So many men in Chichigalpa, Nicaragua, have died from kidney failure, the town is known as the Island of the Widows. The condition that afflicts them — called chronic kidney disease of unknown origin, or CKDu — is, as its name implies, a mystery. It is a tubulointerstitial kidney disease that affects people everywhere. But researchers don’t know why rates are much higher in low-lying, hot agricultural areas like Chichigalpa, which is surrounded by sugarcane fields.
Shuchi Anand, MD, a Stanford Medicine associate professor of nephrology, has been interested in the disease since it was first described in the 1990s.
“Two-thirds of the people with this disease are men, many in their 30s and 40s,” said Anand, who is the director of the Center for Tubulointerstitial Kidney Disease. “This is the prime age of work and income generation. They are the breadwinners. This disease can devastate families.”
Researchers at Ruhr University Bochum, Germany, identified a receptor that plays a crucial role in stress-induced motor incoordination associated with ataxias. These hereditary motor disorders have long been linked to the neurotransmitter norepinephrine.
The team, led by Dr. Pauline Bohne and Professor Melanie Mark from the Behavioral Neurobiology Working Group in Bochum, has now shown that the α1D norepinephrine receptor in the cerebellum is responsible for the symptoms. The team published these findings in the journal Cellular and Molecular Life Sciences on October 6, 2025.
People with ataxia experience recurring episodes of motor incoordination, also known as dystonia. These phases are triggered by various factors, such as physical or emotional stress, fever, alcohol, or caffeine. The episodes are triggered by the release of norepinephrine in the cerebellum, which is the most important brain region for coordinating movement. Currently, there is no cure for ataxia. Therefore, researchers want to gain a better understanding of the underlying mechanisms to find new treatment approaches.
The aim of immunotherapy strategies is to leverage cells in the patient’s own immune system to destroy tumor cells. Using a preclinical model, scientists from the Institut Pasteur and Inserm successfully stimulated an effective anti-tumor immune response by reprogramming the death of malignant B cells. They demonstrated an effective triple-therapy approach for treating forms of blood cancer such as certain lymphomas and leukemias which affect B cells. The study was published on August 15 in the journal Science Advances.
Immunotherapy strategies represent a major breakthrough in cancer treatment. They aim to harness the patient’s immune system so that their own cells can recognize and specifically eliminate tumor cells. Immune cells can act like sentinels, scanning the body and identifying all residual tumor cells to reduce the risk of relapse. Various novel immunotherapy strategies are emerging, one of which makes use of a cell death mechanism known as necroptosis. Unlike apoptosis, which results in silent cell death, necroptosis releases warning signals that attract and stimulate immune cells so that they can kill any remaining tumor cells.
Scientists from the Dynamics of Immune Responses Unit (a joint Inserm/Institut Pasteur unit) set out to explore the effectiveness of this necroptosis-based immunotherapy strategy on hematological malignancies. They began by observing that necroptosis cannot be easily induced in malignant B cells because of the absence of the MLKL protein.
The advent of genetically edited porcine-to-human xenotransplantation has predominantly focused on cardiac and renal applications, with no reported cases of porcine-to-human liver xenotransplantation. This study presents the world’s first successful genetically modified pig auxiliary liver xenotransplantation in a living human, achieving an unprecedented survival of 171 days, and provides valuable insights into the critical factors influencing the procedure’s success.
Several reports demonstrate T and B lymphocyte accumulation in the aortic adventitia in normal (9) and atherosclerotic vessels (9, 85, 86). Adoptive transfer experiments suggest that lymphocytes accumulate in the adventitia through the migration from the adventitial vasa vasorum rather than from the intimal lumen site (9). Local revascularization correlates with an increase in cellular composition within vulnerable regions of human atherosclerotic plaques (Figure 1). In contrast, the inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis (87). Recently, investigators have shown that vasa vasorum can penetrate the media, enter atherosclerotic plaques, and come close to the arterial lumen (88). This is an important direct demonstration of the existence of a vascular network connecting the adventitia with the plaque tissue. Thus, we now better understand the role of neovascularization in atherosclerosis (87), but further studies are necessary to elucidate the role of small adventitial vessels in the immune response during this disease.
The presence of antigen-presenting cells and T cells within atherosclerosis-prone artery walls is well documented, but there is little information about local antigen-dependent activation of T cells. It remains to be determined whether elevated numbers of lymphocytes, which have been seen in atherosclerotic vessels, are a consequence of the accelerated recruitment of activated cells from draining lymph nodes or of local antigen-induced proliferation that leads to the increased aortic lymphocyte numbers.
One of the possible sites of T cell activation in aorta may be vascular-associated tertiary lymphoid structures (Figure 1). The lymphoid-like structures are formed in a variety of autoimmune-mediated diseases, such as rheumatoid arthritis or Hashimoto’s thyroiditis. Conglomerates of leukocytes within the adventitia were reported in the early 1970s; however, only in 1997 did Wick et al. (44) name these conglomerates vascular-associated lymphoid tissues (VALTs). These lymphoid structures are formed within advanced atherosclerosis-prone vessels and contain T and B lymphocytes, plasma cells, CD4+/CD3− inducer (LTi) cells, and some MECA-32+ and HECA-452+ microvessels (9, 86, 89). Follicles located close to the arterial external elastic lamina contain proliferating Ki67+ leukocytes, apoptotic cells, and CD138+ plasma cells, showing local B cell maturation and possible humoral immune response in these structures (86). Whether the VALTs in atherosclerosis are beneficial or proatherogenic is still unclear.
The mammarenavirus matrix Z protein plays critical roles in virus assembly and cell egress. Meanwhile, heterotrimer complexes of a stable signal peptide (SSP) together with glycoprotein subunits GP1 and GP2, generated via co-and post-translational processing of the surface glycoprotein precursor GPC, form the spikes that decorate the virion surface and mediate virus cell entry via receptor-mediated endocytosis. The Z protein and the SSP undergo N-terminal myristoylation by host cell N-myristoyltransferases (NMT1 and NMT2), and G2A mutations that prevent myristoylation of Z or SSP have been shown to affect the Z-mediated virus budding and GP2-mediated fusion activity that is required to complete the virus cell entry process.
Research led by the Max Planck Institute for Biology of Aging in Cologne reports that misincorporation of ribonucleotides into mitochondrial DNA (mtDNA) initiates an inflammatory cascade.
Mitochondria support cell survival through metabolic and signaling roles. Conversely, their disruption has been associated with inflammation, cell death and disease.
Innate immune activation through the cGAS-STING-TBK1 pathway can move a cell from short-term defense to a chronic state of alarm. cGAS-STING activity is linked to autoimmune and inflammatory diseases and contributes to senescence and aging, intertwining immune signaling with tissue decline.
