Forensics

Working with mice, researchers at Johns Hopkins have contributed significant new evidence to support the idea that high doses of cocaine kill brain cells by triggering overactive autophagy, a process in which cells literally digest their own insides. Their results, moreover, bring with them a possible antidote, an experimental compound dubbed CGP3466B.

A summary of the study, which also found signs of autophagy in the brain cells of mice whose mothers received cocaine while pregnant, was published online the week of Jan. 18 in the Proceedings of the National Academy of Sciences.

(Image caption: A neural cell from a mouse brain shows much larger, more numerous vacuoles (orange) after 3 hours of treatment with cocaine than untreated cells. Credit: Prasun Guha, Maged Harraz, Solomon Snyder)

(Image caption: An untreated neural cell from a mouse brain shows no vacuoles. Credit: Prasun Guha, Maged Harraz, Solomon Snyder)

“We performed ‘autopsies’ to find out how cells die from high doses of cocaine,” says Solomon Snyder, M.D., professor of neuroscience at the Johns Hopkins University School of Medicine. “That information gave us immediate insight into how we might use a known compound to interfere with that process and prevent the damage.”

After discovering in 1990 that brain cells use the gas nitric oxide to communicate, Snyder and his research team have spent decades studying its impact. In 2013, the team found that nitric oxide is involved in cocaine-induced cell death through its interactions with GAPDH, an enzyme, but didn’t learn how precisely the cells were dying.

To find out, the research team examined nerve cells from mouse brains for clues. Snyder says cells, like whole animals, can die from extreme temperatures, toxins and physical trauma, but can also commit “suicide” in three ways that are chemically programmed and controlled by different proteins.

One such way is autophagy, a normal and much-needed cellular “cleanup process” that rids cells of debris that accumulates in membrane-enclosed vacuoles, or “bags” within the cell. These bags fuse with other bags, enzyme-rich lysosomes, which are filled with acids that degrade the contents of the vacuoles. Only when this process accelerates and spins out of control does it cause cell death, Snyder explains.

By measuring changes in the levels of proteins that control each cell death program and by observing the cells’ physical changes, the team saw clearly that cocaine causes neuronal cell death through out-of-control autophagy. That confirmed previous results from two other groups that found cocaine-induced autophagy in astrocytes and microglia, which are neuron support cells.

“A cell is like a household that is constantly generating trash,” says Prasun Guha, Ph.D., postdoctoral fellow at Johns Hopkins and lead author of the paper. “Autophagy is the housekeeper that takes out the trash — it’s usually a good thing. But cocaine makes the housekeeper throw away really important things, like mitochondria, which produce energy for the cell.”

Because the team already knew that nitric oxide and GAPDH were involved in the process, they tested the ability of the compound CGP3466B, known to disrupt nitric oxide/GAPDH interactions, to halt cocaine-induced autophagy. They also tested other chemicals known to prevent the other two forms of cellular suicide, but only CGP3466B protected mouse nerve cells in the brain from death by cocaine.

According to previous research from the same team, CGP3466B was also able to rescue the brain cells of live mice from the deadly effects of cocaine, but they had not connected the phenomenon to autophagy. When the scientists recently gave mice a single dose of cocaine and looked for signs of autophagy in their brain cells, they detected autophagy-associated proteins and changes in vacuoles in adults and in mouse pups whose mothers had received cocaine while pregnant.

“Since cocaine works exclusively to modulate autophagy versus other cell death programs, there’s a better chance that we can develop new targeted therapeutics to suppress its toxicity,” says Maged M. Harraz, Ph.D., a research associate at Johns Hopkins and lead co-author of the paper.

New Painkiller May Be A Safer, Non-Addictive Alternative to Morphine

The peptide-based drugs, which mimic a natural brain chemical, target the same pain-relieving opioid receptor as morphine.

New test detects drug use from a single fingerprint

Research published in the journal Analyst has demonstrated a new, non-invasive test that can detect cocaine use through a simple fingerprint. For the first time, this new fingerprint method can determine whether cocaine has been ingested, rather than just touched.

Bones of farce: The discredited relics of Joan of Arc

One of the thrills of being a forensic scientist is positively identifying human remains, which can be hundreds of years old and revered as relics.  Other times forensic science can be used to debunk a hoax, and the really interesting part here is exposing the strange ways the hoax was executed.

A bundle of ashes and bones were discovered in a Paris pharmacy in 1867 with a label that read: “Remains found under the stake of Joan of Arc, virgin of Orleans.”  Joan of Arc (ca. 1412-1431) was a folk hero of France and Catholic saint, who was convicted of heresy and burned at the stake in 1431 in Normandy.

The bundle contained bones and linen that had a dark coating as well as charred wood.  This was consistent with remains gathered from a smoldering pile after someone was burned at the stake.  The relics were recognized as authentic by the Catholic Church and were displayed in the French town of Chinon for more than half a century.

Read more at StrangeRemains

Top image: Philippe Charlier holding the relics that were once thought to belong to Joan of Arc

Understanding 19th Century Criminals - One Head at a Time

The head of 19th century physician and psychiatrist Cesare Lombroso has been preserved in a glass chamber since his death in 1909. The former professor of forensic medicine’s sleeping face is now displayed in the Museum of Criminal Anthropology in Turin, Italy, along with the wax-covered heads, brains, body parts and skulls of the soldiers, civilians and convicts whom he studied.

Although the exhibition opened recently, Lombroso displayed his collection to the public as early as 1884. The spectacle grew as scholars and doctors, who were interested in his work, sent more artifacts from various parts of the world to support his research. In 1892, he established the Psychiatric and Criminology Museum in Turin, where he formally presented the labelled skulls and wax-covered heads of convicts alongside the tools and weapons which they used to commit their crimes. Lombroso was interested in how physical features could indicate whether an individual was prone to crime or ‘madness.’

 5 weird things that happen after you die

1. Your cells burst open. The process in which the human body decomposes starts just minutes after death. When the heart stops beating, we experience algor mortis, or the “death chill,” when the temperature of the body falls about 1.5 degrees Fahrenheit an hour until it reaches room temperature. Almost immediately, the blood becomes more acidic as carbon dioxide builds up. This causes cells to split open, emptying enzymes into the tissues, which start to digest themselves from within.

2. You turn white and purple. Gravity makes its mark on the human body in the first moments after death. While the rest of your body turns deathly pale, heavy red blood cells move to the parts of your body that are closest to the ground. This is because circulation has stopped. The results are purple splotches over your lower parts known as livor mortis. In fact, it is by studying the markings of livor mortis that the coroner can tell exactly what time you died.

3. Calcium makes your muscles contract. We’ve all heard of rigor mortis, in which a dead body becomes stiff and hard to move. Rigor mortis generally sets in about three to four hours after death, peaks at 12 hours, and dissipates after 48 hours. Why does it happen? There are pumps in the membranes of our muscle cells that regulate calcium. When the pumps stop working in death, calcium floods the cells, causing the muscles to contract and stiffen. Thus, there is rigor mortis.

4. Your organs will digest themselves. Putrefaction, or when our bodies start to look like extras in a zombie movie, follows rigor mortis. This phase is delayed by the embalming process, but eventually the body will succumb. Enzymes in the pancreas make the organ begin to digest itself. Microbes will tag-team these enzymes, turning the body green from the belly onwards. As Caroline Williams writes in NewScientist, “the main beneficiaries are among the 100 trillion bacteria that have spent their lives living in harmony with us in our guts.” As this bacterium breaks us down, it releases putrescine and cadaverine, which are the compounds which make the human body smell in death.

How scientists study the effects of marijuana on the brain is changing. Until recently marijuana research largely excluded tobacco users from its participant pool, but scientists at the Center for BrainHealth at The University of Texas at Dallas have found reason to abandon this practice, uncovering significant differences in the brains of individuals who use both tobacco and marijuana and the brains of those who only use marijuana.

In a study that appears online in the journal­­­ Behavioural Brain Research, scientists report an association between smaller hippocampal brain volume and marijuana use. Although the size of the hippocampus, an area of the brain associated with memory and learning, is significantly smaller in both the marijuana group and marijuana plus tobacco group compared to non-using controls and individuals who use tobacco exclusively, the relationship to memory performance is unique.

Hippocampal size of nonusers reflects a direct relationship to memory function; the smaller the hippocampus, the poorer the memory function. Individuals who use marijuana and tobacco show an inverse relationship, i.e., the smaller the hippocampus size, the greater the memory function. Furthermore, the number of nicotine cigarettes smoked per day in the marijuana and nicotine using group appears to be related to the severity of hippocampal shrinkage. The greater the number of cigarettes smoked per day, the smaller the hippocampal volume and the greater the memory performance. There were no significant associations between hippocampal size and memory performance in individuals who only use tobacco or only use marijuana.

“Approximately 70% of individuals who use marijuana also use tobacco,” explained Francesca Filbey, Ph.D., the study’s principal investigator and Director of Cognitive Neuroscience of Addictive Behaviors at the Center for BrainHealth. “Our findings exemplify why the effects of marijuana on the brain may not generalize to the vast majority of the marijuana using population, because most studies do not account for tobacco use. This study is one of the first to tease apart the unique effects of each substance on the brain as well as their combined effects.”

Dr. Filbey’s research team used magnetic resonance imaging (MRI) to examine the hippocampus; an area of the brain that is known to have altered size and shape in association with chronic marijuana use. Participants completed a substance use history assessment and neuropsychological tests three days prior to an MRI head scan. The team compared four groups: nonusers (individuals who have not had any marijuana or tobacco in the past three months), chronic marijuana users (individuals who use marijuana at least four times per week), frequent nicotine users (10 or more times daily) and chronic marijuana plus frequent nicotine users (at least four marijuana uses per week and 10 or more nicotine uses per day).

“We have always known that each substance is associated with effects on the brain and hypothesized that their interaction may not simply be a linear relationship. Our findings confirm that the interaction between marijuana and nicotine is indeed much more complicated due to the different mechanisms at play,” said Filbey. “Future studies need to address these compounding effects of substances.”

Archaeological examples of dental prosthetics provide insight about past cultural practices, technological development, and oftentimes provenience. In this case study, the dentures of an adult female from the Dutch Post-Medieval cemetery site of Middenbeemster are analyzed. Archival records identify this individual as a 43 year-old female. She has large metal and porcelain-glass prosthetics spanning the anterior maxilla and mandible. This individual had extensive antemortem tooth loss and periodontal disease, as well as severe caries in most of the few remaining teeth.

Hand-held X-ray fluorescence (HH-XRF) was used to identify the material composition of the denture base and fake teeth. This analysis showed the base is made of a silver copper alloy, with small amounts of zinc, gold, lead, and nickel. Based on the quantitative levels of elements the fake teeth were made out of porcelain. The abundant presence of manganese (and trace amounts of tungsten) are however anomalous to tableware porcelain, and were probably added to counteract coloration, providing a colorless or a pale yellow result. The exterior of the denture is coated in a glass matrix.

Traces of lead in the silver alloy point to a fabrication date prior to electrolytic refining in the 19th century. The copper-depleted/silver-enriched composition of the brace is consistent with 18th and 19th century alloy standards and correlates more with German, Austrian, or Italian standards rather than a British ‘Sterling’ or ‘Britannia’ standard. This interesting example adds to our understanding of past dental practices in mainland Europe and suggest that by the nineteenth century such novel and likely expensive devices were no longer limited to the very upper class.

The XRF analysis was done by our colleague Dr. Dennis Braeckmans of the Material Culture Studies Group of the Faculty of Archaeology at Leiden University; osteological analysis by Dr. Andrea Waters-Rist, and cemetery archive research by Prof. Hoogland.

TOP:  The remaining tooth is a left first premolar, around which the metal brace was affixed.

BOTTOM:  The remaining tooth is the right first premolar (visible centrally in the picture, partially obscured by a tree root). The other remaining tooth roots visible in the picture are those of the first right incisor, the left second incisor and the left canine.