TMS–EEG experiment sessions are often lengthy, making them challenging for many clinical populations

including children. One factor contributing to study length is that typically 100–200 pulses are collected
and averaged to derive a TEP for each condition or cortical region of interest7,8,9. Enough pulses must
be applied such that, when averaged, the signal of interest (the TEP) is distinct from the ongoing,
background brain activity as well as artifacts (noise). Here, we define a “stable” TEP as one that does not
change with additional pulses and aim to quantify the minimum number of pulses (MNP) required to
achieve this stability. MNP depends on the signal-to-noise ratio (SNR), which can be affected by
experimental factors (e.g., stimulation intensity10,11, stimulation duration12, and coil orientation13)
and biological factors (e.g., age14, gender15, and genetics16). Additionally, certain stimulation sites are
less prone to artifact; for example, a stable primary motor cortex TEP can be derived with less than 100
pulses17,18,19, whereas a parietal cortex TEP may require 130–180 pulses20,21,22. An understanding of
the MNP enhances efficiency, allowing for shorter studies or studies in which researchers can explore a
wider array of conditions within a single experimental day. The SNR may also be enhanced by shorter
study protocols as there will be fewer artifacts related to participant fatigue. Moreover, studies requiring
high temporal precision (e.g., plasticity studies or studies of temporally specific phenomenon like
seizures) benefit from shorter assessment blocks. Therefore, understanding the MNP needed for a given
population is particularly meaningful for efficient design of clinical TMS–EEG studies.

The researchers knocked down genes to mimic milder splicing disruptions instead of knocking them out
entirely. Splicing is so essential that knocking out the splicing machinery can lead to extreme responses
like cell death. In organismal models like zebrafish, those severe phenotypes don’t accurately reflect how
splicing disruptions present in human diseases.

First author Jade Varineau, a graduate student in the Calo lab, was drawn to the project because it
allowed her to explore what was happening at the RNA and cellular level while also observing how
splicing perturbations were affecting the whole organism.

“I think this data can help us reframe the way we think about diseases and cancers that are impacted by
splicing—that a treatment that works for one may work for another because all the symptoms may stem
from the same cellular response,” Varineau says.

Tumors can carry mutations in hundreds of different genes, and each of those genes may be mutated in
different ways — some mutations simply replace one DNA nucleotide with another, while others insert
or delete larger sections of DNA.

Until now, there has been no way to quickly and easily screen each of those mutations in their natural
setting to see what role they may play in the development, progression, and treatment response of a
tumor. Using a variant of CRISPR genome-editing known as prime editing, MIT researchers have now
come up with a way to screen those mutations much more easily.
The researchers demonstrated their technique by screening cells with more than 1,000 different
mutations of the tumor suppressor gene p53, all of which have been seen in cancer patients. This
method, which is easier and faster than any existing approach, and edits the genome rather than
introducing an artificial version of the mutant gene, revealed that some p53 mutations are more harmful
than previously thought.