Swept Confocally Aligned Planar Excitation (SCAPE) Microscopy Provides High Speed 3D Images

A new microscope that can image cells in living things at high speed and in 3D has been developed at Columbia University Medical Center (CUMC). Swept Confocally Aligned Planar Excitation Microscopy or SCAPE is 10 to 100 times faster in 3D imaging than other conventional microscopy systems.

Elizabeth Hillman who is an associate professor of biomedical engineering at Columbia Engineering and of radiology at CUMC developed the microscope. She believes that the advancement of biomedical and neuroscience research has its foundation on real-time 3D imaging at the cellular resolution. She says that, ""With SCAPE, we can now image complex, living things, such as neurons firing in the rodent brain, crawling fruit fly larvae, and single cells in the zebrafish heart while the heart is actually beating spontaneously--this has not been possible until now.""

Unlike other microscopes that uses two objective lenses to help produce the 3d image, SCAPE uses a single-objective lens. A light sheet is swept through the sample producing the 3D image without even moving the lens or the sample.

The image on the left shows that the sample is lit up by a thin sheet of blue light at an angle which is swept back and forth within the sample. This area is then imaged onto a high speed sCMOS (Scientific Complementary Metal–Oxide–Semiconductor) camera through the objective lens. The illuminated plane is always co-aligned with the plane of the camera through de-scanning and image rotation optics. The end result is data equivalent to conventional light-sheet microscopy, but requiring a single, stationary objective lens, no sample translation, and consequently very high speed 3-D imaging. (See image on the left).

Although SCAPE currently does not have the penetration depth of a two photon microscope, the next-generation versions of SCAPE are in development that will deliver even better speed, resolution, sensitivity, and penetration depth.

Aside from neuroscience and biomedical research, where capturing live neurons can now be possible, SCAPE also has future potential in molecular biology and other clinical applications.

Slowing Down Aging Process Through Hematopoietic Stem Cells and Molecular Protein Wnt5a

Human Stem Cell

Scientists are studying a signalling pathway that links hematopoietic stem cells and the Wnt5A protein that can slow or even reverse aging. They noted that the WNT pathway that signals the production of Wnt5a leads to the activation of another protein called Cdc42 which results in stem cell aging. By suppressing the pathway, stem cells are rejuvenated and functionally acts younger.

Stem cells are cells in the body that can transform into other higher types of cells, tissue, or even organs. The stem cell observed in this study are hematopoietic stem cells (HSC). HSCs can be found in the bone marrow and also in the umbilical cord blood, embryo or peripheral blood in the human body. They can transform into many different types of blood cells such as erythrocytes, basophils, neutrophils and B-lymphocytes.

By suppressing the Cdc42 protein through the molecular signalling pathway, HSC starts to function younger which can lead to therapies that will boost their immune systems, fight illnesses and enhance overall vitality especially for the elderly.

Atomic Movement Recorded In Real Time Through Femtosecond Electron Diffraction

Scientists at the University of Toronto were able to observe and record motions of atoms in real time. This is a huge development on the understanding chemistry and biology at the atomic level.

For the first time atomic movement as they undergo chemical transformation has been directly recorded through a process called electron diffraction. As the atoms convert into new structures and adopt new properties, scientists observed and recorded this transitional state as it happens.

For the process to work, an ultrabright femtosecond electron source is used to light up the molecular motions in the organic crystal during its transition phase. Using three key reaction coordinates within the crystal, scientists were able to reconstruct the structural evolution of its molecular system.

Combining the coordinates to make a 3D model and using Femtosecond Electron Diffraction, the duration of the transition and position of the moluecules as well as its reaction trajectory is obtained. (See video)

Development of Broad Spectrum Antivirals For Potential Treatment of Various Viral Infections

There is no effective small-molecule therapy for most viruses, including highly pathogenic viruses such as Ebola, which is associated with mortality rates of up to 90 percent following infection. Filone et al, describe compounds that inhibit the replication of genetically diverse viruses, including Ebola. These compounds can limit virus replication (illustrated as green molecules "blocking" spread of orange Ebola virus virions from an infected cell). These molecules represent probes of a central virus function as well as a lead compound for the development of effective broad-spectrum antivirals.
Credit: Image created by Claire Marie Filone and John Connor, Ebola virus micrograph by Chris Reed at USAMRIID.

Researchers are studying molecules called indolie alkaloids that can be modified to enhance antiviral activity for a possible treatment for various viral infections such as the deadly Ebola virus.

Viruses are small infectious agents that are made up of a chain of genetic DNA or RNA. Viruses needs a host cell to stay alive and replicate.

The difference between bacteria and a virus is that a bacteria is a living single celled organism. A virus is not considered a living organism (there are some arguments for and against this). A virus does not have any cellular parts or internal cellular structure. It consists only of a protein coat that holds a coiled string of nucleic acid, in this case DNA or RNA.

While bacteria can thrive in most surfaces and environments, a virus needs a living host to stay alive. It infects the cells of the host and uses these cells to make copies of it, infecting other cells in the process. Viruses spread from host to host through contact; direct or indirect.

Antibiotics only treat bacterial infections. They address bacterial infections by killing off the bacteria. For viral infections, there are relatively few drugs that can address these. This is because the virus lives inside the cells. Destroying the virus means killing the cells of the host.

Immunizing against a virus is the most common way. Immunization protects the body from contracting the viral infection. But as seen with the common cold or the influenza virus, viruses can mutate and work around the immunization.

Lipoxin A4 Discovered To Serve Dual Purpose In Treatment and Management of Asthma

Scientists from from Brigham and Women's Hospital have discovered a molecule that plays a dual role in the treatment and management of asthma.

Asthma is a breathing disorder wherein air passages start to swell and narrow which restricts the airflow to and from the lungs of the patient. The air passages, called bronchioles, start to swell up and tighten resulting in shortness of breath, coughing, tightening of the chest and a wheezing sound while trying to breath.

Asthma can be triggered by chemicals in the air or food, exercise, weather, stress, medicine, and other allergens. Also it is advised that people suffering from asthma to avoid exposure to cigarette smoke and other air born particles such as pollen.

Asthma is an incurable condition and can only be managed and controlled by medication such as inhaled corticosteroids. These help keep the swelling down and reduce the effects of an asthma attack.

The purpose of asthma medication is to reduce the swelling of the bronchioles. Recently, researchers from Brigham and Women's Hospital have discovered a molecule that can be used to effectively treat and manage asthma attacks by both cutting down on the swelling and also inhibiting further inflammation of the bronchioles.

Lipoxin A4's process of quelling airway inflammation is similar to putting out a forest fire, according to Bruce Levy, M.D., Pulmonary and Critical Care Medicine Division, BWH Department of Internal Medicine. Molecular image courtesy of Levy Lab.
Credit: Levy Lab

Faster Process In Molecular Pharmacological Drug Design Discovered

Scientists at Yale University have discovered a faster and efficient way of designing and assembling drug compounds that can lead to more efficient drug discovery and medical treatment.

Molecular biology focuses on the molecular basis of biological activity; the physiological, chemical, and metabolic processes. It involves the knowledge of how biological molecules such as proteins, polysaccharides, lipids, and nucleic acids interact with each other and other biomolecules in the body.

Because molecular biology focuses on the understanding of cell biology and the bio-chemical interactions involved with it at the molecular level, the study is a prime factor in pharmacology. Through the molecular analysis and study of biomolecules and biochemical processes, pharmacologists are able to design chemicals that acts on a specific signal or metabolic process on a molecular level. The reaction or interaction is controlled, focused, and precise.

This leads to better drugs and medication that efficiently and safely addresses a condition with as little or no adverse effects on the individual.