Small samples, big data: A systems-biology look at a newborn’s first week of life

newborn biology, through tiny blood samples
(PHOTO: ADOBE STOCK)

The first week of a baby’s life is a time of rapid biological change. The newborn must adapt to living outside the womb, suddenly exposed to new bacteria and viruses. Yet scientists know surprisingly little about these early changes.

Reporting in today’s Nature Communications, an international research team provides the most detailed accounting to date of the molecular changes that occur during a newborn’s first seven days. The team pioneered a technique to extract volumes of data from a tiny amount of newborn blood — including what genes are turned on, what proteins the body is making and what metabolites are changing.

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The threat from mosquito-borne diseases: Forecasting mosquitoes’ global spread

Aedes albopictus
Aedes albopictus (ADOBE STOCK)

Outbreaks of mosquito-borne illnesses like yellow fever, dengue, Zika and chikungunya are rising around the world. Climate change has created conditions favorable to mosquitoes’ spread, but so have human travel and migration and accelerating urbanization, creating new mini-habitats for mosquitoes.

In Nature Microbiology yesterday, a large group of international collaborators combined these factors into prediction models that offer insight into the recent spread of two key disease-spreading mosquitoes — Aedes aegypti and Aedes albopictus. The models forecast that by 2050, 49 percent of the world’s population will live in places where these species are established if greenhouse gas emissions continue at current rates.

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How celastrol sensitizes brains to leptin, curbing hunger and obesity

celastrol path of action
Celastrol increases numbers of IL1R1 receptors in the brain, allowing leptin to act. (ILLUSTRATION: ELLA MARU STUDIO)

Here’s what’s known about celastrol, widely hailed in 2015 for its potent anti-obesity effects. It’s derived from the roots of the thunder god vine. It increases the brain’s sensitivity to leptin, the hormone that signals we’ve had enough to eat. It has curbed food intake by nearly 80 percent in obese mice, producing up to a 45 percent weight loss. It’s now in Phase 1 clinical trials conducted by ERX Pharmaceuticals; phase 2 studies are slated to begin this year.

What hasn’t been known is how celastrol makes the brain more sensitive to leptin. A study in today’s Nature Medicine finally provides an answer.

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50-year-old mystery solved — with clues to making more red blood cells

why steroids boost red blood cell production
Red blood cells produced by a single progenitor cell (IMAGE COURTESY HOJUN LI / DANA-FARBER/BOSTON CHILDREN’S VIA CELL PRESS)

Back in the 1950s, doctors began using steroids to treat Diamond-Blackfan anemia, or DBA, a severe condition in which patients cannot make enough red blood cells. There was no real rationale for using steroids, but there was no other good option, aside from regular transfusions. At the time, steroids were being thrown at seemingly everything.

But steroids worked in most patients, at least for a time — at the expense of serious side effects such as weight gain, bone loss, hypertension, diabetes and an increased risk of infections. A new study published yesterday in Developmental Cell finally explains why steroids work — and could provide a foothold for developing safer and better treatments for DBA. It could even pave the way to treatments for other types of bone marrow failure.

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Using mitochondrial DNA to trace cells’ family trees

tracing cell family relationships with mitochondrial DNA
(IMAGE: ADOBE STOCK)

Second in a two-part series on mitochondria. See part 1.

Recent advances in single-cell genomics have made it possible to study individual cells and learn how they develop into specialized cells. However, we have only limited information on cells’ origins and how they’re related to the other cells around them.

Meanwhile, efforts to understand more about how cells differentiate and divide have looked at whole cell categories at a time, offering little knowledge of individual cells.

“It’s like looking at the statistics for a college — you can determine what the average student is like, but you have no idea what any one individual student is doing,” says Vijay Sankaran, MD, PhD, a hematologist at Boston Children’s Hospital. “Learning about cellular relationships is critical — it can help us understand how many stem cells give rise to any tissue in our body, what cell types cancers emerge from, or how some cells can be dysfunctional in particular diseases.”

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EEG data classify ‘autism’ into two distinct groups

[IMAGES FROM BMC NEUROLOGY (DOI 10.1186/s12883-019-1254-1)]

The Diagnostic and Statistical Manual, 5th edition (DSM-5) established a single diagnosis of autism spectrum disorder (ASD) that includes Asperger’s syndrome, formerly considered a separate condition. The change was meant to eliminate diagnostic ambiguities, but it has encouraged schools to take a “one size fits all” approach, putting all children with autistic features in the same classroom.

This concerns many parents and professionals. “Typically, such classrooms focus on the more severely impaired, often non-verbally communicative children without helping the higher functioning children, such as those with Asperger’s,” says Heidelise Als, PhD, a psychologist at Boston Children’s Hospital.

Als and her co-investigator Frank Duffy, MD, a neurologist at Boston Children’s, decided to take an unbiased look at children diagnosed with autism, using data from their EEGs. In a paper in BMC Neurology, they conclude that autism is not a single entity, but falls into two distinct clusters — ripe for additional investigation.

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Eavesdropping on mitochondria, tissue by tissue

mitochondria
(IMAGE: ADOBE STOCK)

First in a two-part series on mitochondria. See part 2.

Mitochondria are essential to life: they produce energy, synthesize building blocks critical to cell function and help regulate cellular activity, including programmed cell death. Mitochondrial diseases can cause severe metabolic disorders in children and dysfunctional mitochondria are thought to play a role in cancer, diabetes, heart attack, stroke, Parkinson’s disease and more.

A new research tool offers an unprecedented glimpse at the workings of these tiny, dynamic organelles, and could aid in the study of mitochondrial dysfunction.

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Light-activated nanoparticles could avoid painful eye injections for ‘wet’ macular degeneration

Could intravitreal injections become a thing of the past?
(PHOTO: ZKALILA1998 / WIKIMEDIA COMMONS)

There are two standard treatments for “wet” age-related macular degeneration (AMD), in which abnormal, leaky blood vessels in the back of the eye lead to fluid buildup and vision loss. The first, injection of medication directly into the eye, can be painful and can cause inflammation, infection and detachment of the retina. The second, ablation therapy, uses lasers to destroy the leaky blood vessels. It, too, is unpleasant to undergo, and the lasers can also destroy surrounding healthy tissue, causing further vision loss.

In today’s Nature Communications, the lab of Daniel Kohane, MD, PhD, provides proof-of-concept of a more tolerable alternative: tiny, drug-carrying nanoparticles that can be injected intravenously, but deliver medication only to the eye.

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Two new options for treating esophageal damage in children

Rusty Jennings, MD, and Michael Manfredi, MD (CREDIT: MICHAEL GODERRE)

A child’s esophagus can become damaged through physical trauma or ingestion of toxic chemicals or foreign objects — such as oven and drain cleaners, lye, laundry and dishwasher detergents and batteries. Depending on the substance and the amount ingested, children can develop esophageal strictures (scar tissue that narrows the esophagus) or esophageal perforations (holes in the esophagus). These problems can also be complications of surgery for esophageal atresia, in which a baby is born without part of the esophagus.

Children with esophageal perforations have traditionally been treated with long courses of antibiotics and not eating by mouth. More recently, perforations have been treated with stents, and strictures with a combination of dilation and stenting. But stenting, while it can be effective, requires up to eight weeks of therapy and can have complications such as pain, retching and local pressure necrosis, a type of ulcer that may worsen perforation. Such concerns have led researchers to investigate alternative treatments for perforation and strictures.

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How the antidepressant ketamine rapidly awakens the brain, and why its effects vary more in women

(CREDIT: NATHALIE PICARD / BOSTON CHILDREN’S HOSPITAL)

In small doses, the anesthetic ketamine is a mildly hallucinogenic party drug known as “Special K.” In even smaller doses, ketamine relieves depression — abruptly and sometimes dramatically, steering some people away from suicidal thoughts. Studies indicate that ketamine works in 60 to 70 percent of people not helped by slower-acting SSRIs, the usual drugs for depression.

Two ketamine-like drugs are in the clinical pipeline, and, as of this week, one appears close to FDA approval. With no significant new antidepressant in more than 30 years, anticipation is high. Yet no one has pinned down how low-dose ketamine works. Studies have implicated various brain neurotransmitters and their receptors — serotonin, dopamine, glutamate, GABA receptors, opioid receptors — but findings have been contradictory.

“We felt it was time to figure this out once and for all,” says neuroscientist Takao Hensch, PhD.

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