Jerusalem Institute for Israel Studies

Aging is a complex multifactorial process that affects cellular function and tissue homeostasis over time. Despite extensive research, the molecular mechanisms driving cellular aging remain poorly understood. Many studies have focused on changes in DNA methylation as an indicator of aging. In particular, the degree of methylation at polycomb CpG islands has been shown to be predictive of phenotypic changes associated with aging. Since many age-related pathological processes, are thought to be of single-cell origin (e.g. cancer), we questioned whether polycomb DNA methylation also occurs preferentially in a subset of cells within the overall population. Using single-cell whole-genome methylation data from multiple ages and tissues, we identify Average Polycomb CpG Methylation as a hallmark of cellular aging. This revealed that aging occurs at varying rates within specific cells, with faster proliferating cells showing accelerated levels. Gene expression analysis in "young" and "old" single cells identified changes in immune response, translation regulation, tumorigenesis, neurodegeneration and other cellular processes associated with aging. These results challenge traditional models of homogeneous cellular aging and suggest that aging itself is a highly individualized process at the single-cell level that may be driven by programmed changes in polycomb CpG island DNA methylation.

Publisher of over 50 scientific journals across the life, physical, earth, and health sciences, both independently and in partnership with scientific societies including Cell, Neuron, Immunity, Current Biology, AJHG, and the Trends Journals.

Genomic imprinting, an epigenetic process resulting in parent-specific gene expression, is essential for normal development and growth. Disruption of imprinting leads to various developmental disorders and cancers, yet our understanding of the full repertoire of imprinted genes in humans remains incomplete. Here, we utilised androgenetic, parthenogenetic and biparental human embryonic stem cells and their neural derivatives to identify novel imprinted genes by analysing their methylome and transcriptome profiles. Our analysis revealed 12 novel putative imprinted genes distributed across four distinct loci, with six of them clustered in an uncharacterised imprinted region on chromosome 19. We identified potential imprinting control regions regulating this novel cluster, suggesting a coordinated regulatory mechanism. Notably, these imprinted genes are enriched in cancer-related pathways, with several showing isoform-specific imprinting patterns. Our analysis also revealed consistent DNA methylation aberrations in pluripotent stem cells at specific imprinted loci, highlighting potential epigenetic instability during culturing. These findings contribute to our understanding of genomic imprinting regulation in human development and highlight potential genomic regions for further investigation of imprinting-related disorders.

Metal‐based anticancer agents offer unique opportunities to integrate multiple therapeutic modalities within a single molecular framework. Herein, we present the first Osmium(II)‐Platinum(IV)‐Ceritinib conjugate (Os‐Pt‐Cer) that synergistically combines photodynamic therapy (PDT), chemotherapy, and immunotherapy via immunogenic cell death (ICD) induction. This heterobimetallic complex features a photoactive osmium(II) polypyridyl core, a platinum(IV) prodrug derived from oxaliplatin, and the kinase inhibitor ceritinib as an axial ligand. Upon deep‐red irradiation (λ = 740 nm), the conjugate exhibits potent antiproliferative activity in ovarian 2D cancer cells and 3D tumour spheroids, with IC50 values in the low nanomolar range. In addition, Os‐Pt‐Cer effectively inhibits cancer cell migration. Mechanistic studies reveal that the conjugate induces hallmarks of ICD, including calreticulin exposure, ATP release, HMGB1 secretion and phagocytosis. This multifunctional approach highlights the potential of osmium(II)‐platinum(IV) conjugates as promising candidates for overcoming resistance and immune evasion in high‐grade ovarian carcinoma.

Marine heatwaves (MHWs) are intensifying, posing an increasing threat to coral reefs globally. Despite warming faster than the global average, the Gulf of Aqaba (GoA, Northern Red Sea) has been regarded as a climate refuge for corals. In this study, we analyzed coral-algae symbiosis integrity based on algal densities, chlorophyll content, and host and symbiont energy reserves (proteins, carbohydrates, lipids) of tagged colonies of Stylophora pistillata and Pocillopora damicornis throughout four consecutive summers characterized by moderate (2022), strong (2021, 2023), and severe (2024) MHWs. The 2024 MHW, lasting 113days, was exceptional, with sea surface temperatures reaching 32.6°C, 3.4°C above the long-term climatology, and accumulating 30 Degree Heating Weeks, the highest recorded globally during 2024. Nonetheless, S. pistillata and P. damicornis persisted without bleaching, while maintaining stable host energy reserves and higher symbiont carbohydrates in 2024 compared to previous summers. To assess potential species-specific responses, we additionally monitored Seriatopora hystrix, Porites spp., and Cyphastrea spp. colonies before, during, and after the severe 2024 MHW. All monitored colonies endured the unprecedented thermal stress without bleaching or photosynthetic impairment. Porites spp. displayed metabolic tolerance with stable values throughout the event. Only Cyphastrea spp. showed significant symbiont reduction (-55%) during peak stress, recovering by January 2025. As climate change places 44% of reef-building corals at risk of extinction, our findings highlight the resilience of GoA corals. However, emerging shallow bleaching suggests that this refuge may be approaching its limit, underscoring the urgent need for regional conservation efforts.

Some of Spain’s greatest humanists—Juan Luis Vives, Antonio de Nebrija, Juan de Ávila, Luis de León, and Benito Arias Montano—were from a converso background. Recent scholarship suggests that two of the three most influential religious movements in sixteenth-century Spain—Juan de Ávila’s evangelical movement and Teresa of Ávila’s Barefoot Carmelites—were founded by conversos and presented converso membership, whose winds of religious innovation to tame Christian Orthodoxy and Counter-Reformation Spanish society, through the influence of Italian Humanism and reform, prioritized spiritual practice, social toleration, and religious concord. Indeed, Santa Teresa de Ávila, a major innovator within the Spanish Church, was herself from a converso family with Jewish ancestry. She became a key female theologist who transcended as an identity marker of the Spanish Baroque, conceived as quintessential of the Spanish Golden Age. Coopted in different periods, she “reappeared” in the 1930s as Patron of the Sección Femenina de la Falange y de las JONS, the women’s branch of the new radical right, turning into a role model of femininity for highly conservative religious women. Consecrated as “Santa de la Raza”, she became the undisputable womanized icon of the so-called “Spanish Crusade”, the slogan which General F. Franco implemented, with the approval of the Spanish Catholic Church, to re-cast in a pseudo-theological narrative the rebellion against the Spanish Second Republic in July 1936. This article examines different appropriations of the figure of Teresa de Ávila as a pillar of “Hispanidad”, in the last centuries within the changing sociopolitical contexts and theological debates in which this instrumentalization appeared. By highlighting the plasticity of this converso figure, the article suggests possible lines of research regarding the Jewish origins of some national icons in Spain.

Abstract Thermal pollution, whether local or driven by global warming, threatens biodiversity in part through its detrimental effects on reproduction. Non-coding small RNAs (sRNAs) are crucial for maintaining germline developmental robustness under heat stress. Remarkably, we uncovered that neuronal sRNAs regulate germ cells’ thermotolerance, affecting both spermatogenic and oogenic germline in a cell non-autonomous manner. Furthermore, we demonstrate that an oxygen-sensing neural circuit antagonizes germline maintenance, likely reflecting the nematode’s innate association of reduced oxygen levels with food availability and reproductive permissive environments. Finally, we provide evidence that sRNAs buffer the negative consequences of laboratory domestication, which otherwise cause the laboratory strain to lose germline integrity and become sterile at elevated temperatures. Hence, our findings reveal that mere sensory perception, independent of direct environmental change, modulates germline integrity through sRNA pathways, highlighting a novel mechanism by which neural circuits integrate environmental information to safeguard reproductive fitness in fluctuating environments.

This study elucidates a rights-based participatory methodology of a qualitative research that explored the experiences with sociopolitical stress and coping strategies among Palestinian children and youth. The first author recruited and facilitated a Children and Youth Advisory Group (CYAG) of seven Palestinian adolescents (aged 13–19) from East Jerusalem, most of whom were enrolled in secondary education and demonstrated high levels of educational engagement. The Lundy Model for child participation (2007), which emphasizes Voice, Space, Audience, and Influence, guided the participatory framework. While the Model offers general principles, concrete mechanisms for involving children as co-researchers, as well as the facilitators and barriers to their meaningful engagement, remain underdeveloped. Concrete knowledge is particularly scant concerning co-researching with children belonging to marginalized ethnic groups during periods of protracted conflict and war. This article addresses that gap through a step-by-step analysis of work with the CYAG and offers novel insights into the challenges and ethical considerations in research with children during a critical period of war and restricted freedom of expression, including concerns around privacy, trust, and both legal and emotional safety. The findings underscore the value of a child’s cultural and generational expertise in shaping context-sensitive methodologies and in fostering authentic participation through power-sharing, aligning competence with advocacy, and maintaining safety without compromising spontaneity. These methodological insights aim to support researchers pursuing participatory and rights-respecting research with children in the context of conflict, oppression, and extreme marginalization.