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A pioneering University of Limerick professor of surgery whose groundbreaking research led to the reclassification of an organ has published new evidence detailing the fundamental order of the abdomen.
J Calvin Coffey, Foundation Chair of Surgery at UL’s School of Medicine in Ireland, whose major discovery led to the reclassification of the mesentery as a new organ in 2016, has published new research on the makeup and structure of the abdomen.
In a research paper published in the Nature Portfolio journal Communications Biology, Professor Coffey’s team has detailed the development and structure of the mesentery. In doing this, they uncovered a new order by which all contents of the abdomen are organised or arranged — or the “fundamental order of the abdomen.”
The importance of these findings on the mesentery and the impact these have on our understanding of the abdomen have been further explained in a review article just published in the Lancet Gastroenterology and Hepatology.
“Since 2016, Kevin Byrnes, Dara Walsh and members of the team been looking at the development and structure of the mesentery,” explained Professor Coffey, who is also Head of Department of Surgery, Consultant General and Colorectal Surgeon at UL Hospitals Group.
“We showed how the mesentery is a single and continuous organ in and on which all abdominal digestive organs develop and then remain connected to throughout life.

A protein that masterminds the way DNA is wrapped within chromosomes has a major role in the healthy functioning of blood stem cells, which produce all blood cells in the body, according to a new study from researchers at Weill Cornell Medicine.
The protein, known as histone H3.3, organizes the spool-like structures around which DNA is wrapped in plants, animals and most other organisms. Histones enable DNA to be tightly compacted, and serve as platforms for small chemical modifications — known as epigenetic modifications — that can loosen or tighten the wrapped DNA to control local gene activity.
The study, which appeared Dec. 27 in Nature Cell Biology, examined H3.3’s role in blood stem cells, also known as hematopoietic stem cells (HSCs), that are a major focus of efforts to develop stem-cell-based medicine. Normally most HSCs stay in a stem-like, uncommitted state where they can survive long-term, slowly self-renewing, while some HSCs mature or “differentiate” to produce all the different lineage-specific blood cell types. The study found that H3.3 is crucial for both processes; deleting the protein from HSCs led to reduced HSC survival, an imbalance in the types of blood cell produced by the HSCs and other abnormalities.
“How hematopoietic stem cells coordinate their self-renewal and differentiation into various blood cell types in a balanced way has been a mystery to a great extent, but this study helps us understand those processes much better at the molecular level and gives us many new clues to pursue in further investigations,” said study co-senior author Dr. Shahin Rafii, director of the Ansary Stem Cell Institute, chief of the Division of Regenerative Medicine and the Arthur B. Belfer Professor in Genetic Medicine at Weill Cornell Medicine.
The study was a collaboration that also included co-first and co-senior authors Dr. Ying Liu and Dr. Peipei Guo, who are senior instructors in the Rafii Laboratory; co-senior author Dr. Duancheng Wen, assistant professor of reproductive medicine research in obstetrics and gynecology; and co-author Dr. Steven Josefowicz, assistant professor of pathology and laboratory medicine and a member of the Sandra and Edward Meyer Cancer Center, all of Weill Cornell Medicine.
HSCs are among the most studied stem cells because of their importance in health and disease, and their potential in regenerative medicine. A single HSC can give rise to all blood cell types, from red blood cells and platelets to T cells, B cells and pathogen-engulfing macrophages. A more precise understanding of how HSCs work could lead to many applications including lab-grown blood for transfusions, and better HSC transplants for cancer patients. In addition, understanding how HSCs, upon acquiring aberrant mutations, give rise to leukemias could lead to development of new therapies for these often-refractory malignant diseases.

Blood tests may enable more accurate diagnosis of ALS at an earlier stage of the disease. As described in a study by researchers at University of Gothenburg and Umeå University, it involves measuring the blood level of a substance that, as they have also shown, varies in concentration depending on which variant of ALS the patient has.
The study, published in Scientific Reports, include Fani Pujol-Calderón, postdoctoral fellow at Sahlgrenska Academy, University of Gothenburg, and Arvin Behzadi, doctoral student at Umeå University and medical intern at Örnsköldsvik Hospital, as shared first authors.
Currently, it is difficult to diagnose amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease, early in the course of the disease. Even after a prolonged investigation, there is a risk of misdiagnosis due to other diseases that may resemble ALS in early stages. Much would be gained from earlier correct diagnosis and, according to the researchers, the current findings look promising.
Neurofilaments — proteins with a special role in the cells and fibers of nerves — are the substances of interest. When the nervous system is damaged, neurofilaments leak into the cerebrospinal fluid (CSF) and in lower concetrations in blood compared to CSF. In their study, scientists at Umeå University and the University Hospital of Umeå, as well as at the University of Gothenburg and Sahlgrenska University Hospital in Gothenburg, demonstrated that CSF and blood levels of neurofilaments can differentiate ALS from other diseases that may resemble early ALS.
More sensitive methods of analysis
Compared with several other neurological diseases, previous studies have shown higher concentrations of neurofilaments in CSF in ALS. Measuring neurofilament levels in the blood has previously been difficult since they occur at much lower concentrations compared to CSF. In recent years, however, new and more sensitive analytical methods have generated new scope for doing so.
The current study shows a strong association, in patients with ALS, between the quantity of neurofilaments in the blood and in CSF. The study is based on blood and CSF samples collected from 287 patients who had been referred to the Department of Neurology at the University Hospital of Umeå for investigation of possible motor neuron disease. After extensive investigation, 234 of these patients were diagnosed with ALS. These had significantly higher levels of neurofilaments in CSF and blood compared to patients who were not diagnosed with ALS.
Higher concentrations
Differences among various subgroups of ALS were also investigated and detected. Patients whose pathological symptoms started in the head and neck region had higher neurofilament concentrations in the blood and worse survival than patients whose disease onset began in an arm or a leg. The study has also succeeded in quantifying differences in blood levels of neurofilaments and survival for the two most common mutations associated to ALS.
“Finding suspected cases of ALS through a blood test opens up completely new opportunities for screening and measuring neurofilaments in blood collected longitudinally enables easier quantification of treatment effects in clinical drug trials compared to longitudinal collection of CSF. Finding ALS early in the disease course may facilitate earlier administration of pharmaceutical treatment, before the muscles have atrophied,” Arvin Behzadi says.
ALS is a neurodegenerative syndrome that leads to loss of nerve cells in both the brain and the spinal cord, resulting in muscle weakness and atrophy. Most of these patients die within two to four years after the symptom onset, but roughly one in ten survive more than ten years after the symptoms first appeared. Several genetic mutations have been associated to ALS. At present, there is no curative treatment. Nevertheless, the current drug available has been shown to prolong the survival in some ALS patients if it is administered in time.
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In cancer research, it has long been known that lactic acid, or lactate, is produced in large quantities by cancer cells and that this lactic acid disrupts our defence against tumours. Until now, however, we did not know exactly how this happens. Prof Jo Van Ginderachter, immunologist and cancer researcher at the Vrije Universiteit Brussel and the Flemish Institute for Biotechnology (VIB), found the answer, in collaboration with PhD student Xenia Geeraerts (VUB), Prof Sarah-Maria Fendt (VIB-KU Leuven) and Prof Jan Van den Bossche of the University of Amsterdam. The findings were published in the renowned journal Cell Reports.
Van Ginderachter: “We found that macrophages, a specific type of immune cells, use lactic acid as a source of energy. Macrophages are present in large numbers in tumours but are, as it were, misled by the tumour in order to help it grow. With the lactic acid of the cancer cells, the macrophages keep themselves alive but eventually develop into tumour-promoting cells. Under the influence of the lactic acid, the macrophages paralyse other ‘killer’ immune cells that can recognise and destroy the cancer cells, thereby helping to weaken the tumour immunity.”
Resistance to immunotherapy
The macrophages thus ultimately contribute to the resistance of tumours to immunotherapy.
“This strong presence of lactic acid in tumours can have consequences for immunotherapy,” Van Ginderachter says. “In immunotherapy, our body’s own ‘killer’ immune cells are triggered to optimally attack cancer cells. Although this therapy is very promising and works very well for skin cancer and is increasingly used for lung cancer, for example, the reality remains that only a proportion of patients respond favourably to it. One of the reasons is probably that macrophages feed on the lactic acid in the tumour and, as a result, switch off the ‘killer immune cells’ that you want to stimulate through immunotherapy. So we need to be able to suppress immune-disrupting cells, such as the macrophages, and still increase the success of immunotherapy.”
Reducing or neutralising lactic acid production
It is therefore important to look at how the formation of lactic acid in tumours can be curbed. Van Ginderachter points out that lactic acid occurs in large quantities in many different tumour types.
“Cancer cells typically produce a lot of lactic acid. And in tumours you also have regions with a very low oxygen concentration, in which lactic acid can be raised to even higher levels. You can try to prevent the production of lactic acid in tumours. This is a strategy that is already being investigated in first-stage clinical trials. However, precisely because we know that in addition to cancer cells, many other cells in the tumour produce lactic acid, it remains to be seen whether these strategies will be sufficient to reduce the lactate to such an extent that its effect on the tumour-supporting macrophages is nullified. On the other hand, one can try to neutralise lactic acid, for example, by administering a kind of buffer solution. Preliminary research on this is also under way. Another option is to use chemicals to ensure that macrophages can no longer feed on the lactic acid. It is important that such a substance is not toxic and that it makes its way to the tumour in a targeted manner. Research is also being carried out in our laboratory into these problems, so that future medicines can be delivered directly to the tumour or the macrophages, thus avoiding side effects.”
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Patients with COVID-19 in the intensive care unit (ICU) prescribed full-dose blood thinners are significantly more likely to experience heavy bleeding than patients prescribed a smaller yet equally effective dose, according to a recent University at Buffalo-led study.
The research, which compared the safety and effectiveness of blood clot treatment strategies for more than 150 critically ill COVID-19 patients at two hospitals, found that almost all patients who experienced significant bleeding were mechanically ventilated and receiving full-dose anticoagulants (blood thinners).
The results, published last month in Hospital Pharmacy, may inform treatment guidelines for blood clots in hospitalized COVID-19 patients, who are at an increased risk for both blood clots and severe bleeding. Previous reports have found that 17% of hospitalized COVID-19 patients experience blood clots, says first author Maya Chilbert, PharmD, clinical assistant professor in the UB School of Pharmacy and Pharmaceutical Sciences.
“A wide variety of practice exists when it comes to approaching blood clots in hospitalized patients with COVID-19, and there is little data to suggest improved outcomes using one strategy versus another,” says Chilbert. “Caution should be used in mechanically ventilated patients with COVID-19 when selecting a regimen to treat blood clots, and the decision to use full-dose blood thinners should be based on a compelling indication rather than lab markers alone.”
Additional investigators in the UB School of Pharmacy and Pharmaceutical Sciences include Collin Clark, PharmD, clinical assistant professor, and Ashley Woodruff, PharmD, clinical associate professor. The research was also conducted by investigators at the Buffalo General Medical Center, Millard Fillmore Suburban Hospital and Erie County Medical Center.
The study analyzed the outcome of blood clot treatments and the rate of bleeding events for more than 150 patients with COVID-19 who received either of two blood thinner regimens: a full-dose based on patient levels of D-dimer (a protein present in the blood after a blood clot dissolves), and the other a smaller but higher-than-standard dosage.
The average patient age was 58, and all experienced elevated levels of D-dimer, fibrinogen (a protein that helps the body form blood clots), and prothrombin time (a test that measures the time it takes for blood plasma to clot).
Nearly 14% of patients who received full-dose blood thinners experienced a significant bleeding event, compared to only 3% of patients who received a higher-than-standard dosage. All patients who experienced bleeding events were mechanically ventilated. No difference was reported in the regimens’ effectiveness at treating blood clots.
Further investigation is needed to determine the optimal strategy for treating blood clots and bleeding in hospitalized COVID-19 patients, says Chilbert.
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Materials provided by University at Buffalo. Original written by Marcene Robinson. Note: Content may be edited for style and length.

An international team of researchers led by Karolinska Institutet in Sweden have discovered that a cell type in the central nervous system known as oligodendrocytes might have a different role in the development of multiple sclerosis (MS) than previously thought. The findings, published in the journal Neuron, could open for new therapeutical approaches to MS.
MS is driven by immune cells attacking oligodendrocytes and the myelin they produce, which is an insulating layer ensheathing nerve cells. These attacks disrupt information flow in the brain and spinal cord and causes nerve damage that triggers symptoms associated with MS such as tremors and loss of gait.
Understanding which mechanisms influence the risk of MS is central to finding effective therapies. Previous genetic studies have found regions in the human genome that contain mutations (single nucleotide polymorphisms) associated with increased risk of MS.Many of these regions are localized near genes that are active in immune cells.
Open configuration of the genome
In this study, the researchers show in mice and human brain samples that oligodendrocytes and their progenitors have an open configuration of the genome near immune genes and at MS-risk associated regions. This suggests that the MS risk mutations may have a role in the activation of nearby genes in oligodendrocytes and their progenitors, meaning they could play a more important part than previously thought in the development of MS.
“Our findings suggest that the risk for multiple sclerosis might manifest by misfunction not only of immune cells, but also of oligodendrocytes and their precursor cells,” says Gonçalo Castelo-Branco, professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, who conducted the study with co-first authors Mandy Meijer, a PhD student, and Eneritz Agirre, a researcher. “These findings indicate that these cells can also be targeted for therapeutical approaches for MS, to prevent misfunction that might be caused by these mutations.”
The study was funded by the European Union Horizon 2020, European Committee for Treatment and Research in Multiple Sclerosis, Swedish Research Council, the Swedish Brain Foundation, the Swedish Cancer Society, Knut and Alice Wallenberg Foundation, the Swedish Society for Medical Research, the Ming Wai Lau Centre for Reparative Medicine, “La Caixa” Foundation, NIH, the National Institute on Aging, the Olav Thon Foundation and Karolinska Institutet.
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Abdominal aortic aneurysm (AAA) is a complex and life-threatening vascular disease with high incidence worldwide. Termed the silent killer, most AAAs are asymptomatic, often going undetected until rupture, and involve a poorly understood set of mechanical and biochemical events. Epidemiologic studies have established associations between AAA and both vascular inflammation and increased stiffness. That the latter is concomitant with aging explains, in part, why AAA affects almost exclusively those over 65 years of age.
Evidence suggests that abnormal acclimation of vascular smooth muscle cells (VSMC) to biomechanical perturbations, such as increased circumferential stress in hypertension, can stimulate AAA development. However, there is a paucity of knowledge of the molecular drivers of altered mechanobiological behaviors of VSMC. Understanding these might provide promising targetable signals that could repress AAA progression and limit rupture incidents.
Now, researchers at NYU Tandon and NYU Langone have demonstrated mechanobiological changes in VSMC and identified a key ion channel that is involved in the development of AAA. In a new study, in Nature Communications, they describe the means by which VSMC gradually adopt a solid-like state by upregulating cytoskeleton crosslinker, α-actinin2, which powers the mechanosensitive ion channel Piezo1.
“Our team applied biomechanical engineering to study aneurysm pathology,” explained Chen. “In contrast to the extensive study of aorta wall properties, we explored how a cell’s mechanical sensitivity, or ‘mechanosensation’ to mechanical stimuli presents an innovative perspective in revealing disease pathogenesis and progression mechanisms.”
The researchers measured misshapen VSMC with a novel ultrasound tweezers system and a single-cell RNA sequencing technique. Their findings pointed to Piezo1, which critically regulates VSMC mechanical sensitivity. They also found that inhibition of Piezo1 prevents mice from developing AAA by alleviating pathological vascular remodeling. The findings concluded that deviations of mechanosensation behaviors of VSMC is detrimental for AAA and identifies Piezo1 as a novel culprit of mechanically fatigued aorta in AAA. This could lead to new mechano-medical approaches to treating this devastating cardiovascular disease.
This research was led by Professor Weiqiang Chen’s Applied Micro-bioengineering Laboratory at NYU Tandon, and Professor Bhama Ramkhelawon’s Lab at NYU Langone. The research was supported by the National Institutes of Health and the American Heart Association.
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In a new study, the group of Johan Auwerx at EPFL’s School of Life Sciences has made the first connection between muscular dystrophy and sphingolipids, a group of bioactive lipids. The study is published in Science Advances.
Muscular dystrophy
Muscular dystrophy is an umbrella term for diseases where gene mutations result in progressive weakness and breakdown of skeletal muscles. About half of all muscular dystrophy cases involve Duchenne muscular dystrophy (DMD). DMD arises from a mutation of the gene that codes for dystrophin, a protein supports muscle structure by anchoring the cytoskeleton of muscle cells with their cytoplasm, the sarcolemma.
Mutations of dystrophin affect various biological pathways causing the hallmark symptoms of Duchenne muscular dystrophy: compromised cells membrane integrity, aberrant calcium homeostasis, chronic inflammation, fibrosis, and impaired tissue remodeling.
The sphingolipid connection
Discovered in 1870 and named after the famous Sphinx, sphingolipids are a group of bioactive lipids thought to be involved in cell signaling, and, surprisingly, many of the symptoms present in DMD. Therefore, the researchers asked whether the synthesis of sphingolipids can be altered in DMD — and if so, if they can be causally involved in the pathogenesis of DMD. To answer this, the researchers studied a mouse model of muscular dystrophy.

Dr. Stefan Schiller and Dr. Matthias Huber from the University of Freiburg’s livMatS Cluster of Excellence have succeeded in developing a muscle solely on the basis of natural proteins. The autonomous contractions of the material, which the researchers presented in the journal Advanced Intelligent Systems, can be controlled with the help of pH and temperature changes. The movements are driven by a chemical reaction that consumes molecular energy for this purpose. “Our artificial muscle is still a prototype,” says Schiller. “However, the high biocompatibility of the material and the possibility of adjusting its composition to match particular tissue could pave the way for future applications in reconstructive medicine, prosthetics, pharmaceutics, or soft robotics.”
In the past, scientists have already taken natural proteins as a basis for developing artificial muscle systems and built them into miniscule molecular machines or into polymers. However, it has not yet been possible to develop synthetic muscle materials that are entirely bio-based and move autonomously with the help of chemical energy.
Material based on the natural protein elastin
The material used by the Freiburg team is based on elastin, a natural fibrous protein that also occurs in humans, for instance giving elasticity to the skin and blood vessels. Following the model of this protein, the researchers developed two elastin-like proteins, one of which responds, for example, to fluctuations in pH, the other to changes in temperature. The scientists combined the two proteins by means of photochemical cross-linking to form a bilayered material. It is possible in this process to flexibly shape the material and set the direction of its movement.
Contractions can be switched on and off with the help of temperature changes
The researchers succeeded in inducing the rhythmic contractions by using a chemical energy source as fuel, in this case sodium sulfite. In an oscillating chemical reaction in which the pH changes in cycles due to a special linkage of several reactions, the added energy was converted into mechanical energy via non-equilibrium states of the material. In this way, the researchers induced the material to contract autonomously in a cyclical manner. They were also able to switch the contractions on and off with the help of temperature changes: The oscillating chemical reaction started at a temperature of around 20 degrees Celsius, and the material began to make rhythmic movements. In the process, it was possible to program certain states for the material to assume and to reset them again with another stimulus. The scientists thus achieved a simple system for implementing learning and forgetting at the material level.
“Since it is derived from the naturally occurring protein elastin and is produced by us through biotechnological means, our material is marked by a high sustainability that is also relevant for technical applications,” explains Schiller. “In the future, the material could be developed further to respond to other stimuli, such as the salt concentration in the environment, and to consume other energy sources, such as malate derived from biomass.”
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A study led by researchers at RCSI University of Medicine and Health Sciences and the Beaumont RCSI Cancer Centre (BRCC) has revealed a potential new way to treat secondary breast cancer that has spread to the brain, using existing drugs.
The study, published in Nature Communications, was funded by Breast Cancer Ireland with support from Breast Cancer Now and Science Foundation Ireland.
Most breast cancer related deaths are a result of treatment relapse leading to spread of tumours to many organs around the body. When secondary breast cancer, also known as metastatic breast cancer, spreads to the brain it can be particularly aggressive, sometimes giving patients just months to live.
The RCSI study focused on genetically tracking the tumour evolution from diagnosis of primary breast to the metastatic spread in the brain in cancer patients. The researchers found that almost half of the tumours had changes in the way they repair their DNA, making these tumours vulnerable to an existing type of drug known as a PARP inhibitor. PARP inhibitor drugs work by preventing cancer cells to repair their DNA, which results in the cancer cells dying.
“There are inadequate treatment options for people with breast cancer that has spread to the brain and research focused on expanding treatment options is urgently needed. Our study represents an important development in getting one step closer to a potential treatment for patients with this devastating complication of breast cancer,” commented Professor Leonie Young, the study’s Principal Investigator.
“By uncovering these new vulnerabilities in DNA pathways in brain metastasis, our research opens up the possibility of novel treatment strategies for patients who previously had limited targeted therapy options,” said study author Dr Damir Varešlija.
The research, led by Beaumont RCSI Cancer Centre investigators Professor Leonie Young, Dr Nicola Cosgrove, Dr Damir Varešlija and Professor Arnold Hill, was carried out in collaboration with the Mayo Clinic and University of Pittsburgh, USA.
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