Macrophages are immune cells at the front line, detecting pathogens and kicking off an inflammatory response when needed. Understanding how macrophages determine when to go all-out and when to keep calm is key to finding new ways to strike the right balance — particularly in cases where inflammation goes too far, such as in sepsis, colitis and other autoimmune disorders.

In a study published October 14, 2020 in the Proceedings of the National Academy of Sciences, researchers at University of California San Diego School of Medicine discovered that a molecule called Girdin, or GIV, acts as a brake on macrophages.

When the team deleted the GIV gene from mouse macrophages, the immune cells rapidly overacted to even small amounts of live bacteria or a bacterial toxin. Mice with colitis and sepsis fared worse when lacking the GIV gene in their macrophages.

The researchers also created peptides that mimic GIV, allowing them to shut down mouse macrophages on command. When treated with the GIV-mimic peptide, the mice’s inflammatory response was tempered.

“When a patient dies of sepsis, he or she does not die due to the invading bacteria themselves, but from an overreaction of their immune system to the bacteria,” said senior author Pradipta Ghosh, MD, professor at UC San Diego School of Medicine and Moores Cancer Center. “It’s similar to what we’re seeing now with dangerous ‘cytokine storms’ that can result from infection with the novel coronavirus SARS-CoV-2. Macrophages, and the cytokines they produce, are the body’s own immune-stimulating agents and when produced in excessive amounts, they do more harm than good.”

Digging deeper into the mechanism at play, Ghosh and team discovered that the GIV protein normally cozies up to a molecule called Toll-like receptor 4 (TLR4). TLR4 is stuck right through the cell membrane, with bits poking inside and outside the cell. Outside of the cell, TLR4 is like an antenna, searching for signs of invading pathogens. Inside the cell, GIV is nestled between the receptor’s two “feet.” When in place, GIV keeps the feet apart, and nothing happens. When GIV is removed, the TLR4 feet touch and kick off a cascade of immune-stimulating signals.

Ghosh’s GIV-mimicking peptides can take the place of the protein when it’s missing, keeping the feet apart and calming macrophages down.

“We were surprised at just how fluid the immune system is when it encounters a pathogen,” said Ghosh, who is also director of the Institute for Network Medicine and executive director of the HUMANOID Center of Research Excellence at UC San Diego School of Medicine. “Macrophages don’t need to waste time and energy producing more or less GIV protein, they can rapidly dial their response up or down simply by moving it around, and it appears that such regulation happens at the level of gene transcription.”

Ghosh and team plan to investigate the factors that determine how the GIV brake remains in place when macrophages are resting or is removed to mount a response to a credible threat. To enable these studies, the Institute for Network Medicine at UC San Diego School of Medicine recently received a new $5 million grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Ghosh shares this award with her colleagues Debashis Sahoo, PhD, assistant professor at UC San Diego School of Medicine and Jacobs School of Engineering, and Soumita Das, PhD, associate professor of pathology at UC San Diego School of Medicine.

Co-authors of the study include: Lee Swanson, Gajanan D. Katkar, Julian Tam, Rama F. Pranadinata, Yogitha Chareddy, Jane Coates, Mahitha Shree Anandachar, Vanessa Castillo, Joshua Olson, Victor Nizet, Irina Kufareva, Soumita Das, all at UC San Diego.

Plant reflectance spectra, or the light profile leaves reflect across different wavelengths, capture the change and diversification of seed plants as a result of evolution, according to Dudu Meireles. The UMaine assistant professor of plant evolution and systematics and colleagues from the United States, Canada, Switzerland and England explored how spectra have evolved and diversified over the last 350 million years of plant evolution.

Researchers found that by measuring the light spectrum reflected by a leaf, they can identify the plant, learn about its chemistry and evolution, and pinpoint its place in the tree of life, Meireles says. Spectra also can be used to “provide breakthrough assessments of leaf evolution and plant phylogenetic diversity at global scales,” the group wrote in its report for the study. Meireles says he hopes to eventually perform these measurements remotely using unmanned aerial vehicles, airplanes, or satellites.

“We know little about how plant traits and chemistry evolved because collecting the data is difficult and slow, but spectra enables us to gather those data at unprecedented rates.” Meireles says.

New Phytologist, an international plant science research journal, published the group’s findings in its October 2020 issue and promoted the study on the cover. The cover also features art by Adriana Cavalcanti of Orono, an Intermedia MFA student. According to the journal, the leaf art created from hole punches of autumn foliage evokes “how light reflectance spectra capture leaf chemical diversity and reveal the evolutionary history of plants.”

Cavalcanti says she created the artwork, titled “Biomimicry,” last fall by hole punching a variety of leaves and gluing the different circles to reclaimed wood to form a multicolored leaf. The ways technology intertwines with science and nature inspired the piece, she says, adding how nature observations have influenced several technological advancements.

While working on his plant reflectance spectra research, Meireles encouraged Cavalcanti, who is also a botanist, to submit “Biomimicry” to New Phytologist, she says. The journal, which accepts original artwork that reflects the primary topic of each issue, selected her piece to represent Merieles’ findings.

“When I heard that my work was selected for the cover, it was a big surprise. First, because I don’t usually see art pieces on the cover of scientific journals. Secondly, because It wasn’t created with that in mind,” Cavalcanti says. “For me, it is just an example of how open minded we need to be about our own art creations; the importance of leaving space for people to get their own perception about art.”

The research team conducted the study using a dataset of more than 16,000 leaf-level reflectance spectra, ranging from visible to infra-red light, from 544 seed plant species in the tropical and temperate latitudes of the Americas and Europe. They measured leaf spectra using two full-range field spectroradiometers, leaf clips and artificial light sources.

While spectra highlights the phylogenetic history of seed plants, the location of the signal presenting that information in spectra can vary among plant lineages, according to researchers. They found, for example, that the signal yielding the evolutionary record for the monocot lineage of plants is located in near-infrared light reflected from their leaves, but the signal for the gymnosperm lineage resides in short-wave infrared light reflected from leaves. To monitor plant diversity, Meireles says scientists have to measure the full spectrum of light reflected from leaves rather than a handful of bands.

The team created a model that can help simulate how different evolutionary dynamics, such as convergent adaptation to shade, affect spectra. Their framework also revealed that evolution constrains the variation of spectra in seed plants to different extents, particularly for the visible region associated with pigments such as chlorophyll and carotenoids.

Meireles and his colleagues hope that increasing availability of high-resolution spectral data not only for leaves, but also at the canopy- and landscape-levels will help improve how scientists monitor plant biodiversity.

“Ecosystem function, and by extension human wellbeing, depend on biodiversity. We must monitor diversity to understand, manage and preserve it, and reflectance spectra is one of the best tools we have to do that job efficiently.” Meireles says.

As the pandemic continues, the global biomedical research community is working urgently to identify coronavirus risk factors and potential therapeutic targets. The potential role of blood type in predicting risk and complications of COVID-19 infection has emerged as an important scientific question. These new studies add evidence that there may be an association between blood type and vulnerability to COVID-19; however, additional research is needed to better understand why and what it means for patients.

Individuals with blood type O may be less vulnerable to COVID-19 infection

Blood type O may offer some protection against COVID-19 infection, according to a retrospective study . Researchers compared Danish health registry data from more than 473,000 individuals tested for COVID-19 to data from a control group of more than 2.2 million people from the general population. Among the COVID-19 positive, they found fewer people with blood type O and more people with A, B, and AB types.

The study results suggest that people with blood types A, B, or AB may be more likely to be infected with COVID-19 than people with type O. The researchers did not find any significant difference in rate of infection between A, B, and AB types. Since blood group distributions vary among ethnic subgroups, the researchers also controlled for ethnicity and maintained that fewer people with blood type O tested positive for the virus.

“It is very important to consider the proper control group because blood type prevalence may vary considerably in different ethnic groups and different countries,” said study author Torben Barington, MD, of Odense University Hospital and the University of Southern Denmark. “We have the advantage of a strong control group — Denmark is a small, ethnically homogenous country with a public health system and a central registry for lab data — so our control is population-based, giving our findings a strong foundation.”

Blood groups A and AB associated with increased risk of severe clinical outcomes of COVID-19 infection People with blood groups A or AB appear to exhibit greater COVID-19 disease severity than people with blood groups O or B, according to a separate retrospective study . Researchers examined data from 95 critically ill COVID-19 patients hospitalized in Vancouver, Canada. They found that patients with blood groups A or AB were more likely to require mechanical ventilation, suggesting that they had greater rates of lung injury from COVID-19. They also found more patients with blood group A and AB required dialysis for kidney failure.

Together, these findings suggest that patients in these two blood groups may have an increased risk of organ dysfunction or failure due to COVID-19 than people with blood types O or B. Furthermore, while people with blood types A and AB did not have longer overall hospital stays than those with types O or B, they did remain in the intensive care unit (ICU) for a longer average time, which may also signal a greater COVID-19 severity level.

“The unique part of our study is our focus on the severity effect of blood type on COVID-19. We observed this lung and kidney damage, and in future studies, we will want to tease out the effect of blood group and COVID-19 on other vital organs,” said study author Mypinder S. Sekhon, MD, of the University of British Columbia. “Of particular importance as we continue to traverse the pandemic, we now have a wide range of survivors who are exiting the acute part of COVID-19, but we need to explore mechanisms by which to risk stratify those with longer-term effects.”

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Materials provided by American Society of Hematology. Note: Content may be edited for style and length.