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Concept: Robert Hooke


Isaac Newton’s reputation was initially established by his 1672 paper on the refraction of light through a prism; this is now seen as a ground-breaking account and the foundation of modern optics. In it, he claimed to refute Cartesian ideas of light modification by definitively demonstrating that the refrangibility of a ray is linked to its colour, hence arguing that colour is an intrinsic property of light and does not arise from passing through a medium. Newton’s later significance as a world-famous scientific genius and the apparent confirmation of his experimental results have tended to obscure the realities of his reception at the time. This paper explores the rhetorical strategies Newton deployed to convince his audience that his conclusions were certain and unchallengeable. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

Concepts: Optics, Physics, Light, Rainbow, Robert Hooke, Gottfried Leibniz, Isaac Newton, Royal Society


Time-lapse imaging is a powerful tool for studying cellular dynamics and cell behavior over long periods of time to acquire detailed functional information. However, commercially available time-lapse imaging systems are expensive and this has limited a broader implementation of this technique in low-resource environments. Further, the availability of time-lapse imaging systems often present workflow bottlenecks in well-funded institutions. To address these limitations we have designed a modular and affordable time-lapse imaging and incubation system (ATLIS). The ATLIS enables the transformation of simple inverted microscopes into live cell imaging systems using custom-designed 3D-printed parts, a smartphone, and off-the-shelf electronic components. We demonstrate that the ATLIS provides stable environmental conditions to support normal cell behavior during live imaging experiments in both traditional and evaporation-sensitive microfluidic cell culture systems. Thus, the system presented here has the potential to increase the accessibility of time-lapse microscopy of living cells for the wider research community.

Concepts: Cell nucleus, Cell, Cell biology, Cytoplasm, Microscope, Cell culture, Design, Robert Hooke


Although there are a number of descriptions of ‘blood infusion’ in antiquity, it was the publication of the discovery of the circulation of blood in 1628 by William Harvey and the work of Christopher Wren and Robert Boyle in 1663 on the infusion of different materials into dogs that paved the way to the possible practical attempts at actual blood transfusion. Although these early experiments, principally by Richard Lower in England and Jean Denis in France provided valuable information regarding inter-species incompatibility and the problems of blood coagulation, it was not until the work of James Blundell in the early part of the 19th century that blood transfusion was used as a means of blood replacement. However, blood transfusion was not to become an accepted therapeutic possibility until the discovery of practical anticoagulation and the ABO blood groups at the start of the 20th century.

Concepts: Blood, Red blood cell, Blood type, 20th century, Blood transfusion, 19th century, ABO blood group system, Robert Hooke


Cell printing is becoming a common technique to fabricate cellularized printed-scaffold for biomedical application. There are still significant challenges in soft tissue bioprinting using hydrogels which requires live cells inside the hydrogels. Moreover, the resilient mechanical properties from hydrogels are also required to mechanically mimic the native soft tissues. Herein, we developed a visible-light crosslinked, single-network, biodegradable hydrogel with high elasticity and flexibility for cell printing, which is different from previous highly elastic hydrogel with double-network and two-components. The single-network hydrogel using only one stimulus (visible-light) to trigger gelation can greatly simplify the cell printing process. The obtained hydrogels possessed high elasticity, and their mechanical properties can be tuned to match various native soft tissues. The hydrogels had good cell compatibility to support fibroblast growth in vitro. Various human cells were bioprinted with the hydrogels to form cell-gel constructs, in which the cells exhibited high viability after 7 days of culture. Complex patterns were printed by the hydrogels, suggesting the hydrogel feasibility for cell printing. We believe that this highly elastic, single-network hydrogel can be simply printed with different cell types, and it may provide a new material platform and a new way of thinking for hydrogel based bioprinting research.

Concepts: Organism, Cell type, Tissues, Soft tissue, Printing, Price elasticity of demand, Robert Hooke, Resilience


This year’s Lasker Basic Medical Research Award is shared by William Kaelin, Peter Ratcliffe, and Gregg Semenza for discovery of the pathway by which animal cells sense and adapt to changes in oxygen availability, which plays an essential role in adaptation to a wide variety of physiologic and pathologic conditions.

Concepts: DNA, Protein, Genetics, Adenosine triphosphate, Organism, Eukaryote, Robert Hooke


Abstract Liposomes are well-known cell simulators and are currently studied as drug delivery systems, for a targeted delivery of higher drug concentrations, in specific cells. Novel biophotonic techniques for manipulation and characterization of liposomes have been developed; among which are optical tweezers. In our work, we demonstrate a novel use of line optical tweezers to manipulate and cause liposome deformations. Optical forces induce tension on liposomes, which are stretched along the line optical trap. The method of dielectrophoresis, combined with optical tweezers, was used to measure the exerted optical forces. As a consequence, in the case of reversible liposome deformations, the value of the shear and bending moduli of liposomes was calculated. We anticipate that the selective manipulation of liposomes will help us toward a better understanding of the cellular-liposome interactions. Studying the biomechanical properties of liposomes will provide an insight into the mechanical behavior of individual living cells, which have recently been implicated in many aspects of human physiology and patho-physiology. The biomechanical properties of cells (i.e. deformability, stiffness and elasticity) can be useful biomarkers for various disease processes and changes of the cell state.

Concepts: Cell nucleus, Chromosome, Cell biology, Cytoplasm, Photonics, Robert Hooke, Optical tweezers, Tweezers


Stem cell therapy has emerged as a promising method for improving motor function of patients with cerebral palsy. The aim of this study is to assess the safety and effectiveness of autologous bone marrow mononuclear stem cell transplantation in patients with cerebral palsy related to oxygen deprivation.

Concepts: Clinical trial, Cell division, Stem cell, Bone marrow, Cell biology, Effectiveness, Vesicle, Robert Hooke


Despite its importance for understanding human infertility and congenital diseases, early mammalian development has remained inaccessible to in toto imaging. We developed an inverted light-sheet microscope that enabled us to image mouse embryos from zygote to blastocyst, computationally track all cells and reconstruct a complete lineage tree of mouse pre-implantation development. We used this unique data set to show that the first cell fate specification occurs at the 16-cell stage.

Concepts: Cell, Human, Embryo, Developmental biology, Cell division, Zygote, Morula, Robert Hooke


Fluorescence-activated cell sorting (FACS) applying flow cytometry to separate cells on a molecular basis is a widespread method. We demonstrate that both fluorescent and unlabeled live cells in a Petri dish observed with a microscope can be automatically recognized by computer vision and picked up by a computer-controlled micropipette. This method can be routinely applied as a FACS down to the single cell level with a very high selectivity. Sorting resolution, i.e., the minimum distance between two cells from which one could be selectively removed was 50-70 micrometers. Survival rate with a low number of 3T3 mouse fibroblasts and NE-4C neuroectodermal mouse stem cells was 66±12% and 88±16%, respectively. Purity of sorted cultures and rate of survival using NE-4C/NE-GFP-4C co-cultures were 95±2% and 62±7%, respectively. Hydrodynamic simulations confirmed the experimental sorting efficiency and a cell damage risk similar to that of normal FACS.

Concepts: Gene, Fibroblast, Cell membrane, Cell division, Stem cell, Cell biology, Flow cytometry, Robert Hooke


Molecular oxygen is one of the most important variables in modern cell culture systems. Fluctuations in its concentration can affect cell growth, differentiation, signaling, and free radical production. In order to maintain culture viability, experimental validity, and reproducibility, it is imperative that oxygen levels be consistently maintained within physiological “normoxic” limits. Use of the term normoxia, however, is not consistent among scientists who experiment in cell culture. It is typically used to describe the atmospheric conditions of a standard incubator, not the true microenvironment to which the cells are exposed. This error may lead to the situation where cells grown in a standard “normoxic” oxygen concentration may actually be experiencing a wide range of conditions ranging from hyperoxia to near-anoxic conditions at the cellular level. This apparent paradox is created by oxygen’s sluggish rate of diffusion through aqueous medium, and the generally underappreciated effects that cell density, media volume, and barometric pressure can have on pericellular oxygen concentration in a cell culture system. This review aims to provide an overview of this phenomenon we have termed “consumptive oxygen depletion” (COD), and includes a basic review of the physics, potential consequences, and alternative culture methods currently available to help circumvent this largely unrecognized problem.

Concepts: DNA, Oxygen, Bacteria, Molecule, Chemistry, Cell culture, Oxygen therapy, Robert Hooke