Our Family Tree

For this study, let's begin the human family tree with Homo erectus, the first bipedal ancestor of us all. H.erectus arose in Africa about 2 million years ago and expanded into Eurasia with isolated groups surviving until approximately 100 000 years ago. 

Evidence suggests that around 650 000 years ago, some H.erectus groups evolved into Neanderthals, Denisovans, and archaic human beings. This was not an acrimonious split with DNA being exchanged between the groups until they were sufficiently different from one another with their own distinctive anatomical features. By 40 000 years ago, the Neanderthals and Denisovans had vanished from the fossil record, leaving our Homo sapiens ancestors as the sole hominids on Earth. 

Well, not quite - we still carry some of their genes in our bodies today. About 2-3% of the genome of Europeans is of Neanderthal origin, and scattered populations of modern humans in the Philippines and Papua New Guinea have comparable levels of Denisovan DNA. 

The 400000-year-old Homo erectus fossils examined in this study thus come from a crucial point in prehistory when all three hominid species were coexistent - and forming the building blocks of our modern species. 

The enamel proteome

Paleontologists like teeth. Teeth make good, resilient fossils and are far more likely to survive than softer bone. The reason for this is enamel, the hard protective layer that protects the teeth and allows its host to eat and, therefore, live. The group set out to study several proteins, collectively called the enamel proteome, in H.erectus fossils. 

Three key findings

The paleontologists used advanced mass spectrometry to examine the ameloblastin (AMBN) protein involved in enamel formation during tooth development. The protein, together with other structural proteins like amelogenin and enamelin, can survive in fossils for several hundred thousand years - long after the fossil DNA has degraded. 

The paper reported three key findings - two protein variants of human AMBN - A253G and M273V were identified, and the biological sex of the fossils was determined by quantifying amelogenin levels in the samples. 

• All six H.erectus fossils in this study contained a unique AMBN protein named A253G. There had been no reports of this variant in other hominids, such as the Denisovan, Neanderthal, or archaic Homo sapiens, suggesting that it could be a unique H. erectus signature protein. The A253G marker, if validated in other fossils, may serve as a useful identifier of H.erectus fossils especially in cases where only the teeth survive. 

• A second AMBN protein variant (M273V) was found in all six H.erectus fossils used in the study. The gene for this variant has been found in more recent Denisovan DNA and in small populations of modern humans in Southeast Asia. This suggests a direct gene flow from H.erectus down to these modern humans via the Denisovan lineage. 

• The group analysed levels of a third sex-specific enamel protein named amelogenin. Human and great ape males have a slightly different form of amelogenin in their teeth compared with females.  The scientists confirmed, based on other hominid fossils of confirmed sex, that their samples comprised five males and one female - the oldest fossils to which this technique has been applied. 

The authors caution that this is a very small sample from a single time period and geographic region. Replicating these findings in other hominids from different periods could help distinguish H.erectus fossils from other contemporary hominid remains. 

So, what's in a tooth? 

Quite a bit, actually. Not only can palaeontologists tell where and when you lived, but also what you were, and who you loved.

Your teeth tell your story; be careful where you leave them.

Preeclampsia is a condition characterised by high blood pressure and proteinuria in the third trimester of pregnancy. It is associated with low birth weight, pre-term delivery and still-birth in infants. In mothers, it raises the risk of organ damage, stroke, seizures and death. The World Health Organisation estimates that it affects between 3-8% of pregnancies worldwide, and may be responsible for up to 16% of maternal deaths. 

The approach, which had been successfully trialled in pregnant baboons, reported the following …

• Up to 25% reduction in sFlt-1 levels after treatment.

• Improvements in blood pressure and proteinuria markers.

• Biomarkers of fetal and subsequent neonatal health remained unchanged.

• Predicted pregnancy duration nearly doubled - this was an estimation, as there were no controls in the pilot study.

Maternal adverse events were reported as mild to moderate and included low serum calcium, headaches and raised liver enzymes. There was one case of intraventricular haemorrhage in a neonate. 

The authors concluded that the approach was “safe and tolerable to mother, fetus and neonate”, and plan to test this therapy in a controlled clinical trial. 

by Cliff Dominy

Mozart Therapeutics, a privately held biotech company based in Seattle, Washington have announced Phase 1b trial results of their flagship compound, MTX-101. The drug targets both CD8 and KIR receptors on regulatory CD8 T-cells. MTX-101 was designed to suppress pathogenic CD4 T-cells linked to beta-cell destruction in the pancreas. 

Population: Five adults with type 1 diabetes (stage 3).

Intervention: Two arms - 0.05 mg/kg (n=2), 0.15 mg/kg (n=3) followed for 20 weeks.

Controls: None. This was a safety/efficacy study of MTX-101 based on Phase 1a data.

Results: Selective activation of beneficial T-reg cells with reduced levels of pathogenic CD4 and CD8 cells.

Reduced autoimmune restimulation.

High-dose patients showed a 5-40% increase in c-peptide from baseline over the trial period.

“We are excited about the encouraging dataset from the Ph1b interim analysis demonstrating MTX 101 selectively modulates a novel regulatory pathway that translates into a meaningful impact on a key clinical biomarker, offering promise for patients with Stage 3 T1D,” said Katie Fanning, President and CEO of Mozart Therapeutics, in the press release. “These findings support our plans to complete the Ph1b study and initiate enrollment in a global Phase 2 study early in 2027.” 

by Cliff Dominy, PhD