The 2018 Science Review
Updated: Jan 24, 2019
Happy new year from AxonMagazine! Now that the festivities are over, we thought we’d take some time to highlight 18 findings and breakthroughs from the wonderful world of Science which have caught our attention throughout the past year. There’s everything from new neurons, to artificial synapses, to printing new organs. Take a peep!
1. Nanoscale Neurons
For the first time, the entire connectome (the structural connections throughout the brain) of a living organism has been mapped at nanoscale resolution. Not too surprisingly, said organism is the fruit fly, which often finds itself the focus of many curiosity-driven neuroscientists, given its remarkable ability to learn and remember information. A team at the Howard Hughes Medical Institute's Janelia Research Campus in Ashburn, Virginia, used two high-speed electron microscopes to capture 21 million images comprised of 7,062 brain slices. Given the unprecedented level of resolution, each individual neuron could be traced to its adjoining neurons and beyond. By extension, the possibility for discovery of new topographical characteristics of neural networks or cell types is possible, and indeed this has been the case in this instance.
Stephan Saalfeld, Richard D. Fetter, Davi D. Bock, “A complete electron microscopy volume of the brain of adult Drosophila melanogaster,” Cell. Published online July 19, 2018. doi: 10.1016/j.cell.2018.06.019
2. LSD and Decision Making
The recent years have been huge for psychedelic science, and there’s no indication that the ball is going to stop rolling. The University of Zurich have contributed to the pool wonderfully, who set themselves the task this year of investigating the role of the 5-HT2A receptor on social influence on aesthetic judgements. By administering LSD - a drug known to affect social perception - to the study participants, they were able to selectively modulate the effect exert by these receptors when making decisions. Key among the plethora of findings yielded from this study were those that showed the capacity of LSD to enhance the adaptation to opinions which more closely map onto one’s own. Following, imaging results indicated this is likely due to changes to social feedback processes, as opposed to those of a explicit decision-making nature.
Preller, K., Schilbach, L., Duerler, P., Pokorny, T., & Vollenweider, F. (2018). T181. LSD Increases Social Adaptation to Opinions Similar to One’s Own. Biological Psychiatry, 83(9), S198.
3. Progress in Pain
Research fronted by the Harvard Medical School identified the nerve-signalling pathways behind deep, sustained pain that occurs immediately following an injury. By making use of an animal model, a set of neurons was identified as responsible for sustained pain and resulting pain-coping behaviours. The results suggest the existence of separate neural pathways that regulate threat avoidance versus injury mitigation. These findings have the potential impact to inform new ways to assess the efficacy of pain therapies by assessing behaviours stemming from distinct neural pathways.
Huang, T., Lin, S. H., Malewicz, N. M., Zhang, Y., Zhang, Y., Goulding, M., ... & Ma, Q. (2018). Identifying the pathways required for coping behaviours associated with sustained pain. Nature, 1.
4. HIV vaccine works in non-human primates
New research has found an experimental HIV vaccine strategy to be effective in non-human primates. Rhesus macaque monkeys can be prompted to produce neutralizing antibodies against one strain of HIV that resembles the resilient viral form that typically infects people, called a Tier 2 virus. The vaccine is, however, still far from human trials.
Pauthner, M. G., Nkolola, J. P., Havenar-Daughton, C., Murrell, B., Reiss, S. M., Bastidas, R., ... & Cottrell, C. A. (2018). Vaccine-induced protection from homologous tier 2 SHIV challenge in nonhuman primates depends on serum-neutralizing antibody titers. Immunity.
5. Safe, blud.
Recent findings from a study conducted at the University of Sheffield suggest that those with an ‘O’ blood type, may be better protected against cognitive decline, as a result of either aging or exposure to degenerative disease. As previous evidence has pointed to a higher prevalence of cognitive deficits in those with ‘AB’ blood types, the researchers set out to examine the structural brain differences between ‘O’ and ‘AB’ individuals who did not suffer from cognitive impairment. As it happens, some temporal and limbic regions in the brains of the non-‘O’ blood types showed lower grey matter volume values, whereas the ‘O’ blood types had increased volume values in the posterior cerebellum. Given that some these temporal and mediotemporal areas are strikingly affected by conditions such as Huntington’s disease, it may be that the ‘O’ blooders may have an advantage in the sense that their blood type confers some level of protection against volumetric loss.
De Marco, M., & Venneri, A. (2015). ‘O’ blood type is associated with larger grey-matter volumes in the cerebellum. Brain research bulletin, 116, 1-6.
6. Ketamine a potential treatment for Major depression?
A study published in The American Journal of Psychiatry revealed that a ketamine-based nasal spray showed promise for the rapid treatment of symptoms of major depression and suicidal thoughts. In the double-blind, multi-center, proof-of-concept Phase II study, the efficacy of standard treatment plus intranasal esketamine or placebo was compared. A significant improvement in depression scores and a decrease in suicidal ideation was reported in the esketamine group compared to those in the placebo.
Canuso, C. M., Singh, J. B., Fedgchin, M., Alphs, L., Lane, R., Lim, P., ... & Drevets, W. C. (2018). Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. American journal of psychiatry, appi-ajp.
7. The Earth BioGenome Project
A 10-year and 5-Billion Dollar Project has been launched this November, with the primary goal of sequencing and documenting the genomes of all eukaryotic life on earth (coming to the modest sum of 1.5 million species). While this is clearly a breath-takingly huge and noble undertaking, gathering and scrutinising this data will be instrumental in guiding our intuitions on the relationships between the genetic profiles of life on earth, while allowing for an informed and more strategic approach to environmental decisions which may affect the biodiversity on our planet.
8. New Subtype of MS identified
A paper in Lancet Neurology released in October reported a new MS subtype had been identified: Myelocortical MS. This new subtype is characterised by the death of the brains nerve cells but without damage to the protective coating of the neurons - the traditional hallmark of MS.
Trapp, B. D., Vignos, M., Dudman, J., Chang, A., Fisher, E., Staugaitis, S. M., ... & Fox, R. J. (2018). Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. The Lancet Neurology, 17(10), 870-884.
9. Potential vaccination for Glioblastoma
In the field of Glioblastoma, research has highlighted potential for the development of novel vaccine treatments. Researchers successfully used a Zika virus vaccine to target and kill human glioblastoma brain cancer stem cells, which had been transplanted into mice. In addition, Northwest Biotherapeutics published interim, blinded survival data from Phase III clinical trial of DVaxâ-L for newly diagnosed glioblastoma; the immunotherapy vaccine (in addition to standard therapy) may extend survival in glioblastoma patients.
Chen, Q., Wu, J., Ye, Q., Ma, F., Zhu, Q., Wu, Y., ... & Li, C. (2018). Treatment of Human Glioblastoma with a Live Attenuated Zika Virus Vaccine Candidate. mBio, 9(5), e01683-18.
10. TH Semen?
Research conducted at Duke University this year has shown that THC, the psychoactive component in cannabis, can alter the genetic profile of men’s sperm. Experiments with rodents and men has shown that DNA methylation undergoes significant alterations from exposure to THC, and that for the humans, cannabis usage was correlated with significantly lower sperm concentration. DNA Methylation is a process whereby Methyl (CH3) groups are added to the DNA – changing and often modifying the function of the gene without altering its sequence. It is unknown at this point if these changes will negatively impact upon the user’s children, developmentally or otherwise. Relatedly, research is due to take place to examine whether or not cessation of cannabis use will lead to the reversal of the aforementioned alterations to the targeted genes in sperm. The headline is that there could be risks worth considering for any men who are looking to have children, who are also partial to a bit of the herb.
Murphy, S. K., Itchon-Ramos, N., Visco, Z., Huang, Z., Grenier, C., Schrott, R., ... & Corcoran, D. L. (2018). Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics, (just-accepted).
11. Promising Neurotechnology Offers The Ability to Walk Again?
Swiss researchers have developed targeted spinal cord stimulation neurotechnology which allows those paralysed from spinal cord injury to walk once more. These injuries are naturally devastating to the individual, who typically suffer from total leg paralysis or serious locomotor deficits. By implanting a pulse generator which applied a series of spatially selective stimulations to the lumbrosacral spinal cord, in time with related and intended movements, the participants regained voluntary control over muscles which they had been unable to use for years. Cycling and walking became a reality whilst under spatiotemporal simulation, which certainly indicates that this novel and innovative technology has the potential to restore activity, life and hope to those deprived of voluntary movement.
Wagner, F. B., Mignardot, J. B., Le Goff-Mignardot, C. G., Demesmaeker, R., Komi, S., Capogrosso, M., ... & Vat, M. (2018). Targeted neurotechnology restores walking in humans with spinal cord injury. Nature, 563(7729), 65.
12. Designing an Artificial Synapse
Engineers at MIT successfully designed a neuromorphic computer chip which emulates the functionality of the human brain. Typically, digital computations are carried out in a binary fashion, with on/off signalling. A chip which mimics brain-style processing however, would be able to process large quantities of parallel streams of information, by exchanging signals in a weighted fashion – much like how the neuron operates. By developing an artificial synapse constructed from silicon germanium, the researchers were able to realise this technology and effectively control the strength of a given current flow. The work is a considerable stepping stone toward the usage of low-power neuromorphic chips in instances where pattern-recognition is required.
13. Neuropsychological outcomes following paediatric anti-NMDAR encephalitis
Anti-NMDAR Encephalitis is an autoimmune disorder which results in inflammation of the brain. Individuals often make good functional recovery following illness, however less is known about the cognitive outcome. In 2018, a group of Dutch researchers investigated 28 children who had been diagnosed with anti-NMDAR encephalitis with the aim to determine the long-term neuropsychological outcomes and the impact of these on quality of life. The study reported that in comparison to normative data, children who had had paediatric anti-NMDAR encephalitis displayed problems with; sustained attention, fatigue and lower long-term verbal memory scores. These were present among high levels of fatigue, which correlated with a lower quality of life. This paper highlights the need greater awareness of the cognitive problems in this patient group, and the considerations of early neuropsychological input.
de Bruijn, M. A., Aarsen, F. K., van Oosterhout, M. P., van der Knoop, M. M., Catsman-Berrevoets, C. E., Schreurs, M. W., ... & Titulaer, M. J. (2018). Long-term neuropsychological outcome following pediatric anti-NMDAR encephalitis. Neurology, 90(22), e1997-e2005.
14. Alzheimer’s: A Viral Basis?
Two studies published in Neuron support a connection between Alzheimer’s disease and herpesvirus. One study found more DNA from strains of HPV in the brains of Alzheimer’s patients versus those of healthy individuals. In particular, researchers found high levels of HHV-6 and HHV-7, two strains of herpesvirus associated with a common childhood illness called roseolna. A second study reported that amyloid-beta plaques in the brain could be a protective reaction to pathogens like herpesvirus. The paper’s hypothesis is referred to as “the antimicrobial protection hypothesis of Alzheimer’s disease” which suggests that herpes microbes trigger the A-beta build-up, which in turn triggers Alzheimer’s disease. However, the connection remains unclear and both papers highlight the need for more research to be done to understand this connection.
Readhead, B., Haure-Mirande, J. V., Funk, C. C., Richards, M. A., Shannon, P., Haroutunian, V., ... & Reiman, E. M. (2018). Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron.
Eimer, W. A., Kumar, V., Kumar, D., Shanmugam, N. K. N., Washicosky, K. J., Rodriguez, A. S., ... & Moir, R. D. (2018). Alzheimer’s Disease-Associated β-amyloid Is Rapidly Seeded by herpes viridae to Protect Against Brain Infection.
15. PsychENCODE Project
Researchers from 15 institutions have completed one of the most comprehensive genomic analysis of the human brain yet, providing insight into the molecular mechanisms underpinning brain development and neuropsychiatric illnesses. The project was established in 2015 and has analysed more than 2,100 brain bank samples of people with and without psychiatric disorders. In 2018 10 papers from the Project were published in Science Advances and Science Translational Medicine.
Li, M., Santpere, G., Kawasawa, Y. I., Evgrafov, O. V., Gulden, F. O., Pochareddy, S., ... & Sousa, A. M. (2018). Integrative functional genomic analysis of human brain development and neuropsychiatric risks. Science, 362(6420), eaat7615.
Gandal, M. J., Zhang, P., Hadjimichael, E., Walker, R. L., Chen, C., Liu, S., ... & Shieh, A. W. (2018). Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science, 362(6420), eaat8127.
Wang, D., Liu, S., Warrell, J., Won, H., Shi, X., Navarro, F. C., ... & Xu, M. (2018). Comprehensive functional genomic resource and integrative model for the human brain. Science, 362(6420), eaat8464.
Zhu, Y., Sousa, A. M., Gao, T., Skarica, M., Li, M., Santpere, G., ... & Yang, M. (2018). Spatiotemporal transcriptomic divergence across human and macaque brain development. Science, 362(6420), eaat8077.
Amiri, A., Coppola, G., Scuderi, S., Wu, F., Roychowdhury, T., Liu, F., ... & Zhu, Y. (2018). Transcriptome and epigenome landscape of human cortical development modeled in organoids. Science, 362(6420), eaat6720.
Rajarajan, P., Borrman, T., Liao, W., Schrode, N., Flaherty, E., Casiño, C., ... & Javidfar, B. (2018). Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk. Science, 362(6420), eaat4311.
An, J. Y., Lin, K., Zhu, L., Werling, D. M., Dong, S., Brand, H., ... & Currall, B. B. (2018). Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder. Science, 362(6420), eaat6576.
Rhie, S. K., Schreiner, S., Witt, H., Armoskus, C., Lay, F. D., Camarena, A., ... & Knowles, J. A. (2018). Using 3D epigenomic maps of primary olfactory neuronal cells from living individuals to understand gene regulation. Science advances, 4(12), eaav8550.
Chen, C., Meng, Q., Xia, Y., Ding, C., Wang, L., Dai, R., ... & Coarfa, C. (2018). The transcription factor POU3F2 regulates a gene coexpression network in brain tissue from patients with psychiatric disorders. Science translational medicine, 10(472), eaat8178.
Meng, Q., Wang, K., Brunetti, T., Xia, Y., Jiao, C., Dai, R., ... & Grennan, K. (2018). The DGCR5 long noncoding RNA may regulate expression of several schizophrenia-related genes. Science translational medicine, 10(472), eaat6912.
16. Discovery of a new cell ‘The Rosehip Neuron’
Researchers from the Allen Institute (DC, USA) and the University of Szeged (Szeged, Hungary) uncovered a previously unknown type of human brain cell which has been named the rosehip neuron. It has never before been seen in any other animal, including rodents. Most neurons have long dendrites – branches that carry electrical signals. This new neuron, however, has very compact dendrites with an abundance of branch points. It is not yet clear what function these cells perform, but they account for approximately 10 percent of the neocortex. Rosehip neurons appear to be inhibitory, responsible for regulating the flow of information to certain parts of the brain. Future research aims to look at brain samples from individuals with neuropsychiatric disorders, to see how these neurons may differ between these individuals.
Boldog, E., Bakken, T. E., Hodge, R. D., Novotny, M., Aevermann, B. D., Baka, J., ... & Faragó, N. (2018). Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type. Nature neuroscience, 21(9), 1185.
17. Designer Babies?
This year we played witness to the birth of the world’s first gene-edited twins babies, courtesy of Chinese scientist Jiankui He, who claimed to have successfully disabled the CCR5 genes of implanted embryo’s by using CRISPR/Cas9 techniques. The CCR5 gene is responsible for the production of a protein which enables a typical form of the HIV virus to gain entry into cells – forming the rationale for the ‘switching off’ of this particular gene. Whether or not this procedure will translate into any real benefit for the girls is quite unlikely – while the girl’s father suffered from HIV, their Mother did not carry the virus and would not have passed it on during childbirth. There is also speculation as to whether or not other genes remain untouched by the editing techniques, or indeed if the editing was totally successful. Either way, the whole thing hints at a black mirror-esque scenario, wherein there exists the ability to alter the genetic profile of embryo’s to our heart’s desire. Such is the worry of many ethicists and biologists, that we might begin to produce ‘designer babies’, whose levels of intelligence, looks, athleticism and immunities are ours to tinker with.
18. Printing Organs
A new 3D printing technique was showcased earlier this January, born of a collaborative effort between Kings College London and Imperial College London. By using a combination of cryogenic and 3D printing, this new method allows for the generation of complex structures which can mirror the mechanical characteristics of the softest bodily organs. The importance of this new capability mustn’t be understated – as these 3D printings are so similar to bodily organs in terms of their softness and structure, their potential for usage as scaffolds around which tissue can regenerate is huge. The applications of 3D structures of this nature have been greatly widened by the efforts of these scientists, and it’s a line of work that’s worth keeping an eye on for 2019.
‘Cryogenic 3D Printing of Super Soft Hydrogels’ by Zhengchu Tan, Cristian Parisi, Lucy Di Silvio, Daniele Dini & Antonio Elia Forte is published in Scientific Reports.
Happy New Year!
Matthew & Caitl