Publisher Health

Scientists have known for decades that pregnancy requires a mother’s body to adjust so that her immune system does not attack the growing fetus as if it were a hostile foreign invader. Yet despite learning a great deal more about the immunology of pregnancy in recent years, a new study shows that the cellular crosstalk between a mother and her offspring is even more complex and long-lasting than expected.
The study was published online Sept. 21, 2023, in the journal Science by a research team led by Sing Sing Way, MD, PhD, Division of Infectious Diseases at Cincinnati Children’s and the Center for Inflammation and Tolerance.
“By investigating how prior pregnancy changes the outcomes of future pregnancies — or in other words how mothers remember their babies — our findings add a new dimension to our understanding of how pregnancy works,” Way says. “Nature has designed built-in resiliency in mothers that generally reduces the risk of preterm birth, preeclampsia, and stillbirth in women who have a prior healthy pregnancy. If we can learn ways to mimic these strategies, we may be better able to prevent complications in high-risk pregnancies.”
In addition to potentially making progress against the leading cause of infant mortality, Way says understanding how the immune system changes during pregnancy could influence other research fields including vaccine development, autoimmunity research, and how to prevent organ transplant rejection.
How Moms Remember Their Babies
In 2012, Way and colleagues published a study in Nature that revealed how the experience of a first pregnancy makes a woman’s body much less likely to reject a second pregnancy with the same father.
In addition to previously known short-term immune system adjustments, the researchers found that the mother’s body keeps a longer-term supply of immune suppressive T cells that specifically recognize the next fetus by the same couple. These suppressive T cells instruct the rest of the immune system to stand down as the pregnancy develops and linger in the mother’s body for years after giving birth.

Immunotherapy, which uses the body’s own immune system to fight cancer, is an effective treatment option, yet many patients do not respond to it. Thus, cancer researchers are seeking new ways to optimize immunotherapy so that it is more effective for more people. Now, Salk Institute scientists have found that manipulating an early step in energy production in mitochondria — the cell’s powerhouses — reduces melanoma tumor growth and enhances the immune response in mice.
The study, published in Science on September 21, 2023, revealed that when electrons take one of two initial routes through mitochondria, genes and proteins become activated that are needed for immune cells to recognize and kill tumor cells.
“We wanted to better understand how tumors acquire the metabolic state that gives them a growth advantage as well as an ability to evade the immune system, which I call the ‘double whammy,'” says Professor Susan Kaech, the paper’s co-senior author and director of the NOMIS Center for Immunology and Microbial Pathogenesis. “And we found a way to make the tumors more recognizable by the immune system and potentially more responsive to immunotherapy.”
It was previously thought that cancer cells do not rely heavily on mitochondria despite still having oxygen and sugars available to them to fuel mitochondrial metabolism. This hypothesis dominated the field of cancer metabolism until recently, when scientists found that mitochondria actually play multiple important roles in tumor growth.
“There’s an explosion of recent research activity from my lab and others revealing how mitochondria regulate the immune system and inflammation, and this study highlights an exciting new chapter in this story,” says Professor Gerald Shadel, co-senior author, holder of the Audrey Geisel Chair in Biomedical Science, and director of the San Diego Nathan Shock Center of Excellence in the Basic Biology of Aging.
Kaech and Shadel teamed up to better understand how mitochondria influence both tumor growth and the way in which the immune system recognizes and responds to cancer. For this study, their labs altered a key step in the electron transport chain, a process that moves electrons through mitochondria, leading to the production of adenosine phosphate (ATP), the main energy-providing molecule in cells.
There are two primary routes by which electrons flow inside mitochondria to initiate ATP production. When the team forced electrons to primarily go through only one of these two routes, it led to the overproduction of a metabolite called succinate. This accumulation of succinate led to expression of immune genes in the nucleus and increased the levels of a protein called MHC on the surface of the tumor. In turn, elevated levels of MHC made the tumor cells more visible to specialized immune cells called “killer” T cells, which recognize and eliminate cancer cells.

In a new study in mice, a team of researchers from UCLA, the Swiss Federal Institute of Technology, and Harvard University have uncovered a crucial component for restoring functional activity after spinal cord injury. The neuroscientists have shown that re-growing specific neurons back to their natural target regions led to recovery, while random regrowth was not effective.
In a 2018 study published in Nature, the team identified a treatment approach that triggers axons — the tiny fibers that link nerve cells and enable them to communicate — to regrow after spinal cord injury in rodents. But even as that approach successfully led to the regeneration of axons across severe spinal cord lesions, achieving functional recovery remained a significant challenge.
For the new study, published this week in Science, the team aimed to determine whether directing the regeneration of axons from specific neuronal subpopulations to their natural target regions could lead to meaningful functional restoration after spinal cord injury in mice. They first used advanced genetic analysis to identify nerve cell groups that enable walking improvement after a partial spinal cord injury.
The researchers then found that merely regenerating axons from these nerve cells across the spinal cord lesion without specific guidance had no impact on functional recovery. However, when the strategy was refined to include using chemical signals to attract and guide the regeneration of these axons to their natural target region in the lumbar spinal cord, significant improvements in walking ability were observed in a mouse model of complete spinal cord injury.
“Our study provides crucial insights into the intricacies of axon regeneration and requirements for functional recovery after spinal cord injuries,” said Michael Sofroniew, MD, PhD, professor of neurobiology at the David Geffen School of Medicine at UCLA and a senior author of the new study. “It highlights the necessity of not only regenerating axons across lesions but also of actively guiding them to reach their natural target regions to achieve meaningful neurological restoration.”
The authors say understanding that re-establishing the projections of specific neuronal subpopulations to their natural target regions holds significant promise for the development of therapies aimed at restoring neurological functions in larger animals and humans. However, the researchers also acknowledge the complexity of promoting regeneration over longer distances in non-rodents, necessitating strategies with intricate spatial and temporal features. Still, they conclude that applying the principles laid out in their work “will unlock the framework to achieve meaningful repair of the injured spinal cord and may expedite repair after other forms of central nervous system injury and disease.”
The research team included scientists from NeuroX Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL); the Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Center for Interventional Neurotherapies (NeuroRestore); Wyss Center for Bio and Neuroengineering; Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne; Departments of Bioengineering, Chemistry and Biochemistry, University of California, Los Angeles; Bertarelli Platform for Gene Therapy, Swiss Federal Institute of Technology; Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology; M. Kirby Neurobiology Center, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles.
This work was supported by the Defitech Foundation, Wings for Life, Riders4Riders, Wyss Center for Bio and Neuroengineering, Swiss National Science Foundation (PZ00P3_185728 to M.A.A. and PZ00P3_208988 to J.W.S.); the Morton Cure Paralysis Foundation (to M.A.A); the ALARME Foundation (to M.A.A. and G.C); the Dr. Miriam and Sheldon G. Adelson Medical Foundation (to M.V.S., Z.H., and T.J.D.); Wings for Life (M.A.A., M.V.S., M.A.S., and M.M); Holcim-Stiftung Foundation (to J.W.S.); and the Canadian Institutes for Health Research (to J.W.S.). We are grateful to J. Ravier and M. Burri for the illustrations and to L. Batti and I. Gantar from the Advanced Lightsheet Imaging Center (ALICe) at the Wyss Center for Bio and Neuroengineering, Geneva. Funding: This work was supported in part using the resources and services of the Gene Expression Core Facility, and the Bertarelli Platform for Gene Therapy at the School of Life Sciences of EPFL.

Previous studies have shown that overweight and obesity are risk factors for several types of cancer. It is also known that obese women have a higher risk of cancer than their male counterparts, and that the risk level decreases with intentional weight loss. However, evidence of a link between obesity, weight loss and haematological cancer has been limited.
The current study, published in the journal Lancet Healthy Longevity, used data from the Swedish Obese Subjects (SOS) study at the University of Gothenburg and data from e.g., the Cancer Registry at the National Board of Health and Welfare.
The researchers studied 2,007 people who underwent bariatric surgery and compared them to a control group of 2,040 individuals, also obese, who did not undergo surgery. The groups were otherwise comparable in terms of e.g., gender, age, body composition, cardiovascular risk factors and psychosocial variables.
Most significant improvements in women
During the follow-up period, 34 individuals in the surgery group developed haematological cancer, in parallel with a significant weight loss. The corresponding number in the control group was 51 haematological cancers, with the group remaining at the level of severe obesity.
Most of the blood cancers were lymphomas, and when these were studied separately, there was a 55% reduction in the risk of lymphoma in the group that had undergone bariatric surgery. The corresponding risk reduction for all blood cancers was 40%.
In particular, women with high blood sugar at the start of the study seemed to benefit from bariatric surgery. This is according to Magdalena Taube, Associate Professor of Molecular and Clinical Medicine at Sahlgrenska Academy, University of Gothenburg, and corresponding author of the study.

New research published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) shows that morning and afternoon physical activity are associated with a lower risk of developing type 2 diabetes across all population levels of education and income, but found no statistically significant association between evening physical activity and risk type 2 diabetes. The study is by Dr Caiwei Tian, Harvard University, Cambridge, MA, USA, and Dr Chirag Patel, Harvard Medical School, Boston, MA. and colleagues.
Physical activity is a preventive factor for type 2 diabetes, but its timing and consistency (in contrast with overall sum of physical activity) has been relatively unexplored. Accelerometer-based devices that measure physical activity provide a new opportunity to objectively measure behaviour throughout the day and week. It has been shown that midday–afternoon but not evening physical activity is associated with a lower risk of mortality compared with morning physical activity, but the relationship with type 2 diabetes remains understudied. In this new study, the authors analysed the relationship between morning, afternoon, or evening physical activity and consistency (routine) and risk of type 2 diabetes.
A cohort of 93,095 UK Biobank participants (mean age 62 years) without a history of type 2 diabetes wore a wrist-worn accelerometer for 1 week. The authors converted accelerometer information to estimate metabolic equivalent of task (MET) (a common measure of physical activity), summing MET-hours of total physical activity.  MET-hour physical activity captures all types of activity undertaken by an individual throughout the day and measured with the accelerometer, including chores, walking, and vigorous activity. The authors measured completed METs within three time segments (morning, afternoon, and evening), divided as 06:00–12:00 hours (morning); 12:00–18:00 hours (afternoon); and 18:00–24:00 hours (evening).
The authors quantified the consistency of physical activity by analysing the variance, or difference of each person’s activity from their own personal average. Those with smaller deviations were more consistent and vice versa. The authors also considered the intensity of exercise: moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA) in association with type 2 diabetes incidence.
The authors observed protective associations of physical activity, with each 1-unit increase in MET being associated with a 10% and 9% reduction in risk of type 2 diabetes in the morning and afternoon, respectively. However, there was no statistically significant association between evening physical activity and risk of type 2 diabetes.
The relationship with morning and afternoon physical activity was largely linear, meaning that those people with more MET-h completed had a much lower risk of developing type 2 diabetes than those with less (10% / 9% per MET-h, for morning and afternoon respectively). 
The authors thought that lifestyle factors, such as amount of sleep and dietary intake, would influence the amount of physical activity in the morning, afternoon, and evening undertaken, and therefore the role activity has in diabetes risk. To address how these factors influence physical activity, the authors considered these factors in their analytic models. They found that when adjusting for lifestyle factors, associations for MET-hours with different times of day became more precise. 
Consistency of MET-measured physical activity was not associated with type 2 diabetes; but intensity was – both MVPA and VPA were associated with decreased risk for type 2 diabetes at all times of the day. The authors say their study is the first report on the effect of consistency of activity, and explain: “The consistency or routine of physical activity was not strongly associated with type 2 diabetes. In other words, individuals who exercise a smaller amount of time more frequently are at no lesser risk for diabetes than individuals who exercise the same total amount, but with less of a routine.”

Many bone remains deposited in prehistoric caves feature cuts and marks, with the scientific community at times attributing to their usage for human consumption. A study presented by University of Cordoba researcher Rafael Martínez Sánchez, and led by Zita Laffranchi and Marco Milella at the University of Bern (Switzerland), together with other researchers from different research centers, has just been published in the journal PLoS one. The work advances our knowledge of the funerary rites that took place as of the Neolithic by documenting how prehistoric societies modified human bones to make use of them.
To this end, more than 400 remains were analyzed. Corresponding to both adults and pre-adults, they were found in the Cueva de los Mármoles (cave) in Priego de Córdoba, and are preserved in the town’s Archaeological Museum. Thanks to high-resolution molds that were studied with an electron microscope, the research team observed that many of the marks on some bones are compatible with a cleaning process carried out in order to use the bone remains as tools and not (at least, in principle) for consumption.
As Martínez Sánchez explains, establishing that the marks of the bones correspond to one use (tools) or another (food) is difficult, especially because these remains were deposited on the surface of the cave, rather than being buried, such that they may have undergone other types of taphonomic modifications (by animals, trampling…) over the years. The study, however, does not see the marks of the bones as suggesting that they were used to obtain soft parts from them, for consumption.Rather, they are seen as evidencing a more careful cleaning process consistent with their instrumental use.Found were a fibula with a pointed end, a modified tibia, and a skull.
In addition, carbon-14 dating of twelve remains has indicated three periods of funerary use in the cave: in 3800 BC, in 2500 BC. C. and around 1,300 or 1,400 BC. The first of these periods, which corresponds to the Neolithic, coincides with a spread in the use of dolmens designed for collective burials. Therefore, it was a time characterized by a great concern with ancestors. This overlap between the first period of burials in the cave and the beginning of Megalithism, together with the fact that the marks on the bones do not seem compatible with consumption, reinforces the research group’s idea that the human remains were fashioned to be used as instruments at a given time. As Martínez Sánchez argues, “it seems that there was the idea of grouping the dead in the same place, cleaning the remains, and using the bones as instruments, perhaps related to some type of ritual performed inside the cavity.”
With this study the team has managed to substantiate a treatment of skeletal remains most likely not linked to consumption, but rather to more complex factors. Thus, it seems that the bones were used for ritual and cultural aspects after their depositing. Moreover, these ways of thinking apparently spanned a great period of time, from the end of the Neolithic to the Bronze Age, a time “in which we did not expect to find that bodies were still deposited in this cavity,” says Martínez Sánchez.

The onset of embryo-specific gene transcription, also known as embryonic genome activation (EGA), is a crucial step in the developmental journey of an organism. Although EGA has been studied to some extent in mice, human EGA remains largely unexplored, mainly due to the lack of novel in vitro cell models and ethical restrictions on the usage of human embryos. Thus, cell models resembling the human blastomere stage — when the embryo undergoes a cell duplication process — are necessary to study the earliest stages of human EGA and understand the events that occur during early embryonic development.
To enable such studies, five independent research groups recently developed different methods to produce human 8-cell-like cells (8CLCs) — a small subpopulation of cells derived from human pluripotent stem cells (hPSCs) — closely resembling the 8-cell-stage embryo. Taubenschmid-Stowers et al. and Moya-Jódar et al. found 8CLCs from naive hPSCs under two different but specific culture conditions, while Mazid et al. optimized culture conditions to determine the existence of 8CLCs in naive hPSCs. Elsewhere, Yu et al. employed chemical screening to promote the conversion of pre-implantation epiblast-like hPSCs to 8CLCs. Yoshihara et al. reprogrammed induced blastomere-like (iBM) cells from human embryonic stem cells (hESCs) by transient expression of DUX4, a transcription factor activated just after fertilization. Although all research groups identified these cells as 8CLCs using single-cell RNA sequencing (scRNA-seq), the extent of similarities or differences among these 8CLC populations remains unknown.
In a new study, Associate Professor Masahito Yoshihara from the Institute for Advanced Academic Research and Graduate School of Medicine at Chiba University, along with Professor Juha Kere from the Department of Biosciences and Nutrition at Karolinska Institutet, Sweden, and University of Helsinki, Finland, set out to bridge this knowledge gap. They compared the transcriptomic profiles of the 8CLCs reported by the five research groups, including theirs, with each other and with 8-cell-stage blastomeres. Their findings were made available online on July 20, 2023, and published in Volume 18, Issue 8 of Stem Cell Reports journal on August 8, 2023.
For this comparison, the researchers first integrated the scRNA-seq data of the five developed 8CLCs with two datasets of human pre-implantation embryos — Petropoulos et al. and the Yan et al. datasets. The Yan et al. dataset included primed hESCs and embryos, while the Petropoulos et al. dataset included data from embryonic day three (8-cell stage) till day seven.
Statistical analysis of the successfully integrated data revealed that the iBM cells reprogrammed by Dr. Yoshihara and his team showed the highest similarity to the 8-cell-stage embryo across both datasets, while the other 8CLCs were heterogenous. These findings were reinforced by the cell type annotation of the 8CLCs using the scRNA-seq data of human pre-implantation embryos as references.
Gene expression analysis of all 8CLCs revealed that EGA genes were highly expressed, with pluripotency gene expression being minimal in iBM cells. The other 8CLCs displayed higher expression of pluripotency genes. The researchers also found compelling evidence suggesting that the origin of 8CLCs, as well as their mode of reprogramming, might affect the final cell properties.
They anticipate that the present findings will trigger more extensive research in the early human embryonic development. As Dr. Yoshihara explains, “The developed cell models will enable us to study the earliest stages of human life without ethical concerns. In addition, reprogrammed cells overcome the constraint of limited study specimens, since they can be produced in large numbers at once.”
With further clarity on the mechanism of normal early human development, it may be possible to find new methods for understanding the causes of infertility and improving the success of in vitro fertilization.

Lung cancer is the leading cause of cancer-related deaths in the United States. Some tumors are extremely small and hide deep within lung tissue, making it difficult for surgeons to reach them. To address this challenge, UNC -Chapel Hill and Vanderbilt University researchers have been working on an extremely bendy but sturdy robot capable of traversing lung tissue.
Their research has reached a new milestone. In a new paper, published in Science Robotics, Ron Alterovitz, PhD, in the UNC Department of Computer Science, and Jason Akulian, MD MPH, in the UNC Department of Medicine, have proven that their robot can autonomously go from “Point A” to “Point B” while avoiding important structures, such as tiny airways and blood vessels, in a living laboratory model.
“This technology allows us to reach targets we can’t otherwise reach with a standard or even robotic bronchoscope,” said Dr. Akulian, co-author on the paper and Section Chief of Interventional Pulmonology and Pulmonary Oncology in the UNC Division of Pulmonary Disease and Critical Care Medicine. “It gives you that extra few centimeters or few millimeters even, which would help immensely with pursuing small targets in the lungs.”
The development of the autonomous steerable needle robot leveraged UNC’s highly collaborative culture by blending medicine, computer science, and engineering expertise. In addition to Alterovitz and Akulian, the development effort included Yueh Z. Lee, MD, PhD, at the UNC Department of Radiology, as well as Robert J. Webster III at Vanderbilt University and Alan Kuntz at the University of Utah.
The robot is made of several separate components. A mechanical control provides controlled thrust of the needle to go forward and backward and the needle design allows for steering along curved paths. The needle is made from a nickel-titanium alloy and has been laser etched to increase its flexibility, allowing it to move effortlessly through tissue.
As it moves forward, the etching on the needle allows it to steer around obstacles with ease. Other attachments, such as catheters, could be used together with the needle to perform procedures such as lung biopsies.
To drive through tissue, the needle needs to know where it is going. The research team used CT scans of the subject’s thoracic cavity and artificial intelligence to create three-dimensional models of the lung, including the airways, blood vessels, and the chosen target. Using this 3-D model and once the needle has been positioned for launch, their AI-driven software instructs it to automatically travel from “Point A” to “Point B” while avoiding important structures.

Small cell lung cancer accounts for about 15 percent of all diagnosed lung cancers and is still associated with a high mortality rate. SCLC tumours often develop resistance to chemotherapy and thus poor prognosis is due to tumour recurrence which occurs within only five to 14 months after initial diagnosis. As a recent research study led by Balazs Döme and Karin Schelch from MedUni Vienna shows, resistant cell lines can be successfully fought with a combination of two already available therapeutic agents. The study results were published in the medical journal Clinical Cancer Research and offer a promising approach for the development of new therapies for this particularly aggressive type of tumour.
The study follows on from earlier, highly regarded findings by the research group led by Balazs Döme and Karin Schelch (Department of Thoracic Surgery at MedUni Vienna), according to which small cell lung cancer (SCLC) can be divided into subtypes that respond differently to chemotherapeutic agents and targeted drugs. In this context, histone deaceylase inhibitors (HDACi) have been shown to be effective in two SCLC subtypes (known as SCLC-A and SCLC-N). HDACi are drugs that have already been shown in trials to be effective in fighting cells of different tumour types and have now been further investigated for their use in SCLC.
Combination instead of single therapy
SCLC affects about 15 percent of lung cancer patients. This particularly aggressive tumour, which usually occurs in smokers, grows rapidly and has a high tendency to metastasise. About 70 per cent of advanced cases are fatal within a year. “The high mortality rate is due to the rapid and virtually inevitable recurrence of the disease, which is often accompanied by resistance to treatment,” says principal investigator Karin Schelch, outlining the problem. HDACi in combination with standard chemotherapeutic agents turned out to be a possible solution during the studies. This significantly slowed down the growth of tumour cells that were resistant to individual therapy.
Mechanism of resistance deciphered
In further analyses, the molecular mechanism underlying therapy resistance was also revealed. The findings of the MedUni Vienna research group thus contribute significantly to a better understanding of the biology of SCLC, a disease in which promising progress in the development of therapeutic innovations has been decades in waiting. “Our findings can provide the basis for research into successful new therapies that are superior to the resistance mechanisms of SCLC,” says first author Anna Solta, also from MedUni Vienna’s Department of Thoracic Surgery, highlighting the study’s high clinical relevance.

Published41 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, AFPBy Nomsa MasekoBBC News, JohannesburgSouth Africa’s parliament has passed a bill which would expunge criminal records for those convicted of breaching Covid-19 lockdown laws.South Africa had some of the world’s toughest restrictions, which saw more than 400,000 arrested for not wearing masks, consuming alcohol and breaking curfew, among other violations.Those who admitted guilt and paid fines will now have their records cleared.South Africans have broadly welcomed this bill.It has to be approved by the National Council of Provinces, and then signed into law by President Cyril Ramaphosa but there is little doubt it will become law. The Judicial Matters Amendment Bill gained broad political support when it was debated in parliament.The opposition African Christian Democratic Party (ACDP), which supported the bill, highlighted how having a criminal record affected some people’s chances of finding jobs.”May we never again have such irrational regulations which were passed without parliamentary intervention or oversight,” said ACDP MP Steven Swart. In April 2021, police minister Bheki Cele said 411,309 people had been arrested for breaching lockdown regulations.It’s unclear how many of those who were arrested were ultimately convicted. However, not all MPs voted for the bill to be passed into law. The left-wing Economic Freedom Fighters (EFF) welcomed part of the bill but said it couldn’t support the bill as a whole. “The prosecutions and persecutions that came about as a result of the regulations flowing from the Disaster Management Act during the pandemic demonstrated the depth into which our judiciary system could be used to severely limit the rights of individuals,” said EFF MP Veronica Mente.”May the law never again be used in pursuit of sinister motives such as what happened during the Covid-19 pandemic.”More on this storyWhat can South Africa teach us about Omicron?Published16 December 2021Was South Africa ignored over mild Omicron evidence?Published20 January 2022South Africa battles Omicron fear and vaccine mythsPublished3 December 2021