Dual-Action Microbicide Attacks HIV and HIV-Friendly Fibrils in Semen

A small molecule previously investigated as a means of fighting Alzheimer’s disease and other neurodegenerative disorders is showing promise as a way to reduce HIV transmission and prevent AIDS. This molecule, called CLR01, keeps amyloid proteins from forming aggregates, or clumps. CLR01, it turns out, works not only on the amyloid proteins that can aggregate in the brain, but also on similar amyloids that can form fibrils in semen.

By using CLR01 against amyloid fibrils in semen, scientists hope to inhibit the transmission of HIV. These fibrils are known to enhance the transmission of HIV. They trap viral particles, helping the virus attach to the membranes surrounding human cells, increasing the risk of infection.

Scientists based at the University of Pennsylvania and the University of Ulm reasoned that a treatment capable of reducing the levels of amyloid fibrils in semen might also be able to reduce HIV transmission. They decided to test this approach with CLR01, which has been described as a pair of molecular tweezers.

The scientists were gratified to discover that CLR01 not only disrupts the amyloids in semen that promote HIV infection, the tweezers-shaped molecule also attacks the virus itself. These findings appeared August 18 in the journal eLife, in an article entitled, “A molecular tweezer antagonizes seminal amyloids and HIV infection.”

“[CLR01] inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils,” wrote the authors. “Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion–amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses.”

In the presence of CLR01, human cells exposed to semen that contained HIV were at least 100-fold less likely to become infected with the virus. Remarkably, CLR01 does not affect cell membranes, which suggests it could be safely incorporated into a vaginal or anal gel to prevent HIV infection—without the risk of side effects.

Unexpectedly, the scientists determined that CLR01 was also effective at directly disrupting other enveloped viruses such as hepatitis C virus, human cytomegalovirus, and herpes simplex virus. It was ineffective, however, against the non-enveloped human adenovirus type 5, reinforcing the idea that CLR01 is effective, in part, because of its ability to directly disrupt membranes that surround viruses.

“We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a nonspecific, colloidal mechanism,” the authors continued. “CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself.”

"We think that CLR01 could be more effective than other microbicides that are in development because of its dual action, its safety in terms of side effects and its potential broad application," said Professor James Shorter from the University of Pennsylvania School of Medicine.

"The tweezer has been tested and is safe in zebrafish and mice. The next step could be to assess safety and efficacy in non-human primates," added Professor Jan Münch from the University of Ulm.

The scientists anticipate that synthesizing CLR01 in large quantities will be straightforward, which will facilitate its development as a microbicide.

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Molecule that targets HIV in semen to prevent infection

The researchers believe that the compound could be incorporated into a vaginal or anal gel to prevent HIV infection - without the risk of side effects.

Semen, the male reproductive fluid that contains deposits of protein fragments called amyloid fibrils is the main vector for sexual HIV transmission.

The researchers found that the "molecular tweezer" called CLR01, not only not only destroys HIV particles but also blocks the infection-promoting activity of semen amyloids.

"We think that CLR01 could be more effective than other microbicides that are in development because of its dual action, its safety in terms of side effects and its potential broad application," said James Shorter, professor at University of Pennsylvania School of Medicine in the US.

"The tweezer has been tested and is safe in zebrafish and mice. The next step could be to assess safety and efficacy in non-human primates," professor Jan Munch from University of Ulm in Germany pointed out.

Semen contains proteins that assemble into amyloid fibrils, which can enhance HIV infectivity by up to 10,000 times.

The antiviral activity of CLR01 is based on the way it selectively interacts with and destroys the viral membrane.

The way CLR01 operates means that it is also effective against many other sexually transmitted viruses, including Hepatitis C and viruses in the herpes family.

It may also be effective against many other "enveloped" viruses including flu and Ebola, the study said.

The use of other preventive treatments has been undermined in some countries by the stigma associated with HIV.

As CLR01 is effective against many viruses besides HIV, it could be more widely acceptable as a general protective agent in communities struggling with HIV stigma, suggested the study detailed in the journal eLife.

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The Paleo diet has it wrong: Cavemen did eat carbs?

The low-carbohydrate Paleo diet has attracted star advocates, including professional golfer Phil Mickelson, actor Matthew McConaughey, and Republican presidential candidate Jeb Bush. But experts are now debating whether or not people in the Paleolithic Era did actually eat carbs.

he goal of the Paleo diet is to consume the same food groups as our hunter-gatherer ancestors, whose nutritional practices between 2.6 million and 10,000 years ago helped form our modern genetic makeup. These foods include fruits, vegetables, grass-fed meats, fish, seafood, free-range eggs, nuts and seeds. The diet discourages frequent consumption of dairy, starch and processed foods.

Despite the modern diet’s effectiveness at helping some people lose weight, the findings from the study suggest that these may not be the only foods our long-ago ancestors ate.

“Eating meat may have kick-started the evolution of bigger brains, but cooked starchy foods together with more salivary amylase genes made us smarter still,” the study concluded.

The study says that to truly eat Paleo, starch and higher levels of carbohydrates are necessary. It explains that the human brain uses about a quarter of the body’s energy budget and about 60% of blood glucose — energy needs that wouldn't have been met on a low-carbohydrate diet. Additional glucose was necessary for pregnancy and lactation. The study also found evidence that the genes that code for the enzymes needed to digest starch evolved about 1 million years ago, in the midst of the Paleolithic era, further suggesting a diet that included significant levels of starch.

Thus, the study concludes, the Paleo diet’s exclusion of starch doesn't take into account the role it played in the development of the modern genome.

“Up until now, there has been a heavy focus on the role of animal protein and cooking in the development of the human brain over the last 2 million years, and the importance of carbohydrate, particular in form of starch-rich plant foods, has been largely overlooked,” the study found. Researchers at the University of Chicago compiled archaeological, anthropological, genetic, physiological and anatomical data to study the prominence of carbohydrates in Paleolithic era humans for the study.

As obesity rates rise, the weight-loss market has become a growing industry. The commercial diet industry was a $2.5 billion market in 2014, and is expected to grow at an annual rate of 5.5% for the next five years, research firm IBISWorld estimates.

Interest in the Paleo diet concept, which reportedly originated in 1985 in a paper published in the “New England Journal of Medicine,” has also surged. Google searches for the term “Paleo diet” increased steadily between 2009 and 2012, and peaked in 2013 — dubbed the “year of the Paleo” due to the proliferation of books, blogs and online recipes. With advocates ranging from famous athletes to politicians, the diet has been able to sustain its popularity.

Paleo diet experts, however, aren’t convinced by the study’s findings. “[Starch] is a poverty food and has little place in the modern diet meant to save you from the constant, huge stream of glucose and simple starches in our modern world,” Arthur De Vany, author of “The New Evolution Diet: What Our Paleolithic Ancestors Can Teach Us about Weight Loss, Fitness, and Aging,” writes in an email interview.

De Vany disagrees with the suggested role of starch and carbohydrates in the study, saying that nutrition from seafood and other prey was the key to rapid brain development, or encephalization.

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Christchurch bar owner turns to Facebook after egging

Two boys who threw a "couple hundred" eggs at a band member's car are alleged to have egged two more cars on the same night. Allen St Live owner Tarquyn Read posted CCTV footage to the bar's Facebook page after two boys egged the car of a member of covers band Unhinged about 1am on Sunday. The footage shows one of the boys pelting a parked car with eggs while the other films the egging on his phone.

The two boys are alleged to have egged two other cars.
Lone Star Manchester St's general manager, Camille Le Lievre, said two female staff members had their cars egged on the same night.

The cars were parked at Mike Greer Hills, about a five minute walk from Allen St.

"The cars were egged pretty badly - they thought it was staff playing a trick on them," Le Lievre said.

Read said the band member was "furious".

"He had to clean it straight away; it was freezing - it's not a job you want to do at the end of the night."

Read posted the footage to Facebook because he wanted the pair to be "responsible for their actions".

"I was completely pissed off, there's just no point to it, it's just stupid.

"We don't feel that it's fair that the band member's car was egged; he's actually a good guy who plays music to feed his family."

If the pair do not come forward, Read will contact police.

"We've got some jobs for them to do around Allen St, they might be picking up rubbish on a Saturday night or something like that."

Read is the latest Christchurch business owner to turn to social media to solve a crime.

In April, Cafe Valentino owner Michael Turner posted CCTV footage of a man walking through the restaurant's back door. The man spent less than a minute in the back entrance before leaving with a chef's bag, which had a wedding ring inside, among other items.

Last year, the Thai Container in Bealey Ave released footage of a vandal, who was identified in 30 minutes and later arrested.

At the time, police said it was positive to see retailers embracing "the power of social media".

In December, an east Christchurch shop owner used social media to identify a man who took off with a $900 surfboard.

Within two hours, she received 15 private messages and three phone calls identifying the man by name.

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Sandra Bland had big plans to help women before she died

On July 13, #BlackLivesMatter activist Sandra Bland was found dead in a police holding cell, three days after being arrested by a Texas state trooper during a routine traffic stop. Her death led to calls for an investigation and protests across the country.
At the time of her arrest, Bland was collaborating with longtime friend and writing partner Chenai Okammor on a website — called Woman4Woman — devoted to empowering women around the world to write and share their stories.
Okammor spoke with “Girls” creator and Lenny newsletter co-founder Lena Dunham about Bland’s life and death, and their passion for helping women express themselves.

Lena Dunham: Where did you meet Sandra?

Chenai Okammor: We met when I retired and joined a church committee that she was on. She reminded me of myself when I was younger. There was a lot in me but the self-confidence wasn’t there.

I was born in Rhodesia, now Zimbabwe, and came from a tradition where women and young girls have a very specific role. If I was sitting down to have dinner I would not start eating until all the older people around me had started. As a woman in my culture, you don’t talk about a lot of things.

Sandy was raised by a single mother with a bunch of sisters. And she said that when she was growing up, she held back her thoughts at times. What became clear to me as I met more with Sandra was that she was finding her own voice.

She once said to me, “I’m 28 and I’m just now beginning to identify what I stand for.” When she started working on this project, I asked her what she wanted to accomplish with it. She said, “I want to be able to share my story with young women out there.” Because she still thought she was alone in her quirkiness.
She had such a commitment to having women tell their own stories, and she helped them talk about things they hadn’t talked about before.

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6 Ways To Stop Overeating

Humans have an instinctual (even good) fear of hunger. Take the book Into the Wild—when the main character can't find food, his hunger drives him to a screaming, shake-his-fist-at-the-heavens rage, a stark example of the primal nature of our need for nourishment. Today, most of us know where our next meal is coming from, yet our reaction to hunger has not evolved with our convenience-centered world.

This is why even the thought of being hungry may send you running to the mini-mart for sustenance. If you want to lose weight , however, you must tune in to your body's signal to eat.
"Hunger is a physical cue that you need energy," says Dawn Jackson Blatner, RD, author of The Flexitarian Diet. It can be your best diet ally and if you listen to your body, you'll instinctively feed it the right amount. Fall out of touch, though, and hunger becomes diet enemy number one: You may eat more than you need or get too hungry and stoke out-of-control cravings.

These 6 tips will teach you how to eat less and spot hunger so that you eat to stay satisfied. You'll be able to control calories and shed pounds without “dieting.”

1. Use the hunger scale
Do you really know what hunger feels like? Before you can rein it in, you must learn to recognize the physical cues that signal a true need for nourishment. Prior to eating, use our hunger scale below to help figure out your true food needs:
Starving: An uncomfortable, empty feeling that may be accompanied by light-headedness or the jitters caused by low blood sugar levels from lack of food. Binge risk: high.
Hungry: Your next meal is on your mind. If you don't eat within the hour, you enter dangerous "starving" territory.
Moderately hungry: Your stomach may be growling, and you're planning how you'll put an end to that nagging feeling. This is optimal eating time. Satisfied: You're satiated—not full, but not hungry, either. You're relaxed and comfortable and can wait to nosh.
Full: If you're still eating, it's more out of momentum than actual hunger. Your belly feels slightly bloated, and the food does not taste as good as it did in the first few bites.
Stuffed: You feel uncomfortable and might even have mild heartburn from your stomach acids creeping back up into your esophagus.

2. Refuel every 4 hours
Still can't tell what true hunger feels like? Set your watch. Moderate to full-fledged hunger (our ideal window for eating) is most likely to hit 4 to 5 hours after a balanced meal. Waiting too long to eat can send you on an emergency hunt for energy—and the willpower to make healthful choices plummets. "Regular eating keeps blood sugar and energy stable, which prevents you from feeling an extreme need for fuel," says Kate Geagan, RD, author of Go Green Get Lean: Trim Your Waistline with the Ultimate Low-Carbon Footprint Diet.
To slim down: If you're feeling hungry between meals, a 150-calorie snack should help hold you over. Here are a few ideas: Munch on whole foods such as fruit and unsalted nuts—they tend to contain more fiber and water, so you fill up on fewer calories. Bonus: They're loaded with disease-fighting nutrients. Avoid temptation by packing healthful, portable snacks such as dried fruit in your purse, desk drawer, or glove compartment.
3. Eat breakfast without fail
A study published in the British Journal of Nutrition tracked the diets of nearly 900 adults and found that when people ate more fat, protein, and carbohydrates in the morning, they stayed satisfied and ate less over the course of the day than those who ate their bigger meals later on. Unfortunately, many Americans start off on an empty stomach. In one survey, consumers reported that even when they eat in the morning, the meal is a full breakfast only about one-third of the time.
To slim down: If you're feeling full-blown hunger before noon, there's a chance you're not eating enough in the morning. Shoot for a minimum of 250 calories and make it a habit with these three strategies.

Prepare breakfast before bed (cut fruit and portion out some yogurt).
Stash single-serving boxes of whole grain cereal or packets of instant oatmeal and shelf-stable fat-free milk or soy milk at work to eat when you arrive.
Eat a late breakfast if you can't stomach an early one. "Don't force anything," says John de Castro, PhD, a behavioral researcher and dean of the College of Humanities and Social Sciences at Sam Houston State University. "Just wait a while and eat at 9 or 10 AM. It will help you stay in control later in the day."

MORE: 10 Belly-Flattening Morning Meals

4. Build high-volume meals
Solid foods that have a high fluid content can help you suppress hunger. "When we eat foods with a high water content like fruits and vegetables, versus low water-content foods like crackers and pretzels, we get bigger portions for less calories," says Barbara Rolls, PhD, author of The Volumetrics Eating Plan and a professor of nutritional sciences at Pennsylvania State University. Bottom line: You consume more food but cut calories at the same time. Rolls found a similar effect in foods with a lot of air. In one study, people ate 21% fewer calories of an air-puffed cheese snack, compared with a denser one.
To slim down: Eat fewer calories by eating more food. Try the following healthy ways to fill up.

Start dinner with a salad, or make it into your meal (be sure to include protein such as lean meat or beans).
Choose fresh fruit over dried. For around the same amount of calories, you can have a whole cup of grapes or a measly 3 tablespoons of raisins.
Boost the volume of a low-cal frozen dinner by adding extra veggies such as steamed broccoli or freshly chopped tomatoes and bagged baby spinach.

5. Munch fiber all day long
Fiber can help you feel full faster and for longer. Because the body processes a fiber-rich meal more slowly, it may help you stay satisfied long after eating. Fiber-packed foods are also higher in volume, which means they can fill you up so you eat fewer calories. One review published in the Journal of the American Dietetic Association linked a high intake of cereal fiber with lower body mass index and reduced risk of type 2 diabetes and heart disease.
To slim down: Aim to get at least 25 g fiber a day with these tips. Include produce such as apples and carrots—naturally high in fiber—in each meal and snack. Try replacing some or all of your regular bread, pasta, and rice with whole grain versions.

6. Always include protein
When researchers at Purdue University asked 46 dieting women to eat either 30% or 18% of their calories from protein, the high-protein eaters felt more satisfied and less hungry. Plus, over the course of 12 weeks, the women preserved more lean body mass, which includes calorie-burning muscle.
To slim down: Have a serving of lean protein such as egg whites, chunk light tuna, or skinless chicken at each meal. A serving of meat is about the size of a deck of cards or the palm of your hand—not including your fingers. Another protein option is incorporating beans into your meals. Black beans, chickpeas, and edamame (whole soybeans) are low in fat, high in fiber, and packed with protein.

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Scientists Make Breakthrough In Pancreatic Cancer Research With Urine Test

A urine test for pancreatic cancer could soon be widely available after a breakthrough by British scientists. Researchers have discovered that a combination of three proteins found at high levels in urine can accurately detect early-stage pancreatic cancer, which could lead to a non-invasive, inexpensive test to screen people at high risk of developing the disease.

A team at Barts Cancer Institute, Queen Mary University of London, has shown that the three-protein 'signature' can both identify the most common form of pancreatic cancer when still in its early stages - and distinguish between this cancer and the inflammatory condition chronic pancreatitis, which can be hard to tell apart.

The study, published in the journal Clinical Cancer Research, looked at 488 urine samples: 192 from patients known to have pancreatic cancer, 92 from patients with chronic pancreatitis and 87 from healthy volunteers. A further 117 samples from patients with other benign and malignant liver and gall bladder conditions were used for further validation.

Around 1,500 proteins were found in the urine samples, with around half being common to both male and female volunteers. Of these, three proteins - LYVE1, REG1A and TFF1 - were selected for closer examination, based on biological information and performance in statistical analysis.

Patients with pancreatic cancer were found to have increased levels of each of the three proteins when compared to urine samples from healthy patients, while patients suffering from chronic pancreatitis had significantly lower levels than cancer patients.

The researchers said that, when combined, the three proteins formed a "robust panel" that can detect patients with stages I-II pancreatic cancer with more than 90 per cent accuracy.

With few specific symptoms even at a later stage of the disease, more than 80 per cent of people with pancreatic cancer are diagnosed when the cancer has already spread. This means they are not eligible for surgery to remove the tumour - currently the only potential cure.

The five-year survival rate for pancreatic cancer in Britain is the lowest of any common cancer, at just three per cent. The figure has barely improved in 40 years. There is no early diagnostic test available.

Lead researcher Dr Tatjana Crnogorac-Jurcevic said: "We've always been keen to develop a diagnostic test in urine as it has several advantages over using blood. It's an inert and far less complex fluid than blood and can be repeatedly and non-invasively tested. It took a while to secure proof of principle funding in 2008 to look at biomarkers in urine, but it's been worth the wait for these results. We're hopeful that a simple, inexpensive test can be developed and be in clinical use within the next few years."

Although there is no universal cause of pancreatic cancer, people at higher risk of developing the disease include those with a family history of pancreatic cancer, heavy smokers, the obese and people over 50 years with new-onset diabetes.

Professor Nick Lemoine, co-author and Director of Barts Cancer Institute, added: "For a cancer with no early stage symptoms, it's a huge challenge to diagnose pancreatic cancer sooner, but if we can, then we can make a big difference to survival rates.

"With pancreatic cancer, patients are usually diagnosed when the cancer is already at a terminal stage, but if diagnosed at stage 2, the survival rate is 20 per cent, and at stage 1, the survival rate for patients with very small tumours can increase up to 60 per cent."

Pancreatic Cancer Research Fund chief executive Maggie Blanks said: "This is an exciting finding and we hope to see this research taken forward into a much needed early diagnostic test.

"Early diagnosis is an important part of our overall efforts against this aggressive cancer, alongside developing new treatments to tackle the disease once diagnosis is made."

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