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Molecular mechanism of extreme mechanostability in a pathogen adhesin

Sciencemag.org / Milles, L. F., Schulten, K., Gaub, H. E., Bernardi, R. C. - High resilience to mechanical stress is key when pathogens adhere to their target and initiate infection. Using atomic force microscopy–based single-molecule force spectroscopy, we explored the mechanical stability of the prototypical staphylococcal adhesin SdrG, which targets a short peptide from human fibrinogen β. Steered molecular dynamics simulations revealed, and single-molecule force spectroscopy experiments confirmed, the mechanism by which this complex withstands forces of over 2 nanonewtons, a regime previously associated with the strength of a covalent bond. The target peptide, confined in a screwlike manner in the binding pocket of SdrG, distributes forces mainly toward the peptide backbone through an intricate hydrogen bond network. Thus, these adhesins can attach to their target with exceptionally resilient mechanostability, virtually independent of peptide side chains.

Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk

Sciencemag.org / Zhang, D.-L., Wu, J., Shah, B. N., Greutelaers, K. C., Ghosh, M. C., Ollivierre, H., Su, X.-z., Thuma, P. E., Bedu-Addo, G., Mockenhaupt, F. P., Gordeuk, V. R., Rouault, T. A. - Malaria parasites invade red blood cells (RBCs), consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron supplementation therapy inexplicably exacerbates malarial infections. Here we found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the Fpn gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. In humans, a prevalent FPN mutation, Q248H (glutamine to histidine at position 248), prevented hepcidin-induced degradation of FPN and protected against severe malaria disease. FPN Q248H appears to have been positively selected in African populations in response to the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress and malaria infection.

Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity

Sciencemag.org / Ferrari de Andrade, L., Tay, R. E., Pan, D., Luoma, A. M., Ito, Y., Badrinath, S., Tsoucas, D., Franz, B., May, K. F., Harvey, C. J., Kobold, S., Pyrdol, J. W., Yoon, C., Yuan, G.-C., Hodi, F. S., Dra - Ads from Inoreader • Remove MICA and MICB are expressed by many human cancers as a result of cellular stress, and can tag cells for elimination by cytotoxic lymphocytes through natural killer group 2D (NKG2D) receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA and MICB proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA and MICB by human cancer cells. These antibodies inhibited tumor growth in multiple fully immunocompetent mouse models and reduced human melanoma metastases in a humanized mouse model. Antitumor immunity was mediated mainly by natural killer (NK) cells through activation of NKG2D and CD16 Fc receptors. This approach prevents the loss of important immunostimulatory ligands by human cancers and reactivates antitumor immunity.

Rats can’t puke, which is bad news for them and great news for us

Popsci.com / Erin Blakemore - Ads from Inoreader • Remove Animals We could use their unique talents to develop better chemo drugs. Consider, if you will, a repulsive case of food poisoning. You may try to hold it in, but at some point you’re gonna spew. But not every species is that lucky—and one…

Honeybees may unlock the secrets of how the human brain works

Medicalxpress.com - Ads from Inoreader • Remove Researchers from the University of Sheffield have discovered that looking at honeybees in a colony in the same way as neurons in a brain could help us better understand the basic mechanisms of human behaviour.

Prep for fetal surgery involves kickball, chicken breasts

Futurity.org / Marin Hedin-Johns Hopkins - To rehearse for complex surgery on the spinal cords of fetuses, surgeons are practicing on kickballs and chicken breasts. These items, combined with high-tech 3D printing technology, are providing surgical teams with the practice they need to perform a complex but minimally invasive new surgical repair of a particular form of spina bifida. “A kickball is about the size of a uterus at that time in pregnancy.” Spina bifida is the failure of the spinal column to close normally during early fetal development. It occurs in about three to four of every 10,000 pregnancies. It can result in permanent nerve damage if left untreated. The new procedure, called fetoscopic myelomeningocele repair, involves a maternal fetal medicine specialist and a pediatric neurosurgeon working together. A handful of hospitals, including Johns Hopkins Hospital, have adopted the surgery. They use two small ports rather than an open, large incision in the womb of the mother carrying the affected fetus. Training has been challenging, the team at Johns Hopkins reports. To address the difficulty, they prepared for their first such procedure last year on the fetus of a 31-year-old woman 25 weeks pregnant by creating practice models. The surgeons used a 10-inch diameter kickball secured to a Plexiglas base to mimic a uterus. “A kickball is about the size of a uterus at that time in pregnancy,” says Jena L. Miller, assistant professor of gynecology and obstetrics at the Johns Hopkins University School of Medicine. “It holds its shape pretty well when sealed and, unlike other trainers for laparoscopic surgery, it’s not see-through, so it’s a more realistic model.” A doll in the kickball The surgeons used ultrasound to obtain an accurate image of the fetal spine and lesion. Then, they created mesh models of the region to be operated on and generated a 3D-printed model of the area using flexible materials. To practice, the team cut two slits in the top of the kickball to serve as ports for surgical instruments. Inside the kickball, they had placed the 3D-printed model with its silicone cover secured to a plastic fetus over a layer of marbles to mimic the intraoperative motion and instability of the fetus. Besides practicing on the 3D-printed model, they also used a section of a skin-on chicken breast secured to a model of a fetus—placed inside the kickball—to get a better sense of touch for operating on multiple layers of tissue. This was helpful, Miller says, because chicken has more realistic properties than the 3D printed model. Seven live surgeries The more common, standard approach to spina bifida repair is to close the spine as soon after birth as possible, Miller says. For some patients, though, prenatal—or fetal—surgery is performed by making an incision on the mother’s abdomen and womb to expose the baby’s back, close the spinal opening, sew up the womb and maternal abdomen, and let the pregnancy continue. Although that approach can successfully reduce the risk of spinal cord damage and disability, it carries risks for the mother’s health and her ability to sustain future pregnancies. Johns Hopkins is using the new approach instead of this more invasive form of fetal surgery. The first live surgery went well, and the team was able to make a complete watertight closure without complications. The woman had a vaginal delivery at term and the newborn has not required any additional procedures. The team has since used the technique to prepare for six additional cases. Surgery and stem cells might cure spina bifida “Repetitive practice by a dedicated surgical team in a patient-matched model lets us know exactly what to anticipate specific to each case,” Miller says. The goal of rehearsals, Miller adds, is to identify potential obstacles and decrease operating time and risks. While the new procedure is promising, the surgeons caution that more study is needed to improve training, continue advancing the surgical technique and reduce surgical time and potential risks. The surgical team described its approach in a letter in the journal Ultrasound in Obstetrics & Gynecology. Coauthors of the letter were from Johns Hopkins and the US Army’s Medical Modeling and Simulation Innovation Center in Frederick, Maryland. The Fetal Health Foundation paid for the work. Source: Johns Hopkins University The post Prep for fetal surgery involves kickball, chicken breasts appeared first on Futurity.

Infants as young as 17 months expect fairness and equity

Medicalxpress.com - Children as young as 17 months recognise whether resources are being shared fairly, the first time researchers have found evidence that infants so young are sensitive to principles of "distributive justice".

Scientists develop new tool to study nicotine receptors

Medicalxpress.com - Ads from Inoreader • Remove A team of scientists has developed a new technique to better understand the effects of nicotine on the brain. In a study published in Nature Methods, the investigators described the creation of a novel light-activated nicotine compound, which will allow scientists to better study receptors that play a key role in nicotine addiction.

Drug-resistant gene goes from pig farms to patients worldwide

Medicalxpress.com - A troublesome gene that is resistant to an antibiotic often used as a last resort has been tracked from its origins on Chinese pig farms to hospital patients worldwide in a new study led by UCL and Peking University People's Hospital.

Mobile apps could hold key to Parkinson's research, care

Medicalxpress.com - A new study out today in the journal JAMA Neurology shows that smartphone software and technology can accurately track the severity of the symptoms of Parkinson's disease. The findings could provide researchers and clinicians with a new tool to both develop new drugs and better treat this challenging disease.

Newly-discovered human organ may help explain how cancer spreads

Newscientist.com - A newly discovered network of fluid-filled channels in the human body may be a previously-unknown organ, and it seems to help move cancer cells around the body

Meet Your 'Interstitium,' A Newfound Organ

Livescience.com - Researcher say they've found a network of fluid-filled spaces in tissue that hadn't been seen before.

Treating triple negative breast cancer by targeting pair of receptors

Medicalxpress.com - Ads from Inoreader • Remove Triple negative breast cancer (TNBC) is a particularly aggressive form of breast cancer that lacks known targets for therapies, making it difficult to treat. However, a new study by a group of researchers and physician-scientists, led by Baylor College of Medicine, has identified a novel treatment strategy that may be effective for TNBC patients. The study appears in Nature Medicine.

For Women With Low-Risk Pregnancies, Technology Can Reduce Doctor Visits

Npr.org / Michelle Andrews - Ads from Inoreader • Remove In a program called OB Nest, The Mayo Clinic has been using a telemedicine program that allows low-risk expectant mothers to forgo some standard prenatal visits.(Image credit: Mike Harrington/Getty Images)

Newfound 'organ' had been missed by standard method for visualizing anatomy

Medicalxpress.com - Ads from Inoreader • Remove Researchers have identified a previously unknown feature of human anatomy with implications for the function of all organs, most tissues and the mechanisms of most major diseases.

Ian Paterson: Disgraced surgeon's patients at 'heart' of inquiry

Bbc.co.uk - Ads from Inoreader • Remove More than 150 patients have contributed to the inquiry into Ian Paterson's botched operations.

300 million hepatitis B sufferers but only one in 20 treated: study

Medicalxpress.com - Some 300 million people worldwide are living with the deadly hepatitis B virus (HBV), but only one in 20 received adequate treatment, researchers reported Tuesday.

S.Africa's DIY battle against HIV

Medicalxpress.com - Ads from Inoreader • Remove Self-testing kits and vending machines distributing prescription drugs are two ways that HIV treatment is being automated to reduce stigma in South Africa, home of the world's biggest HIV epidemic.

Neuroscientists say daily ibuprofen can prevent Alzheimer's disease

Medicalxpress.com - A Vancouver-based research team led by Canada's most cited neuroscientist, Dr. Patrick McGeer, has successfully carried out studies suggesting that, if started early enough, a daily regimen of the non-prescription NSAID (nonsteroidal anti-inflammatory drug) ibuprofen can prevent the onset of Alzheimer's disease. This means that by taking an over-the-counter medication, people can ward off a disease that, according to Alzheimer's Disease International's World Alzheimer Report 2016, affects an estimated 47 million people worldwide, costs health care systems worldwide more than US$818 billion per year and is the fifth leading cause of death in those aged 65 or older.

An apple a day really does work: The flavonoid-rich fruit improves cardiovascular health, decreases risk of disease

Naturalnews.com / Michelle Simmons - (Natural News) Apples once again show that they can keep the doctor away. A study has found that the flavonoid-rich fruit enhances cardiovascular health and reduces the risk of disease by improving endothelial function. Just eat it with its skin for more benefits. Past studies have shown that there is an inverse association between apple...

Hibiscus extracts can be used to provide natural food coloring WITH health benefits

Naturalnews.com / Michelle Simmons - (Natural News) Extracts from hibiscus calyces could be used as a natural food coloring, which can provide health benefits at the same time, according to a study published in the journal Food Science and Human Wellness. The study, written by Aly R. Abdel-Moemin from Helwan University in Egypt, evaluated the effect of hibiscus calyces extract on the chemical and...