AI Helps Unravel Mystery of Neurological Disorders

JEREMY ISENBERG | June 13, 2019 | 102 views

Neurological disorders are estimated to affect up to 1 billion people around the world—including nearly 100 million Americans—with roughly 7 million people dying of the maladies every year worldwide. The vast spectrum of more than 600 neurological disorders includes Alzheimer’s, Parkinson’s disease, strokes, multiple sclerosis, epilepsy, migraines and brain injuries.

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QCMD

Quality Control for Molecular Diagnostics (QCMD) evolved from the successful European Union Concerted Action programmes which were initiated in the early 1990s to address quality control within the clinical diagnosis of viral Meningitis and Encephalitis.

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MedTech

Top 10 biotech IPOs in 2019

Article | October 7, 2022

The big question at the start of 2019 was whether the IPO window would stay open for biotech companies, particularly those seeking to pull off ever-larger IPOs at increasingly earlier stages of development. The short answer is yes—kind of. Here’s the long answer: In the words of Renaissance Capital, the IPO market had “a mostly good year.” The total number of deals fell to 159 from 192 the year before, but technology and healthcare companies were standout performers. The latter—which include biotech, medtech and diagnostics companies—led the pack, making up 43% of all IPOs in 2019. By Renaissance’s count, seven companies went public at valuations exceeding $1 billion, up from five the year before

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Medical

Cell Out? Lysate-Based Expression an Option for Personalized Meds

Article | July 14, 2022

Cell-free expression (CFE) is the practice of making a protein without using a living cell. In contrast with cell line-based methods, production is achieved using a fluid containing biological components extracted from a cell, i.e., a lysate. CFE offers potential advantages for biopharma according to Philip Probert, PhD, a senior scientist at the Centre for Process Innovation in the U.K.

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MedTech

Closing bacterial genomes from the human gut microbiome using long-read sequencing

Article | July 13, 2022

In our lab, we focus on the impact of the gut microbiome on human health and disease. To evaluate this relationship, it’s important to understand the particular functions that different bacteria have. As bacteria are able to exchange, duplicate, and rearrange their genes in ways that directly affect their phenotypes, complete bacterial genomes assembled directly from human samples are essential to understand the strain variation and potential functions of the bacteria we host. Advances in the microbiome space have allowed for the de novo assembly of microbial genomes directly from metagenomes via short-read sequencing, assembly of reads into contigs, and binning of contigs into putative genome drafts. This is advantageous because it allows us to discover microbes without culturing them, directly from human samples and without reference databases. In the past year, there have been a number of tour de force efforts to broadly characterize the human gut microbiota through the creation of such metagenome-assembled genomes (MAGs)[1–4]. These works have produced hundreds of thousands of microbial genomes that vastly increase our understanding of the human gut. However, challenges in the assembly of short reads has limited our ability to correctly assemble repeated genomic elements and place them into genomic context. Thus, existing MAGs are often fragmented and do not include mobile genetic elements, 16S rRNA sequences, and other elements that are repeated or have high identity within and across bacterial genomes.

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Selexis Cell Line Development Strategies

Article | February 11, 2020

In today’s biotechnology landscape, to be competitive, meet regulations, and achieve market demands, “we must apply Bioprocessing 4.0,” said Igor Fisch, PhD, CEO, Selexis. In fact, in the last decade, “Selexis has evolved from cloning by limiting dilution to automated cell selection to nanofluidic chips and from monoclonality assessment by statistical calculation to proprietary bioinformatic analysis,” he added. Single-use processing systems are an expanding part of the biomanufacturing world; as such, they are a major component of Bioprocessing 4.0. “At Selexis, we use single use throughout our cell line development workflow. Currently, we have incorporated single-use automated bioprocessing systems such as ambr® and the Beacon® optofluidic platform for accelerated cell line development. By using these systems and optimizing our parameters, we were able to achieve high titers in shake flasks. Additionally, the Beacon systems integrate miniaturized cell culture with high-throughput liquid handling automation and cell imaging. This allows us to control, adjust, and monitor programs at the same time,” noted Fisch.

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Spotlight

QCMD

Quality Control for Molecular Diagnostics (QCMD) evolved from the successful European Union Concerted Action programmes which were initiated in the early 1990s to address quality control within the clinical diagnosis of viral Meningitis and Encephalitis.

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Using Machine Learning To Reveal How the Brain Encodes Memories

Technology Networks | November 28, 2019

Researchers working in The N.1 Institute for Health at NUS, led by Assistant Professor Camilo Libedinsky from NUS Psychology, and Senior Lecturer Shih-Cheng Yen from the Innovation and Design Programme at NUS Engineering, have discovered that a population of neurons in the brain’s frontal lobe contain stable short-term memory information within dynamically-changing neural activity. This discovery may have far-reaching consequences in understanding how organisms have the ability to perform multiple mental operations simultaneously, such as remembering, paying attention and making a decision, using a brain of limited size. In the human brain, the frontal lobe plays an important role in processing short-term memories. Short-term memory has a low capacity to retain information. “It can usually only hold six to eight items. Think for example about our ability to remember a phone number for a few seconds – that uses short-term memory,” Libendisky explained.

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Electronic Chip Allows Synaptic Connectivity to Be Mapped at High Level

GEN | September 24, 2019

Scientists from Harvard University say they have developed an electronic chip that can perform high-sensitivity intracellular recording from thousands of connected neurons simultaneously. This advance allowed them to map synaptic connectivity at an unprecedented level, identifying hundreds of synaptic connections. “Current electrophysiological or optical techniques cannot reliably perform simultaneous intracellular recordings from more than a few tens of neurons. Here we report a nanoelectrode array that can simultaneously obtain intracellular recordings from thousands of connected mammalian neurons in vitro. The array consists of 4,096 platinum-black electrodes with nanoscale roughness fabricated on top of a silicon chip that monolithically integrates 4,096 microscale amplifiers, configurable into pseudocurrent-clamp mode (for concurrent current injection and voltage recording) or into pseudovoltage-clamp mode (for concurrent voltage application and current recording),” the investigators wrote. “We used the array in pseudovoltage-clamp mode to measure the effects of drugs on ion-channel currents. In pseudocurrent-clamp mode, the array intracellularly recorded action potentials and postsynaptic potentials from thousands of neurons. In addition, we mapped over 300 excitatory and inhibitory synaptic connections from more than 1,700 neurons that were intracellularly recorded for 19 minutes. This high-throughput intracellular-recording technology could benefit functional connectome mapping, electrophysiological screening, and other functional interrogations of neuronal networks.” “Our combination of the sensitivity and parallelism can benefit fundamental and applied neurobiology alike, including functional connectome construction and high-throughput electrophysiological screening,” said Hongkun Park, PhD, the Mark Hyman Jr. professor of chemistry and professor of physics, and co-senior author of the paper.

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Cancer Cells Form Synaptic Connections with Neurons

GEN | September 23, 2019

In aggressive glioblastoma, cancer cells plug into the brain’s neuronal network and receive impulses that appear to stimulate tumor growth. These impulses, which are transmitted via synaptic connections, may explain how brain tumors spread so quickly. They may also be subject to jamming—that is, to interference by drugs. If so, it may be possible to pull the plug on brain cancer. The shocking discovery that cancer tissue, like brain tissue, may be electrically active was reported by scientists from Heidelberg University Hospital and the German Cancer Research Center. In a paper (“Glutamatergic synaptic input to glioma cells drives brain tumor progression”) that appeared in Nature, these scientists noted that previous research had already established that glioblastoma cells connect with one another rather like neurons. This finding has been extended in the new research, which argues that tumor cells not only interconnect like neurons, they also interconnect with neurons. Even more intriguingly, the interconnections are active. “We report a direct communication channel between neurons and glioma cells in different disease models and human tumors: functional bona fide chemical synapses between presynaptic neurons and postsynaptic glioma cells,” the authors of the Nature article wrote. “These neurogliomal synapses show a typical synaptic ultrastructure, are located on tumor microtubes, and produce postsynaptic currents that are mediated by glutamate receptors of the AMPA subtype.”

Read More

Using Machine Learning To Reveal How the Brain Encodes Memories

Technology Networks | November 28, 2019

Researchers working in The N.1 Institute for Health at NUS, led by Assistant Professor Camilo Libedinsky from NUS Psychology, and Senior Lecturer Shih-Cheng Yen from the Innovation and Design Programme at NUS Engineering, have discovered that a population of neurons in the brain’s frontal lobe contain stable short-term memory information within dynamically-changing neural activity. This discovery may have far-reaching consequences in understanding how organisms have the ability to perform multiple mental operations simultaneously, such as remembering, paying attention and making a decision, using a brain of limited size. In the human brain, the frontal lobe plays an important role in processing short-term memories. Short-term memory has a low capacity to retain information. “It can usually only hold six to eight items. Think for example about our ability to remember a phone number for a few seconds – that uses short-term memory,” Libendisky explained.

Read More

Electronic Chip Allows Synaptic Connectivity to Be Mapped at High Level

GEN | September 24, 2019

Scientists from Harvard University say they have developed an electronic chip that can perform high-sensitivity intracellular recording from thousands of connected neurons simultaneously. This advance allowed them to map synaptic connectivity at an unprecedented level, identifying hundreds of synaptic connections. “Current electrophysiological or optical techniques cannot reliably perform simultaneous intracellular recordings from more than a few tens of neurons. Here we report a nanoelectrode array that can simultaneously obtain intracellular recordings from thousands of connected mammalian neurons in vitro. The array consists of 4,096 platinum-black electrodes with nanoscale roughness fabricated on top of a silicon chip that monolithically integrates 4,096 microscale amplifiers, configurable into pseudocurrent-clamp mode (for concurrent current injection and voltage recording) or into pseudovoltage-clamp mode (for concurrent voltage application and current recording),” the investigators wrote. “We used the array in pseudovoltage-clamp mode to measure the effects of drugs on ion-channel currents. In pseudocurrent-clamp mode, the array intracellularly recorded action potentials and postsynaptic potentials from thousands of neurons. In addition, we mapped over 300 excitatory and inhibitory synaptic connections from more than 1,700 neurons that were intracellularly recorded for 19 minutes. This high-throughput intracellular-recording technology could benefit functional connectome mapping, electrophysiological screening, and other functional interrogations of neuronal networks.” “Our combination of the sensitivity and parallelism can benefit fundamental and applied neurobiology alike, including functional connectome construction and high-throughput electrophysiological screening,” said Hongkun Park, PhD, the Mark Hyman Jr. professor of chemistry and professor of physics, and co-senior author of the paper.

Read More

Cancer Cells Form Synaptic Connections with Neurons

GEN | September 23, 2019

In aggressive glioblastoma, cancer cells plug into the brain’s neuronal network and receive impulses that appear to stimulate tumor growth. These impulses, which are transmitted via synaptic connections, may explain how brain tumors spread so quickly. They may also be subject to jamming—that is, to interference by drugs. If so, it may be possible to pull the plug on brain cancer. The shocking discovery that cancer tissue, like brain tissue, may be electrically active was reported by scientists from Heidelberg University Hospital and the German Cancer Research Center. In a paper (“Glutamatergic synaptic input to glioma cells drives brain tumor progression”) that appeared in Nature, these scientists noted that previous research had already established that glioblastoma cells connect with one another rather like neurons. This finding has been extended in the new research, which argues that tumor cells not only interconnect like neurons, they also interconnect with neurons. Even more intriguingly, the interconnections are active. “We report a direct communication channel between neurons and glioma cells in different disease models and human tumors: functional bona fide chemical synapses between presynaptic neurons and postsynaptic glioma cells,” the authors of the Nature article wrote. “These neurogliomal synapses show a typical synaptic ultrastructure, are located on tumor microtubes, and produce postsynaptic currents that are mediated by glutamate receptors of the AMPA subtype.”

Read More

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