Tuesday, 16 October 2018

Researchers develop 3D printed objects that can track and store how they are used

Cheap and easily customizable, 3-D printed devices are perfect for assistive technology, like prosthetics or "smart" pill bottles that can help patients remember to take their daily medications.
Cell Tissue Science 2019
Researchers at the University of Washington have developed 3D printed assistive technology that can track and store their use — without using batteries or electronics. Credit: Mark Stone/University of Washington

But these plastic parts don't have electronics, which means they can't monitor how patients are using them. Now engineers at the University of Washington have developed 3-D printed devices that can track and store their own use -- without using batteries or electronics. Instead, this system uses a method called backscatter, through which a device can share information by reflecting signals that have been transmitted to it with an antenna.
"We're interested in making accessible assistive technology with 3-D printing, but we have no easy way to know how people are using it," said co-author Jennifer Mankoff, Professor, UW's Paul G. Allen School of Computer Science & Engineering. "Could we come up with a circuitless solution that could be printed on consumer-grade, off-the-shelf printers and allow the device itself to collect information? That's what we showed was possible in this paper."
Previously the team developed the first 3-D printed objects that connect to Wi-Fi without electronics. These purely plastic devices can measure if a detergent bottle is running low and then automatically order more online.
"Using plastic for these applications means you don't have to worry about batteries running out or your device getting wet. That can transform the way we think of computing," said Shyam Gollakota, Associate Professor, Allen School. "But if we really want to transform 3-D printed objects into smart objects, we need mechanisms to monitor and store data."
The researchers tackled the monitoring problem first. In their previous study, their system tracks movement in one direction, which works well for monitoring laundry detergent levels or measuring wind or water speed. But now they needed to make objects that could monitor bidirectional motion like the opening and closing of a pill bottle.
"Last time, we had a gear that turned in one direction. As liquid flowed through the gear, it would push a switch down to contact the antenna," said lead author Vikram Iyer, Doctoral Student, UW Department of Electrical & Computer Engineering. "This time we have two antennas, one on top and one on bottom, that can be contacted by a switch attached to a gear. So opening a pill bottle cap moves the gear in one direction, which pushes the switch to contact one of the two antennas. And then closing the pill bottle cap turns the gear in the opposite direction, and the switch hits the other antenna."
Both of the antennas are identical, so the team had to devise a way to decode which direction the cap was moving.
"The gear's teeth have a specific sequencing that encodes a message. It's like Morse code," said co-author Justin Chan, Doctoral Student, Allen School. "So when you turn the cap in one direction, you see the message going forward. But when you turn the cap in the other direction, you get a reverse message."
In addition to tracking, for example, pill bottle cap movement, this same method can be used to monitor how people use prosthetics, such as 3-D printed e-NABLE arms. These mechanical hands, which attach at the wrist, are designed to help children with hand abnormalities grasp objects. When children flex their wrists, cables on the hand tighten to make the fingers close. So the team 3-D printed an e-NABLE arm with a prototype of their bidirectional sensor that monitors the hand opening and closing by determining the angle of the wrist. The researchers also wanted to create a 3-D printed object that could store its usage information while out of Wi-Fi range. For this application, they chose an insulin pen that could monitor its use and then signal when it was getting low.
"You can still take insulin even if you don't have a Wi-Fi connection," Gollakota said. "So we needed a mechanism that stores how many times you used it. Once you're back in the range, you can upload that stored data into the cloud."
This method requires a mechanical motion, like the pressing of a button, and stores that information by rolling up a spring inside a ratchet that can only move in one direction. Each time someone pushes the button, the spring gets tighter. It can't unwind until the user releases the ratchet, hopefully when in range of the backscatter sensor. Then, as the spring unwinds, it moves a gear that triggers a switch to contact an antenna repeatedly as the gear turns. Each contact is counted to determine how many times the user pressed the button. These devices are only prototypes to show that it is possible for 3-D printed materials to sense bidirectional movement and store data. The next challenge will be to take these concepts and shrink them so that they can be embedded in real pill bottles, prosthetics or insulin pens, Mankoff said.
"This system will give us a higher-fidelity picture of what is going on," she said. "For example, right now we don't have a way of tracking if and how people are using e-NABLE hands. Ultimately what I'd like to do with these data is predict whether or not people are going to abandon a device based on how they're using it."
We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem CellRegenerative MedicineStem Cell TherapyCancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . For more info visit :Cell Tissue Science 2019

Sunday, 14 October 2018

CRISPR Helps Identify New Biomarker For Alzheimer’s Disease

STIM1 protein expression decreases with the progression of neurodegeneration in Alzheimer’s disease, new research indicates.

Conducted at the Institute of Molecular Pathology Biomarkers, University of Extremadura,Spain, the study’s aim was to develop a model for studying Alzheimer’s disease (AD) of sporadic origin—in other words, AD that is not due to a hereditary genetic mutation. While Alzheimer’s disease of familial or hereditary type is responsible for around 5 percent of all cases, it is thought that 95 percent of incidents are of unknown or sporadic origin.
“In Alzheimer’s of family origin, there already exist animal models, because we know which genes are linked to this illness. However, in Alzheimer’s disease of unknown origin, to date there are no models that enable us to study how it develops,”said Francisco Javier Martin-Romero.

Genetic Cut-and-paste

The researchers analysed cultures of damaged brain tissue from a region called medial frontal gyrus, with clinically confirmed alterations provoked by Alzheimer’s. These clinical samples were analysed and compared with healthy tissue from patients of the same age.
As a result of this comparative study, the scientists found a deficiency in the protein Stromal interaction molecule 1 (STIM1) in brain tissue from patients with AD.
“We have been working with this protein for 10 years, but we weren’t expecting these results with sporadic Alzheimer’s,”said Martin-RomeroThe next step the researchers took was to observe the involvement of this protein STIM1 in the neurodegeneration of the neuron, and they did so using the genetic editing system CRISPR, known popularly as “genetic cut-and-paste.”
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STIM1 expression during differentiation of SH-SY5Y cells
Credit: Carlos Pascual-Caro et al, CC-BY

The researchers applied a strategy to eliminate the expression of the gene STIM1 in the neuroblastoma SH-SY5Y cell line, editing the genome with CRISPR/Cas9 using an in vitro model to examine the phenotype of the neuronal cells deficient in STIM1.
“We use the CRISPR technique on a regular basis in the Faculty of Sciences at the UEx, as it has the great advantage that the genome remains stable despite the cuts in the DNA. In this specific case, CRISPR silences the gene that permits the expression of the protein STIM1 in the neuron. Thus, we were able to simulate what occurs in the neuron without this protein, and we observed alterations very similar to those seen in tissues with Alzheimer’s,”Martin-Romero said.

L-type Voltage-gated Calcium Channels

Up to now, the effects of a deficiency in this protein critical to sporadic Alzheimer’s were not known, and so this research offers a new biomarker for the illness, an indicator of the progression of the neurodegenerative process.

One of the alterations observed due to the deficiency of STIM1 is in the transport of calcium ions through the plasma membrane of the neurons.
“This calcium is necessary for the cell to be fully viable, and an alteration in this process affects its entire physiology, finally causing its death. The cell is unable to halt the transport of calcium, which becomes unregulated and out of control,"said Martin-Romero. The investigator added that this transport takes place through calcium ion channels regulated by a voltage.
These L-type voltage-gated calcium channels can be blocked using pharmaceuticals based on dihydropyridine. In fact, the researchers were able to halt cell death in vitro using pharmaceuticals based on dihydropyridine because of that blocking action, representing an important new finding in the treatment of Alzheimer’s.

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Loss of mitochondrial function in STIM1-KO differentiated cells Credit: Carlos Pascual-Caro et al, CC-BY

The next step for the investigators will be to work with pluripotent stem cells and differentiate them into neurons, first for mice and then for humans, to make development of a model possible. This will allow a description of how the absence of stimulus or reduction in the protein STIM1 determines cell aging in sporadic Alzheimer’s disease.

We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem CellRegenerative MedicineStem Cell TherapyCancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” .For more info visit :Cell Tissue Science 2019

Friday, 12 October 2018

Bug that causes stomach cancer could play a role in colorectal cancer

A bacterium known for causing stomach cancer might also increase the risk of certain colorectal cancers, particularly among African Americans, according to a study led by Duke Cancer Institute researchers.

The finding describes an association between antibodies to H. pylori bacteria and an increased risk of colorectal cancers, although it does not establish the bacteria as a definitive cause; those studies are ongoing.

But in an analysis of more than 4,000 colorectal cancer cases culled from large, diverse cohort studies, the researchers found a significant correlation between colorectal cancer incidence and those who had been infected with a virulent strain of H. pylori that is especially common among African Americans.
"The link between infection and cancer is intriguing, particularly if we can eradicate it with a simple round of antibiotics," said Meira Epplein, Ph.D., Co-leader of Cancer Control and Population Sciences at Duke Cancer Institute. "Our study provides strong evidence that we need to pursue this research to establish a definitive cause-and-effect."
They analyzed blood samples from more than 8,400 ethnically and regionally diverse study participants -- half who went on to develop colorectal cancer and the other half with no such diagnosis.

The researchers found that H. pylori infections were equally common in both the cancer and non-cancer group, with 4 in 10 patients in both groups testing positive for exposure to the bacterium.

But stark racial differences also appeared. White patients had below average H. pylori infection rates, and Asian Americans had average rates. For black and Latino patients, however, the rates were much higher. Among African Americans, 65 percent of the non-cancer patients and 71 percent of the colorectal cancer patients had H. pylori antibodies; among Latinos, 77 percent of the non-cancer group and 74 percent of the cancer group had antibodies.

Further analysis showed that antibodies to four H. pylori proteins were most often present among the different ethnic groups with colorectal cancer. One H. pylori protein in particular, VacA, had the strongest association with increased odds of colorectal cancer among the African American patients in the study, and, specifically, high levels of antibodies to this protein were associated with colorectal cancer incidence in both African Americans and Asian Americans.
"It was surprising to find VacA antibodies increased the odds of colorectal cancer in African Americans and Asian Americans, and not in whites and Latinos," Epplein said. "This is a big question -- are people harboring different bacteria based on genetic origin or heritage? This is part of what we need to figure out."
Epplein said additional studies might also determine whether antibodies to the H. pylori VacA protein could serve as a marker of colorectal cancer risk if it isn't causing the cancer directly.
We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem CellRegenerative MedicineStem Cell TherapyCancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . For more info visit :Cell Tissue Science 2019

Thursday, 11 October 2018

Redrawing the structure of an immune system protein

Researchers have revealed the structure of an essential immune protein, creating future possibilities to develop more effective medicines for a range of illnesses from cancer to neurological diseases. University of Tokyo researchers made this discovery with computerized image analysis and modern electron microscope imaging.
Cell Tissue Science2019
Electron microscopes and modern computer image processing allowed University of Tokyo researchers to uncover the correct structure of a protein essential in the immune system, IgM, and a much smaller protein that is bound inside, AIM. IgM is the larger, incomplete hexagon shape and AIM is the smaller broad bean shape inside the wedge-shape gap. In the right-side image, AIM is more easily recognized as the bright white, broad-bean-shaped spot.
Credit: Image by Hiramoto et al., originally published in Science Advances, CC-BY
Researchers verified the structure of natural immunoglobulin M (IgM) protein, an important part of the immune system, using mouse and human versions of the protein. IgM is now understood to be shaped like an incomplete hexagon, or a pentagon with a wedge-shaped gap.

IgM is the first immune system protein that develops in the human fetus and remains the first responder to pathogens throughout life. The structure of IgM was first identified in 1969 as a "five-pointed, star-shaped table" and updated in 2009 to be a five-sided dome or "mushroom cap."
"The original IgM model was made by looking at a few individual molecules by hand with what today we think is a low-resolution microscope. Now we have clearer pictures and the computer can examine thousands of individual IgM molecules," said Miyazaki.
The 2018 discovery of the incomplete hexagon was actually a secondary interest for Miyazaki, originally a medical doctor who has built his research career studying a different protein called apoptosis inhibitor of macrophage (AIM).

Since identifying the correct shape of IgM, researchers now understand that inactive AIM is nestled inside the gap of the IgM incomplete hexagon. The structural connection between IgM and AIM means that drugs with the ability to regulate the release of AIM could be used to create AIM-based disease therapies.
"We can think of AIM as a fighter jet and IgM as the aircraft carrier ship. When other molecules activate the immune system, IgM releases AIM. The much smaller AIM protein goes around the body to clear away damaged cells and prevent disease," said Miyazaki.
Miyazaki identified AIM in 1999 while working at the Basel Institute for Immunology Institute in Switzerland. Its small size means AIM is easily eliminated from the body by the kidneys and excreted in urine, so staying bound within the larger IgM protects AIM from being removed before it is needed.

AIM is a common molecule in the bloodstream, but it is only active when the body develops a disease. AIM is known to be important for preventing obesity, fatty liver disease, hepatocellular carcinoma (liver cancer), multiple sclerosis (MS), fungus-induced peritonitis (inflammation of the abdominal wall membrane), and acute kidney injury.

The incomplete hexagon structure is still only a 2D understanding of IgM structure. Miyazaki and his team continue to do additional analysis and hope to report the 3D structure of IgM soon.
We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem CellRegenerative MedicineStem Cell TherapyCancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . For more info visit :Cell Tissue Science 2019

Wednesday, 10 October 2018

There's a better way to decipher DNA's epigenetic code to identify disease

A new method for sequencing the chemical groups attached to the surface of DNA is paving the way for better detection of cancer and other diseases in the blood, according to research from the Perelman School of Medicine at the University of Pennsylvania
These chemical groups mark one of the four DNA "letters" in the genome, and it is differences in these marks along DNA that control which genes are expressed or silenced.

Cell Tissue Science 2019
Enzymes, rather than harsh chemical reactions, can be used to reveal the epigenetic code in DNA.
Credit: Rahul Kohli, Univeristy of Pennsylvania

To detect disease earlier and with increased precision, researchers have a growing interest in analyzing free-floating DNA in settings in which there is a limited amount, such as that extruded from tumors into the bloodstream.
"We're hopeful that this method offers the ability to decode epigenetic marks on DNA from small and transient populations of cells that have previously been difficult to study, in order to determine whether the DNA is coming from a specific tissue or even a tumor." said Rahul Kohli, MD, PhD, Assistant Professor of Biochemistry and Biophysics, and Medicine.
For the last several decades, the major methods used to decipher the epigenetic code have relied on a chemical called bisulfite. While bisulfite has proven useful, it also presents major limitations: it is unable to differentiate the most common modifications on the DNA building block cytosine, and more significantly, it destroys much of the DNA it touches, leaving little material to sequence in the lab.

The new method described in this paper builds on the fact that a class of immune-defense enzymes, called APOBEC DNA deaminases, can be repurposed for biotech applications. Specifically, the deaminase-guided chemical reaction is able to achieve what bisulfite could do, but without harming DNA.
"This technological advance paves the way to better understand complex biological processes such as how the nervous system develops or how a tumor progresses," said Hao Wu, PhD, Assistant Professor of Genetics. 
Using this method, the team showed that determining the epigenetic code of one type of neuron used 1,000-times less DNA than required by the bisulfite-dependent methods. From this, the new method could also differentiate between the two most common epigenetic marks, methylation and hydroxmethylation.
"We were able to show that sites along the genome that appear to be modified are in fact very different in terms of the distribution of these two marks," Kohli said. "This finding suggests important and distinctive biological roles for the two marks on the genome."
We encourage researchers all around the globe to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem CellRegenerative MedicineStem Cell TherapyCancer Cell Biology , Technical Advancements in cancer treatment  ,Epigenetics and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . For more info visit :Cell Tissue Science 2019

Monday, 8 October 2018

Novel mechanism for generating our skeleton

There are more than 200 bones in the human body. Bone is formed during embryonic and postnatal skeletogenesis by two distinct, well-organized processes, intramembranous and endochondral ossification.

Mesenchymal stem cells differentiate into chondrocytes to form a cartilaginous template, which, for long bones, induces bone formation through endochondral ossification. Extracellular signal-regulated kinase 5 (Erk5), which is a member of the mitogen-activated protein kinase (MAPK) family, is phosphorylated by MAPK/Erk kinase-5 (Mek5) to regulate the function of various cell types.

Although the MAPK Erk1/2 pathway is well known for regulating skeletogenesis, the in vivo physiological role of the Mek5/Erk5 pathway in skeletal development has been largely unclear to date, because of the early embryonic lethality of global Erk5 knockout mice.

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Schematic model of this study.


By using cell-specific mouse genetics approaches revealed that Erk5 plays a crucial role in skeletogenesis in vivo. Paired-related homeobox 1 (Prx1) is expressed in mesenchymal stem cells in the limb buds. Mesenchymal stem cell-specific Erk5 knockout embryos (Prx1-Cre;Erk5fl/fl embryos) displayed wider long bones and impaired mineralization of the metatarsal. In contrast, chondrocyte-specific Erk5 knockout embryos (Col2a1-Cre;Erk5fl/fl embryos) recapitulated only the wider long bone phenotype of Prx1-Cre;Erk5fl/fl embryos. Accordingly, the investigators revealed that Erk5 controls.
  1. Early chondrogenic differentiation of mesenchymal stem cells, including mesenchymal condensation, through its expression in skeletogenic progenitors
  2. Chondrogenic differentiation after the formation of mesenchymal condensations through its expression in chondrocytes.
Subsequent biochemical analyses found that Erk5 directly phosphorylates Smad1 at Ser206 in the linker region, which is known to trigger its proteasomal degradation in a Smad-specific E3 ubiquitin ligase 1 (Smurf1)-dependent manner. In addition, Erk5 directly phosphorylates Smurf2 at Thr249, leading to accelerated proteasomal degradation of Smad proteins (Smad1, 2 and 3).

The study demonstrated that Smads transcriptionally activate the expression in mesenchymal stem cells of sex-determining region within the Y-type high-mobility group box protein 9 (Sox9), which is the principal transcription factor involved in skeletogenesis. Moreover, using mouse genetic rescue experiments, the investigators revealed that Sox9 is a critical mediator of Erk5-dependent skeletogenesis.

 In conclusion, the Mek5/Erk5 pathway is critical for skeletogenesis in vivo through its expression in mesenchymal stem cells and modulation of Smad protein stability (Smad1, 2, and 3) via Smurf activity (Smurf1 and 2). These findings improve our understanding of the molecular mechanisms underlying skeletal development and spur the development of drugs targeting human cartilage diseases associated with abnormal chondrocyte differentiation and maturation. Moreover, since the Smurf2/Smads cascade is associated with other diseases, including cancer and ageing, the newly identified Mek5/Erk5/Smurf2/Smads/Sox9 cascade is a candidate target for developing drugs to treat a variety of human diseases.
 
We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem CellRegenerative MedicineStem Cell TherapyCancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . For more info visit :Cell Tissue Science 2019

Friday, 5 October 2018

A grape constituent protects against cancer

Lung cancer is the deadliest form of cancer in the world, and 80% of death are related to smoking. In addition to tobacco control, effective chemoprevention strategies are therefore needed. A team of scientists from the University of Geneva (UNIGE), Switzerland, studied a well-known natural product, resveratrol, which is found in grapes and in red wine. While its chemopreventive properties against cancers affecting the digestive tract have been documented by previous studies, resveratrol has so far shown no effect on lung cancers. Thanks to nasal administration, the UNIGE team obtained very promising results in a study conducted in mice and described in the journal Scientific Reports.
"We tried to prevent lung cancer induced by a carcinogen found in cigarette smoke by using resveratrol, an already well-documented molecule, in a mouse model," explains Muriel Cuendet, Associate Professor, School of pharmaceutical sciences, UNIGE Faculty of Science.
This 26 week long study contained four groups of mice.
  • The first one, the control, received neither carcinogen nor resveratrol treatment.
  • The second received only the carcinogen.
  • The third received both the carcinogen and the treatment.
  • Fourth received only the treatment.
"We observed a 45% decrease in tumor load per mouse in the treated mice. They developed fewer tumors and of smaller size than untreated mice," says Muriel Cuendet. When comparing the two groups that were not exposed to carcinogen, 63% of the mice treated did not develop cancer, compared to only 12.5% of the untreated mice. "Resveratrol could therefore play a preventive role against lung cancer," she continues.
This formulation is applicable to humans
However, resveratrol does not seem suitable for preventing lung cancer: when ingested, it is metabolized and eliminated within minutes, and therefore does not have time to reach the lungs. "This is why our challenge was to find a formulation in which resveratrol could be solubilized in large quantities, even though it is poorly soluble in water, in order to allow nasal administration. This formulation, applicable to humans, allows the compound to reach the lungs," explains Aymeric Monteillier, scientist,School of pharmaceutical sciences of the UNIGE Faculty of Science.The resveratrol concentration obtained in the lungs after nasal administration of the formulation was 22 times higher than when taken orally. The chemoprevention mechanism is probably related to apoptosis, a process by which cells program their own death and from which cancer cells escape. The UNIGE research team will now focus on finding a biomarker that could contribute to the selection of people eligible for preventive treatment with resveratrol.
Towards a preventive treatment?
Resveratrol is an already well-known molecule, which is found in food supplements, meaning that no further toxicological study would be needed prior to commercialisation as a preventive treatment. "This discovery is unfortunately of little economic interest to pharmaceutical groups. The molecule is indeed simple and non-patentable and cancer prevention studies require a follow-up over many years," regrets Muriel Cuendet, without excluding the development of preventive treatment in humans..
 
We welcome researchers from different part of the to submit abstract on their latest research at our upcoming conference Cell Tissue Science 2019 which is mainly focuses on the complications the consequences of Stem CellRegenerative MedicineStem Cell TherapyCancer Cell Biology , Technical Advancements in cancer treatment and many more.We welcome you to the our upcoming conference “ 12th World Congress on Cell & Tissue Science” . For more info visit :Cell Tissue Science 2019

Researchers develop 3D printed objects that can track and store how they are used

Cheap and easily customizable, 3-D printed devices are perfect for assistive technology, like prosthetics or "smart" pill bottl...