Cover-all mapping of the distribution of neurons in the human brain would have a significant impact on the deep understanding of brain function. Therefore, complete knowledge of the structural organization of different human brain regions at the cellular level would allow understanding their role in the functions of specific neural networks. Recent advances in tissue clearing techniques have allowed

Although determination of structures of biological molecules became a real possibility after the first X-ray analyses of crystals by the William Henry Bragg and his son Lawrence in 1913, the crystal structure determination of globular proteins became a possibility only in 1934 with the demonstration of X-ray diffraction from pepsin by J D Bernal and Dorothy Crowfoot, later Hodgkin, who had realised

The evolution of early life and of contemporary viruses has been driven in significant part by random genetic mutations, while modern unicellular and organismal evolution primarily leverages evolved, efficient and active cell biology processes for adaptive changes prior to selection. Random mutations are often buffered by cell homeostasis, or they have a negative role, e.g., by causing death or monogenic

A recent symposium on cancer and evolution has bought many innovative thinkers together to challenge the status quo of current cancer research. Professor Henry Heng's presentation considers cancer as a new system emerging via macro-evolution, where genome chaos-mediated information creation and maintenance plays an important role. This concept departs from the neo-Darwinian influenced somatic mutation

The vulnerabilities of cancer at the cellular and, recently, with the introduction of immunotherapy, at the tissue level, have been exploited with variable success. Evaluating the cancer system vulnerabilities at the organismic level through analysis of network topology and network dynamics can potentially predict novel anti-cancer drug targets directed at the macroscopic cancer networks. Theoretical

Breast cancer is the most common cancer in women worldwide and despite improved treatment strategies, it persists as the second leading cause of death of women globally. Overall prognosis drops drastically once the cancer has metastasized, which is also associated with resistance to therapy. The evolution from a localized breast cancer to metastatic disease is complex and multifactorial. Metabolic

Discovered some 40 years ago, the If current has since been known as the “pacemaker” current due to its role in the initiation and modulation of the heartbeat and of neuronal excitability. But this is not all, the funny current keeps entertaining the researchers; indeed, several data discovering novel and uncanonical roles of f/HCN channel are quickly accumulating. In the present review, we provide

Extracellular vesicles (EVs) are nano-sized membrane enclosed vesicles that are released by cells. While initially thought to be cellular detritus or particles involved in eliminating waste from cells, EVs have been recognised as important mediators of intercellular communication by transferring their bioactive cargoes. Notably, over the last two decades, a substantial research effort has been undertaken

Cancer or cancer-like phenomena pervade multicellular life, implying deep evolutionary roots. Many of the hallmarks of cancer recapitulate unicellular modalities, suggesting that cancer initiation and progression represent a systematic reversion to simpler ancestral phenotypes in response to a stress or insult. This so-called atavism theory may be tested using phylostratigraphy, which can be used to

Cancer progression has been attributed to somatic changes in single-nucleotide variants, copy-number aberrations, loss of heterozygosity, chromosomal instability, epistatic interactions, and the tumor microenvironment. It is not entirely clear which of these changes are essential and which are ancillary to cancer. The dynamic nature of cancer evolution in a patient can be illuminated using several

If you cut a mobius strip in half, the edges form a Trefoil Knot, which can be untied to form a circle, proving it's a true mathematical knot. The cell is a homologue of the mathematical knot since it, too, must be able to unknot itself to form the egg and sperm meiotically in order to reproduce. The homology between a knot and a cell is thought-provoking biologically because the Trefoil Knot is a

The optical clearing of the cardiac tissue has always been a challenging goal to obtain successful three-dimensional reconstructions of entire hearts. Typically, the developed protocols are targeted at the clearing of the brain; cardiac tissue requires proper arrangements to the original protocols, which are usually tough and time-consuming to figure out. Here, we present the application of three different

The present study scrutinized some of the crucial advancements in the synthesis and functionalisation of self-assembling biomaterials for application in biomedicine. The basic concept of self-organization was discussed along with the mechanisms and methods involved in its implementation with biomaterials. Further, several recent applications of this technology in the biological and medical domain,

The altered function of the Hyperpolarization-activated Cyclic-Nucleotide-gated (HCN) ion channels plays an important role in the pathogenesis of epilepsy in humans. In particular, HCN1 missense mutations have been recently identified in patients with different epileptic phenotypes, varying from mild to severe. Their electrophysiological characterization shows that mutated channels can act both with

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, expressed in a variety of cell types and in all tissues, control excitation and rhythm. Since their discovery in neurons and cardiac pacemaker cells, they attracted the attention of medicinal chemistry and pharmacology as novel targets to shape (patho)physiological mechanisms. To date, ivabradine represents the first-in-class drug

Hyperpolarization-gated, cyclic nucleotide-activated (HCN1-4) channels are inwardly rectifying cation channels that display voltage dependent activation and de-activation. Pathogenic variants in HCN1 are associated with severe developmental and epileptic encephalopathies including the de novo HCN1 M305L variant. M305 is located in the S5 domain that is implicated in coupling voltage sensor domain movement

The coronavirus disease (COVID-19) arises from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which is an enveloped RNA virus. COVID-19 has rapidly spread throughout the world by infecting more than 143 million people and causing 3.04 million deaths worldwide by 22 April 2021, confirmed by the World Health Organization. It caused great concern and pandemic all over the world, therewithal

Medicinal plants serve as a valuable source of secondary metabolites since time immemorial. Computational Research in 21st century is giving more attention to medicinal plants for new drug design as pharmacological screening of bioactive compound was time consuming and expensive. Computational methods such as Molecular Docking, Molecular Dynamic Simulation and Artificial intelligence are significant

Bone remodeling is a complex physiological process that spans across multiple spatial and temporal scales and is regulated by both mechanical and hormonal cues. An imbalance between bone resorption and bone formation in the process of bone remodeling may lead to various bone pathologies. One powerful and non-invasive approach to gain new insights into mechano-adaptive bone remodeling is computer modeling

The sinoatrial node (SAN) is the natural pacemaker of the heart, producing the electrical impulse that initiates every heart beat. Its activity is tightly controlled by the autonomic nervous system, and by circulating and locally released factors. Neurohumoral regulation of heart rate plays a crucial role in the integration of vital functions and influences behavior and ability to respond to changing

The pulmonary epithelial sodium ion channel (ENaC) is gaining importance for its sodium gating and mechanosensitive roles. The mechano functional studies on ENaC suggest direct molecular interactions between the ENaC protein with cytoskeleton microtubules and other extracellular matrix components. Also, in few mechanotransduction studies, ENaC was shown to respond both to membrane stretch as well as

Tissue and organ regeneration is the dynamic process by which a population of cells rearranges into a specific form with specific functions. Traditional tissue regeneration utilizes tissue grafting, cell implantation, and structured scaffolds to achieve clinical efficacy. However, tissue grafting methods face a shortage of donor tissue, while cell implantation may involve leakage of the implanted cells

Light Sheet Fluorescence Microscopy (LSFM) has revolutionized how optical imaging of biological specimens can be performed as this technique allows to produce 3D fluorescence images of entire samples with a high spatiotemporal resolution. In this manuscript, we aim to provide readers with an overview of the field of LSFM on ex vivo samples. Recent advances in LSFM architectures have made the technique

In recent years, light-sheet fluorescence microscopy (LSFM) has found a broad application for imaging of diverse biological samples, ranging from sub-cellular structures to whole animals, both in-vivo and ex-vivo, owing to its many advantages relative to point-scanning methods. By providing the selective illumination of sample single planes, LSFM achieves an intrinsic optical sectioning and direct

During the fifty years since President Nixon declared the “War on Cancer”, those inside and outside the cancer community have witnessed the systematic moving of the goalposts attitude to accommodate evidence into an inadequate theory, that is, the Somatic Mutation Theory (SMT). This sorry state promoted a renewable yearly promise that at the end of the next 10-year period the promises uttered in 1971

The funny current, and the HCN channels that form it, are affected by the direct binding of cyclic nucleotides. Binding of these second messengers causes a depolarizing shift of the activation curve, which leads to greater availability of current at physiological membrane voltages. This review outlines a brief history on this regulation and provides some evidence that other cyclic nucleotides, especially

The biological damage caused by the environmental factors such as radiation and its control methods are one of the frontiers of life science research that has received widespread attention. Ionizing radiation can directly interact with target molecules (such as DNA, proteins and lipids) or decomposed by radiation from water, leading to changes in oxidative events and biological activities in cells

Over the last ten years, developments in whole-brain microscopy now allow for high-resolution imaging of intact brains of small rodents such as mice. These complex images contain a wealth of information, but many neuroscience laboratories do not have all of the computational knowledge and tools needed to process these data. We review recent open source tools for registration of images to atlases, and

Most primary sensory neurons (PSNs) generate a slowly-activating inward current in response to membrane hyperpolarization (Ih) and express HCN1 along with additional isoforms coding for hyperpolarization-activated channels (HCN). Changes in HCN expression may affect the excitability and firing patterns of PSNs, but retinal and inner ear PSNs do not fire action potentials, suggesting HCN channel roles

In contrast to Darwinian evolution, which is founded on the material competition between organisms, cellular epigenetic evolution focuses on cell-cell communication of data from one stage of life to another-developmentally, phylogenetically, as injury-repair – ultimately governed by the First Principles of Physiology. By merging ontogeny and phylogeny, since both are based on cell-cell communication

The funny current, If, was first recorded in the heart 40 or more years ago by Dario DiFrancesco and others. Since then, we have learnt that If plays an important role in pacemaking in the sinus node, the innate pacemaker of the heart, and more recently evidence has accumulated to show that If may play an important role in action potential conduction through the atrioventricular (AV) node. Evidence

Hyperpolarization activated cyclic nucleotide gated (HCN) channels and the current they carry, Ih, are widely and diversely distributed in the central nervous system (CNS). The distribution of the four subunits of HCN channels is variable within the CNS, within brain regions, and often within subcellular compartments. The precise function of Ih can depend heavily on what other channels are co-expressed

Compressed sensing (CS) is a signal processing approach that solves ill-posed inverse problems, from under-sampled data with respect to the Nyquist criterium. CS exploits sparsity constraints based on the knowledge of prior information, relative to the structure of the object in the spatial or other domains. It is commonly used in image and video compression as well as in scientific and medical applications

Background Despite the many studies carried out over the past 40 years, the contribution of the HCN4 encoded hyperpolarization-activated ‘funny’ current (If) to pacemaker activity in the mammalian sinoatrial node (SAN), and the human SAN in particular, is still controversial and not fully established. Objective To study the contribution of If to diastolic depolarization of human SAN cells and its dependence

There are strong parallels between the evolutionary origin of species within populations of organisms and new concepts for the origin of cancers within cell populations in the tissues of the body. The analogy is that cancers can be regarded as a new somatic species developing within the host organism. In both cases, understanding the processes involved requires a multi-scale analysis, including higher-level

Since its first description in 1979, the hyperpolarization-activated funny current (If) has been the object of intensive research aimed at understanding its role in cardiac pacemaker activity and its modulation by the sympathetic and parasympathetic branches of the autonomic nervous system. If was described in isolated tissue strips of the rabbit sinoatrial node using the double-electrode voltage-clamp

Recent developments in clearing and microscopy enable 3D imaging with cellular resolution up to the whole organ level. These methods have been used extensively in neurobiology, but their uptake in other fields has been much more limited. Application of this approach to the human heart and effective use of the data acquired present challenges of scale and complexity. Four interlinked issues need to

Murburn concept is a new perspective to metabolism which posits that certain redox enzymes/proteins mediate catalysis outside their active site, via diffusible reactive oxygen species (DROS, usually deemed as toxic wastes). We have recently questioned the proton-centric chemiosmotic rotary ATP synthesis (CRAS) explanation for mitochondrial oxidative phosphorylation (mOxPhos) and proposed an oxygen-centric

DNA undergoes spontaneous point mutations, which are believed to be central to the evolution of the organisms and which are thought to occur by tautomerization of the canonical Guanine-Cytosine (G-C) base pair into non-canonical G*-C* base pair via the double proton tunneling. In the present work, we close a gap in the literature by computing the time delay during the proton tunneling. Our results

The evolutionary origin of language remains unknown despite many efforts to determine the origin of this signature human trait. Based on epigenetic inheritance, the current article hypothesizes that language evolved from cell-cell communication as the basis for generating structure and function embryologically and phylogenetically, as did all physiologic traits. Beginning with lipids forming the first

The physics–biology continuum relies on the fact that life emerged from prebiotic molecules. Here, I argue that life emerged from the coupling between nucleic acid and protein synthesis during which proteins (or proto-phenotypes) maintained the physicochemical parameter equilibria (or proto-homeostasis) in the proximity of their encoding nucleic acids (or proto-genomes). This protected the proto-genome

The maintenance of genome integrity is critical for the faithful replication of the genome during cell division and for protecting cells from accumulation of DNA damage, which if left unrepaired leads to a loss of genetic information, a breakdown in cell function and ultimately cell death and cancer. ATM and ATR are master kinases that are integral to homologous recombination-mediated repair of double

Advancements in neuroscience research have led to steadily accelerating data production and sharing. The online community repository of neural reconstructions NeuroMorpho.Org grew from fewer than 1000 digitally traced neurons in 2006 to more than 140,000 cells today, including glia that now constitute 10.1% of the content. Every reconstruction consists of a detailed 3D representation of branch geometry

Research purpose The sinus node (SN) is the heart's primary pacemaker. Key ion channels (mainly the funny channel, HCN4) and Ca2+-handling proteins in the SN are responsible for its function. Transcription factors (TFs) regulate gene expression through inhibition or activation and microRNAs (miRs) do this through inhibition. There is high expression of macrophages and mast cells within the SN connective

Cancer is traditionally labeled a “cellular growth problem.” However, it is fundamentally an issue of macroevolution where new systems emerge from tissue by breaking various constraints. To study this process, we used experimental platforms to “watch evolution in action” by comparing the profiles of karyotypes, transcriptome, and cellular phenotypes longitudinally before, during, and after key phase

Advanced cancer is one of the major problems in oncology as currently, despite the recent technological and scientific advancements, the mortality of metastatic disease remains very high at 70–90%. The field of oncology is in urgent need of novel ideas in order to improve quality of life and prognostic of cancer patients. The Cancer and Evolution Symposium organized online October 14–16, 2020 brought

Cancer is responsible for the deaths of millions of people worldwide each year. Once metastasized, the disease is incurable and shows resistance to all anti-cancer therapies. The already-elevated level of reactive oxygen species (ROS) in cancer cells is further increased by therapies. The oxidative stress activates the DNA damage response (DDR) and the stressed cancer cell moves towards cell cycle

The gene can be described as the foundational concept of modern biology. As such, it has spilled over into daily discourse, yet it is acknowledged among biologists to be ill-defined. Here, following a short history of the gene, I analyse critically its role in inheritance, evolution, development, and morphogenesis. Wilhelm Johannsen's genotype-conception, formulated in 1910, has been adopted as the

Cognition—sensing and responding to the environment—is the unifying principle behind the genetic code, origin of life, evolution, consciousness, artificial intelligence, and cancer. However, the conventional model of biology seems to mistake cause and effect. According to the reductionist view, the causal chain in biology is chemicals → code → cognition. Despite this prevailing view, there are no examples

One lens with which to understand the complex phenomenon of cancer is that of developmental biology. Cancer is the inevitable consequence of a breakdown of the communication that enables individual cells to join into computational networks that work towards large-scale, morphogenetic goals instead of more primitive, unicellular objectives. This perspective suggests that cancer may be a physiological

The common belief that the neo-Darwinian Modern Synthesis (MS) was buttressed by the discoveries of molecular biology is incorrect. On the contrary those discoveries have undermined the MS. This article discusses the many processes revealed by molecular studies and genome sequencing that contribute to evolution but nonetheless lie beyond the strict confines of the MS formulated in the 1940s. The core

Detecting and treating cancer effectively involves understanding the disease as one of somatic cell and tumor macroevolution. That understanding is key to avoid triggering an adverse reaction to therapy that generates an untreatable and deadly tumor population. Macroevolution differs from microevolution by karyotype changes rather than isolated localized mutations being the major source of hereditary

Despite significant signs of progress in cancer treatment over the past decade, either cancer prevalence or mortality continuously grow worldwide. Current anti-cancer agents show insignificant effectiveness, followed by serious side effects. It is important to find new, highly efficient pharmacological agents to increase cancer patients’ clinical outcomes. Curcumin, a polyphenolic compound, has gained