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From chicken embryo stem cells to snake-tooth-shaped microneedle patches, here are some stunning pictures selected from the annual photos of The Scientist Magazine 2019, let’s experience the beauty of science and art together.


1. Trajectory of chicken embryonic stem cells during development

Within 16 hours, the location of developing chicken endoderm cells was marked by colored traces. Over time, it turns purple at the beginning and white at the end.

Scientists are tracking the process by which stem cells become tissues and organs to understand how genes and molecules guide this process and which forces are at work.

They looked at a group of developing chicken stem cells (called endoderm cells). These stem cells initially formed a flat sheet on the surface of the embryo, and moved to the center as the embryo developed, on the way they formed a hollow digestive tube, and eventually became the lining of the respiratory and gastrointestinal tracts.

The scientists focused their attention on the hindgut, which produces parts of the small, large, and colon. They tracked the movement of endoderm cells over time. The study, published in the January 16 issue of Nature, revealed that the formation of the hindgut is a response to the massive migration of endoderm cells triggered by chemical signals and physical forces.


2. Hair follicles in mice inflamed during cancer treatment

During EGFR suppression, mouse hair follicles showed increased immune cells (red) associated with the infection.

Cancer is usually treated with drugs that limit the activity of the epidermal growth factor receptor (EGFR, a protein involved in cell growth, which may be overactive during the disease). However, EGFR inhibitor drugs can cause serious side effects such as rash. According to a study published December 11 in Science Translational Medicine, scientists have determined that the appearance of the rash appears to be caused by infection after hair growth, and have developed a method to prevent skin damage in mice.
In general, after hair grows from the skin, skin stem cells create a safe barrier around the hair follicles, preventing microorganisms from entering the skin and causing infections. A research team led by cancer researcher Maria Sibilia at the Medical University of Vienna found that inhibiting EGFR in mice can also interfere with the barrier-generating ability of skin stem cells, causing bacteria such as S. aureus to infect damaged skin and cause inflammation. This could explain the skin-related side effects of EGFR inhibitors in cancer patients.
The team also found that treating EGFR-deficient mice with growth factor FGF7 preserves the skin barrier and does not cause tumor growth. FGF7 has the potential to prevent skin damage in cancer-treated patients.


3. Prenatal exposure to cannabis can affect fetal brain development

Mothers who smoke marijuana during pregnancy are more likely to have children with depression, ADHD, and inattention.

As early as 1940, scientists discovered cannabinoids as a group of pharmacologically active substances in cannabis, but the existence of the endocannabinoid system (ECS) has been confirmed for another half a century. In the early 1990s, in about three years, neuroscientists discovered the first cannabinoid receptor (CB1R) in mammals, and then identified the second cannabinoid receptor (CB2R). Later, the first endocannabinoid was identified and named anandamide after the word “blessing” in Sanskrit.

CB1R is considered to be the most widely expressed G protein-coupled receptor in the brain.Its role is to regulate body temperature, transmit hunger signals and process sensory input, and participate in countless other physiological and cognitive states. Cannabis contains at least 108 exogenous cannabinoids, including Δ9-THC bound to CB1R, and dozens of other pharmacologically active compounds such as terpenes and flavones. They interact with ECS, cause changes in mental state, and mediate numerous other effects of drugs in the brain and body.

When marijuana is smoked during pregnancy, exogenous cannabinoids easily enter the bloodstream and cross the placental barrier because of their high lipophilicity. Depending on the dose and frequency used, the active metabolite can be circulated for 5 days, allowing the fetus to be “effectively and permanently” exposed to the active compounds of cannabis. Therefore, researchers expect that this exposure will have a profound effect on the development of fetal ECS.

To date, the three largest longitudinal studies of offspring of women who smoke cannabis once a week or more during pregnancy have identified their significant and consistent impact on early offspring development and adulthood. Results: In infancy, this includes impulsivity , Increased ADHD and bad behavior, and decreased memory impairment and IQ scores. In adolescence and early adulthood, this has been linked to persistent declines in memory and attention, higher drug use, ADHD, depressive symptoms, and increased incidence of psychotic and schizophrenia-like symptoms. Increasing reports from parents and school teachers about problematic behaviors and violations of children exposed to cannabis are further evidence of these mental health issues.

However, the nature of this relationship remains unclear. In addition, quantifying cannabis intake is fraught with challenges, such as the potency of cannabis and the proportions of various active cannabinoids it contains. Therefore, researchers cannot yet confidently say how drug doses affect these correlations. Now, researchers in the laboratory are linking observations about mental health with the biological mechanisms of cannabis use to better manage the risks of cannabis use during pregnancy.


4. Microneedle patches inspired by snake teeth

Microneedle patch displayed on human thumb. When applied to its surface with gentle pressure, it can deliver liquid medication. The upper left scale is 100 μm, and the lower right scale is 5 mm.

When a snake bites its prey, it injects venom through its grooved teeth. Inspired by snake fangs, scientists designed a flexible patch covered with microneedles to deliver liquid medications through the skin. The research results were published in the journal Science Translational Medicine on July 31. Newly invented microneedles similar in shape to snake teeth can quickly inject lidocaine and inactivated influenza viruses into mice and guinea pigs.

The vaccine strengthens the immune system of laboratory animals, making them resistant to lethal doses of influenza virus. Scientists hope to test their invention on large animal models next.


5. Cerebrospinal fluid is drained through the lymphatic vessels of the skull base

Fine imaging of the central nervous system of rodents reveals new information about the path of cerebrospinal fluid away from the brain. The hot spots of the meningeal lymphatic vessels (green) shown in the red blood vessels at the bottom of the cranial bone of rodents are specifically used to drain cerebrospinal fluid.

For years, scientists have thought that the brain lacks a lymphatic system, which raises questions about how fluids, macromolecules, and immune cells leave the brain. In 2015, two studies in mice provided evidence that the brain actually has a traditional lymphatic system on the outermost layer of the meninges-these coverings protect the brain and help maintain its shape, but scientists haven’t figured out what the cerebrospinal fluid and The exact route of the molecule.

In a study published in the journal Nature on July 24, researchers found that a hot spot of meningeal lymphatics in the base of the skull of rodents was specifically used to expel cerebrospinal fluid and allow proteins and other large molecules to leave the brain.

Kari Alitalo, from the University of Helsinki, who was not involved in this latest study, but who participated in the early 2015 study, said: “I’m relieved that we got a lot of opposite comments when we published our article in 2015, and some people don’t believe that lymphatics are really Can participate in cerebrospinal fluid drainage. ”
After seeing evidence published by Kipnis and Alitalo’s team, Gou Young Koh, a researcher at the Korea Academy of Science and Technology, wanted to figure out how cerebrospinal fluid was lost. He and his colleagues used transgenic mice to observe the anatomy and morphology of the lymphatic system of the brain, and found that in contrast to the meningeal lymphatics (ie, dorsal meningeal lymphatics) in the upper part of the skull, the basal lymphatics were very close to the fluid-filled space around the brain, and There are specialized valves and junctions that allow them to both retract and transport cerebrospinal fluid.

Antoine Louveau, who has studied the dorsal meningeal lymphatics at the Cleveland Clinic, said: “This is important data to convince the field that the meningeal lymphatic network is indeed actively involved in the drainage of cerebrospinal fluid. Dorsal lymphatic and basal lymphatic vessels The anatomical differences between them and their possible role in neurological diseases are the main goals of future research. If the dorsal lymphatics are not used for drainage, then this raises a question as to why they were here from the beginning “Why does the body allow these lymph vessels to extend to a non-functional area?”

Others in the industry question whether the study reveals the full story. Steven Proulx, who also studied cerebrospinal fluid outflow pathways at the University of Bern, said: “My main concern with this paper is that they have ignored some of the other outflow pathways we have shown, as well as many outflow pathways shown in the past. This is still an important issue. , What are the main outflow pathways, and how this changes between different species. People are eager to see what is happening in humans, but it is very difficult to translate these research results. ”


6. Microorganisms on the hand

Hand microorganisms growing on agar plates.

The research direction of Cat Bishop, a scientist at the University of Oklahoma in the United States, is how to use chemical probes to treat resistant Clostridium difficile (very sensitive to oxygen and difficult to isolate and culture), but for the annual agar art competition of the American Society of Microbiology, She wanted to cultivate other kinds of bacteria for artistic creation, so she chose the microbes growing on her hands.

Bishop said, “When I saw it after 48 hours of incubation, I thought it was beautiful, so I decided to publish (on Twitter) the photos to make my fellow scientists ‘Monday brighter, with the caption saying’ My hand The flowers are waving to you, good morning Monday! ‘”.

At present, the research team has not formally identified these bacteria, but Bishop found Pseudomonas and Staphylococcus and a yeast colony near the center of the petri dish. “I think this cool project is a good example of the teamwork and curiosity of our lab,” Bishop said excitedly.


7. Cross section of brain organoids

Researchers have developed organoids that show EEG activity, making it possible for epilepsy research.

Cortical organoids-Three-dimensional nerve bundles and glial cells from induced pluripotent stem cells grown in petri dishes look like miniature brains. Although the gene expression, cell types, and tissue structures found in these spherical structures are similar to those in the developing cerebral cortex, it is unclear whether they are also a suitable model to explore how neural networks are formed.

In a study published August 29 in the Cell Stem Cell journal, researchers found that organoids derived from human stem cells generate brain waves, and that brain waves become more complex as development progresses. This synchronized neural activity can be blocked by drugs, which are signals that cells communicate with each other and form functional neural circuits in the miniature brain.

Previous research has shown that neurons in cortical organoids can fire everywhere. Alysson Muotri, a biologist at the University of California, San Diego, said he initially suspected that these organisms could create more complex neural networks, at least in part because they lacked some of the cell types found in the developing brain.

To explore this issue, he and his team used “reprogramming induced pluripotent stem cells from healthy adult male fibroblasts” to culture organoids and confirmed that the typical cell types found in the cortex are organized and developing The cerebral cortex is similar. They then cultivated miniature brains on special petri dishes containing multiple electrode arrays for recording neural activity.

When the culture was about two months old, researchers began to observe rhythmic spikes in action potentials on multiple neurons near the electrode array. As the organoids mature, the frequency and complexity of neural activity continues to increase and may be disrupted by drugs that block synaptic activity, suggesting the existence of neural networks.

Muotri’s team next studied the possible similarities between organoid brain waves and the human brain, and found it difficult to distinguish organoids from EEG data in preterm infants aged 25-38 weeks. Muotri said that this result may mean that organoid electrical activity follows a development trajectory similar to that of the human brain. In the future, this model system may be used to study situations where neural network functions are different, such as epilepsy.

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