Hello World: The New TS Digest is Here

Our latest offering is the perfect bite-sized digital content fix for your fast-science craving.

A three-egg omelet with a side of hash browns and a thick stack of syrup-laden pancakes sat on the table in front of me. I stared, worried about how I would get through this “regular portion” breakfast that the nation adored during my first visit to a popular US diner 10 years ago. A hearty meal that provides maximum value for the money makes sense, yet a paradoxical food trend is on the rise today. 

          Conceptual illustration showing a scrollable page with bite sized content
Modified from © istock.com, everything bagel, gmast3r, Voysla, Rezeda Akhmadishina, PCH-Vector, OllyKava; Designed by Ashleigh Campsall

Acclaimed restaurants have popularized the concept of a tasting menu: an exquisite, multi-course meal comprised of a variety of small-portioned dishes. The chef carefully crafts the menu to ensure that each course, although barely a few morsels, bursts with unique flavors and delights the consumer. 

Why do food connoisseurs chase tasting menus despite the exorbitant prices? To feel special. Knowing that a skilled expert put thought into creating the highest quality product with their satisfaction in mind makes for a coveted experience.

Our new interactive TS Digest is the literary equivalent of a fine dining tasting menu. We have created bite-sized content pieces in diverse formats, crafted with the convenience of the reader in mind. You can now quickly browse a brief news story, play a video clip, solve a crossword puzzle, or peruse an infographic—all during your short coffee break. 

In this first edition, our team of creative writers has compiled an excellent selection of scientific content, bound to enthrall the readers. Danielle’s fly pheromone story will attract your attention; Mariella’s neuroscientist interview will spark your brain cells; and Emilie’s bacterial nanomotion infographic will transfix you. 


In this digital age of unlimited possibilities and limited time, the TS Digest offers respite for those craving quality science stories in an easy-to-browse online format. Contrary to the fine dining world, here, exceptional does not mean exclusive and expensive. True to our mission to provide concise, accurate, and accessible stories, the TS Digest is freely available to everyone. There is no free lunch, but there are free snacks for thought. 

I hope you enjoy this product of our passion and hard work. We look forward to your feedback.

Illustration of gut microbes

Microbial Menace in Cancer Patients

Fyza Shaikh investigates how microbes shape cancer patients’ health and recovery.

Image Credit:

© istock.com, DrAfter123

From influencing immunotherapy responses to causing life-threatening infections, microbes pose a significant yet underappreciated threat to cancer patients. Fyza Shaikh, a cancer researcher at Johns Hopkins School of Medicine, uses her broad research background and clinical experiences to understand the processes underlying these threats and advocate for better treatment options.

     Image of Fyza Shakih
Fyza Shakih explores the myriad ways microbes affect cancer patients.
Fyza Shaikh

How do you study the role of microbes during cancer treatment? 

The gut microbiome influences the response of many tumor types to checkpoint inhibitors. I analyze patient samples to determine what microbes and metabolites facilitate this response. I also put those microbes into mice to understand the pathways affecting the immune cells.

How do antimicrobial resistant microbes come to infect cancer patients?

Patients who have their immune systems diminished by cancer treatments often present with infections initially related to gut bacteria. Neutrophils form a barrier in the gut lining, and if a patient lacks these cells, bacteria can translocate from the colon to the bloodstream, causing an infection. We prescribe a broad-spectrum antibiotic to such immunocompromised patients. At some point, they may encounter a bacterium that is resistant to that antibiotic, and we hope that there is a backup antibiotic available. If we cannot treat a patient who has a nonfunctional immune system, it puts us in a tough place.

What is the solution to this problem?

There are very few antibiotics in the development pipeline, so there needs to be more investment in research and development. This is difficult because it is not the most lucrative area; physicians hope to use antibiotics rarely and as a last line of defense. We also need to explore other treatments such as phage therapy, small molecule inhibitors, chemistry modification of existing therapeutics, or different combinations of current drugs. Also, it is important to have good public health surveillance and containment strategies within the high-risk healthcare environment to stop infection spread.

This interview has been condensed and edited for clarity.

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Illustration of neuron cells network

A Complete Brain Wiring Map

Scientists developed new tools for brain reconstruction and analysis to create and characterize a complete brain wiring map of the fruit fly larva for the first time.

Image Credit:

© istock.com, imaginima

To date, scientists have created complete connectomes—maps of all the neural connections in the brain—for only three organisms with just a few hundred brain cells each.1-3 Now, with a study published in Science, the mighty Drosophila larva joins the ring as the heavy-weight with the largest 3-D whole brain reconstruction to date.4  

Mapping the fruit fly larva connectome was no easy feat. It required a transatlantic tour de force. Marta Zlatic, a neuroscientist at the University of Cambridge and coauthor of the study, previously collected thousands of high-resolution images of a Drosophila larva’s brain cells and their connections using volume electron microscopy.5 However, researchers had only partially reassembled these images before now.   

Imaging is no longer the rate limiting steps with these small brains. 

—Marta Zlatic, University of Cambridge

To speed up this painstaking process, Zlatic’s team developed computer-assisted reconstruction software.4 After many hours spent aligning and stitching together the remaining neural connections, the team was rewarded with the largest synaptic-resolution connectome to date, which included 3,016 neurons and 548,000 synapses. 

To explore this rich synaptic wiring map, Zlatic and her team developed novel computational tools that characterized neurons based on connectivity profiles and predicted behavioral roles for these circuits. These efforts revealed novel circuit motifs, or connectivity patterns, and circuit hubs, many of which are involved in learning processes. 

 

Marta Zlatic and her colleagues created a 3-D reconstruction of more than 3000 neurons and their connections in the fruit fly larva brain.
Johns Hopkins University, University of Cambridge

Although this connectome project was years in the making, Zlatic said that their reconstruction software in combination with advancements in volume electron microscopy will greatly facilitate experimental connectomics. “Imaging is no longer the rate limiting step with these small brains,” said Zlatic. What previously took them a year to image now only takes weeks.

Harald Hess, a microscopist at the Howard Hughes Medical Institute’s Janelia Research Campus who was not involved in the study, noted that connectomics efforts have been key to advancing volume electron microscopy technologies. “It's really cool right now with the drive in the connectomics field to really access larger volumes,” said Hess. “It makes other non-neuroscience applications more achievable and accessible.”

References

  1. White JG, et al. Phil Trans R Soc B. 1986;314:1-340.
  2. Ryan K, et al. eLife. 2016:5:353-356.
  3. Verasztó C, et al. bioRxiv. 2020;2020-08.
  4. Winding M, et al. Science. 2023;379:eadd9330.
  5. Ohyama T, et al. Nature. 2015;520:633-639.

Using Multiple Techniques for Gene Expression Analysis

A single approach rarely addresses all research needs. Learn when and how to employ sequencing and PCR-based methods.

          qPCR Data icon

Reverse Transcription Quantitative PCR 
(RT-qPCR)
Custom primer pairs target genes of interest, and fluorescence from reporter molecules measured over time indicates gene expression. While RT-qPCR is the most common and cost-effective approach, it is semi-quantitative, and PCR inhibitors can skew results.

          Test tube icon

Digital PCR (dPCR)
Each PCR reaction is partitioned into thousands of nanoreactions, which allows this method to detect low-abundance targets. dPCR also tolerates common PCR inhibitors and provides absolute quantification of nucleic acids without the need for standard curves.

          RNA transcript sample icon

RNA Sequencing (RNA-seq)
This method sequences all of the RNA transcripts in a sample, even if certain gene sequences are unknown. RNA-seq provides a comprehensive and unbiased view of the transcripts but is costly and requires expertise to analyze.

          Puzzle piece icon

Combine multiple methods to fully answer your research question.

Step 1: RNA-seq

An RNA-seq approach allows you to characterize many genes at once, and new advancements make sequencing at the tissue or single-cell level possible.

Step 2: RT-qPCR or dPCR

Validate your RNA-seq results with PCR-based approaches, which are faster, easier, and more affordable than RNA-seq.



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Image of yeast cells

Yeast Cells Reconfigure Their Metabolomes to Live Longer

Yeast cells share metabolites through extracellular space to extend the lifespan of the entire community.

Image Credit:

© istock.com, Artur Plawgo

A complex orchestration of metabolic processes creates energy and influences cell survival. But metabolism is not a cloistered, intracellular process. In a study published in Cell, scientists showed how yeast cells that shared a specific metabolite reshaped their communal metabolic environment and lived longer.1  

Yeast are single-celled organisms, but their lives are far from solitary. “Microbes love communities,” said Markus Ralser, a biologist at the Francis Crick Institute and senior author of the study. One benefit of communal living is collaborating on energy-intensive activities. Some cells export metabolites into their surroundings, which nearby cells import to fulfill their own metabolic needs. 

Curious about how this exchange influences aging, Ralser turned his sights to aging yeast communities. Studying metabolite exchange within microbial communities is challenging, as single-cell techniques overlook the extracellular space. To overcome this limitation, the team generated self-establishing metabolically cooperating communities (SeMeCos) of yeast that are designed to only produce or consume key amino acids.2 

          Microscopy image
In this fluorescence microscopy image of a self-establishing metabolically cooperating community (SeMeCo), fluorescent tags identify which amino acid a particular cell produced (leucine is green, methionine is red, and histidine is blue).
License CC-BY, Campbell et al., 2015, eLife.2

Rasler was surprised to find that SeMeCos lived significantly longer than wild-type yeast communities. A closer look into the extracellular metabolites—exometabolome—revealed that cells lived longer if they produced the amino acid methionine or neighbored methionine-producers. 

These findings intrigued Ralser and his team. Upon further investigation into the metabolome, they found that methionine-consuming cells reconfigured their metabolism to export protective metabolites, such as glycerol, which extends yeast lifespans, back into the metabolome.3 Ralser’s team then looked at cross-generational cells and linked these beneficial methionine exchange interactions in the exometabolome to elevated concentrations of anti-aging metabolites in older cells. 

Kiran Patil, a biologist at Cambridge University who was not involved in the study, noted that the findings support a new way of looking at fundamental biological processes like aging. “We like to look inside the cell. At the same time, equally important is the environment, what's outside the cells, because that determines what the selection pressure is but also how the cell responds to it.”

References

  1. Correia-Melo C, et al. Cell. 2023;186:63-79.
  2. Campbell K, et al. eLife. 2015;4:e09943.
  3. Wei M, et al. PLoS Genet. 2009;5:e1000467.
Illustration of glowing fireflies

Glow-in-the-dark Diagnostics

A nucleic acid detection platform that marries CRISPR diagnostic tools with bioluminescence could accelerate treatment decisions in the clinic.

Image Credit:

© istock.com, akkachai thothubthai

Diagnostic platforms for point-of-care settings must be sensitive, easy, and fast. In a paper recently published in ACS Central Science, researchers showcased just that: a new diagnostic platform that rapidly detects viral RNA with a simple bioluminescent readout.1

          Digital camera capturing bioluminescent readout
Researchers easily capture the bioluminescent readout using a digital camera.
Maarten Merkx

Scientists commonly identify pathogens by their nucleic acid fingerprints. Quantitative polymerase chain reaction (qPCR) is the gold-standard method, but diagnostics developers are adopting a quicker and easier alternative: recombinase polymerase amplification (RPA), which amplifies samples at 37°C in 20 minutes.2,3 “RPA is a fantastic technique famous for amplifying DNA super, super quickly,” said Helena de Puig, a biomedical engineer at the Massachusetts Institute for Technology, who was not involved in the study.

The beauty of bioluminescence is its simplicity. 

—Maarten Merkx, Eindhoven University of Technology

To detect RNA, Maarten Merkx, a biomedical engineer at Eindhoven University of Technology and author of the study, along with his team, combined reverse transcription with RPA (RT-RPA) to rapidly transcribe viral RNA and amplify the resulting double stranded DNA (dsDNA). 

The lower temperature in RPA increases the risk of nonspecific amplification, so Merkx sought a sensitive solution. Recent successful COVID-19 diagnostics used CRISPR enzymes for specificity.2 While those methods leveraged Cas12a and Cas13a nucleases, which trigger collateral cleavage of nucleic acids along with target sequence cleavage, Merkx had a different approach in mind. He chose endonuclease dead Cas9 (dCas9), which finds specific sequences in the dsDNA but lacks the machinery to cleave them, for his assay. 

For the detection part, the team borrowed from nature.

“The beauty of bioluminescence is its simplicity,” said Merkx. The team split luciferase, an enzyme that produces bioluminescence, between two dCas9 proteins. When the dCas9 proteins bound to neighboring target sequences, the luciferase fragments combined and enabled bioluminescence, which the researchers captured with a digital camera. 

The team tested this platform on COVID-19 samples and detected SARS-CoV-2 RNA within 30 minutes. Next, Merkx wants to apply this tool to rapidly detect sexually transmitted diseases to facilitate immediate treatment decisions in the clinic. 

References

  1. van der Veer HJ, et al. ACS Cent Sci. 2023;9:657-667.
  2. Kaminski MM, et al. Nat Biomed Eng. 2021;5:643-656.
  3. Cherkaoui D, et al. Biosens Bioelectron. 2021;189:113328.
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The Cellular Intricacies of the Human Placenta

Rare samples saved 35 years ago helped researchers map gene expression and cell differentiation in first trimester placentas.

Apart from possibly the great apes, no animal has a placenta quite like ours,1 which makes it difficult to study. But studying the placenta is critical since it plays a role in life-threatening pregnancy disorders such as pre-eclampsia. With this in mind, Ashley Moffett from the University of Cambridge saved samples from first trimester hysterectomies carried out as treatment for cervical cancer 35 years ago. Today, we vaccinate against a common viral cause for cervical cancer, so early pregnancy hysterectomies are extremely rare, making these samples precious.

          A fluorescence microscopy image of placenta tissue made up of cells dyed blue, purple, pink and green on a black background.
An analysis of precious old hysterectomy samples has revealed the cellular trajectory of placenta formation and development. The image shows different cells of the placenta.
kenny roberts

“I wouldn’t let anyone near them because I knew, at some point, people would be able to actually do something [with them],” Moffett said. That point has arrived.

In collaboration with the Wellcome Sanger Institute, Moffett and her colleagues used these samples to map gene expression in the early placenta at the resolution of a single cell. Using spatial transcriptomics, single-cell RNA sequencing, and chromatin accessibility assays, they pinned down cell differentiation trajectories of the fetus-produced organ as it invades the uterus and transforms maternal arteries.2 “It’s an amazing effort,” commented Nardhy Gomez-Lopez, a maternal-fetal immunologist at Wayne State University, who was not involved in the study. 

Moffett hopes that the map will help improve placenta models so that scientists can better understand diseases and test drugs. It has already showed that trophoblast organoids (self-assembled miniature placentas) reproduce the relevant cell differentiation, even though they do not reach full functionality, probably due to missing maternal signals.  

The next step is to understand what happens in the second trimester where most of the diseases occur, said Gomez-Lopez, but securing samples will be hard as they depend on unusually late terminations. Any progress made, however, will benefit both those pregnant and their children, said Moffett. “What happens to you as a baby in utero affects the whole of the rest of your life. … It’s about the next generation.”

References

  1. Carter A M. Int J Mol Sci 2021;22(15):8099.
  2. Arutyunyan A, et al. Nature 2023;616(7955):143-151.
A male tsetse fly smells a tsetse fly pheromone

Elusive Tsetse Pheromones

Researchers discovered novel attractants that may improve Tsetse fly traps and help control disease spread.

Image Credit:

MODIFIED FROM © istock.com, VectorMine; MODIFIED FROM © SHUTTERSTOCK.COM, LynxVector; Designed by Erin Lemieux

Tsetse, a pest in sub-Saharan Africa, is notorious for spreading diseases to humans and livestock through the trypanosome parasites they harbor. Baiting traps with volatile pheromones, or odors that attract mates from a distance, is a promising strategy for controlling these blood-sucking insects. “Scientists have been studying tsetse for over 100 years, but no one has actually found a volatile pheromone in this species,” said John Carlson, a biologist at Yale University. Now, for the first time, Carlson and his research team reported the discovery of volatile tsetse pheromones in a paper recently published in Science.1

Scientists have been studying tsetse for over 100 years, but no one has actually found a volatile pheromone in this species.

—John Carlson, Yale University

Carlson’s team concocted tsetse perfumes by soaking female flies in hexane. When the researchers spritzed the extracted female tsetse scents on a knotted string of black yarn, the male tsetse quickly attached itself to the aromatic decoy. Intrigued, Carlson’s team next ran a gas chromatography-mass spectrometry analysis on the fly extracts and identified six volatile compounds. 

The team found that one of these compounds, methyl palmitoleate (MPO), was a particularly strong attractant, arrestant, and aphrodisiac in the male tsetse. By measuring electrophysiological responses, the research team observed that MPO activated the same subset of olfactory neurons that respond to livestock odors currently used in tsetse traps, consistent with the idea that MPO activates a kind of attraction circuit. While the observations were specific to the tsetse species, G. moristans, similar approaches could reveal novel pheromones in other tsetse species.

One challenge is that the pheromone is most effective at short range. “If we know the receptors and the fidelity of these ligands, then we can modify the ligands to make them long-lasting and more volatile so they become long-range,” said Zain Syed, a chemical ecologist at the University of Kentucky, who was not involved in the work. 

Carlson is working with colleagues in Kenya to test MPO’s allure in the field. 

Reference

  1. Ebrahim S, et al. Science. 2023; 379:eade1877.
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Image of in vitro fertilization

Should the scientific community abandon the 14-day rule for research on human embryos?

Research on human embryos is usually limited to the first 14 days of development, but as scientific capabilities improve, some argue that it is time to go further.

Image Credit:

© istock.com, iLexx

Cultivating human embryos is a delicate issue because they have the potential to develop into viable pregnancies if implanted into wombs.1 The global scientific community has consequently operated under a general rule to limit in vitro research on human embryos to the first 14 days of development, a boundary that when first suggested in 1979 was far beyond technological capabilities to break.2 

However, that is no longer the case, and in 2021, the International Society for Stem Cell Research (ISSCR) removed the rule from its guidelines and encouraged case-by-case review.3 Yet in many countries, the rule remains enshrined in law. We asked two experts in the field whether it’s time to leave it behind.

          Image of Naomi Moris
Naomi Moris is a developmental biologist at the Francis Crick Institute. She works with 3D stem cell structures that model human embryos.
THE FRANCIS CRICK INSTITUTE

Naomi Moris

I think that we definitely need to reconsider the rule. The science is pushing up against it from multiple directions: We’re getting better and better at culturing embryos in a lab environment, and we are developing these embryo-like models, such as blastoids, that are really challenging what the word embryo means. The rule is unclear when it comes to them. The ISSCR suggestion of operating on a case-by-case basis allows us to push the boundaries and show the public the benefit of the research before having a wider discussion about going further. It’s probably the most workable solution given how fast the science is moving.


          Image of Kirstin Matthews
Kirstin Matthews is a policy scholar in biomedical research at Rice University’s Baker Institute for Public Policy; she has a background in molecular biology.
RICE UNIVERSITY

Kirstin Matthews

It would be fine to withdraw the 14-day rule if we replace it with another guardrail that communicates that we, as a profession, have guidelines and that we consider embryos to be special entities. We did an assessment4 where I brought in scholars who were hesitant about relaxing the rule, and a lot of what they wanted was to ensure that the science was thoughtful and respected public beliefs, whereas the people interested in removing the restriction focused on what knowledge could be gained. There is probably a compromise where everyone’s slightly unhappy, but I think that’s where we need to go.


These interviews have been edited for length and clarity.

References

  1. Amato P, et al. Fertil Steril. 2020;113:270-294.
  2. Hyum I, et al. Nat. 2016;533:169-171.
  3. ISSCR Guidelines, 2021.
  4. Matthews KRW, et al. Hastings Cent Rep. 2021;51:47-51.

Jiggling Bacteria Reveal Antibiotic Resistance

Finding an effective antibiotic against an infection can easily take 24 hours. Faster testing could save lives and help doctors avoid broad-spectrum antibiotics, which can foster resistance.


Infographic showing a new way to assess antibiotic effectiveness based on how much bacteria jiggle
© ISTOCK.COM, BLUERINGMEDIA; © ISTOCK.COM, TTSZ; DESIGNED BY ERIN LEMIEUX


References

  1. Kasas S, et al. Proc Natl Acad Sci, 2015;112(2): 378-381.
  2. Villalba MI, et al. Proc Natl Acad Sci, 2023;120(18): e2221284120.
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Two human brain illustrations

An Advocate for the Female Brain

Rebecca Shansky studies both female and male rodents to ensure that scientists have a complete and unbiased picture of the brain.

Image Credit:

modified from © ISTOCK.COM, filo

Neuroscientists have historically defaulted to male subjects for research. This was true even for those studying disorders more common in women such as post-traumatic stress disorder1 and depression.2 Limited knowledge about the female brain motivated Rebecca Shansky, a neuroscientist at Northeastern University, to study both sexes in rat and mouse models to explore how stress and fear change the brain structure and function.

By excluding female subjects, we rule out half of what's possible. That's going to slow down science.

—Rebecca Shansky, Northeastern University

          A female scientist is in a laboratory wearing blue gloves and holding a conical tube. She is standing in front of a refrigerator.
Rebecca Shansky is a group leader at Northeastern University. She works with male and female animal models to explore stress and fear effects on the brain.
Vivika Sheppard

Why should neuroscientists consider both sexes when studying the brain?

We miss a lot when we don’t study female models. Female brains are organized differently. They have different mechanisms for executing fundamental biological processes. If neuroscientists aim to provide knowledge that will be translated into human health, we need to understand what's possible. And by excluding female subjects, we rule out half of what's possible. That's going to slow down science.

What are the challenges in studying both sexes?

Some of our behavior tests are not going to work as well in female animals, and we may need to make some adjustments or think about better investigational metrics. Also, some people still have biases, and that's a challenge for everybody. There is also a trend in academic publishing that favors studies with sophisticated techniques only in male models over more careful but less flashy work using both sexes. This practice disincentivizes researchers to take sex as a biological variable (SABV) work seriously. That needs to change so that the goals of NIH’s SABV policy and the goals of scientists better align.

This interview has been edited for length and clarity.

Correction notice (July 25): The photo caption in this article has been updated to specify that Rebecca Shansky is a group leader at Northeastern University. 

References

  1. McLean CP, et al. J Psychiatr Res. 2011;45:1027-1035.
  2. Hasin DS, et al. Arch Gen Psychiatry. 2005;62:1097-1106.
July 2023 crossword image

It’s Crossword Time

Put on your thinking cap, and take on this fun challenge.

Image Credit:

MODIFIED FROM © istock.com, VectorMine; MODIFIED FROM © SHUTTERSTOCK.COM, LynxVector; Designed by Erin Lemieux


          July 2023 crossword puzzle
Click the puzzle for a full-size, interactive version.
STELLA ZAWISTOWSKI
ACROSS

7. Staple that needs a hot and humid climate
8. Self-organized structure from a stem cell culture
9. Groups smaller than families
10. Metallic element with antimicrobial properties
11. Word before "tooth" or "tuning"
12. Non-native and harm-producing
15. Airtight, as a seal
17. Mammary passage
18. Scorpions' attacks
21. "On the ___ of Species"
22. Insect's respiratory opening
23. Organs with sclerae

DOWN

1. Approximately four weeks, for a skin cell
2. Intense, as drought or disease
3. Plant anatomy specialist, for example
4. Some gametes
5. Bond relationships in chemistry
6. Result of combustion
13. Fluid-filled spaces in cells
14. Preparations whose effectiveness may be boosted with squalene
16. Kingdom name no longer used in taxonomy
17. Oncogene, vis-avis cancer
19. Blood classification
20. Pollen-carrying structures

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