Lifeboat Foundation

In order to cover the different areas and to manage the large volume of research that has been conducted on the serotonin system, we conducted an ‘umbrella’ review. Umbrella reviews survey existing systematic reviews and meta-analyses relevant to a research question and represent one of the highest levels of evidence synthesis available [23]. Although they are traditionally restricted to systematic reviews and meta-analyses, we aimed to identify the best evidence available. Therefore, we also included some large studies that combined data from individual studies but did not employ conventional systematic review methods, and one large genetic study. The latter used nationwide databases to capture more individuals than entire meta-analyses, so is likely to provide even more reliable evidence than syntheses of individual studies.

We first conducted a scoping review to identify areas of research consistently held to provide support for the serotonin hypothesis of depression. Six areas were identified, addressing the following questions: Serotonin and the serotonin metabolite 5-HIAA–whether there are lower levels of serotonin and 5-HIAA in body fluids in depression; Receptors — whether serotonin receptor levels are altered in people with depression; The serotonin transporter (SERT) — whether there are higher levels of the serotonin transporter in people with depression (which would lower synaptic levels of serotonin); Depletion studies — whether tryptophan depletion (which lowers available serotonin) can induce depression; SERT gene – whether there are higher levels of the serotonin transporter gene in people with depression; Whether there is an interaction between the SERT gene and stress in depression.

We searched for systematic reviews, meta-analyses, and large database studies in these six areas in PubMed, EMBASE and PsycINFO using the Healthcare Databases Advanced Search tool provided by Health Education England and NICE (National Institute for Health and Care Excellence). Searches were conducted until December 2020.

Research on RNA diversity in human tissues, led by scientists from the New York Genome Center and the Broad Institute, is described in a recent study published in Nature. When the genetic code is transcribed to RNA, one gene typically produces several different forms of RNA molecules, or transcripts, with different functions. While this phenomenon has been known for decades, the catalog of human transcripts has remained incomplete.

“Equipped with the latest sequencing technology, we were able to read segments of over one thousand nucleotides, compared to less than one hundred with standard approaches,” describes Dr. Beryl Cummings, one of the leaders of the project and formerly a postdoctoral fellow at the Broad Institute. “Importantly, we were able to do this at scale of over 80 samples from many tissues, which led to discovery of tens of thousands of novel transcripts,” she adds.

The researchers used their data to characterize how genetic and environmental differences can manifest in differences in the transcriptome. “Genetic differences between individuals can affect how genes are regulated. We were able to describe with a finer resolution than before how transcript structures are affected. This helps to understand molecular underpinnings of variants that contribute to disease risk,” explains Dr. Dafni Glinos from the New York Genome Center and co-first author of the study.

Circa 2020 Reversing the biological clock to essentially reverse aging.

Expression of three Yamanaka transcription factors in mouse retinal ganglion cells restores youthful DNA methylation patterns, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice, suggesting that mammalian tissues retain a record of youthfu…

Genetic mutations which cause a debilitating hereditary kidney disease affecting children and young adults have been fixed in patient-derived kidney cells using a potentially game-changing DNA repair-kit. The advance, developed by University of Bristol scientists, is published in Nucleic Acids Research.

In this new study, the international team describe how they created a DNA repair vehicle to genetically fix faulty podocin, a common genetic cause of inheritable Steroid Resistant Nephrotic Syndrome (SRNS).

Podocin is a protein normally located on the surface of specialised kidney cells and is essential for kidney function. Faulty podocin, however, remains stuck inside the cell and never makes it to the surface, terminally damaging the podocytes. Since the disease cannot be cured with medications, gene therapy which repairs the genetic mutations causing the faulty podocin offers hope for patients.

For scientists searching for the brain’s ‘control room, an area called the claustrum has emerged as a compelling candidate. This little-studied deep brain structure is thought to be the place where multiple senses are brought together, attention is controlled, and consciousness arises. Observations in mice now support the role of the claustrum as a hub for coordinating activity across the brain. New research from the RIKEN Center for Brain Science (CBS) shows that slow-wave brain activity, a characteristic of sleep and resting states, is controlled by the claustrum. The synchronization of silent and active states across large parts of the brain by these slow waves could contribute to consciousness.

A serendipitous discovery actually led Yoshihiro Yoshihara, team leader at CBS, to investigate the claustrum. His lab normally studies the sense of smell and the detection of pheromones, but they chanced upon a genetically engineered mouse strain with a specific population of brain cells that was present only in the claustrum. These neurons could be turned on using optogenetic technology or selectively silenced through genetic manipulation, thus enabling the study of what turned out to be a vast, claustrum-controlled network. The study by Yoshihara and colleagues was published in Nature Neuroscience on May 11.

They started out by mapping the claustrum’s inputs and outputs and found that many higher-order brain areas send connections to the claustrum, such as those involved in sensation and motor control. Outgoing connections from the claustrum were broadly distributed across the brain, reaching numerous brain areas such as prefrontal, orbital, cingulate, motor, insular, and entorhinal cortices. “The claustrum is at the center of a widespread brain network, covering areas that are involved in cognitive processing,” says co-first author Kimiya Narikiyo. “It essentially reaches all higher brain areas and all types of neurons, making it a potential orchestrator of brain-wide activity.”

A research team led by Rice University neuroengineers has created wireless technology to remotely activate specific brain circuits in fruit flies in under one second.

The team – an assemblage of experts in genetic engineering, nanotechnology, and electrical engineering – used magnetic signals to activate targeted neurons that controlled the body position of freely moving fruit flies in an enclosure.

Continue reading “Neuroengineers hack fruit fly brain and remotely control its movements” »

The Virus Zoo is my latest educational blog post! I’ve written up ~1 page ‘cheat sheets’ on the molecular biology of specific viruses. I cover genome, structure, and life cycle. So far, my zoo includes adeno-associated virus (AAV), adenovirus, and herpes simplex virus 1 (HSV-1). However, I plan to add more viruses as time goes on! Some others I would like to incorporate later are coronavirus, HIV, anellovirus, lentivirus, ebolavirus, and MS2 bacteriophage. Feel free to suggest other interesting viruses in the comments! All images were created by me. #virology #molecularbiology #biotechnology #genetherapy #virus #biochemistry #genetics

Genome and Structure:

AAV genomes are about 4.7 kb in length and are composed of ssDNA. Inverted terminal repeats (ITRs) form hairpin structures at ends of the genome. These ITR structures are important for AAV genomic packaging and replication. Rep genes (encoded via overlapping reading frames) include Rep78, Rep68, Rep52, Rep40.¹ These proteins facilitate replication of the viral genome. As a Dependoparvovirus, additional helper functions from adenovirus (or certain other viruses) are needed for AAVs to replicate.

Continue reading “The Virus Zoo: A Quick Primer on Molecular Virology” »

Circa 2015

New software being developed at MIT is proving able to autonomously repair software bugs by borrowing from other programs and across different programming languages, without requiring access to the source code. This could save developers thousands of hours of programming time and lead to much more stable software.

Bugs are the bane of the software developer’s life. The changes that must be made to fix them are often trivial, typically involving changing only a few lines of code, but the process of identifying exactly which lines need to be fixed can be a very time-consuming and often very frustrating process, particularly in larger projects.

Continue reading “MIT system can fix your software bugs on its own (by borrowing from other software)” »