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PSMD1 and PSMD2 regulate HepG2 cell proliferation and apoptosis via modulating cellular lipid droplet metabolism

Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC). The lipid-rich environment enhances the proliferation and metastasis abilities of tumor cells. Pre...

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The effect of BACE1-AS on β-amyloid generation by regulating BACE1 mRNA expression

The BACE1 antisense transcript (BACE1-AS) is a conserved long noncoding RNA (lncRNA). The level of BACE1-AS is significantly increased and the level of the BACE1 mRNA is slightly increased in subjects with AD....

Overlapping transcriptional expression response of wheat zinc-induced facilitator-like transporters emphasize important role during Fe and Zn stress

Hexaploid wheat is an important cereal crop that has been targeted to enhance grain micronutrient content including zinc (Zn) and iron (Fe). In this direction, modulating the expression of plant transporters i...

MiR-32-5p influences high glucose-induced cardiac fibroblast proliferation and phenotypic alteration by inhibiting DUSP1

The current study aimed to investigate the effects of miR-32-5p on cardiac fibroblasts (CFs) that were induced with high levels of glucose; we also aimed to identify the potential mechanisms involved in the re...

Correction to: A protocol for custom CRISPR Cas9 donor vector construction to truncate genes in mammalian cells using pcDNA3 backbone

The original article [1] contains three erroneous mentions of usage of a restriction enzyme— Bst Z17I—in the Methods section as displayed in the following sentences.

The original article was published in BMC Molecular Biology 2018 19 :3

Comparison of miRNA - 101a - 3p and miRNA - 144a - 3p regulation with the key genes of alpaca melanocyte pigmentation

Many miRNA functions have been revealed to date. Single miRNAs can participate in life processes by regulating more than one target gene, and more than one miRNA can also simultaneously act on one target mRNA....

Correction to: MicroRNA-325-3p protects the heart after myocardial infarction by inhibiting RIPK3 and programmed necrosis in mice

The original article [1] contains an error whereby Fig. 7 displays incorrect results; the correct version of Fig. 7 can be viewed ahead in this Correction article and should be considered in place of the origi...

The original article was published in BMC Molecular Biology 2019 20 :17

MicroRNA-325-3p protects the heart after myocardial infarction by inhibiting RIPK3 and programmed necrosis in mice

Receptor-interacting serine-threonine kinase 3 (RIPK3)-mediated necroptosis has been implicated in the progression of myocardial infarction (MI), but the underlying mechanisms, particularly whether microRNAs (...

The Correction to this article has been published in BMC Molecular Biology 2019 20 :18

Giant group I intron in a mitochondrial genome is removed by RNA back-splicing

The mitochondrial genomes of mushroom corals (Corallimorpharia) are remarkable for harboring two complex group I introns; ND5-717 and COI-884. How these autocatalytic RNA elements interfere with mitochondrial ...

Exploration of carbohydrate binding behavior and anti-proliferative activities of Arisaema tortuosum lectin

Lectins have come a long way from being identified as proteins that agglutinate cells to promising therapeutic agents in modern medicine. Through their specific binding property, they have proven to be anti-ca...

Characterization of cadmium-responsive MicroRNAs and their target genes in maize ( Zea mays ) roots

Current research has shown that microRNAs (miRNAs) play vital roles in plant response to stress caused by heavy metals such as aluminum, arsenic, cadmium (Cd), and mercury. Cd has become one of the most hazard...

Identification and validation of reference genes for real-time quantitative RT-PCR analysis in jute

With the availability of genome sequences, gene expression analysis of jute has drawn considerable attention for understanding the regulatory mechanisms of fiber development and improving fiber quality. Gene e...

Small nucleolar RNA Sf-15 regulates proliferation and apoptosis of Spodoptera frugiperda Sf9 cells

Small nucleolar RNAs (snoRNAs) function in guiding 2′- O -methylation and pseudouridylation of ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). In recent years, more and more snoRNAs have been found to play ...

Key genes differential expressions and pathway involved in salt and water-deprivation stresses for renal cortex in camel

Camels possess the characteristics of salt- and drought-resistances, due to the long-time adaption to the living environment in desert. The camel resistance research on transcriptome is rare and deficient, esp...

Development of a novel selection/counter-selection system for chromosomal gene integrations and deletions in lactic acid bacteria

The underlying mechanisms by which probiotic lactic acid bacteria (LAB) enhance the health of the consumer have not been fully elucidated. Verification of probiotic modes of action can be achieved by using sin...

Selection of reference genes for the quantitative real-time PCR normalization of gene expression in Isatis indigotica fortune

Isatis indigotica , a traditional Chinese medicine, produces a variety of active ingredients. However, little is known about the key genes and corresponding expression profiling involved in the biosynthesis pathwa...

MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells

Myocyte enhancer factor 2A (MEF2A) plays an important role in cell proliferation, differentiation and survival. Functional deletion or mutation in MEF2A predisposes individuals to cardiovascular disease mainly...

Transcriptomic responses to grazing reveal the metabolic pathway leading to the biosynthesis of domoic acid and highlight different defense strategies in diatoms

A major cause of phytoplankton mortality is predation by zooplankton. Strategies to avoid grazers have probably played a major role in the evolution of phytoplankton and impacted bloom dynamics and trophic ene...

RNA sequencing, selection of reference genes and demonstration of feeding RNAi in Thrips tabaci (Lind.) (Thysanoptera: Thripidae)

Thrips tabaci is a severe pest of onion and cotton. Due to lack of information on its genome or transcriptome, not much is known about this insect at the molecular level. To initiate molecular studies in this ins...

A fragment activity assay reveals the key residues of TBC1D15 GTPase-activating protein (GAP) in Chiloscyllium plagiosum

GTPase-activating proteins (GAPs) with a TBC (Tre-2/Bub2/Cdc16) domain architecture serve as negative regulators of Rab GTPases. The related crystal structure has been studied and reported by other members of ...

HexA is required for growth, aflatoxin biosynthesis and virulence in Aspergillus flavus

Woronin bodies are fungal-specific organelles whose formation is derived from peroxisomes. The former are believed to be involved in the regulation of mycotoxins biosynthesis, but not in their damage repair fu...

Genome-wide identification of brain miRNAs in response to high-intensity intermittent swimming training in Rattus norvegicus by deep sequencing

Physical exercise can improve brain function by altering brain gene expression. The expression mechanisms underlying the brain’s response to exercise still remain unknown. miRNAs as vital regulators of gene ex...

Graphene oxide down-regulates genes of the oxidative phosphorylation complexes in a glioblastoma

Recently different forms of nanographene were proposed as the material with high anticancer potential. However, the mechanism of the suppressive activity of the graphene on cancer development remains unclear. ...

MiRNAs differentially expressed in skeletal muscle of animals with divergent estimated breeding values for beef tenderness

MicroRNAs (miRNAs) are small noncoding RNAs of approximately 22 nucleotides, highly conserved among species, which modulate gene expression by cleaving messenger RNA target or inhibiting translation. MiRNAs ar...

The Dictyostelium discoideum homologue of Twinkle, Twm1, is a mitochondrial DNA helicase, an active primase and promotes mitochondrial DNA replication

DNA replication requires contributions from various proteins, such as DNA helicases; in mitochondria Twinkle is important for maintaining and replicating mitochondrial DNA. Twinkle helicases are predicted to a...

Matrix association region/scaffold attachment region (MAR/SAR) sequence: its vital role in mediating chromosome breakages in nasopharyngeal epithelial cells via oxidative stress-induced apoptosis

Oxidative stress is known to be involved in most of the aetiological factors of nasopharyngeal carcinoma (NPC). Cells that are under oxidative stress may undergo apoptosis. We have previously demonstrated that...

Molecular analysis of NPAS3 functional domains and variants

NPAS3 encodes a transcription factor which has been associated with multiple human psychiatric and neurodevelopmental disorders. In mice, deletion of Npas3 was found to cause alterations in neurodevelopment, as w...

Integration of transcriptome and proteome profiles in glioblastoma: looking for the missing link

Glioblastoma (GB) is the most common and aggressive tumor of the brain. Genotype-based approaches and independent analyses of the transcriptome or the proteome have led to progress in understanding the underly...

Analyses of changes in myocardial long non-coding RNA and mRNA profiles after severe hemorrhagic shock and resuscitation via RNA sequencing in a rat model

Ischemia–reperfusion injury has been proven to induce organ dysfunction and death, although the mechanism is not fully understood. Long non-coding RNAs (lncRNAs) have drawn wide attention with their important ...

Coincidence cloning recovery of Brucella melitensis RNA from goat tissues: advancing the in vivo analysis of pathogen gene expression in brucellosis

Brucella melitensis bacteria cause persistent, intracellular infections in small ruminants as well as in humans, leading to significant morbidity and economic loss worldwide. The majority of experiments on the tr...

Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression

Core canonical histones are required in the S phase of the cell cycle to pack newly synthetized DNA, therefore the expression of their genes is highly activated during DNA replication. In mammalian cells, this...

Evaluation of suitable reference genes for qRT-PCR normalization in strawberry ( Fragaria  ×  ananassa ) under different experimental conditions

Strawberry has received much attention due to its nutritional value, unique flavor, and attractive appearance. The availability of the whole genome sequence and multiple transcriptome databases allows the grea...

Laser capture microdissection for transcriptomic profiles in human skin biopsies

The acquisition of reliable tissue-specific RNA sequencing data from human skin biopsy represents a major advance in research. However, the complexity of the process of isolation of specific layers from fresh-...

Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides

Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recently, it has been demonstrated that gastric cancer cells display a specific miRNA expression profile, with increasing eviden...

Quantitative profiling of BATF family proteins/JUNB/IRF hetero-trimers using Spec-seq

BATF family transcription factors (BATF, BATF2 and BATF3) form hetero-trimers with JUNB and either IRF4 or IRF8 to regulate cell fate in T cells and dendritic cells in vivo. While each combination of the heter...

pH-mediated upregulation of AQP1 gene expression through the Spi-B transcription factor

Bicarbonate-based peritoneal dialysis (PD) fluids enhance the migratory capacity and damage-repair ability of human peritoneal mesothelial cells by upregulating AQP1. However, little is known about the underly...

A protocol for custom CRISPR Cas9 donor vector construction to truncate genes in mammalian cells using pcDNA3 backbone

Clustered regularly interspaced short palindromic repeat (CRISPR) RNA-guided adaptive immune systems are found in prokaryotes to defend cells from foreign DNA. CRISPR Cas9 systems have been modified and employ...

The Correction to this article has been published in BMC Molecular Biology 2019 20 :20

Recommendations for mRNA analysis of micro-dissected glomerular tufts from paraffin-embedded human kidney biopsy samples

Glomeruli are excellent pre-determined natural structures for laser micro-dissection. Compartment-specific glomerular gene expression analysis of formalin-fixed paraffin-embedded renal biopsies could improve r...

Nutrient depletion and TOR inhibition induce 18S and 25S ribosomal RNAs resistant to a 5′-phosphate-dependent exonuclease in Candida albicans and other yeasts

Messenger RNA (mRNA) represents a small percentage of RNAs in a cell, with ribosomal RNA (rRNA) making up the bulk of it. To isolate mRNA from eukaryotes, typically poly-A selection is carried out. Recently, a...

An optimized rapid bisulfite conversion method with high recovery of cell-free DNA

Methylation analysis of cell-free DNA is a encouraging tool for tumor diagnosis, monitoring and prognosis. Sensitivity of methylation analysis is a very important matter due to the tiny amounts of cell-free DN...

Sumoylation in p27kip1 via RanBP2 promotes cancer cell growth in cholangiocarcinoma cell line QBC939

Cholangiocarcinoma is one of the deadly disease with poor 5-year survival and poor response to conventional therapies. Previously, we found that p27kip1 nuclear-cytoplasmic translocation confers proliferation ...

An optimised protocol for isolation of RNA from small sections of laser-capture microdissected FFPE tissue amenable for next-generation sequencing

Formalin-fixed paraffin embedded (FFPE) tissue constitutes a vast treasury of samples for biomedical research. Thus far however, extraction of RNA from FFPE tissue has proved challenging due to chemical RNA–pr...

Physical shearing imparts biological activity to DNA and ability to transmit itself horizontally across species and kingdom boundaries

We have recently reported that cell-free DNA (cfDNA) fragments derived from dying cells that circulate in blood are biologically active molecules and can readily enter into healthy cells to activate DNA damage...

Interaction between NFATc2 and the transcription factor Sp1 in pancreatic carcinoma cells PaTu 8988t

Nuclear factors of activated T-cells (NFATs) have been mainly characterized in the context of immune response regulation because, as transcription factors, they have the ability to induce gene transcription. N...

Splicing arrays reveal novel RBM10 targets, including SMN2 pre-mRNA

RBM10 is an RNA binding protein involved in message stabilization and alternative splicing regulation. The objective of the research described herein was to identify novel targets of RBM10-regulated splicing. ...

Growth arrest specific gene 2 in tilapia ( Oreochromis niloticus ): molecular characterization and functional analysis under low-temperature stress

Growth arrest specific 2 ( gas2 ) gene is a component of the microfilament system that plays a major role in the cell cycle, regulation of microfilaments, and cell morphology during apoptotic processes. However, li...

Identification of G-quadruplex structures that possess transcriptional regulating functions in the Dele and Cdc6 CpG islands

G-quadruplex is a DNA secondary structure that has been shown to play an important role in biological systems. In a previous study, we identified 1998 G-quadruplex-forming sequences using a mouse CpG islands D...

Mitochondrial RNA processing in absence of tRNA punctuations in octocorals

Mitogenome diversity is staggering among early branching animals with respect to size, gene density, content and order, and number of tRNA genes, especially in cnidarians. This last point is of special interes...

Microarray expression profiling in the denervated hippocampus identifies long noncoding RNAs functionally involved in neurogenesis

The denervated hippocampus provides a proper microenvironment for the survival and neuronal differentiation of neural progenitors. While thousands of lncRNAs were identified, only a few lncRNAs that regulate n...

Early growth response protein 1 regulates promoter activity of α -plasma membrane calcium ATPase 2, a major calcium pump in the brain and auditory system

Along with sodium/calcium (Ca 2+ ) exchangers, plasma membrane Ca 2+ ATPases (ATP2Bs) are main regulators of intracellular Ca 2+ levels. There are four ATP2B paralogs encoded by four different genes. Atp2b2 encodes t...

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Articles on Molecular biology

Displaying 1 - 20 of 58 articles.

An AI tool for predicting protein shapes could be transformative for medicine, but it challenges science’s need for proof

Sam McKee , Manchester Metropolitan University

Iron fuels immune cells – and it could make asthma worse

Benjamin Hurrell , University of Southern California and Omid Akbari , University of Southern California

What is metabolism? A biochemist explains how different people convert energy differently − and why that matters for your health

Travis Nemkov , University of Colorado Anschutz Medical Campus

We discovered a ‘gentle touch’ molecule is essential for light tactile sensation in humans – and perhaps in individual cells

Kate Poole , UNSW Sydney and Mirella Dottori , University of Wollongong

Customizing mRNA is easy, and that’s what makes it the next frontier for personalized medicine − a molecular biologist explains

Angie Hilliker , University of Richmond

Ever wonder how your body turns food into fuel? We tracked atoms to find out

James Carter , Griffith University ; Brian Fry , Griffith University , and Kaitlyn O'Mara , Griffith University

A ‘memory wipe’ for stem cells may be the key to better therapies

Sam Buckberry , Australian National University

Zooming across time and space simultaneously with superresolution to understand how cells divide

Somin Lee , University of Michigan

How does RNA know where to go in the city of the cell? Using cellular ZIP codes and postal carrier routes

Matthew Taliaferro , University of Colorado Anschutz Medical Campus

Visualizing the inside of cells at previously impossible resolutions provides vivid insights into how they work

Jeremy Berg , University of Pittsburgh

Helping the liver regenerate itself could give patients with end-stage liver disease a treatment option besides waiting for a transplant

Satdarshan (Paul) Singh Monga , University of Pittsburgh

Nigeria’s missing virus hunters: university decline robs country of virologists

Oyewale Tomori , Nigerian Academy of Science

Nobel Prize: How click chemistry and bioorthogonal chemistry are transforming the pharmaceutical and material industries

Heyang (Peter) Zhang , University at Buffalo

Gonorrhea became more drug resistant while attention was on COVID-19 – a molecular biologist explains the sexually transmitted superbug

Kenneth Keiler , Penn State

Yorkicystis , the 500 million-year -old relative of starfish that lost its skeleton

Samuel Zamora , Instituto Geológico y Minero de España (IGME - CSIC)

We found a genetic link between routine blood test results and mental health disorders

William Reay , University of Newcastle

We’re recycling potato skins to make prebiotics: here’s why that’s good for your gut – and the planet

Eleanor Binner , University of Nottingham and Afroditi Chatzifragkou , University of Reading

Florence Bell: the ‘housewife’ who played a key part in our understanding of DNA

Kersten Hall , University of Leeds

Antarctic bacteria live on air and make their own water using hydrogen as fuel

Pok Man Leung , Monash University ; Chris Greening , Monash University , and Steven Chown , Monash University

The 2021 Nobel Prize for medicine helps unravel mysteries about how the body senses temperature and pressure

Steven D. Munger , University of Florida

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The Year in Biology

December 19, 2023

Video : During 2023, Quanta turned a spotlight on important research progress into the nature of consciousness, the origins of our microbiomes and the timekeeping mechanisms that govern our lives and development, among many other discoveries.

Ibrahim Rayintakath for Quanta Magazine (cover); Emily Buder/ Quanta Magazine and Taylor Hess and Noah Hutton for Quanta Magazine  (video)

Introduction

Revolutions in the biological sciences can take many forms. Sometimes they erupt from the use of a novel tool or the invention of a radical theory that suddenly opens so many new avenues for research, it can feel dizzying. Sometimes they take shape slowly, through the slow accumulation of studies, each one representing years of painstaking work, that collectively chip away at the prevailing wisdom and reveal a stronger, better intellectual framework. Both kinds of revolution unleash avalanches of new ideas and insights that improve our understanding of how life works.

This past year has had no shortage of these. For example, researchers successfully grew “embryo models” — lab-grown artificial embryos that mature like real ones — that reached a more advanced developmental stage than ever before. That accomplishment could eventually yield valuable new insights into how human fetuses grow, although debate about the ethical status of those models seems likely, too. Meanwhile, in the world of neuroscience, researchers studying depression have continued to move away from the theory that has generally guided much of the research and pharmaceutical treatment of that disease for decades.

But those kinds of biological revolution involve human ingenuity, with researchers in the life sciences coming to new realizations. Revolutions also occur in the biology itself — when evolution has enabled organisms to do something unprecedented. Biologists have recently discovered many more instances of this kind of breakthrough.

Keeping track of time, for instance, is a function that’s essential to all living things, from microorganisms biding their time till the next cell division to embryos growing limbs and organs, to more complex critters tracking the passage of day and night. Teams of researchers plugging away in laboratories around the world have recently discovered that some key features of timekeeping are tied to cellular metabolism — which means that the organelle called the mitochondrion is both a generator and a clock. Other aspects of timekeeping are metered by the progress of a molecular ballet in which specialized proteins pirouette together before separating again.

Researchers also hope to soon make important discoveries now that they can culture some of the primitive, long-lost cells called Asgard archaea . A billion years ago, Asgard archaea (or cells much like them) took the outrageous step of forming permanent partnerships with the ancestors of mitochondria, thereby giving birth to the first complex cells. The secrets of how and why that biological breakthrough happened may be lurking in those exotic cell cultures. Meanwhile, other researchers are scrutinizing the “grit crust” microbes that live in the infamously arid Atacama Desert of Chile for clues to how the first land-dwelling cells survived.

Enough marvelous biological innovations were discovered in 2023 to form a veritable parade: plankton that supercharged their photosynthetic abilities by repurposing one of their membranes, and underground microbes that learned to make oxygen in total darkness . An immunological trick that protects babies in the womb, and a neurological trick that lets the brain map out social relationships like physical landscapes. A simple mutation that transformed ants into complex social parasites virtually overnight, and a strategic demolition of DNA that worms use to safeguard their genomes.

Quanta chronicled all those and more this year, and as new breakthroughs in fundamental biology come to light in the years ahead, we will be there for them too.

University of Cambridge

Pushing the Bounds of Synthetic Life

In the same way that physical scientists build simple model systems as steppingstones to understanding more complex phenomena, some biologists prefer to learn how life works by creating simpler versions. This year they made progress on two fronts: on large scales, in creating “embryo models,” and on small scales, in studying the most minimal cell possible.

Embryo models, or synthetic embryos, are laboratory products of stem cells that can be induced to grow faithfully through the early stages of development, although they self-terminate before reenacting the full embryonic development process. They were devised as potential tools for the ethical experimental study of human development. This year, research groups in Israel and the United Kingdom showed that they could nurture embryo models all the way up through (and possibly beyond) the stage at which research on live human embryos is legally allowed. Researchers in China even briefly initiated pregnancies in monkeys with embryo models. Those successes are considered major breakthroughs for a technique that could help scientists answer important questions about prenatal development, and they might eventually pay off in preventing miscarriages and birth defects. At the same time, the experiments reawakened ethical arguments about this line of research, given that as the embryo models become more developmentally advanced, they can also start to seem more intrinsically deserving of protection.

Synthetic life isn’t always ethically contentious. This year, researchers tested the limits of “minimal” cells , simple organisms derived from bacteria that have been stripped down to their genomic bare bones. These minimal cells have the tools to reproduce, but any genes that aren’t otherwise essential have been removed. In an important validation of how naturally lifelike the minimal cells are, researchers discovered that this minimal genome was able to evolve and adapt. After 300 days of growth and natural selection in the lab, the minimal cells could successfully compete against the ancestral bacteria from which they were derived. The findings demonstrated the robustness of the rules of life — that even after being robbed of nearly every genetic resource, the minimal cells could use the tools of natural selection to recover into more successful life forms.

Señor Salme for Quanta Magazine

The Investigation of Consciousness

Consciousness is the feeling of being — the awareness of having a unique self, a picture of reality and a place in the world. It’s long been the terrain of philosophers, but recently scientists have made progress (of sorts) in understanding its neurobiological basis.

In an interview on the Joy of Why podcast released in May, the neuroscience researcher Anil Seth of the University of Sussex described consciousness as a kind of “ controlled hallucination , ” in that our experience of reality emerges from within us. None of us can directly know what the world is like; indeed, every organism (and individual) experiences the world differently. Our sense of reality is shaped by the sensory information we take in and the way our brain organizes it and constructs it in our consciousness. In that sense, our entire experience is a hallucination — but it is a controlled hallucination, the brain’s best-guess description of the immediate environment and larger world based on its memories and other encoded information.

Our minds are constantly taking in new external information and also creating their own internal imagery and narratives. How can we distinguish reality from fantasy? This year, researchers discovered that the brain has a “ reality threshold ” against which it constantly evaluates processed signals. Most of our mental images have a pretty weak signal, and so our reality threshold easily consigns them to the “fake” pile. But sometimes our perceptions and imagination can mix, and if those images are strong enough, we can get confused — potentially mistaking our hallucinations for real life.

How does consciousness emerge in the mind? Is it more about thinking, or is it a product of sensory experiences? This year, the results of a high-profile adversarial collaboration that pitted two major theories of consciousness against each other were announced. Over the course of five years, two teams of researchers — one representing global neuronal workspace theory, which focuses on cognition, and the other representing integrated information theory, which focuses on perception — co-created and then led experiments aimed at testing which theory’s predictions were more accurate. The results may have been a letdown for anyone hoping for definitive answers. Onstage in New York City, at the 26th meeting of the Association for the Scientific Study of Consciousness, the researchers acknowledged ways in which the experiments had challenged both theories and highlighted differences between them, but they declined to pronounce either theory the winner. However, the evening wasn’t entirely unsatisfying: The neuroscientist Christof Koch of the Allen Institute for Brain Science conceded a 25-year-old bet with the philosopher David Chalmers of New York University that the neural correlates of consciousness would have been identified by now.

Harol Bustos for Quanta Magazine

New Ideas About Anguish

It’s often taken for granted that depression is caused by a chemical imbalance in the brain: specifically, a chronic deficiency of serotonin, a neurotransmitter that carries messages between nerve cells. Yet even though millions of depressed people around the world get relief from taking Prozac and the other drugs known as selective serotonin reuptake inhibitors, or SSRIs, based on that theory, decades’ worth of neuropsychiatric research has failed to validate the assumptions of that model. The hum of scientific dissent has been growing louder: An international team of scientists screened more than 350 papers and found no convincing evidence that lower levels of serotonin are associated with depression.

The realization that serotonin deficiency may not be the cause is forcing researchers to fundamentally rethink what depression is. It’s possible that SSRIs alleviate some symptoms of depression by altering other chemicals or processes in the brain that are more direct causes of depression. It’s also possible that what we call “depression” encompasses a variety of disorders that manifest with a similar set of symptoms, including fatigue, apathy, changes in appetite, suicidal thoughts and sleep issues. If that’s the case, significant additional research will be needed to unpack this complexity — to differentiate the kinds and causes of depression and to develop better treatments.

Depression can be an isolating experience. But it is distinct from loneliness, an emotional condition that neuroscientists have better defined in recent years. Loneliness is not the same as social isolation, which is an objective measure of the number of relationships a person is in: Someone can be in many relationships and still be lonely. Nor is it social anxiety, which is a fear of relationships or of certain relational experiences.

Instead, a growing body of neurobiological research suggests that loneliness is a bias in the mind toward interpreting social information in a negative, self-punishing way. It’s as if a survival signal that evolved to urge us to reconnect with the people we rely on has short-circuited, creating a self-perpetuating loop of felt isolation. Scientists haven’t yet found a medical treatment for loneliness, but perhaps simply understanding that negative loop can help the chronically lonely to escape the cycle and find comfort in their existing connections or in new ones.

Andreas Klingl, Ludwig Maximilian University; modified by Quanta

The Origins of Complex Life

Where do we come from, and how did we get here? Those timeless questions could be answered in many ways, and they have set numerous biologists on a search for the origins of the eukaryotes — the 2-billion-year-old lineage of life that includes all animals, plants and fungi and many single-celled creatures more complex than bacteria.

The search for the first eukaryote has researchers painstakingly coaxing rare microbes from seafloor sludge. Recently, after six years of work, a European laboratory became only the second to successfully cultivate one of the Asgard archaea — a group of primitive single-celled organisms that have genomes with eyebrow-raising similarities to those of eukaryotes, and that are thought to be ancestral to them. Scientists hope that directly studying the cells in the lab will reveal new information about how eukaryotes evolved and edge us closer to understanding our origins.

The evolutionary journey of that first eukaryote is shrouded in mystery. This year, scientists found a way to fill in an 800-million-year gap in the molecular fossil record between the appearance of the earliest eukaryote and that of the most recent ancestor of all eukaryotes alive today. Previously, when seeking information about eukaryotes that lived in the blank space from roughly 800 million to 1.6 billion years ago, scientists couldn’t find the molecular fossils they expected. But when an Australian team tweaked their search filter to look for fossilized versions of more primitive molecules, they found them in abundance. The findings revealed what the authors call “a lost world” of eukaryotes that helps tell the story of the early evolutionary history of our ancient ancestors.

Tagide deCarvalho

Microbiomes Evolve With Us

Research over the last decade has better characterized the microbiome — the collection of microorganisms that live in our guts and elsewhere in our body — and the subtle ways in which it influences our health. This year, scientists revealed in the greatest detail yet where our microbiomes come from and how they evolve throughout our lives.

Unsurprisingly, the first seeds of our microbiome usually come from mom — transmitted during birth and also through breastfeeding. Research published this year found that a mother’s contributions aren’t only whole microbial organisms, but also small snippets of DNA called mobile genetic elements. Up through the first year of life, these mobile genetic elements hop from the mother’s bacteria to the baby’s through a process called horizontal gene transfer. The discovery surprised researchers, who didn’t expect the high degree of coevolution between the mother’s microbiome and the baby’s to go on for so long after birth.

That’s not the end of the story: The microbiome evolves throughout our lives. The largest analysis yet of human microbiome transmission, also published this year, revealed how microbiomes shuffle and reassemble over many decades. It provided clear evidence that microbiome organisms spread between people, especially those with whom we spend the most time, such as family members, partners and roommates. And the study raised the intriguing possibility that some illnesses considered noncommunicable might actually be transmissible, in sometimes subtle ways, through gut flora.

Carlos Arrojo for Quanta Magazine

How Life Keeps Time

Eons before the invention of sundials, watches and atomic clocks, organisms evolved biological tools to keep time. They need internal circadian clocks that can keep their metabolic processes in sync with the cycle of day and night, and also clocks akin to calendars to keep their developmental processes on track. This year, researchers made important advances in understanding both.

A flurry of research over the past several years, made possible by new stem cell technologies, has proffered new explanations for what’s known as developmental tempo. All vertebrates start life as a simple embryo — but the rate at which an embryo develops, and the timing of when its tissues mature, dramatically varies between species and determines their final form. What controls the ticking of the developmental clock? This year, a series of careful experiments in labs around the world, focusing on different species and systems, pointed to a common explanation: that fundamental metabolic processes, including biochemical reactions and the gene expression that underlies them, all set the pace. Those metabolic processes appear to be organized fundamentally by the mitochondria, which may very well serve dual roles as the complex cell’s timekeeper and power source.

While those researchers were scattered across the world, novel work on the circadian clock has been done in the lab of a single scientist: the biochemist Carrie Partch at the University of California, Santa Cruz. Partch is driven by a unique obsession not only with the basic steps of the clock, but also with the intricate dance that clock proteins perform as they are built and as they interact and degrade. Like any watchmaker, she isn’t satisfied with knowing what the gears and cogs are — she also needs to understand how they fit together. In paying such close attention to a single system over the course of her career, she has made discoveries about the dance of clock proteins that represent broader truths, for example that unstructured or even disordered proteins are fundamental to biological processes.

David Robertson, ICR / Science Source

Refining the Brain’s Complexity

One sign of the progress in neuroscience is that it grows continually more precise. Using new tools that are more firmly grounded in sound science, scientists can now focus their attention on defining the quirks of individual brain cells. This year they located the social map of bats, which turned out to be superimposed on the bats’ map of their physical environment — the same exact brain cells in the hippocampus encode multiple kinds of environmental information. Other researchers seem to have resolved a 30-year debate over whether some of the brain’s glial cells — historically considered to be barely more than padding for the more prestigious neurons — can stimulate electrical signals . A team of neuroscientists and clinical researchers, helped by epilepsy patients who had electrodes implanted to improve their medical care, discovered that the brain has different systems for representing small and large numbers. And for the very first time, researchers visualized in three dimensions how an olfactory receptor grabs onto an odor molecule — a significant step in understanding how the nose and brain can intercept airborne chemicals and gain crucial sensory information about the environment.

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Methods in molecular biology and genetics: looking to the future

Diego a. forero.

1 School of Health and Sport Sciences, Fundación Universitaria del Área Andina, Bogotá, Colombia

Vaibhav Chand

2 Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, USA

Associated Data

Not applicable.

In recent decades, advances in methods in molecular biology and genetics have revolutionized multiple areas of the life and health sciences. However, there remains a global need for the development of more refined and effective methods across these fields of research. In this current Collection, we aim to showcase articles presenting novel molecular biology and genetics techniques developed by scientists from around the world.

A brief overview of the development of methods of molecular biology and genetics

Since ancient times, humankind has recognized the influence of heredity, based on familial resemblance, selective breeding of livestock, and climate-adapted crops. Prior to Gregor Johann Mendel’s work in the nineteenth century, there was no clear scientific theory to explain heredity. Mendel’s work remained essentially theoretical until the discovery of DNA and confirmation of its role as the principal agent of heredity in organisms in the twentieth century [ 1 ]. In addition, the resolution of the DNA structure paved the way for the invention of the Polymerase Chain Reaction (PCR) (by Kary Mullis), nucleotide synthesis [ 2 ] and the Sanger sequencing method [ 3 ] which revolutionized the field of genetics and led to the development of several sub-disciplines, including cytogenetics, biotechnology, bioprocess technology, and molecular biology. Automation of Sanger sequencing led to the Human Genome Project in 1990 [ 1 ], soon followed by sequencing the complete genomes of numerous other species of flora and fauna [ 4 ].

In recent decades, advances in methods in molecular biology and genetics have revolutionized multiple areas of life and health sciences [ 2 ]. As a major example from health sciences, PCR-based methods have advanced our understanding of the aetiology of a myriad of acute and chronic diseases, in addition to allowing the diagnosis of multiple disorders [ 1 , 5 ]. As a recent global application of molecular methods, the PCR-based approaches have led to the processing of hundreds of millions of samples for the analysis of the SARS-CoV-2 virus [ 6 ]. In addition, molecular methods have been key for the creation of multiple companies, products and jobs [ 7 ].

The development of sequencing technologies and their iterative improvements have been instrumental in advancing the understanding of DNA and RNA, their identification, association with various proteins, their covalent modifications, the function of the genes they carry, and the function of the non-coding portion of DNA and RNA in normal and diseased cells, in pathogenic bacteria and viruses, and in plants [ 8 , 9 ]. By producing RNA-based vaccines, we were able to combat the recent SARS-CoV2 pandemic. This was made possible by sequencing and in vitro nucleotide synthesis technologies [ 10 ].

Gene editing technologies, such as restriction endonuclease digestion, transcription activator-like effector nucleases (TALENs), and the clustered regularly interspaced short palindromic repeats (CRISPR-Cas) system, are an additional development in the field of molecular biology that has aided in the understanding of DNA and genes. There is optimism about the use of CRISPR-Cas9 technology in the treatment of a wide variety of diseases, such as cancer, blood-related diseases, hereditary blindness, cystic fibrosis, viral diseases, muscular dystrophy, and Huntington´s disease, due to its precision and its constant improvement, in comparison with other gene-editing technologies [ 15 ].

Need for novel methods in molecular biology and genetics

There is a global need for the development of novel methods for molecular biology and genetics. Particularly, in the area of human health, there is a need for further approaches that facilitate point-of-care molecular analysis (particularly miniaturized and portable platforms), for infectious and non-transmissible diseases [ 11 ], the development of more efficient methods for DNA sequencing [ 3 ], which facilitate cost-effective genome-wide analysis of patients, among others.

In addition, three key factors would also help push this field forward: additional research comparing the performance of different methods for molecular biology [ 12 ], the broader use of reporting standards (such as the Minimum Information for Publication of Quantitative Real-Time PCR Experiments -MIQE-, which describes details of experimental conditions) [ 13 ], and the increased participation of scientists from the Global South.

Although older techniques, such as x-ray crystallography, gene cloning, PCR, and sequencing, have been instrumental in the study of various aspects of genetics, these techniques have several limitations that result in gaps, missing links, and incomplete understanding of the genome. Advances in these techniques are needed to fill in these missing pieces of the puzzle to better comprehend genetics and accelerate the discovery of the causes of various genetically linkeddiseases. From a technological standpoint, the accuracy of sequencing and coverage across the genome remain major issues, especially for GC-rich regions and long homopolymer stretches of DNA. Furthermore, the short read lengths generated by the majority of current platforms severely restrict our ability to accurately characterize large repeat regions, numerous indels, and structural variation, rendering large portions of the genome opaque or inaccurate. Fragmentation of the genome for sequencing continues to be a major source of disruption in the continuity of the correct genomic sequence [ 14 , 15 ].

Recent advances in CRISPR technology provide hope for the medical treatment of cancer and other fatal diseases. Despite significant advances in this field, a number of technical obstacles remain, including off-target activity, insufficient indel or low homology-directed repair (HDR) efficiency, in vivo delivery of the Cas system components, and immune responses. This requires a substantial amount of technological advancement or the creation of new, superior methods to combat severe diseases with minimal side effects [ 14 , 16 ].

Additional considerations

As high-throughput, automated methods commonly produce very large amounts of data, deeper interaction between wet-lab and dry-lab researchers is required, to facilitate the design of efficient assays [ 17 ] and allow effective analysis and interpretation of results. Interdisciplinary collaborations, between biologists, engineers and professionals in the health sciences, might lead to newer and better methods of addressing current and future needs.

Further collaborations between scientists from academia and industry (in addition to researchers from government agencies) [ 18 ] would help to facilitate the development of novel methods, and aid in promoting their implementation around the world. For many countries, the main barrier to the broad use of molecular methods is the high cost of equipment and reagents [ 19 ]. Strategies aimed at lowering costs would be helpful for multiple institutions around the globe. In terms of intellectual property, fair licensing to institutions in the Global South as well as the implementation of Open Innovation and Open Science policies would be appropriate [ 20 ].

Overview of the current collection

In this current Collection, we are calling for articles showcasing novel methods from molecular biology and genetics, written by scientists from around the world. It is our goal to compile a set of articles that will help to address the challenges faced by the fields of molecular biology and genetics and broaden our understanding of genetic disorders and potential treatment strategies. We invite researchers working on such methods to consider submitting to our collection.

Acknowledgements

DAF has been previously supported by research grants from Minciencias and Areandina. VC has been previously supported by research grants from NIH and VA.

Author contributions

DAF and VC wrote an initial draft of the manuscript. All authors read and approved the final manuscript.

Data availability

Declarations.

DAF is a Senior Editorial Board Member of BMC Research Notes. VC is a Guest Editorial Board Member of BMC Research Notes.

DAF is a medical doctor, Ph.D. in Biomedical Sciences and Professor and Research Leader at the School of Health and Sport Sciences, Fundación Universitaria del Área Andina (Bogotá, Colombia). He has worked with multiple methods of molecular biology and genetics and is an author of more than 100 articles in international journals, has been peer reviewer for more than 115 international scientific journals, in addition to being part of editorial boards of several international journals. VC is a Research Assistant Professor in the Department of Biochemistry and Molecular Genetics at the University of Illinois at Chicago. His expertise in Biochemistry, Molecular Biology, Genetics, Oncology, and Cancer Biology is extensive. He is an invited reviewer for more than fourteen international peer review journals and is the author of fourteen articles with high impact.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Diego A. Forero, Email: oc.ude.anidnaera@14orerofd .

Vaibhav Chand, Email: ude.ciu@50dnahcv .

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