Earth

Bottom Line: An analysis of nearly 16,000 young patients with cancer in Utah revealed that exposure to fine particulate matter was associated with increased mortality at five and 10 years after diagnosis of certain cancers.

Journal in Which the Study was Published: Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research; this paper will be featured in a forthcoming Environmental Carcinogenesis Focus section in the journal.

Author: Judy Ou, PhD, research scientist at the Huntsman Cancer Institute at the University of Utah in Salt Lake City

Background: "It is estimated that roughly 40 percent of Americans live in communities with unhealthy levels of air pollution," said Ou. "Currently, there are no guidelines for long-term cancer survivors that advise reducing exposure to air pollution, nor are cancer patients considered a population vulnerable to mortality or illness from air pollution. Our results suggest that limiting exposure to fine particulate matter may be important for the survival of younger cancer patients with specific cancers."

Studies have shown associations between increased exposure to fine particulate matter, defined as atmospheric particles less than 2.5 micrometers in diameter, and cancer mortality among adult breast, liver, and lung cancer patients, yet the underlying biology of cancers in young patients potentially differs from cancers in adults, Ou explained. "Because the associations observed between exposure to fine particulate matter and increased cancer mortality in adults cannot be easily extrapolated to younger cancer patients, we wanted to study how continued exposure to fine particulate matter after diagnosis affected survival outcomes in this specific population," she said.

How the Study was Conducted: Using information from the Utah Population Database and Utah Cancer Registry, Ou and colleagues followed 2,444 pediatric (ages 0 to 14) and 13,459 young adult and adolescent (AYA; ages 15 to 39) patients diagnosed with cancer while living in Utah from 1986 to 2015. These patients were followed from diagnosis to the clinically relevant time points of five and 10 years after diagnosis.

To estimate cumulative exposure to fine particulate matter, the researchers used data from stationary monitors provided by the Environmental Protection Agency (EPA). Using this information, the researchers could model the association between cumulative exposure and mortality from cancer and all-causes. The exposure to fine particulate matter was measured continuously (in increments of 5 micrograms per cubic meter of air; μg/m3) and categorically (if exposure was equal to/exceeded the EPA annual standard of 12 μg/m3, based on the three-year average of annual mean concentration of fine particulate matter) for these models. Models were adjusted for sex, race/ethnicity, and socioeconomic status, among other factors.

Results: Among pediatric patients, exposure to fine particulate matter was associated with an increased risk of death for the following specific cancers:

Lymphomas had increased cancer mortality and all-cause mortality at both time points, when exposure was measured continuously;

Central nervous system and intracranial/spinal neoplasms had increased cancer mortality and all-cause mortality at both time points, when exposure was measured continuously;

Lymphoid leukemias had increased all-cause mortality at five years post diagnosis, when exposure was measured both continuously and categorically;

Hepatic tumors had increased all-cause mortality at 10 years post diagnosis, when exposure was measured continuously.

Overall, among AYA patients, exposure to fine particulate matter was associated with an increased risk of cancer mortality and all-cause mortality at both time points when exposure was measured categorically. Exposure to fine particulate matter was associated with an increased risk of all-cause mortality at five years post diagnosis when exposure was measured continuously.

Further, among AYA patients, exposure to fine particulate matter was associated with an increased risk of death for the following specific cancers:

Central nervous system and intracranial/spinal neoplasms had increased cancer mortality and all-cause mortality at both time points, when exposure was measured both continuously and categorically;

Skin melanomas had increased cancer mortality at five years post diagnosis when exposure was measured categorically and increased all-cause mortality at both time points when exposure was measured categorically;

Carcinomas (excluding skin), when analyzed collectively, had increased cancer mortality and all-cause mortality at both time points when exposure was measured either continuously or categorically;

Lymphomas had increased all-cause mortality at five years post diagnosis when exposure was measured categorically.

Author's Comments: "Exposure to air pollution is preventable to a degree on an individual level, but the responsibility ultimately lies with government policy to protect the public from this major health hazard," said Ou. "We need patients and their caregivers to become informed advocates to support enforcing air quality policies at the local, state, and federal levels."

Study Limitations: As a limitation to the study, data for 1999 to 2015 were collected from stationary monitors measuring fine particulate matter throughout the state of Utah, but the data for 1986 to 1998 were collected from stationary monitors measuring coarse particulate matter, defined as atmospheric particles less than 10 micrometers in diameter, in four Utah counties that contain 80 percent of Utah's population. "While fine particulate matter was not measured directly from 1986 to 1998, coarse particulate matter and fine particulate matter measurements are highly related, allowing us to extrapolate measures of fine particulate matter during these years," Ou explained.

Prague, 15 May 2020 - Researchers led by Jiri Kaleta of IOCB Prague have synthesized regular 2D assemblies of isotopically labelled molecular switches and measured the properties of their isomerization, revealing that formation of such an assembly doesn't hamper the photochemical switching properties of the embedded molecules. The isotopic labels came into use when measuring the switching properties using an analytic technique dependent on the labels. The team published the results in the Journal of the American Chemical Society.

Self-organization of individual molecular machines, such as motors, rotors, and switches, into regular and well-defined two- (2D) or three-dimensional (3D) arrays is a promising path towards a new generation of smart materials. Two-dimensional assemblies seem to be particularly interesting because of their possible application in fields such as optics (OLEDs) and nanoelectronics (memory devices, frequency filters, etc.).

In collaboration with researchers from the Faculty of Science, Charles University in Prague and the University of Colorado, the IOCB Prague team obtained these assemblies with a method previously tested on other molecular machines in accordance with their ongoing research in the 2D arrays of such supramolecular systems. The researchers mounted the molecular switch moieties (substituted azobenzenes) onto rod-like molecules and distributed them on the porous nanocrystals of a tris(o-phenylenedioxy)cyctlotriphosphazene (TPP) matrix. The regularly distributed straight pores enforced the regular spread and parallel orientation of these structures.

The researchers labelled the switches 15N, which allowed them to use solid-state 15N NMR spectroscopy to detect the cis/trans isomerization. A suite of other analytical techniques confirmed the regular structure of the assemblies. Comparison of thermal steps in solution and supramolecular surface inclusions revealed that switching of individual molecules is not compromised by the close proximity of neighbors.

Binding the molecular switches to the surface of a solid material produces several key advantages. Unlike in bulk crystals, the switch segments of the molecules have enough space to change their configuration. And unlike in a solution, the molecules are part of a solid periodical system, giving more control of their position, which may lead to the potential use of such materials in applications where their specific position plays a role, e.g. memory devices.

There are immune cells in our bodies that directly destroy infected or cancer cells - they are called natural killer cells. Recently, a POSTECH research team has developed an integrative cancer therapy using adoptive natural killer cell therapy and chemotherapy.

A research team led by Professor Won Jong Kim of POSTECH's Department of Chemistry developed a treatment for solid cancers using the formation of natural killer-tumor cell immunological synapse through a joint research with GI Cell. The research findings were published as a front cover for the latest online edition of Advanced Materials, a leading academic journal in the field of material science.

To date, three methods including surgery, radiation therapy, and chemotherapy are implemented to treat cancer. While surgery and radiation therapy are helpful in reducing the size of tumors in treating solid cancer, there is a high risk of recurrence due to residual or metastatic cells. The residual cells and metastatic cells are treated by administering chemotherapy to patients, but their use is limited due to serious side effects in all parts of the body.

However, there is an immune system in the human body that can distinguish cancer cells from normal cells and selectively induce their death, and using this mechanism in anticancer immunotherapy not only has fewer side effects but also a higher survival rate for patients compared to chemotherapy.

In particular, treatments using natural killer cells during chemotherapy have low side effects and are more effective in treating leukemia. However, unlike leukemia cells where individual cells float in blood, in solid cancers, the extracellular layer surrounding the cancer tissues reduces the penetration rate of the natural killer cells, thus lowering their efficacy. Studies are being conducted to overcome this issue.

The research team hypothesized that the acidity would decrease rapidly near the immunological synapses based on the fact that the natural killer cells form immunological synapses and secrete low acidic granules at the boundary of natural killer-tumor cells in order to induce the death of cancer cells.

Based on this hypothesis, if the surface of natural killer cells is equipped with polymeric micelles*1, which can respond to low acidity and release anticancer drugs, it may provide a pragmatic platform that allows natural killer cells to selectively release anticancer drugs in tumor cells.

It was also anticipated that cancer drugs could induce the death of cancer cells in the deep parts of the tumor as their size is small enough to penetrate the dense extracellular layer around the tumor tissues. In the treatment of solid cancer, the team fused the adoptive natural killer cell therapy and chemotherapy to overcome the low therapeutic effects and high side effects. They implemented a system that can release anticancer drugs only when natural killer cells recognize the cancer cells and induce their death.

In addition, video footages filmed using a confocal scanning fluorescence microscope confirmed that acidity was reduced in the immunological synapses formed between natural killer and cancer cells and that the ReNK*2 system selectively released anticancer drugs.

It also confirmed that the delivery efficiency to cancer tissues increased significantly when anticancer drugs were delivered using ReNK in animal models with solid cancer.

Professor Won Jong Kim, who led the study as a corresponding author, stated, "This study is significant in that it has developed a strategy to enhance the effectiveness of cell therapy using natural killer cells in treating solid cancers." He added, "This method can be applied to any cell with a simple process, so we expect to apply it to treatments currently on the market or in clinical trials."

To assess the degree to which early stone tool using hominins modified their tool manufacturing behaviours in Eastern Asia, Shixia Yang and colleagues examined three well-known archaeological sites from the Nihewan Basin in North China. Stone tool comparisons between the archaeological sites of Xiaochangliang, Cenjiawan and Donggutuo indicate that technological skills increase at ca. 1.1-1.0 million years ago. The stone tools at Cenjiawan and Donggutuo show increasing levels of control in manufacturing procedures and some degree of planning in the tool-making process to produce desired end-products.

The technological innovations at ca. 1.1-1.0 million years ago in the Nihewan Basin correspond with a major climate transition which occurred between 1.2 million years ago to 700,000 years ago (called the Mid-Pleistocene Climate Transition). A series of global and regional palaeoclimatic and palaeoenvironmental changes occurred during this period, such as increases in aridity and monsoonal intensity and decreases in sea surface temperatures in the North Atlantic.

At 1.1 million years ago the early human inhabitants of the Nihewan Basin lived under a changeable and unstable environment, experiencing strengthened aridification. As climatic variability produced ecological changes, including landscape alterations and mammalian extinctions, novel technological innovations likely provided benefits to early hominin populations in the Nihewan Basin. The unstable environmental conditions at the onset of this period provides a good example of the adaptive versatility of hominins in China, contrasting with the notion of long-lasting conservative behaviours described by other archaeologists. Yet, the increasingly harsh and oscillating climatic conditions of this period likely undermined sustained population in North China, illustrating that technological and cultural solutions did not always overcome environmental challenges.

There is currently a strong demand to replace organic liquid electrolytes used in conventional rechargeable batteries, with solid-state ionic conductors which will enable the batteries to be safer and have higher energy density.

To that end, much effort has been devoted to finding materials with superior ionic conductivities. Among the most promising, are solid-state ionic conductors that contain polyanions such as B12H122- (Fig. 1a). They constitute a particular class of materials due to their unique transport behavior, which has the polyanions rotating at an elevated temperature, thereby greatly promoting cation conductivities.

However, a major drawback is the high temperature (=energy) required to activate the rotation, which conversely means low conductivities at room temperature.

To address that problem, a research group at Tohoku University, led by Associate Professor Shigeyuki Takagi and Professor Shin-ichi Orimo, has established a new principle for room-temperature superionic conduction. Its findings were recently published in Applied Physics Letters.

The research group was able to reduce the activation temperature by using transition metal hydride complexes as a new class of rotatable polyanions, wherein hydrogen is the sole ligand species, covalently binding to single transition metals. Unlike in B12H122- polyanions (Fig. 1a), the rotation of transition metal hydride complexes only requires displacements of highly mobile hydrogen (Figs. 1b, 1c) and can therefore be expected to occur with low activation energy.

The group then studied the dynamics of transition metal hydride complexes in several existing hydrides, and found them reoriented - as if rotating by repeating small deformations (Fig. 2) - even at room temperature.

This kind of motion is known as "pseudorotation," and is rarely observed in solid matter. Due to the small displacements of hydrogen atoms, the activation energy of the pseudorotation is relatively low - more than 40 times lower than what's reportedly needed for the rotation of B12H122-.

As a result of a cation conduction being promoted from a low temperature region by pseudorotation, the lithium ion conductivity in Li5MoH11 containing MoH93- (Fig. 1b), for example, can reach 79 mS cm-1 at room temperature (Fig. 3). This is more than three times the world record of room-temperature lithium ion conductivity reported so far. This suggests that an all-solid-state lithium ion battery with shorter charging time at room temperature can be realised.

The discovered mechanism is quite general and would be useful in lowering the temperature required to activate the rotation of polyanions. This may positively contribute towards finding compositions that are amenable to room-temperature superionic conductors.

Underwater sound devices called "pingers" could be an effective, long-term way to prevent porpoises getting caught in fishing nets with no negative behavioural effects, newly published research suggests.

The study of harbour porpoises off Cornwall found they were 37% less likely to be found close to an active pinger.

Concerns have been raised about porpoises becoming used to pingers and learning to ignore them, but the eight-month study - by the University of Exeter and Cornwall Wildlife Trust - found no decrease in effectiveness.

There have also been worries that continual pinger use could affect porpoise behaviour by displacing them from feeding grounds, but when pingers were switched off the animals returned "with no delay".

The effect was found to be "very localised" - the 37% reduction in porpoise detection at the active pinger compared to a drop of 9% just 100 metres away.

Harbour porpoises are the most common cetaceans (whales, dolphins and porpoises) seen at the Cornish coast, where accidental catching by fishing boats ("bycatch") is a persistent problem.

"Cornwall Wildlife Trust have been monitoring local dolphin and porpoise deaths through our standings scheme for over 25 years, and bycatch is still the biggest threat to these animals in the South West with large numbers washing ashore every year," said Ruth Williams, of Cornwall Wildlife Trust.

"Together with other NGOs we have campaigned to try to find a solution to reduce bycatch, that will work in our inshore fisheries.

"The results of this latest research show that there is a practical solution that is both effective and does not impact or change the animals' behaviour, a positive result for both conservation and fishermen alike."
Lead author Dr Lucy Omeyer, of the University of Exeter and Fishtek, said: "Based on our findings, it seems likely that pingers would reduce harbour porpoise bycatch in gill-net fisheries with no negative consequences.

"Indeed, we found no evidence that long-term and continual use decreased the effectiveness of pingers or affected harbour porpoise behaviour."

Pingers are acoustic deterrent devices which are fitted on to fishing nets.

They work by emitting a randomised sonic noise, or "ping", which can be heard by dolphins and porpoises and highlights the presence of the nets, thereby preventing accidental entanglement.

The porpoises' own click sounds can be way above 100 times louder than the pings from the pinger.

In the study, Fishtek Banana Pingers were placed in the water along with two acoustic loggers (one beside the pinger and one 100m away) to record cetacean activity.

With small-scale operations the main form of fishing in UK waters, the researchers say there is an "acute need" for cost-effective strategies to prevent bycatch, such as pingers.

The study was partly funded by Whale and Dolphin Conservation.

Cornwall Wildlife Trust's marine strandings report recorded 245 cetacean strandings in Cornwall in 2019.

The paper, published in the journal Frontiers in Marine Science, is entitled: "Assessing the effects of Banana Pingers as a bycatch mitigation device for harbour porpoises (Phocoena phocoena)."

Rates of neonatal abstinence syndrome (NAS) have plateaued after 20 years of increasing frequency across the country, according to a new study published in Health Affairs. NAS is a withdrawal syndrome experienced by some opioid-exposed newborns after birth.

The National Institutes of Health-funded study led by Ashley Leech, PhD, assistant professor of Health Policy at Vanderbilt University Medical Center (VUMC), finds that rates of NAS per 1,000 live births stabilized in 2016 after peaking in 2014 at the beginning of a surge in opioid-related deaths in the United States.

"Evidence is beginning to show that we're holding down the rising trend in NAS," Leech said. "While encouraging, rates are significantly higher than they were 20 years ago; we still have more work to do."

From 2004 to 2014, the rate of NAS increased nearly six-fold from 1.6 infants per 1,000 births to 8.1 per 1,000 births by 2014. The rate was 8.8 per 1,000 births in 2016, showing evidence of stabilization.

"In 2016, one baby was born every 15 minutes with NAS," said Leech. "Rates may have plateaued, but are still high, and there is a need for continued action to improve outcomes for pregnant women and infants affected by the opioid crisis."

In 2016, there were an estimated 31,765 infants with NAS cared for in U.S. hospitals.

Geographically, the study found the lowest overall rates of NAS in the West and the highest overall rates in the Northeast. These results were consistent with previous research. The study uses the most recent data on NAS available.

Several federal policies have sought to address the effect of the opioid crisis on mothers and infants, including legislation in 2015, 2016 and the Substance Use-Disorder Prevention That Promotes Recovery and Treatment (SUPPORT) for Patients and Communities Act of 2018.

"Recent federal policy changes like the SUPPORT Act were steps towards supporting moms and babies affected by the opioid crisis," said Stephen Patrick, MD, MPH, director of the Vanderbilt Center for Child Health Policy and senior author of the study. "What's critical is for decision makers hoping to reduce the effect of the opioid crisis on pregnant women and infants to continue to promote evidence-based policies that improve treatment access and reduce punitive measures. We know these steps improve outcomes for both mom and baby."

What The Study Did: Centers for Disease Control and Prevention data were used to examine changes in rates of deaths attributed to cardiovascular disease from 1999 to 2017 in urban and rural areas of the U.S. overall and by age, sex and race/ethnicity.

Authors: Haider J. Warraich, M.D., of the VA Boston Healthcare System in Boston, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jama.2020.2047)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What The Study Did: Researchers looked at the association between prenatal alcohol and tobacco smoking exposure and brain activity in 1,700 newborns measured during sleep.

Authors: William P. Fifer, Ph.D., of Columbia University Medical Center in New York, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.4714)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Scientists at Sanford Burnham Prebys Medical Discovery Institute and Loma Linda University Health have demonstrated the promise of applying magnetic resonance imaging (MRI) to predict the efficacy of using human neural stem cells to treat a brain injury--a first-ever "biomarker" for regenerative medicine that could help personalize stem cell treatments for neurological disorders and improve efficacy. The researchers expect to test the findings in a clinical trial evaluating the stem cell therapy in newborns who experience a brain injury during birth called perinatal hypoxic-ischemic brain injury (HII). The study was published in Cell Reports.

"In order for stem cell therapies to benefit patients, we need to be thoughtful and scientific about who receives these treatments," says Evan Y. Snyder, M.D., Ph.D., professor and director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys, and corresponding study author. "I am hopeful that MRI, which is already used during the course of care for these newborns, will help ensure that infants who experience HII get the best, most appropriate treatment possible. In the future, MRI could help guide the use of stem cells to treat--or in some instances, not treat--additional brain disorders such as spinal cord injury and stroke."

Scientists now understand that, in many instances, human neural stem cells are therapeutic because they can protect living cells--in contrast to "re-animating" or replacing nerve cells that are already dead. As a result, understanding the health of brain tissue prior to a stem cell transplant is critical to the treatment's potential success. Tools that help predict the efficacy of neural stem cell therapy could increase the success of clinical trials, which are ongoing in people with Parkinson's disease, spinal cord injury and additional neurological conditions, while also sparing people who will not respond to treatment from an invasive procedure that offers false hope.

"We know that stem cell therapies hold extraordinary promise, but, like other medicines, they also need to be given at the right time and to the right patients," says Steve Lin, Ph.D., senior science officer at the California Institute for Regenerative Medicine, which partially funded the research. "This study suggests that a readily available technique, MRI--which is already used in many brain injuries to determine the extent of neurological damage--may be a useful tool to determine who will or will not benefit from neural stem treatment."

Protecting newborns from brain damage

Snyder, a neonatologist and pediatric neurologist, has long envisioned using human neural stem cells to protect newborns with acute perinatal HII from brain damage. He and his colleagues made the discovery that MRI could be used as an objective, quantifiable, readily available basis for inclusion and exclusion criteria for this treatment while engaged in preclinical studies required prior to starting human clinical trials for babies with HII. This birth injury affects two to four newborns out of every 1,000 babies born in the U.S. and is attributable to a number of complications, including umbilical cord compression, disrupted maternal blood pressure and maternal infection.

"My hope is that human neural stem cells can help rescue enough injured and vulnerable--though not dead--neural cells," explains Snyder. "This could help prevent the most severely affected infants from developing cerebral palsy, epilepsy, intellectual disability or other neurological disorders that often arise after HII if left untreated."

In the study, the scientists used MRI to measure two areas surrounding the regions of HII brain injury in rats: the penumbra, a region that consists of mildly injured, "stunned" neurons; and the core, an area that consists of dead neurons. They found that rats with a larger penumbra and smaller core that received human neural stem cells had better neurological outcomes--including improved memory--demonstrated by the ability to swim to a hidden platform (Morris Water Maze test), and a greater willingness to venture into a brightly lit area (open field test).

In these rats, the penumbra--to which the neural stem cells homed avidly--became normal tissue (based on MRI and histological standards), while the core remained unimproved and attracted few cells. Penumbra that did not receive cells became part of the core, populated by dead neurons--indicating the benefit of the stem cell treatment.

"This approach to brain lesion classification is a powerful patient stratification tool that allows us to identify newborns who may benefit from this stem cell therapy--and protect others from undergoing unnecessary treatment," says Snyder. "Based on our findings, only newborns with a large penumbral volume in relation to core volume should receive a transplant of human neural stem cells. Equally important, newborns so severely injured that only a core is present, or babies with such a mild case of HII that not even a penumbra is present, should not receive human neural stem cells, as the treatment is unlikely to be impactful."

Scientists at the Kennedy Institute of Rheumatology in the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences have discovered a new way for T cells to attack cells infected by viruses or deranged by cancer.

Published online by the journal Science on Thursday 7 May 2020, the new research from the Dustin Group describes the structure and composition of supramolecular attack particles (SMAPs) and their role in killing targeted cells.

Cytotoxic T lymphocytes (CTLs) are essential components in the immune response against viruses and cancer. CTLs are known to recognise infected or damaged cells and release soluble protein molecules, which create perforations in the membrane of the targeted cell. These holes allow toxic enzymes to enter and initiate a self-destruct program, killing the targeted cell (cytotoxicity).

The new study reveals a complementary mechanism of cytotoxicity in the CTLs. The team identified SMAPs, ~120 nm diameter protein particles released by CTLs to kill other cells, for example, if virally infected or cancerous. SMAPs have a core of cytotoxic proteins surrounded by a glycoprotein shell.

The core-shell structure was demonstrated in collaboration with the B24 beam line at the Diamond Light Source at the Harwell Science and Innovation Campus using cryo-soft-x-ray tomography. "Using this national resource we were able to determine the physical nature of the particles. This confirmed and extended our observations with super-resolution fluorescence microscopy," said Stefan Balint, Postdoctoral research assistant in molecular immunology who spearheaded the work at the Kennedy Institute.

The core-shell structure of the SMAPs allowed for the whole unit to be released from the CTL and immediately attach to a target to kill it. The study also showed the potential for SMAPs to exist independently and autonomously from the CTL. "The CTL could leave it in the environment like a land mine," said Mike Dustin, Director of Research of the Kennedy Institute. "If the cytotoxic proteins are like bullets in the CTL's arsenal then the SMAP is a bomb."

A better understanding of SMAPs could be useful to develop new strategies to reinforce CTL activity in anti-viral immunity, cancer immunotherapy, regulation of the immune response and many other settings. SMAPs have been discovered in CTL and natural killer cells, but proteinaceous particles with core-shell structures may have wider implications for physiology and disease. "We are particularly excited about the potential for engineering SMAPs to very specific targeting of tumours and other patient specific treatments," added Mike Dustin.

When magnetic materials are nanometric at least in one dimension, the surface effect often dominates the static and transport behaviors due to the limited long-range order and broken translation symmetry. The perturbations in spin-spin correlation length and unperfect spin coordination structures make low-dimensional magnetic materials an ideal platform for exploring magnetism in reduced dimensions. Low dimension materials, especially those in two-dimensional (2D) pose a conceptual flatland for mechanically flexible, engineerable and biocompatible devices with complex functionalities via a patterning or assembling manner to integrated objects.

As a typical two sublattice antiferromagnetic order, rutile-type fluorides MF2 (M=Mn, Fe, and Co) are proven very useful in the context of antiferromagnetic spintronics, especially in the THz range with optical manipulation. However, it remains a challenge to initiate and sustain the solution processability of fluorides in a predictable, controlled and deterministic manner, leaving some instructive information unclarified, such as how the size effect matters, and how the subtle interplay between the surface spin arrangement and phase transitions operates.

In a new research paper published in the Beijing-based National Science Review, researchers from Peking University, Shenzhen University and the National Institute for Materials Science (NIMS) report an asymmetric passivation proposal to control the dimension of fluorides nanocrystals. In their protocols, four kinds of surfactants, i.e. oleic acid (OAc), oleyl amine (OAm), tetraethylenepentamine (TEPA) and oleyl alcohol (OAl) are evaluated through density functional theory (DFT) methods to clarify their role in controlling the growth manner.

'According to the calculation results, a preferential capping on (001) facet is found in all the evaluated molecules, revealing that the growth direction of the c-axis is impeded. Besides, the asymmetric adsorption of {110} facets with subsequent blocking serves as the origin of rod formation in a direction perpendicular to (110) or (1-10) facet when OAc, OAm and OAl molecules are used.' they declare.

'The experimental results are in good agreement with theoretical predictions, where FeF2 nanocrystals with well-defined crystalline orientations are obtained.' the authors add.

The authors further introduced high-resolution X-ray photoelectron spectrum, recoil-free 57Fe Mössbauer spectrometry, high angle annular dark-field scanning electron microscopy and their corresponding elemental maps, and electron energy loss spectroscopy to discriminate the surface and phase information. A possible oxygen trapping manner was verified, which greatly affect the magnetic behavior of the system.

'A cluster spin-glass like surface layer is identified from the disrupted translation symmetry at the surface, which exerts a pinned FM moment upon the AFM core. Anomalous positive exchange bias HE and enhanced magnetic phase transition temperature are observed due to the interactions between pinned FM moments and the associated structural order parameters, which is qualified within the framework of Landau theory.' the researchers state.

'These high-quality fluorides nanocrystals are strong candidates for flexible antiferromagnetic devices and sensors.' they add.

'Moreover, we believe that this approach of anisotropic direction of growing process will pave the way to the solution synthesis of other low-dimensional halide nanocrystals for emerging spintronics, such as the 2D FeCl2 and CrI3.' the researchers predict.

Barcelona, 12 May, 2020.- Tumours are not a uniform mass of cells. Colon cancers bear differentiated-like cells, similar to the functional cells of the intestinal wall, and pluripotent cells--the so-called tumour stem cells. The latter fuel tumour growth and cause metastasis. A group of scientists headed by Eduard Batlle, ICREA researcher, group leader at the CIBER for Cancer (CIBERONC), and head of the Colorectal Cancer lab at IRB Barcelona, has demonstrated that the essence of pluripotency in colon cancer stem cells lies in their ability to synthesise proteins, a property that could be investigated further as a therapeutic target.

"Current treatments for colon cancer are not efficient because they do not eliminate all pluripotent cells. Various research groups, including ours, have observed that when cancer stem cells are removed via experimental approaches, other differentiated cells can return to a pluripotent state and regenerate the tumour. This is a phenomenon that we call plasticity," explains Batlle.

In this study, the Colorectal Cancer Lab at IRB Barcelona has observed that protein synthesis in tumours occurs in specific regions that coincide with cancer stem cell niches. Moreover, tumours exhibit a protein production gradient, and once this activity is exhausted, tumour cells irreversibly lose their capacity to return to the cancer stem cell state. Thus, it is their biosynthetic capacity that allows cancer stem cells to contribute unlimitedly to tumour growth.

"This discovery is an attempt to eradicate cancer stem cells based on their function rather than on their identity," explains Batlle. "A desirable next step would be to investigate whether it is possible to therapeutically interfere with the biosynthetic capacity of tumour stem cells in order to stop tumour growth and prevent metastasis," he adds.

Blocking biosynthetic capacity halts tumour growth

"Using mouse models of colon cancer, we observed that by blocking protein synthesis in cancer cells or by eliminating those cells with this capacity we could stop tumour growth in an irreversible manner. The next step is to study the signals in the tumour environment that confer or maintain the biosynthetic capacity in certain tumour cells," explains Clara Morral, first author of the study.

Organoids and CRISPR, key developments for research success

The work has been conducted using organoids--mini-tumours derived from patients that are grown in the lab--, which allow the study of tumour cell heterogeneity and organisation. The organoid culture system is a powerful tool to mimic the characteristics of the cancers found in patients. The study also involved genetic modification of tumour cells using CRISPR-Cas9. This technique allowed researchers to specifically eliminate cells with biosynthetic capacity and thus examine their contribution to tumour growth.

In a new study, researchers from the University of Copenhagen have discovered two important functions of a protein called RTEL1 during cell division. The researchers hope that the new knowledge will help to find new cancer treatments.

One of the body's most important processes is cell division, which occurs throughout life. Normal cells only have a limited number of divisions, while in cancer cells the cell division goes awry and is uncontrollable.

Two important phases

The cell division cycle contains several phases. The two most important are S-phase when the cell's DNA is duplicated or replicated, and mitosis when the duplicated DNA is divided equally between the two daughter cells.

Therefore, much research is being done to identify the proteins that play key roles in the cell division of human cells. In a new study, researchers from the University of Copenhagen have uncovered two important functions of a special protein during the cell division cycle of cancer cells.

The new study shows that this protein - called RTEL1 - plays an important role in both S-phase and mitosis. The results have been published in the scientific journal Nature Structural & Molecular Biology.

"We discovered RTEL1 has two key functions. In the S-phase, RTEL1 can prevent damaging clashes between the processes of DNA replication and transcription (when RNA is made), which otherwise can cause DNA damage and chromosome instability. It does this by 'ironing out' certain unusual structures that can form between DNA and RNA called R-loops."

"The second feature is that RTEL1 promotes a process called MiDAS, which is very common in cancer cells and happens in mitosis," says Ying Liu, Associate Professor at the Center for Chromosome Stability (CCS), Department of Cellular and Molecular Medicine.

Tests with Three Forms of Cancer

MiDAS stands for "mitotic DNA synthesis" and occurs at the early stage of mitosis. This process was discovered at the CCS in 2015 in a study led by Professor Ian Hickson.

"Our earlier data showed that cancer cells utilize this unusual form of DNA replication far more often than normal cells, because cancer cells have a lot of 'replication stress' in S-phase due to the cell division cycle being perturbed by the over-activity of cancer-causing genes called oncogenes," says Ian Hickson.

MiDAS helps cells to finish DNA replication that is not completed in S-phase.

"If MiDAS cannot take place, it leads to cell death or mutations in the surviving cells. In the case of cancer, this means that the cancer cell has the potential to become even more abnormal due to the new mutations," Ying Liu explains.

In the new study, which is a continuation of the previous findings in the CCS, the researchers have primarily done tests on different types of cancer cells including bone, cervical and colon cancer.

Two Roles in One Cell Division

It was a surprise to the researchers to see how big a role the RTEL1 protein plays in cell division.

"We were investigating which proteins help cancer cells to use MiDAS. And then this protein, RTEL1, came up, which was a surprise. We did not expect it had such a big effect.''

"We believe that this RTEL1 function is critical for any cancer cells that rely on MiDAS, which is more than 80 percent of the known cancer types based on our knowledge. Therefore, we can use this to design drugs to inhibit RTEL1 and hopefully selectively kill cancer cells," says Ying Liu.

Their next step will be to investigate how RTEL1 performs its two roles and whether they are connected. They will also investigate exactly how RTEL1 promotes MiDAS in mitosis.

Walking is one of the most important motor skills for animals and humans. And for almost all people, being able to walk is deeply essential. In spite of this, researchers are still working to map out which signals and electrical impulses from the brain control our walking.

In a new study in mice, researchers from the Department of Neuroscience at the University of Copenhagen have come a little closer to understanding how the walking movement is controlled. They have mapped how certain neurons in the brain may be said to be the 'brain's steering wheel' because they can control whether the mouse turns right or left.

'It is an important discovery because movement is fundamentally one of the most basic features controlled by the brain. At the same time, motor disorders can be very disabling. Therefore, knowledge of the basic mechanisms of the brain and the spinal cord which control our movements is important', says Professor Ole Kiehn.

The neuronal networks that are directly responsible for coordination of the walking movement are located in the spinal cord and are relatively well described. But researchers have now found that a particular group of neurons in the brainstem, which can be identified by their expression of a particular molecular marker called Chx10, signals to the spinal cord and controls the direction.

'The control is done by simply applying the 'brake' to the walking movment on the side that the mice turn to - then the muscles will contract on the same side. In this way, the length of the steps on one side becomes short and on the other side long, making the mouse turn. Thus, the Chx10 cells constitute a motor turning system - a kind of steering wheel', explains first author of the study Jared Cregg, Postdoc at the Department of Neuroscience.