The protein, known as histone H3.3, organizes the spool-like structures around which DNA is wrapped in plants, animals and most other organisms. Histones enable DNA to be tightly compacted, and serve as platforms for small chemical modifications — known as epigenetic modifications — that can loosen or tighten the wrapped DNA to control local gene activity.

The study, which appeared Dec. 27 in Nature Cell Biology, examined H3.3’s role in blood stem cells, also known as hematopoietic stem cells (HSCs), that are a major focus of efforts to develop stem-cell-based medicine. Normally most HSCs stay in a stem-like, uncommitted state where they can survive long-term, slowly self-renewing, while some HSCs mature or “differentiate” to produce all the different lineage-specific blood cell types. The study found that H3.3 is crucial for both processes; deleting the protein from HSCs led to reduced HSC survival, an imbalance in the types of blood cell produced by the HSCs and other abnormalities.

“How hematopoietic stem cells coordinate their self-renewal and differentiation into various blood cell types in a balanced way has been a mystery to a great extent, but this study helps us understand those processes much better at the molecular level and gives us many new clues to pursue in further investigations,” said study co-senior author Dr. Shahin Rafii, director of the Ansary Stem Cell Institute, chief of the Division of Regenerative Medicine and the Arthur B. Belfer Professor in Genetic Medicine at Weill Cornell Medicine.

The study was a collaboration that also included co-first and co-senior authors Dr. Ying Liu and Dr. Peipei Guo, who are senior instructors in the Rafii Laboratory; co-senior author Dr. Duancheng Wen, assistant professor of reproductive medicine research in obstetrics and gynecology; and co-author Dr. Steven Josefowicz, assistant professor of pathology and laboratory medicine and a member of the Sandra and Edward Meyer Cancer Center, all of Weill Cornell Medicine.

HSCs are among the most studied stem cells because of their importance in health and disease, and their potential in regenerative medicine. A single HSC can give rise to all blood cell types, from red blood cells and platelets to T cells, B cells and pathogen-engulfing macrophages. A more precise understanding of how HSCs work could lead to many applications including lab-grown blood for transfusions, and better HSC transplants for cancer patients. In addition, understanding how HSCs, upon acquiring aberrant mutations, give rise to leukemias could lead to development of new therapies for these often-refractory malignant diseases.

H3.3 also has been a major focus of interest for biologists in recent years, as evidence of its importance in HSCs and other stem cells — and its role in various cancers when mutated — has mounted. But just what histone H3.3 does in HSCs, and in other cell types where it appears, has been far from clear.

“Added to the complexity of this project, is that two different genes (H3.3A and H3.3B) code for the same H3.3 protein. Therefore, we had to painstakingly delete both genes in mice by genetic engineering, a herculean task that required a great deal of genetic manipulation of stem cells,” Dr. Wen said.

“Our powerful mouse model allows inducible and complete deletion of the H3.3 protein in all organs, or specific types of organs, at selected developmental stage of a mouse,” said Dr. Liu, who is also a research associate in Dr. Rafii’s lab. “Employing this approach, we showed that H3.3’s absence in adulthood primarily causes a depletion of the long-term, self-renewing HSCs on which future blood-cell production depends. At the same time, affected HSCs differentiated into mature blood cell types with an abnormal skew or bias towards certain types of white blood cell, including granulocytes and macrophages.

“Most importantly, we found evidence that H3.3 has its effects on HSCs in part by anchoring several key epigenetic marks at developmental genes and endogenous retroviruses (ERVs),” she added, “which are remnants of viruses that once inscribed themselves into our distant evolutionary ancestors’ DNA.”

“One intriguing observation was that H3.3’s deletion caused the loss of epigenetic marks that normally suppress ERVs, which led in turn to the activation of an inflammatory response in affected cells, and then drove the cells’ skewed production of blood cell types — a skew that is similar to what is seen in some leukemias,” said Dr. Guo, who is also a research associate in Dr. Rafii’s laboratory.

“H3.3 appears to be acting as a master regulator of self-renewal and differentiation in HSCs — which is wild, and hints at a very broad potential as a therapeutic target someday,” said co-author Andrew Daman, a Weill Cornell Graduate School of Medical Sciences doctoral candidate in the Josefowicz lab.

“Our take-home message is that normal blood cell development requires the proper epigenetic regulation provided by H3.3,” Dr. Liu said.

The team now plans further studies, in HSCs and other cell types, to understand in more detail how H3.3 exerts its effects and what happens when it is absent. More importantly, developing approaches to monitor the H3.3 command of the epigenetic landscape could enable them to more effectively increase blood production. “Finally, our team is investigating how H3.3 controls the function of the nurturing niche cells, such as blood vessels that orchestrate stem cell self-renewal and possibly block the emergence of malignancies such as leukemias,” said Dr. Rafii, who is also a member of the Meyer Cancer Center.

“It has been widely accepted that traditional superconductors result from electrons interacting with phonons, where the phonons pair two electrons as an entity and the latter can run in a material without resistance,” said Yao Wang, assistant professor of physics and astronomy at Clemson University.

However, in cuprates, strong repulsions known as the Coulomb force were found between electrons and were believed to be the cause of this special and high-temperature superconductivity.

Phonons are the vibrational energy that arise from oscillating atoms within a crystal. The behavior and dynamics of phonons are very different from those of electrons, and putting these two interacting pieces of the puzzle together has been a challenge.

In November 2021, writing in the journal Physical Review Letters, Wang, along with researchers from Stanford University, presented compelling evidence that phonons are in fact contributing to a key feature observed in cuprates, which may indicate their indispensable contribution to superconductivity.

The study innovatively accounted for the forces of both electrons and phonons together. They showed that phonons impact not only electrons in their immediate vicinity, but act on electrons several neighbors away.

“An important discovery in this work is that electron-phonon coupling generates non-local attractive interactions between neighboring electrons in space,” Wang said. When they used only local coupling, they calculated an attractive force an order of magnitude smaller than the experimental results. “This tells us that the longer-range part is dominant and extends up to four unit cells,” or neighboring electrons.

Wang, who led the computational side of the project, used the National Science Foundation (NSF)-funded Frontera supercomputer at the Texas Advanced Computing Center (TACC) — the fastest academic system in the world — to replicate experiments carried out at the Stanford Synchrotron Radiation Lightsource and presented in Sciencein Sept. 2021 in a simulation.

The results relied not only on Frontera’s super-fast parallel computing capabilities, but on a new mathematical and algorithmic method that allowed for far greater accuracy than ever before.

The method, called variational non-Gaussian exact diagonalization, can perform matrix multiplications on billions of elements. “It’s a hybrid method,” Wang explained. “It treats the electron and phonon by two different approaches that can adjust with each other. This method performs well and can describe strong coupling with high precision.” The method development was also supported by a grant from NSF.

The demonstration of phonon-mediated attraction has a significant impact even beyond the scope of superconductors. “Practically, the results mean we’ve found a way to manipulate Coulomb interactions,” Wang said, referring to the attraction or repulsion of particles or objects because of their electric charge.

“If superconductivity comes from Coulomb forces only, we cannot easily manipulate this parameter,” he said. “But if part of the reason comes from the phonon, then we can do something, for instance, putting the sample on some substrate that will change the electron-phonon interaction. That gives us a direction to design a better superconductor.”

“This research gives new insights into the mystery of cuprate superconductivity that may lead to higher temperature superconducting materials and devices,” said Daryl Hess, a program director in Division of Materials Research at NSF. “They may find their way into future cell phones and quantum computers. A journey started by human creativity, clever algorithms, and Frontera.”

Wang and collaborator Cheng-Chien Chen, from the University of Alabama, Birmingham, also applied this new approach and powerful TACC supercomputers to study laser-induced superconductivity. They reported these findings in Physical Review X in November 2021. And working with a team from Harvard, Wang used TACC supercomputers to study the formation of Wigner crystals in work published in Nature in June 2021.

As is the case in many fields of science, supercomputers are the only tool that can probe the quantum behavior and explain the underlying phenomena at play.

“In physics, we have very beautiful frameworks to describe an electron or an atom, but when we’re talking about real materials with 10²³ atoms, we don’t know how to use these beautiful frameworks,” Wang said.

For quantum or correlated materials in particular, physicists have had a hard time applying ‘beautiful’ theory. “So instead, we use ugly theory — numerical simulation of the materials. Although we don’t have a well-established quantum computer for now, using classical high performance computers, we can push the problem forward a lot. Ultimately, this will guide experiment.”

Wang is currently working with IBM and IonQ to develop quantum algorithms to test on current and future quantum computers. “Supercomputing is our first step.”

When it comes to big future developments in technology, Wang believes computational studies, in conjunction with experiment, observation and theory, will help untangle mysteries and achieve practical goals, like tunable superconducting materials.

“A new algorithm can make a difference. More numerical precision can make a difference,” he said. “Sometimes we don’t understand the nature of a phenomenon because we didn’t look closely enough at the details. Only when you push the simulation and zoom in to the nth digit will some important aspect of nature show up.”

All-polymer blend solar cells are formed by combining two polymer solutions that solidify into a film on an electrode with in the form of interpenetrating networks, a kind of “phase-separation.” The introduction of solvent additives to the polymer solution has been shown to increase the efficiency of all-polymer blend solar cells. However, the exact process underlying this improvement has not been fully understood. Now, in a study recently published in ACS Applied Polymer Materials, researchers from Nara Institute of Science and Technology have investigated the performance enhancement mechanism using photoconductive atomic force microscopy (PC-AFM). Their findings are expected to help accelerate the widespread application of polymer-based solar cells.

“The empirical nature of solvent additive-mediated efficiency enhancement has hindered the optimization of all-polymer blend solar cell performance, so there has been an urgent need for a greater understanding of the process,” explains senior author Hiroaki Benten. “To that end, we used PC-AFM to interrogate the nanoarchitecture that underpins the performance enhancement.”

PC-AFM is an advanced microscopy technique that allows photocurrents to be visualized with nanometer-scale resolution. The researchers found that trace solvent additives improved the power conversion and photocurrent density of an all-polymer blend solar cell by a factor of up to ~3 by enhancing the ordering and crystallization of the polymer microstructure in the solar cell without damaging the phase-separated structure.

Absorption spectroscopy measurements further confirmed that the trace additives improved the ordering in the polymer microstructures. By forming a network that efficiently transports the photogenerated charges to the external electrode, the flow of photocurrent is increased.

“We found that local photocurrents were enhanced, somewhat like forming a new charge current highway, while the scale of phase separation that is critical to device functionality was retained,” says coauthor Masakazu Nakamura. “We believe that this insight will be broadly applicable to all-polymer blend solar cells, not just those based on our choice of polymers.”

The results of the study are expected to be important for optimizing the performance of all-polymer blend solar cells. By using the findings to minimize laboratory trial-and-error, it is hoped researchers can speed up ongoing bench-to-market efforts, taking us a step closer to high-performance solar cells that are environmentally sustainable and easy to produce on a large scale.

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The study, published in Nature Communications, was funded by Breast Cancer Ireland with support from Breast Cancer Now and Science Foundation Ireland.

Most breast cancer related deaths are a result of treatment relapse leading to spread of tumours to many organs around the body. When secondary breast cancer, also known as metastatic breast cancer, spreads to the brain it can be particularly aggressive, sometimes giving patients just months to live.

The RCSI study focused on genetically tracking the tumour evolution from diagnosis of primary breast to the metastatic spread in the brain in cancer patients. The researchers found that almost half of the tumours had changes in the way they repair their DNA, making these tumours vulnerable to an existing type of drug known as a PARP inhibitor. PARP inhibitor drugs work by preventing cancer cells to repair their DNA, which results in the cancer cells dying.

“There are inadequate treatment options for people with breast cancer that has spread to the brain and research focused on expanding treatment options is urgently needed. Our study represents an important development in getting one step closer to a potential treatment for patients with this devastating complication of breast cancer,” commented Professor Leonie Young, the study’s Principal Investigator.

“By uncovering these new vulnerabilities in DNA pathways in brain metastasis, our research opens up the possibility of novel treatment strategies for patients who previously had limited targeted therapy options,” said study author Dr Damir Varešlija.

The research, led by Beaumont RCSI Cancer Centre investigators Professor Leonie Young, Dr Nicola Cosgrove, Dr Damir Varešlija and Professor Arnold Hill, was carried out in collaboration with the Mayo Clinic and University of Pittsburgh, USA.

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“Nurses are already at risk for higher rates of depression and insufficient sleep compared to other professions, thanks to the stress of patient care and the nature of shift work. The pandemic seems to have further exacerbated these issues to the detriment of nurses’ well-being,” said Amy Witkoski Stimpfel, PhD, RN, assistant professor at NYU Rory Meyers College of Nursing and the lead author of the study, which was published in the Journal of Occupational and Environmental Medicine.

Nurses have faced unparalleled challenges working on the frontlines of the COVID-19 pandemic, including staffing shortages, an early lack of personal protective equipment (PPE), and witnessing widespread suffering and death. Research is beginning to reveal the impact of these ongoing stressors on nurses’ mental health and well-being.

In this study, the researchers surveyed 629 nurses and interviewed 34 nurses from June through August 2020. The nurses, who worked across healthcare settings in 18 states, were asked about their experiences working during the first six months of the pandemic in the U.S.

The survey revealed high rates of depression (22 percent), anxiety (52 percent), and insomnia (55 percent) among nurses. Notably, difficulty sleeping was both a contributing factor to and an outcome of poor mental health.

Only sleeping for five hours or less before a shift increased the odds of depression, anxiety, and insomnia. However, nurses also described how anxiety and thinking about stressful working conditions — understaffing, being redeployed to a COVID unit, lack of PPE, and many patient deaths — led to difficulty falling asleep and waking up at night. In addition to stress-related sleep problems, changes in nurses’ work schedules from either working extra hours or abruptly switching between day and night shifts led to nurses getting fewer hours of sleep.

“We found that sleep problems were interwoven with anxiety and depressive symptoms,” said Witkoski Stimpfel. “Prior research supports this bidirectional relationship between sleep and mental health. We know that getting sufficient sleep fosters mental and emotional resilience, while not getting enough sleep predisposes the brain to negative thinking and emotional vulnerability.”

To better support nurses and their well-being, the researchers urge employers to take action to address work stress and factors that influence sleep. In addition to making sure that nurses have the resources like staffing, beds, and PPE to effectively do their jobs, employers can offer training on stress management and provide referrals to mental healthcare professionals for those in need. Employers should also pay attention to scheduling, ensuring nurses have time away from work, protecting them from excessive overtime hours and shifts that quickly switch between day and night, and offering flexible working arrangements.

“Our findings help us better understand the difficulty nurses are facing — and why some nurses are leaving their jobs or the field altogether — but also reveal opportunities for hospitals and other employers to support this critical workforce,” said Witkoski Stimpfel.

Additional study authors include Lloyd Goldsamt and Victoria Vaughan Dickson of NYU Meyers and Lauren Ghazal of the University of Michigan. The research was supported by an NYU COVID-19 Research Catalyst grant.

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“Our artificial leaf system can be deployed outside the lab, where it has the potential to play a significant role in reducing greenhouse gases in the atmosphere thanks to its high rate of carbon capture, relatively low cost and moderate energy, even when compared to the best lab-based systems,” said Meenesh Singh, assistant professor of chemical engineering in the UIC College of Engineering and corresponding author on the paper.

Using a ?previously reported theoretical concept, the scientists modified a standard artificial leaf system with inexpensive materials to include a water gradient — a dry side and a wet side — across an electrically charged membrane.

On the dry side, an organic solvent attaches to available carbon dioxide to produce a concentration of bicarbonate, or baking soda, on the membrane. As bicarbonate builds, these negatively charged ions are pulled across the membrane toward a positively charged electrode in a water-based solution on the membrane’s wet side. The liquid solution dissolves the bicarbonate back into carbon dioxide, so it can be released and harnessed for fuel or other uses.

The electrical charge is used to speed up the transfer of bicarbonate across the membrane.

When they tested the system, which is small enough to fit in a backpack, the UIC scientists found that it had a very high flux — a rate of carbon capture compared with the surface area required for the reactions — of 3.3 millimoles per hour per 4 square centimeters. This is more than 100 times better than other systems, even though only a moderate amount of electricity (0.4 KJ/hour) was needed to power the reaction, less than the amount of energy needed for a 1 watt LED lightbulb. They calculated the cost at $145 per ton of carbon dioxide, which is in line with recommendations from the Department of Energy that cost should not exceed around $200 per ton.

“It’s particularly exciting that this real-world application of an electrodialysis-driven artificial leaf had a high flux with a small, modular surface area,” Singh said. “This means that it has the potential to be stackable, the modules can be added or subtracted to more perfectly fit the need and affordably used in homes and classrooms, not just among profitable industrial organizations. A small module of the size of a home humidifier can remove greater than 1 kilogram of CO₂ per day, and four industrial electrodialysis stacks can capture greater than 300 kilograms of CO₂ per hour from flue gas.”

The UIC scientists report on the design of their artificial leaf and the results of their experiments in “Migration-assisted, moisture gradient process for ultrafast, continuous CO₂ capture from dilute sources at ambient conditions,” which is published in Energy & Environmental Science.

The research is funded by a grant (DE-SC-0022321) from the U.S. Department of Energy. A patent application titled “Artificial photosynthetic systems for integrated carbon capture and conversion” has been filed by the Office of Technology Management at UIC.

Co-authors of the paper from UIC, Argonne National Laboratory, Oklahoma State University and Braskem are Aditya Prajapati, Rohan Sartape, Tomas Rojas, Naveen Dandu, Pratik Dhakal, Amey Thorat,?Jiahan Xie, Ivan Bessa, Miguel Galante,?Marcio Andrade, Robert Somich, Marcio Rebouças, Gus Hutras, Nathalia Diniz, Anh Ngo and Jindal Shah.

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