’s exciting stuff to learn that could benefit thousands of people in the future.
“Collectively, this study demonstrates that 3D kinematics of ipsilateral arm movements are encoded in human ECoG signals,” the researchers write.
“These results strengthen evidence that the ipsilateral hemisphere plays a role in planning and executing voluntary motor movements with important implications for neuroprosthetic and neuro-rehabilitation applications.”
The findings are reported in JNeurosci.
The ministry of health has decided to revise regulations pertaining to manufacturing practices under Schedule M of the Drugs and Cosmetics Rules of 1945 to make them on par with the World Health Organisation good manufacturing practice (WHO-GMP) standards.
A draft proposal to amend the D&C Rules to modify the schedule has come close on the heels of an interest subvention scheme announced by the government to facilitate small pharmaceutical companies upgrade their technology and infrastructure to meet WHO-GMP norms.
According to industry sources, the proposed Schedule M revision has come as no surprise as the government is getting ready to implement uniform standards for drug manufacturing industry ahead of joining the Pharmaceutical Inspection Cooperation Scheme (PICS), a global mechanism to improve cooperation in GMPs between regulators.
At present, while majority of small and medium manufacturers in India comply with Schedule M, only around 20 per cent of the firms meet WHO GMP norms, leading to dual standards of quality.
“The process to join PICS would take at least five years, but it will promote our drug exports by offering greater market access. Most countries only accept import and sale of medicines that have been manufactured to internationally recognised GMP. The move to revise Schedule M is adopted in order to fulfil this objective,” a CDSCO official said.
The draft document, reviewed by Pharmabiz, details various requirements of premises, plant and equipment for manufacturing pharmaceutical products. GMP will be applicable to life-cycle stages from the manufacture of investigational medicinal products, technology transfer and commercial manufacturing, to product discontinuation. The quality system can extend to the drug development stage and shall facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activity.
The revised norms underscore provisions for regular quality checks, procedure for self-inspection and periodic management reviews. In accordance with GMP, each company should identify what validation work is required to prove that its critical operational aspects are controlled. The key elements of validation must be defined and documented in a master plan. There should also be a system in place to recall defective products from the market.
According to the notification, the proposed changes in rules won’t apply to presently licensed manufacturers until October 31, 2020. The firms are expected to evolve methodology, systems and procedures to implement these changes that should be documented and maintained for inspection and reference. The draft proposal is open for comments and suggestions from industry stakeholders till November 5.
The paper, written by two University of Alberta researchers and the co-founder of a New York pharmaceutical company, was controversial because, as various experts told the magazine Science, someone could use a very similar process to bring back a related virus: smallpox.
Smallpox, you’ll recall, killed hundreds of millions of people before the World Health Organization declared it eradicated in 1980. That was the result of a long vaccination campaign – so the idea of piecing the virus back together from bits of DNA raises the specter of a horrifying pandemic.
Two journals rejected the paper before PLOS One, an open access peer-reviewed journal, published it.
Critics argue that the paper not only demonstrates that you can synthesize a deadly pathogen for what Science reported was about US$100,000 in lab expenses, but even provides a slightly-too-detailed-for-comfort overview of how to do it.
Some of the horsepox scientists’ coworkers are still pretty upset about this. PLOS One’s sister Journal, PLOS Pathogens, just published three opinion pieces about the whole flap, as well as a rebuttal by the Canadian professors.
Overall, everyone’s pretty polite. But you get the sense that microbiologists are really, really worried about someone reviving smallpox.
MIT biochemist Kevin Esvelt, for instance, wrote on Thursday that the threat is so grim that we shouldn’t even talk about it:
At present, we decidedly err on the side of spreading all information.
Despite entirely predictable advances in DNA assembly, every human with an internet connection can access the genetic blueprints of viruses that might kill millions.
These and worse hazards are conveniently summarized by certain Wikipedia articles, which helpfully cite technical literature relevant to misuse.
Note the deliberate absence of citations in the above paragraph. Citing or linking to already public information hazards may seem nearly harmless, but each instance contributes to a tragedy of the commons in which truly dangerous technical details become readily accessible to everyone.
Given that it takes just one well-meaning scientist to irretrievably release a technological information hazard from the metaphorical bottle, it may be wise to begin encouraging norms of caution among authors, peer reviewers, editors, and journalists.
Then, in a Q&A with an MIT blogger, also published Thursday, Esvelt blamed interest in smallpox synthesis on people who talk to the media as well:
DNA synthesis is becoming accessible to a wide variety of people, and the instructions for doing nasty things are freely available online.
In the horsepox study, for instance, the information hazard is partly in the paper and the methods they described.
But it’s also in the media covering it and highlighting that something bad can be done. And this is worsened by the people who are alarmed, because we talk to journalists about the potential harm, and that just feeds into it.
The Canadian professors – though not their colleague from the pharmaceutical company, interestingly – fired back by arguing that, well, it was gonna happen anyway:
Realistically all attempts to oppose technological advances have failed over centuries.
We suggest that one should instead focus on regulating the products of these technologies while educating people of the need to plan mitigating strategies based upon a sound understanding of the risks that such work might pose.
In these discussions, a long-term perspective is essential.
It’s grim to envision engineered smallpox infecting and killing humans, the way its naturally-evolved predecessor did. Perhaps some subjects aren’t worth studying, after all.
GE Healthcare is on an aggressive mode to step up its future growth in India with strategic investments for development of imaging technology, artificial intelligence (AI) embedded diagnostics and related therapies. It will capitalise on the talent capability and infrastructure for research and manufacture of medical technologies in the country. It is now working towards operating as a standalone company outside GE Group.
Of the 145 countries where GE is having operations, India is ranked among the top five markets. “Our future investments will be in the digital technology space focusing on AI and machine learning. This is a business of scale. We are looking to drive down cost and improve patient outcomes,” said Kieran Murphy, president, and CEO, GE Healthcare.
The US$ 20 billion company with a workforce of 50,000 has built its growth both through organic and inorganic routes. “India is key for our future growth prospects and we are looking at high productivity and faster time-to-market. The slew of public private partnerships (PPPs) with 200 installations of CT and MRIs across 20 states sees us position ourselves in precision diagnostics and monitoring. This would enable preventive healthcare that will save medical expenses,” stated Murphy who is in India for the two-day pulse: GE Healthcare Media event.
“We will combine expertise and leadership to serve the needs of healthcare providers, bio-pharma and medical tech companies. We are looking at developing smarter machines to enable data integration. The future of healthcare is a network of collaborations,” he added.
GE has now inked a pact with Society for Applied Microwave Electronics Engineering and Research (SAMEER), the R&D unit under Department of Electronics and Information Technology (DeitY), for the development of an Indigenous 1.5T MRI system. The two companies will also collaborate to develop AI and machine learning based solutions.
“We have the know-how and our MRI technology is one of the most advanced and complex form of medical imaging. The SAMEER partnership is in sync with the Union government’s ‘Make in India’ initiative and will support Ayushman Bharat to access our affordable MRI technology,” said GE Healthcare chief.
India has taken a lead in technology adoption and the Ayushman Bharat is expected to provide the much-needed non-contributory financial access to Indians compared to the US government’s Medicare, he noted.
According to Nalinikanth Gollagunta, president and CEO, GE Healthcare South Asia, Indian healthcare has an infrastructure matching the western world with 38 JCI accredited hospitals and 544 NABH certified facilities. The cost of treatment is at one-tenth versus that of the US. The price points of our healthcare and the success rate of outcomes have been recognised globally.
“There is frugal innovation by entrepreneurs which enabled create India’s technology infrastructure. We will now increase our focus on precision engineering, cloud computing and artificial intelligence to overcome challenges in healthcare. The investments will be towards localisation and digitization,” added Gollagunta.
GE Healthcare partnered with the Healthcare Sector Skills Council (HSSC) and has so far trained 2,500 students to ensure easy availability of skilled personnel. By 2019, it will train 5,000 community health workers and 3,000 underprivileged young people of which a large chunk will be women workforce entering the healthcare mainstream operating GE Healthcare medical equipment, said Marut Setia head, education business, GE Healthcare.
By deleting key sequences of DNA in embryonic stem cells harvested from female mice, Chinese researchers successfully kicked off a new generation of the tiny mammals without the need for males to fertilise any eggs.
These fatherless mice not only made it to adulthood, they also went on to have babies of their own, demonstrating the method is a vast improvement on earlier attempts to assist reproduction without the need for both a male and female parent.
Biologists from the Chinese Academy of Sciences used a special editing technique on male- and female-derived ‘haploid’ embryonic stem cells (ESCs). These are effectively blank-slate cells that contain just half of a species’ chromosomes, not unlike tissues associated with the production of sex cells.
Reproduction without the need for sperm – a process called parthenogenesis – is nothing new in the animal kingdom. Many insects can pop out clones of their mother. So can a number of fish. There are even lizards and amphibians without daddies.
Mammals, on the other hand, drew the short straw when it comes to creative means of having babies.
“We were interested in the question of why mammals can only undergo sexual reproduction,” says the study’s co-senior author Qi Zhou.
It was already well known that specific genes were epigenetically silenced during the development of those ‘blank’ stem cells in mammals, with the genes depending on whether the cells came from the mother or the father.
This process of ‘genomic imprinting‘ means that combining a half-dose of genetic material from just two eggs or two sperm runs the risk of having both copies of an essential gene silenced – something we definitely don’t want in single-sex parent situations.
In 2004, Japanese researchers successfully navigated their way around this hurdle by selecting a maternal set of chromosomes that contained the fewest imprints.
This sperm-analogue was then used to fertilise a typical ova, making a mouse with two mothers which they named Kaguya, after a fairy-tale character.
As effective as this technique was in the end, it left a lot to be desired as far as efficiency and reliability.
“The generated mice still showed defective features, and the method itself is very impractical and hard to use,” says Zhou.
Years later, genetic editing technology has improved to the point that researchers can now selectively edit these imprint regions.
The research team cultured haploid ESCs from female mice to have minimal levels of genomic imprinting.
“We found in this study that haploid ESCs were more similar to primordial germ cells – the precursors of eggs and sperm,” says Baoyang Hu, also a co-senior author on the study.
They then deleted three specific imprinted regions on the stem cells’ chromosomes, effectively ‘erasing’ their imprinting. These ‘female sperm’ were then implanted into healthy donor cells to fertilise them.
The process is still far from flawless. Of the 210 embryos produced this way, only 29 live mice were born. But those that made it lived to maturity and had their own litters of pups, this time the old-fashioned way.
But the news wasn’t so good for achieving motherless babies from male-only mice. In a similar process, seven imprinted regions were edited in haploid ESCs taken from male mice.
These were then injected into an ova that had its maternal chromosomes removed, and combined with DNA from an unedited sperm cell; the embryo was then implanted into a surrogate mother. Sadly, twelve pups were born, but none made it past the first 48 hours.
If we’re hoping to apply any of this to assisted reproductive technologies for humans, we’ve still got a long way to go. Not just practically, but ethically.
“If the research is reproducible, and also works in humans, it still has to be shown to be safe,” says Bob Williamson, the Chair of the Board of Stem Cells Australia, who wasn’t involved in the research.
“The experiments are, however, important, because they may shine a light on some causes of serious handicap in children.”
This is still one monumental step forward in understanding mammalian development and laying the groundwork for new medical processes.
“This research shows us what’s possible,” says co-author Wei Li.
“We saw that the defects in bimaternal mice can be eliminated and that bipaternal reproduction barriers in mammals can also be crossed through imprinting modification.”
This research was published in Cell Stem Cell.