When Dark Matter Could Be Produced? (Cosmology / Thermodynamics / Astronomy)

Mambrini and Olive proposed the production of dark matter through the gravitational scattering of the inflaton. They found that sufficient GeV-ZeV dark matter can be obtained with reasonable values of reheating temperature (TRH) and maximum temperature (Tmax) by pure gravitational production through inflaton scattering. Their study recently published in ArXiv on dated 11 Feb 2021.

Inflation is a period of supercooled expansion, when the temperature drops by a factor of 100,000 or so. This relatively low temperature is maintained during the inflationary phase. When inflation ends, the temperature returns to the pre-inflationary temperature; this is called reheating or thermalization because the large potential energy of the inflaton field decays into particles and fills the Universe with Standard Model particles, including electromagnetic radiation, starting the radiation dominated phase of the Universe.

Illustration of the production of dark matter through the gravitational scattering of the inflaton. © Mambrini and Olive

They showed that the final abundance of dark matter depends not only on the reheating temperature, but also on the maximum temperature attained and hence on the detailed evolution of the reheating process.

We saw that GeV-ZeV dark matter can be obtained with reasonable values of TRH and Tmax by pure gravitational production through inflaton scattering

— said Olive

As per Mambrini and Olive, during reheating, a thermal bath is quickly generated with a maximum temperature Tmax, and the temperature decreases as the inflaton continues to decay until the energy densities of radiation and inflaton oscillations are equal, at TRH. During these oscillations, s-channel gravitational production of dark matter occurs.

During these oscillations, the inflaton density is high and the leading contribution to dark matter production occurs at the start of reheating at Tmax. This represents an absolute minimal amount of dark matter production and it contributes independent of any interactions the dark matter may have with the Standard Model (or another dark sector if present).

— said Mambrini.

Reference: Yann Mambrini, Keith A. Olive, “Gravitational Production of Dark Matter during Reheating”, Astronomical Journal, pp. 1-6, 2021. https://arxiv.org/abs/2102.06214


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Cancer Tricks Immune Cells, Immunotherapy Can Take Advantage (Medicine)

A paper published today in Nature shows how chemicals in the areas surrounding tumors—known as the tumor microenvironment—subvert the immune system and enable cancer to evade attack. These findings suggest that an existing drug could boost cancer immunotherapy.

The study was conducted by a team of scientists at UPMC Hillman Cancer Center and the University of Pittsburgh School of Medicine, led by Greg Delgoffe, Ph.D., Pitt associate professor of immunology. By disrupting the effect of the tumor microenvironment on immune cells in mice, the researchers were able to shrink tumors, prolong survival and increase sensitivity to immunotherapy. 

“The majority of people don’t respond to immunotherapy,” said Delgoffe. “The reason is that we don’t really understand how the immune system is regulated within this altered tumor microenvironment.” 

The immune system is made up of many kinds of cells, chief among them T cells. One type, called killer T cells, fights off invaders, such as viruses, bacteria and even cancer. Another type, called regulatory T cells, or “T-reg cells” for short, counteracts killer T cells by acting as protectors of the cells that belong to the body. T-reg cells are important for preventing autoimmune diseases, such as type I diabetes, Crohn’s disease and multiple sclerosis, where overactive killer T cells assault the body’s healthy tissues. 

For all of these different immune cells to do their jobs, they need to produce energy. Delgoffe’s team studied how these different types of T cells have different appetites, and how tumors—which have large appetites—compete for nutrients with infiltrating immune cells. The researchers found that killer T cells and regulatory T cells have very different appetites, and cancer cells exploit this.

How Tumor Microenvironment Tricks the Immune System: Cancer evades the immune system by “feeding” the T cells that protect the tumor and “starving” the T cells that would attack. © UPMC, created with BioRender.com

“Cancer is wise to the whole situation,” Delgoffe said. “Cancer cells don’t just starve T cells that would kill them but actually feed these regulatory T cells that would protect them.” 

In short, Delgoffe’s team found that tumors gobble up all the vital nutrients in their vicinity that killer T cells would need to attack. Further, they also excrete lactic acid, which feeds the regulatory T cells, convincing them to stand guard. T-regs can turn the lactic acid into energy, using a protein called MCT1, so nuzzling up with the tumor is a good way for these immune cells to stay fed.

“What better way to recruit a cell than food?” Delgoffe said.

Then, using mice with melanoma, the researchers found that silencing the gene that codes for the MCT1 protein caused tumor growth to slow down. The mice also lived longer. 

“We starved the T-regs,” said Delgoffe. “When T-reg cells are not being sustained by the tumor, killer T cells can come in and kill the cancer.”

Importantly, when Delgoffe’s team combined MCT1 inhibition with immunotherapy, the anti-cancer effects were stronger than either strategy alone.

Clinically, the same effect might be achievable using drugs that inhibit MCT1—one of which is currently being tested in people with advanced lymphoma, and it appears to be well-tolerated. 

Additional authors on the study include McLane Watson, Paolo Vignali, Steven Mullett, Abigail Overacre-Delgoffe, Ph.D., Ronal Peralta, Stephanie Grebinoski, Ashley Menk, Natalie Rittenhouse, Kristin DePeaux, Ryan Whetstone, Ph.D., Dario Vignali, Ph.D., Timothy Hand, Ph.D., Amanda Poholek, Ph.D., and Stacy Wendell, Ph.D., of Pitt and UPMC; and Brett Morrison, M.D., Ph.D., and Jeffrey Rothstein, M.D., Ph.D., of Johns Hopkins University.

Funding for this study was provided by the Sidney Kimmel FoundationNational Institutes of Health (DP2AI136598, P50CA121973, P50CA097190 R01DK089125, R01CA203689, P01AI108545, T32CA082084, F31AI149971, F30CA247034, F31CA247129, T32AI089443 and F31AI147638), the American Association for Cancer Research (SU2CAACR-IRG-04-16), the Alliance for Cancer Gene Therapy, the Mark Foundation for Cancer ResearchCancer Research Institute, the Sy Holzer Endowed Immunotherapy Fund and the Damon Runyon Cancer Research Foundation.

Featured image: Greg Delgoffe, Ph.D., associate professor of immunology, University of Pittsburgh School of Medicine, and member of the Cancer Immunology and Immunotherapy Program at UPMC Hillman Cancer Center. © Abigail Overacre-Delgoffe


Reference: Watson, M.J., Vignali, P.D.A., Mullett, S.J. et al. Metabolic support of tumour-infiltrating regulatory T cells by lactic acid. Nature (2021). https://doi.org/10.1038/s41586-020-03045-2


Provided by UPMC

New Immunotherapy Target Discovered For Malignant Brain Tumors (Medicine)

Scientists say they have discovered a potential new target for immunotherapy of malignant brain tumors, which so far have resisted the ground-breaking cancer treatment based on harnessing the body’s immune system. The discovery, reported in the journal CELL, emerged from laboratory experiments and has no immediate implications for treating patients.

Scientists from Dana-Farber Cancer Institute, Massachusetts General Hospital, and the Broad Institute of MIT and Harvard said the target they identified is a molecule that suppresses the cancer-fighting activity of immune T cells, the white blood cells that seek out and destroy virus-infected cells and tumor cells.

The scientists said the molecule, called CD161, is an inhibitory receptor that they found on T cells isolated from fresh samples of brain tumors called diffuse gliomas. Gliomas include glioblastoma, the most aggressive and incurable type of brain tumor. The CD161 receptor is activated by a molecule called CLEC2D on tumor cells and immune-suppressing cells in the brain, according to the researchers. Activation of CD161 weakens the T cell response against tumor cells.

To determine if blocking the CD161 pathway could restore the T cells’ ability to attack the glioma cells, the researchers disabled it in two ways: they knocked out the gene called KLRB1 that codes for CD161, and they used antibodies to block the CD161-CLEC2D pathway. In an animal model of gliomas, this strategy strongly enhanced the killing of tumor cells by T cells, and improved survival of the animals. The researchers were also encouraged because blocking the inhibitory pathway appeared to reduce T-cell exhaustion – a loss of cell-killing function in T cells that has been a been a major hurdle in immunotherapy.

In addition, “we showed that this pathway is also relevant in a number of other major human cancer types,” including melanoma, lung, colon, and liver cancer, said Kai Wucherpfennig, MD, PhD, director of the Center for Cancer Immunotherapy Research at Dana-Farber. He is corresponding author of the report along with Mario Suva, MD, PhD, of Massachusetts General Hospital; Aviv Regev, PhD, of the Broad Institute, and David Reardon, MD, clinical director of the Center for Neuro-Oncology at Dana-Farber.

Many cancer patients are now being treated with immunotherapy drugs that disable “immune checkpoints” – molecular brakes exploited by cancer cells to suppress the body’s defensive response by T cells against tumors. Disabling these checkpoints unleashes the immune system to attack cancer cells. One of the most frequently targeted checkpoints is PD-1. However, recent trials of drugs that target PD-1 in glioblastomas have failed to benefit patients. In the current study, the researchers found that fewer T cells from gliomas contained PD-1 than CD161. As a result, they said, “CD161 may represent an attractive target, as it is a cell surface molecule expressed by both CD8 and CD4 T cell subsets [the two types of T cells involved in response against tumor cells] and a larger fraction of T cells express CD161 than the PD-1 protein.”

Prior to the current study, the researchers said little was known about the expression of genes and the molecular circuits of immune T cells that infiltrate glioma tumors, but fail to halt their growth. To open a window on these T cell circuits, the investigators took advantage of new technologies for reading out the genetic information in single cells – a method called single-cell RNA-seq. They applied RNA-seq to glioma-infiltrating T cells from fresh tumor samples from 31 patients and created an “atlas” of pathways that regulate T cell function. In analyzing the RNA-seq data, the researchers identified the CD161 protein, encoded by the KLRB1 gene, as a potential inhibitory receptor. They then used CRISPR/Cas9 gene-editing technology to inactivate the KLRB1 gene in T cells and showed that CD161 inhibits the tumor cell-killing function of T cells.

“Our comprehensive atlas of T cell expression programs across the major classes of diffuse gliomas thus identifies the CD161-CLEC2D pathway as a potential target for immunotherapy of diffuse gliomas and other human cancers,” the authors of the report said.

This strategy was tested in two different animal models created by implanting “gliomaspheres” – 3-dimensional clusters of tumor cells from human patients – into rodents, which developed aggressive tumors that invaded the brain. The scientists subsequently injected T cells with the KLRB1 gene edited out into the cerebrospinal fluid of some of the animals, and T cells that hadn’t had the KLRB1 gene deleted. Transfer of the gene-edited T cells slowed the growth of the tumors and “conferred a significant survival benefit,” in both of the animal models of gliomas, the scientists said.

The research was supported by a grant from the Ben and Catherine Ivy Foundation and the Bridge project, along with National Institutes of Health grants R01 CA238039, P01 CA236749, R37CA245523, and others. Wucherpfennig is a member of the Parker Institute for Cancer Immunotherapy.

Wucherpfennig is a co-founder and advisory board member of Immunitas Therapeutics. He serves on the scientific advisory board of TCR2 Therapeutics, T-Scan Therapeutics, SQZ Biotech, and Nextechinvest and received sponsored research funding from Bristol-Myers Squibb and Novartis.

Featured image: Kai Wucherpfennig, MD, PhD, Dana-Farber Cancer Institute © Dana-Farber Cancer Institute


Reference: Nathan D. Mathewson, Orr Ashenberg et al., “Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis”, Cell, 2021. https://doi.org/10.1016/j.cell.2021.01.022


Provided by Dana Farber Cancer Institute

Light Used to Detect Quantum Information Stored in 100,000 Nuclear Quantum Bits (Quantum)

Researchers have found a way to use light and a single electron to communicate with a cloud of quantum bits and sense their behaviour, making it possible to detect a single quantum bit in a dense cloud.

We don’t have a way of ‘talking’ to the cloud and the cloud doesn’t have a way of talking to us. But what we can talk to is an electron: we can communicate with it sort of like a dog that herds sheep

— Mete Atatüre

The researchers, from the University of Cambridge, were able to inject a ‘needle’ of highly fragile quantum information in a ‘haystack’ of 100,000 nuclei. Using lasers to control an electron, the researchers could then use that electron to control the behaviour of the haystack, making it easier to find the needle. They were able to detect the ‘needle’ with a precision of 1.9 parts per million: high enough to detect a single quantum bit in this large ensemble.

The technique makes it possible to send highly fragile quantum information optically to a nuclear system for storage, and to verify its imprint with minimal disturbance, an important step in the development of a quantum internet based on quantum light sources. The results are reported in the journal Nature Physics.

The first quantum computers – which will harness the strange behaviour of subatomic particles to far outperform even the most powerful supercomputers – are on the horizon. However, leveraging their full potential will require a way to network them: a quantum internet. Channels of light that transmit quantum information are promising candidates for a quantum internet, and currently there is no better quantum light source than the semiconductor quantum dot: tiny crystals that are essentially artificial atoms.

However, one thing stands in the way of quantum dots and a quantum internet: the ability to store quantum information temporarily at staging posts along the network.

“The solution to this problem is to store the fragile quantum information by hiding it in the cloud of 100,000 atomic nuclei that each quantum dot contains, like a needle in a haystack,” said Professor Mete Atatüre from Cambridge’s Cavendish Laboratory, who led the research. “But if we try to communicate with these nuclei like we communicate with bits, they tend to ‘flip’ randomly, creating a noisy system.”

The cloud of quantum bits contained in a quantum dot don’t normally act in a collective state, making it a challenge to get information in or out of them. However, Atatüre and his colleagues showed in 2019 that when cooled to ultra-low temperatures also using light, these nuclei can be made to do ‘quantum dances’ in unison, significantly reducing the amount of noise in the system.

Now, they have shown another fundamental step towards storing and retrieving quantum information in the nuclei. By controlling the collective state of the 100,000 nuclei, they were able to detect the existence of the quantum information as a ‘flipped quantum bit’ at an ultra-high precision of 1.9 parts per million: enough to see a single bit flip in the cloud of nuclei.

“Technically this is extremely demanding,” said Atatüre, who is also a Fellow of St John’s College. “We don’t have a way of ‘talking’ to the cloud and the cloud doesn’t have a way of talking to us. But what we can talk to is an electron: we can communicate with it sort of like a dog that herds sheep.”

Using the light from a laser, the researchers are able to communicate with an electron, which then communicates with the spins, or inherent angular momentum, of the nuclei.

By talking to the electron, the chaotic ensemble of spins starts to cool down and rally around the shepherding electron; out of this more ordered state, the electron can create spin waves in the nuclei.

“If we imagine our cloud of spins as a herd of 100,000 sheep moving randomly, one sheep suddenly changing direction is hard to see,” said Atatüre. “But if the entire herd is moving as a well-defined wave, then a single sheep changing direction becomes highly noticeable.”

In other words, injecting a spin wave made of a single nuclear spin flip into the ensemble makes it easier to detect a single nuclear spin flip among 100,000 nuclear spins.

Using this technique, the researchers are able to send information to the quantum bit and ‘listen in’ on what the spins are saying with minimal disturbance, down to the fundamental limit set by quantum mechanics.

“Having harnessed this control and sensing capability over this large ensemble of nuclei, our next step will be to demonstrate the storage and retrieval of an arbitrary quantum bit from the nuclear spin register,” said co-first author Daniel Jackson, a PhD student at the Cavendish Laboratory.

“This step will complete a quantum memory connected to light – a major building block on the road to realising the quantum internet,” said co-first author Dorian Gangloff, a Research Fellow at St John’s College.

Besides its potential usage for a future quantum internet, the technique could also be useful in the development of solid-state quantum computing.

The research was supported in part by the European Research Council (ERC), the Engineering and Physical Sciences Research Council (EPSRC) and the Royal Society.


Reference:
D. M. Jackson et al. ‘Quantum sensing of a coherent single spin excitation in a nuclear ensemble.’ Nature Physics (2021). DOI: 10.1038/s41567-020-01161-4


Provided by University of Cambridge

Strange Creatures Accidentally Discovered Beneath Antarctica’s Ice Shelves (Earth Science)

Far underneath the ice shelves of the Antarctic, there’s more life than expected, finds a recent study in the journal Frontiers in Marine Science.

During an exploratory survey, researchers drilled through 900 meters of ice in the Filchner-Ronne Ice Shelf, situated on the south eastern Weddell Sea. At a distance of 260km away from the open ocean, under complete darkness and with temperatures of -2.2°C, very few animals have ever been observed in these conditions.

But this study is the first to discover the existence of stationary animals – similar to sponges and potentially several previously unknown species – attached to a boulder on the sea floor.

“This discovery is one of those fortunate accidents that pushes ideas in a different direction and shows us that Antarctic marine life is incredibly special and amazingly adapted to a frozen world,” says biogeographer and lead author, Dr Huw Griffiths of British Antarctic Survey.

More questions than answers

“Our discovery raises so many more questions than it answers, such as how did they get there? What are they eating? How long have they been there? How common are these boulders covered in life? Are these the same species as we see outside the ice shelf or are they new species? And what would happen to these communities if the ice shelf collapsed?”

Floating ice shelves represent the greatest unexplored habitat in the Southern Ocean. They cover more that 1.5m sq km of the Antarctic continental shelf, but only a total area similar in size to a tennis court has been studied through eight prior boreholes.

Stationary animals – similar to sponges and potentially several previously unknown species – attached to a boulder on the sea floor. © Dr Huw Griffiths/British Antarctic Survey

Current theories on what life could survive under ice shelves suggest that all life becomes less abundant as you move further away from open water and sunlight. Past studies have found some small mobile scavengers and predators, such as fish, worms, jellyfish or krill, in these habitats. But filter feeding organisms – which depend on a supply of food from above – were expected to be amongst the first to disappear further under the ice.

So, it came as a surprise when the team of geologists, drilling through the ice to collect sediment samples, hit a rock instead of mud at the bottom of the ocean below. They were even more surprised by the video footage, which showed a large boulder covered in strange creatures.

New Antarctic expedition needed

This is the first ever record of a hard substrate (ie a boulder) community deep beneath an ice shelf and it appears to go against all previous theories of what types of life could survive there.

Given the water currents in the region, the researchers calculate that this community may be as much as 1,500km upstream from the closest source of photosynthesis. Other organisms are also known to collect nutrients from glacial melts or chemicals from methane seeps, but the researchers won’t know more about these organisms until they have the tools to collect samples of these organisms–a significant challenge in itself.

“To answer our questions we will have to find a way of getting up close with these animals and their environment – and that’s under 900 meters of ice, 260km away from the ships where our labs are,” continues Griffiths. “This means that as polar scientists, we are going to have to find new and innovative ways to study them and answer all the new questions we have.”

Griffiths and the team also note that with the climate crisis and the collapse of these ice shelves, time is running out to study and protect these ecosystems.

Featured image: British Antarctic Survey camera travelling down the 900-meter-long bore hole in the Filchner-Ronne Ice Shelf. (Marine creature pictured is unrelated to the discovery) © Dr Huw Griffiths/British Antarctic Survey


Reference: Huw J. Griffiths, Paul Anker et al., “Breaking All the Rules: The First Recorded Hard Substrate Sessile Benthic Community Far Beneath an Antarctic Ice Shelf”, Front. Mar. Sci., 15 February 2021 | https://doi.org/10.3389/fmars.2021.642040


Provided by Frontiers

Peeking At the Pathfinding Strategies Of The Hippocampus in the Brain (Neuroscience)

Observed the pattern of change in place cells in animal experiments using cue-poor and cue-rich spatial environments. Suggesting new directions in the treatment of brain disorders like Alzheimer’s and amnesia, and advancement in the AI

We find routes to destination and remember special places because there is an area somewhere in the brain that functions like a GPS and navigation system. When taking a new path for the first time, we pay attention to the landmarks along the way. Owing to such navigation system, it becomes easier to find destinations along the path after having already used the path. Over the years, scientists have learned, based on a variety of animal experiments, that cells in the brain region called hippocampus are responsible for spatial perception and are activated in discrete positions of the environment, which which reason they are called “place cells”. However, how place cells store long-term memories of locations and encode particular positions in the environment is still not understood.

The Korea Institute of Science and Technology (KIST) announced that the research team led by Sebastien Royer at KIST Brain Science Institute (BSI), in collaboration with a research team at New York University (NYU), uncovered that place cells in the hippocampus encode spatial information using interchangeably two distinct information processing mechanisms referred to as a rate code and a phase code, somewhat analogue to the number and spatial arrangement of bars in bar codes. In addition, the research team found that parallel neural circuits and information processing mechanisms are used depending on the complexity of the landmarks along the path.

The KIST and NYU research teams identified fundamental principles of information processing in the hippocampus by conducting two types of spatial exploration experiments. In the first type of experiment, the researchers used a treadmill with a long belt, a well controlled spatial environment for mice, and trained the animals to run on the belt sequentially through a section cleared of any objects and another section furnished with small objects. The second type of experiment was carried with rats foraging in a circular arena that was either completely empty or filled with objects. To analyze neural activity, they implanted silicon probe electrodes in CA1, the subregion generating the main output of the hippocampus, and in CA3, a subregion of the hippocampus suspected of playing an important role in spatial memory formation.

Firing rate (left) and spike-phase (right) maps of representative CA1 place cells while a rat was exploring an open empty maze © Korea Institute of Science and Technology(KIST)

Results of the two experiments were consistent. It was found that the hippocampus uses different neural circuits and information processing strategies depending on the environmental conditions. In the object-free environments, a group of cells located in the superficial region of CA1 tends to be active and uses a rate code since the animal position is best predicted by changes in the frequency of action potentials discharged by single neurons. In contrast, in a complex, object-strewn environment, a group of cells in the deep region of CA1 tend to be active and uses a phase code since the animal position is best predicted by the timing of a neuron action potentials relative to the ensemble of active neurons.

These findings suggest that the circuit using the rate code is more strongly associated with providing information about overall positioning and spatial perception, whereas the circuit using the phase code is more strongly associated with remembering the precise location of an object and spatial relationships. Aside from this, the respective contribution of inputs from CA3 and the entorhinal cortex was also analysed. It is known that CA1 receive information from both the CA3 region and the entorhinal cortex. In this study, based on differences in fast network oscillations called “gamma”, it was found that superficial CA1 cells receive information primarily from CA3 in the simple environments whereas deep CA1 cells receive information primarily from the entorhinal cortex in the complex environments.

Dr. Sebastien Royer, Brain Science Institute(BSI), KIST © Korea Institute of Science and Technology(KIST)

Sebastien Royer, Principal investigator at KIST said “this study improves our understanding on how the hippocampus processes information, which is a critical step for understanding the general mechanisms of memory.” He added that “such basic level understanding will eventually help the development of technologies for the diagnosis and treatment of brain disorders related to hippocampal injury such as Alzheimer’s type dementia, amnesia, and cognitive impairment, and might inspire the development of some AI.”

The research team headed by Sebastien Royer, PhD has been gradually expanding the understanding of information storage and processing in memory-related brain areas using diverse approaches. In a study combining mouse experiment and neural network modeling published last year in the journal “Nature Communications”, the same team identified the process by which granule cells in the dentate gyrus region of the hippocampus develop a uniform mapping of the space during spatial learning.

The study was conducted as a KIST major project and funded by the Ministry of Science and ICT (MSIT). The study findings were published in the latest issue of the international academic journal, “Neuron.”

Featured image: Treadmill experiments to determine the rate and phase code of CA1 © Korea Institute of Science and Technology(KIST)


Reference: Farnaz Sharif, Behnam Tayebi et al., “Subcircuits of Deep and Superficial CA1 Place Cells Support Efficient Spatial Coding across Heterogeneous Environments”, Neuron, 109(2), pp. 363-376, 2021. https://doi.org/10.1016/j.neuron.2020.10.034


Provided by National Research Council of Science and Technology

Neanderthals and Homo sapiens used Identical Nubian Technology (Archeology)

New analysis of a fossil tooth and stone tools from Shukbah Cave reveals Neanderthals used stone tool technologies thought to have been unique to modern humans

Long held in a private collection, the newly analysed tooth of an approximately 9-year-old Neanderthal child marks the hominin’s southernmost known range. Analysis of the associated archaeological assemblage suggests Neanderthals used Nubian Levallois technology, previously thought to be restricted to Homo sapiens. 

With a high concentration of cave sites harbouring evidence of past populations and their behaviour, the Levant is a major centre for human origins research. For over a century, archaeological excavations in the Levant have produced human fossils and stone tool assemblages that reveal landscapes inhabited by both Neanderthals and Homo sapiens, making this region a potential mixing ground between populations. Distinguishing these populations by stone tool assemblages alone is difficult, but one technology, the distinct Nubian Levallois method, is argued to have been produced only by Homo sapiens.

In a new study published in Scientific Reports, researchers from the Max Planck Institute for the Science of Human History teamed up with international partners to re-examine the fossil and archaeological record of Shukbah Cave. Their findings extend the southernmost known range of Neanderthals and suggest that our now-extinct relatives made use of a technology previously argued to be a trademark of modern humans. This study marks the first time the lone human tooth from the site has been studied in detail, in combination with a major comparative study examining the stone tool assemblage. 

“Sites where hominin fossils are directly associated with stone tool assemblages remain a rarity – but the study of both fossils and tools is critical for understanding hominin occupations of Shukbah Cave and the larger region,” says lead author Dr Jimbob Blinkhorn, formerly of Royal Holloway, University of London and now with the Pan-African Evolution Research Group (Max Planck Institute for the Science of Human History).

Photo and 3D reconstruction of a tooth of a 9-year-old Neanderthal child © Trustees of the Natural History Museum, London © Blinkhorn, et al., 2021

Shukbah Cave was first excavated in the spring of 1928 by Dorothy Garrod, who reported a rich assemblage of animal bones and Mousterian-style stone tools cemented in breccia deposits, often concentrated in well-marked hearths. She also identified a large, unique human molar. However, the specimen was kept in a private collection for most of the 20th century, prohibiting comparative studies using modern methods. The recent re-identification of the tooth at the Natural History Museum in London has led to new detailed work on the Shukbah collections.  

“Professor Garrod immediately saw how distinctive this tooth was. We’ve examined the size, shape and both the external and internal 3D structure of the tooth, and compared that to Holocene and Pleistocene Homo sapiens and Neanderthal specimens. This has enabled us to clearly characterise the tooth as belonging to an approximately 9 year old Neanderthal child,” says Dr. Clément Zanolli, from Université de Bordeaux. “Shukbah marks the southernmost extent of the Neanderthal range known to date,” adds Zanolli.

Although Homo sapiens and Neanderthals shared the use of a wide suite of stone tool technologies, Nubian Levallois technology has recently been argued to have been exclusively used by Homo sapiens. The argument has been made particularly in southwest Asia, where Nubian Levallois tools have been used to track human dispersals in the absence of fossils.

Photos of Nubian Levallois cores associated with Neanderthal fossils © UCL, Institute of Archaeology & courtesy of the Penn Museum, University of Pennsylvania © Blinkhorn, et al., 2021 / CC BY 4.0

“Illustrations of the stone tool collections from Shukbah hinted at the presence of Nubian Levallois technology so we revisited the collections to investigate further. In the end, we identified many more artefacts produced using the Nubian Levallois methods than we had anticipated,” says Blinkhorn. “This is the first time they’ve been found in direct association with Neanderthal fossils, which suggests we can’t make a simple link between this technology and Homo sapiens.”

“Southwest Asia is a dynamic region in terms of hominin demography, behaviour and environmental change, and may be particularly important to examine interactions between Neanderthals and Homo sapiens,” adds Prof Simon Blockley, of Royal Holloway, University of London. “This study highlights the geographic range of Neanderthal populations and their behavioural flexibility, but also issues a timely note of caution that there are no straightforward links between particular hominins and specific stone tool technologies.”

“Up to now we have no direct evidence of a Neanderthal presence in Africa,” said Prof Chris Stringer of the Natural History Museum. “But the southerly location of Shukbah, only about 400 km from Cairo, should remind us that they may have even dispersed into Africa at times.”

Partnerships

Researchers involved in this study include scholars from the Max Planck Institute for the Science of Human History, Royal Holloway, University of London, the Université de Bordeaux, the Max Planck Institute for Chemical Ecology, the University of Malta, and the Natural History Museum, London. This work was supported by the Leverhulme trust (RPH-2017-087).

Featured image: The view from Shukbah Cave © Amos Frumkin


Reference: James Blinkhorn, Clément Zanolli, Tim Compton, Huw S. Groucutt, Eleanor M.L. Scerri, Lucile Crété, Chris Stringer, Michael D. Petraglia, Simon Blockley, “Nubian Levallois technology associated with southernmost Neanderthals”, Scientific Reports, 2021. https://www.nature.com/articles/s41598-021-82257-6


Provided by Max Planck Institute for the Science of Human History

Overlooked Helpers: Membrane Building Blocks Play a Decisive Role in Controlling Cell Growth (Botany)

Lipids are the building blocks of a cell’s envelope – the cell membrane. In addition to their structural function, some lipids also play a regulatory role and decisively influence cell growth. This has been investigated in a new study by scientists at Martin Luther University Halle-Wittenberg (MLU). The impact of the lipids depends on how they are distributed over the plasma membrane. The study was published in “The Plant Cell”.

If plant cells want to move, they need to grow. One notable example of this is the pollen tube. When pollen lands on a flower, the pollen tube grows directionally into the female reproductive organs. This allows the male gametes to be delivered, so fertilisation can occur. The pollen tube is special in that it is made up of a single cell that continues to extend and, in extreme cases, can become several centimetres long. “This makes pollen tubes an exciting object for research on directional growth processes,” says Professor Ingo Heilmann, head of the Department of Plant Biochemistry at MLU.

For the current study, Heilmann’s team focused on the phospholipids of pollen tubes, which, as the main component of the plasma membrane, are responsible for separating the cell’s interior from its surroundings. “Lipids are generally known to have this structuring function,” says Dr Marta Fratini, first author of the study. It has only recently come to light that some phospholipids can also regulate cellular processes. The scientists from Halle have now been able to show that a specific phospholipid called phosphatidylinositol 4,5-bisphosphate (“PIP2”) can control various aspects of cell growth in pollen tubes – depending on its position at the plasma membrane. They did this by labelling the lipid with a fluorescent marker. “We found it is either distributed diffusely over the entire tip of the pollen tube without a recognisable pattern, or is concentrated in small dynamic nanodomains,” Fratini explains. One can imagine a group of people on a square: either individuals remain 1.5 metres apart as currently prescribed, or they form small groups.

Pollen tube with swollen tip (green: one of the enzymes responsible for lipid production, magenta: the lipid nano domains discovered and described in the study) / Foto: Marta Fratini

It appears that different enzymes are responsible for the varying distribution of PIP2. “Plant cells have several enzymes that can produce this one phospholipid,” explains Heilmann. Like the lipids, some of these enzymes are widely distributed over the membrane and others are concentrated in nanodomains, as shown by the current study. Depending on which of the enzymes the researchers artificially increased, either the cytoskeleton – a structure important for directed growth – stabilised and the pollen tube swelled at the tip, or more pectin – an important building material for plant cell walls – was secreted. This made the cell branch out at the tip. To make sure that the distribution of the lipids was indeed responsible for these growth effects, the biochemists artificially changed the arrangement of the enzymes at the plasma membrane – from clusters to a wide scattering or vice versa. It turns out they were able to control the respective effects on cell growth. 

“As far as I know, our study is the first to trace the regulatory function of a lipid back to its spatial distribution in the membrane,” says Heilmann. Further research is now needed to clarify exactly how the membrane nanodomains assemble and how the distribution of PIP2 at the membrane can have such varying effects. 

The research was funded by the Deutsche Forschungsgemeinschaft (German Research Association, DFG) through various programmes, including the Research Training Group 2498 “Communication and Dynamics of Plant Cell Compartments”, and supported by the Centre for Innovation Competence HALOmem at MLU. 

Featured image: A pollen tube that grows out of a pollen grain (green: one of the enzymes responsible for the production of lipids that control cell growth, magenta: actin cytoskeleton). / Foto: Marta Fratini


Study: Fratini et al. Plasma membrane nano-organization specifies phosphoinositide effects on Rho-GTPases and actin dynamics in tobacco pollen tubes. The Plant Cell (2020). doi: 10.1093/plcell/koaa035


Provided by Martin Luther University Halle-Wittenberg

Capuchin Monkey Genome Reveals Clues To Its Long Life And Large Brain (Biology)

An international team of scientists has sequenced the genome of a capuchin monkey for the first time, uncovering new genetic clues about the evolution of their long lifespan and large brains.

Published in PNAS, the work was led by the University of Calgary in Canada and involved researchers at the University of Liverpool.

“Capuchins have the largest relative brain size of any monkey and can live past the age of 50, despite their small size, but their genetic underpinnings had remained unexplored until now,” explains Professor Joao Pedro De Magalhaes, who researches ageing at the University of Liverpool.

The researchers developed and annotated a reference assembly for white-faced capuchin monkeys (Cebus imitator) to explore the evolution of these traits.

Through a comparative genomics approach spanning a wide diversity of mammals, they identified genes under evolutionary selection associated with longevity and brain development.

“We found signatures of positive selection on genes underlying both traits, which helps us to better understand how such traits evolve. In addition, we found evidence of genetic adaptation to drought and seasonal environments by looking at populations of capuchins from a rainforest and a seasonal dry forest,” said senior author and Canada Research Chair Amanda Melin who has studied capuchin monkey behaviour and genetics for almost 20 years.

The researchers identified genes associated with DNA damage response, metabolism, cell cycle, and insulin signalling. Damage to the DNA is thought to be a major contributor to ageing and previous studies by Professor de Magalhaes and others have shown that genes involved in DNA damage responses exhibit longevity-specific selection patterns in mammals.

“Of course, because aging-related genes often play multiple roles it is impossible to be sure whether selection in these genes is related to ageing or to other life-history traits, like growth rates and developmental times, that in turn correlate with longevity,” said Professor De Magalhaes.

“Although we should be cautious about the biological significance of our findings, it is tempting to speculate that, like in other species, changes to specific aging-related genes or pathways, could contribute to the longevity of capuchins,” he added.

The team’s insights were made possible thanks to the development of a new technique to isolate DNA more efficiently from primate faeces.

FecalFACS utilises an existing technique that has been developed to separate cells types in body fluids – for example to separate different cell types in blood for cancer research – and applies it to primate faecal samples.

“This is a major breakthrough because the typical way to extract DNA from faeces results in about 95-99% of the DNA coming from gut microbes and food items. A lot of money has been spent sequencing genomes from different organisms than the mammals we’re actually trying to study. Because of this, when wildlife biologists have required entire genomes, they have had to rely on more pure sources of DNA, like blood, saliva, or tissue – but as you can imagine, those are very hard to come by when studying endangered animals,” explained the study’s lead author, Dr Joseph Orkin, who completed work on this project as a postdoctoral scholar at the University of Calgary, and in his present location at Universitat Pompeu Fabra-CSIC in Barcelona.

“FecalFACS finally provides a way to sequence whole genomes from free-ranging mammals using readily available, non-invasive samples, which could really help future conservation efforts,” he added.


Research reference

Orkin et al., The genomics of ecological flexibility, large brains, and long lives in capuchin monkeys revealed with fecalFACS, PNAS, https://doi.org/10.1073/pnas.2010632118


Provided by University of Liverpool