This research article investigates the mechanistic link between high iron levels and the development of colorectal cancers (CRCs), focusing on the reactivation of telomerase, an enzyme associated with cellular immortalization. The authors identify Pirin, an iron-sensing protein, as a crucial mediator that binds with oxidized iron (Fe3+) to reactivate the human telomerase reverse transcriptase (hTERT) subunit. This finding provides a molecular explanation for the known association between high dietary iron intake (such as red meat consumption) and increased CRC risk. Furthermore, the study pinpoints a small molecule, SP2509, which inhibits this process by competing with Fe3+ for binding to Pirin, suggesting a novel therapeutic approach for targeting telomerase-driven cancers, particularly those of the CMS3 subtype. The mechanism involves iron-activated Pirin stabilising the transcription factor Sp1 by repressing the E3 ubiquitin ligase FBXW7, which consequently drives hTERT expression.
Research paper:
Shanmugam R, Majee P, Shi W, Ozturk MB, Vaiyapuri TS, Idzham K, Raju A, Shin SH, Fidan K, Low JL, Chua JYH, Kong YC, Qi OY, Tan E, Chok AY, Seow-En I, Wee I, Macalinao DC, Chong DQ, Chang HY, Lee F, Leow WQ, Murata-Hori M, Xiaoqian Z, Shumei C, Tan CSH, Dasgupta R, Tan IB, Tergaonkar V. Iron (Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers. Cancer Discov. 2024 Oct 4;14(10):1940 1963.
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This academic paper explores the impact of parenting styles, specifically harsh and warm approaches, on adolescent brain architecture and subsequent mental health outcomes in early adulthood. It investigates whether these associations are dependent on the child's developmental stage, early, middle, or late childhood, rather than simply accumulating over time. The study found that psychological aggression in early childhood was linked to widespread changes in brain organisation, while later aggression affected specific emotional regulation circuits. Conversely, warm parenting during middle childhood was associated with positive changes in corticolimbic regions, which, in turn, predicted lower anxiety and depression in young adults, even during the stress of the COVID-19 pandemic. These findings highlight the importance of timing and type of parental intervention for supporting neurodevelopment and long-term well-being.
Research paper:
Michael C, Gard AM, Tillem S, Hardi FA, Dunn EC, Smith ADAC, McLoyd VC, Brooks-Gunn J, Mitchell C, Monk CS, Hyde LW. Developmental Timing of Associations Among Parenting, Brain Architecture, and Mental Health. JAMA Pediatrics. 2024 Dec 1;178(12):1326-1336.
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This article provides an overview of DNA methylation aging clocks, which are molecular tools used to measure an individual's age based on specific chemical modifications to their DNA. The authors discuss the current understanding and significant challenges in utilising these clocks, particularly in distinguishing between chronological age and biological aging. They also explore the utility of tissue- and disease-specific clocks and the importance of integrating epigenetics into large-scale longitudinal population studies to better understand aging dynamics. This paper then addresses the need for broader genome-wide analyses and the exploration of other epigenomic marks, as well as the potential and challenges of single-cell analysis to uncover cellular heterogeneity in aging. Finally, the authors emphasise the necessity of robust non-human data for mechanistic insights and the critical ethical and legal frameworks required for responsible application of these technologies.
Review paper:
Bell, C.G., Lowe, R., Adams, P.D. et al. DNA methylationaging clocks: challenges and recommendations. Genome Biol 20, 249 (2019)
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This research article investigates the long-term effects of early-life sugar intake on the development of type 2 diabetes and hypertension. Utilising a natural experiment from the end of sugar rationing in the UK in 1953, the study compares adults with varying levels of sugar exposure during their first 1000 days. The findings suggest that restricted sugar intake in early life significantly reduced the risk and delayed the onset of both conditions. This highlights the critical impact of early nutrition on lifelong metabolic health, with in-utero sugar restriction also showing a protective effect.
Review paper:
Gracner T, Boone C, Gertler PJ. Exposure to sugar rationing in the first 1000 days of life protected against chronic disease. Science. 2024 Nov 29;386(6725):1043-1048.
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This review article thoroughly examines vaccine reactogenicity, which encompasses the common, often mild, inflammatory responses individuals experience post vaccination, such as soreness or fever. The authors explore the underlying biological mechanisms that cause these reactions, detailing how the body's immune system responds to vaccine components. Furthermore, the paper investigates various factors that can influence reactogenicity, including host characteristics, vaccine composition, and administration techniques. Ultimately, the article aims to enhance understanding among healthcare professionals and the public to maintain confidence in vaccination programmes by managing expectations and mitigating anxiety related to side effects.
Review paper:
Hervé, C., Laupèze, B., Del Giudice, G. et al. The how’s and what’s of vaccine reactogenicity. npj Vaccines 4, 39 (2019).
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This research investigated the connection between the Dietary Inflammatory Index (DII) and the risk of all-cause mortality in adults with coronary heart disease (CHD) using data from a national health survey. The study found that higher DII scores, indicating a more pro-inflammatory diet, were associated with a greater risk of death in these patients. Notably, this association appeared stronger in women with CHD. The findings suggest that managing dietary inflammation could be an important factor in improving outcomes for individuals with CHD, particularly for females. However, due to the study's design, further research is needed to confirm a direct cause-and-effect relationship.
Research paper:
Wang, E., Fang, C., Zhang, J. et al. Association between dietary inflammatory index and all-cause mortality risk in adults with coronary heart disease in the United States. Sci Rep 14, 23998 (2024).
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This research article investigates how long-term memories persist despite the turnover of brain molecules. The study reveals that a protein called KIBRA physically interacts with the enzyme PKMζ at synapses activated during learning. This KIBRA-PKMζ complex acts as a stable anchor, maintaining the synaptic changes underlying memory storage. Blocking this interaction with specific inhibitors disrupts established long-term potentiation and erases both recent and remote memories in animal models, highlighting the crucial role of this continuous molecular coupling in memory maintenance.
Review paper:
Tsokas P, Hsieh C, Flores-Obando RE, Bernabo M, Tcherepanov A, Hernández AI, Thomas C, Bergold PJ, Cottrell JE, Kremerskothen J, Shouval HZ, Nader K, Fenton AA, Sacktor TC. KIBRA anchoring the action of PKMζ maintains the persistence of memory. Sci Adv. 2024 Jun 28;10(26):eadl0030.
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This research investigated the durability of SARS-CoV-2 specific plasma cells generated after mRNA vaccination by examining bone marrow samples. The study found that, unlike influenza and tetanus, SARS-CoV-2-specific antibody secreting cells were largely absent from the long-lived plasma cell compartment in the bone marrow up to 33 months post-vaccination. Consequently, the waning of SARS-CoV-2 serum antibodies observed after vaccination could be attributed to this lack of establishment in the long lived compartment. The findings suggest that mRNA vaccines for SARS-CoV-2 do not induce the same durable plasma cell response in bone marrow as traditional vaccines, offering a potential explanation for the relatively short-livedprotection against infection. This highlights the need for strategies to improve the longevity of antibody responses elicited by SARS-CoV-2 vaccines.
Research paper:
Nguyen, D.C., Hentenaar, I.T., Morrison-Porter, A. et al. SARS CoV-2-specific plasma cells are not durably established in the bone marrow long-lived compartment after mRNA vaccination. Nat Med 31, 235–244 (2025).
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This research introduces a novel biosensing strategy using surface-enhanced Raman spectroscopy (SERS) for the multiplexed detection of serum cardiac markers, crucial for diagnosing acute myocardial infarction. The method employs a specially designed plasmonic metasurface with enhanced electric and magnetic fields to improve SERS signal consistency. Furthermore, it utilises nanomechanical perturbations to transduce signals as frequency shifts, overcoming limitations associated with SERS intensity fluctuations. By integrating this metasurface with 3D-printed microfluidics, the study demonstrates a single-antibody-based assay capable of simultaneously and specifically detecting multiple cardiac biomarkers in serum samples, presenting a significant advancement in quantitative optical diagnostics.
Research paper:
P. Zheng, L. Wu, P. Raj, J. H. Kim, S. K. Paidi, S. Semancik, I. Barman, Multiplexed SERS Detection of Serum Cardiac Markers Using Plasmonic Metasurfaces. Adv. Sci. 2024, 11, 2405910.
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This scientific review from Molecular Medicine explores the intricate link between diabetes mellitus and its cardiovascular complications, focusing on the emerging role of epigenetic modifications such as DNA methylation and histone alterations. The authors highlight how these heritable changes in gene function, influenced by environmental factors like hyperglycaemia, contribute to the pathophysiological mechanisms and the "metabolic memory" seen in diabetic vascular damage. Furthermore, the article discusses potential therapeutic strategies targeting these epigenetic processes, including “epidrugs” like BET inhibitors and the observed epigenetic activity of existing antidiabetic medications, ultimately considering the future of personalised epigenetic therapies for diabetes-related cardiovascular disease.
Research paper:
Damiano, G., Rinaldi, R., Raucci, A. et al. Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies. Mol Med 30, 161 (2024).
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This study investigated the connection between prior infections and long-term brain health. The study found that a history of infections like influenza and herpes viruses is associated with accelerated brain volume loss in specific regions and an increased risk of developing dementia. By analysing blood proteins, the researchers identified immunological drivers that may mediate this link between infection and neurodegeneration. Furthermore, genetic analysis suggested a potential causal role for certain infection-related proteins in brain atrophy, highlighting possible pathways for future interventions.
Research paper:
Duggan, M.R., Peng, Z., Sipilä, P.N. et al. Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline. Nat Aging 4, 1263–1278 (2024).
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This research used CRISPR–Cas9 screening in mice to identify genes that regulate the activation of neural stem cells (NSCs) during ageing. They discovered several gene knockouts, particularly those involved in cilium organisation and glucose import, that could restore the function of old NSCs both in vitro and in vivo. Notably, the knockout of Slc2a4 (GLUT4), a glucose transporter, significantly improved NSC activation and the production of new neurons in older brains. The study found that glucose uptake increases in NSCs with age, and reducing this uptake, either genetically or through starvation, could rejuvenate old NSCs. This work establishes valuable screening platforms for uncovering genetic interventions to counter age-related regenerative decline in the brain.
Research paper:
Ruetz, T.J., Pogson, A.N., Kashiwagi, C.M. et al. CRISPR–Cas9 screens reveal regulators of ageing in neural stem cells. Nature 634, 1150–1159 (2024).
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This research paper explores the genetic basis of the human sex ratio at birth, which is the proportion of males to females. It challenges a long-held scientific principle, known as Fisher’s principle, which suggests that the sex ratio should naturally converge to 50/50 through natural selection. The authors argue that previous studies were underpowered and unable to detect genetic variations in sex ratio due to significant measurement errors associated with the relatively small number of offspring per human. The research involved a large-scale genome wide association study (GWAS) using data from the UK Biobank, which yielded a single significant SNP associated with a reduced sex ratio. Despite this, the authors found that the heritability of sex ratio is effectively zero, likely due to measurement error. Through simulations of human sex ratio evolution under different selection pressures, the authors demonstrate that their observations are compatible with Fisher's principle, suggesting the possibility of multiple, but mostly small effect, sex ratio-influencing genes segregating in the human population.
Research paper:
Song Siliang and Zhang Jianzhi 2024In search of the genetic variants of human sex ratio at birth: was Fisher wrong about sex ratio evolution? Proc R Soc B 291:20241876
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This study investigates the association between frailty and cardiovascular disease (CVD) in three large, prospective cohorts from China, the UK, and the USA. The researchers assessed participants' frailty status using the Rockwood frailty index, taking into account changes in frailty over time. The findings show that frailty progression, particularly from robust to pre-frail or frail, significantly increases the risk of incident CVD, while frailty recovery, specifically from frail to robust or pre frail, decreases CVD risk. This research suggests that frailty is a modifiable risk factor for CVD and highlights the importance of early intervention to prevent frailty progression and promote recovery from frailty.
Research paper:
He D, Wang Z, Li J, Yu K, He Y, He X, Liu Y, Li Y, Fu R, Zhou D, Zhu Y. Changes in frailty and incident cardiovascular disease in three prospective cohorts. Eur Heart J. 2024 Mar 27;45(12):1058-1068. Erratum in: Eur Heart J. 2024 May 21;45(19):1768.
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This review from the European Heart Journal focuses on the use of Mendelian randomization (MR) in cardiovascular epidemiology. MR leverages genetic variants to uncover causal relationships between modifiable risk factors and various cardiovascular diseases (CVDs). By drawing parallels to randomized controlled trials (RCTs), the authors explore the principles, advantages, and limitations of MR. The article also examines MR applications in predicting the efficacy and safety of drugs targeting CVD risk factors and explores the repurposing potential of existing medications.
Research paper:
Larsson SC, Butterworth AS, Burgess S. Mendelian randomization for cardiovascular diseases: principles and applications. Eur Heart J. 2023 Dec 14;44(47):4913-4924.
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This systematic review examines the ways healthcare systems are contributing to climate change and explores strategies and tactics to reduce their carbon footprint. The authors analyzed 205 studies, reports, and frameworks from 18 years of research to identify themes and overarching strategies for mitigating the impact of healthcare on the environment. The review also identifies key areas for policy and practice, including the need for effective governance, robust measuring tools, and the implementation of decarbonisation tactics like changing clinical and surgical practices, reducing waste, and minimising travel.
Research paper:
Braithwaite J, Smith CL, Leask E, Wijekulasuriya S, Brooke-Cowden K, Fisher G, Patel R, Pagano L, Rahimi Ardabili H, Spanos S, Rojas C, Partington A, McQuillan E, Dammery G, Carrigan A, Ehrenfeld L, Coiera E, Westbrook J, Zurynski Y. Strategies and tactics to reduce the impact of healthcare on climate change: systematic review. BMJ. 2024 Oct 8;387:e081284.
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This study, conducted by the Prospective Physical Activity, Sitting, and Sleep (PROPASS) consortium, looked at the relationship between various movement behaviours and cardiometabolic health outcomes. They analysed data from over 15,000 participants from six studies across five countries using thigh-worn accelerometers to track movement behaviour. The study found that increasing time spent in moderate-to vigorous physical activity was the most strongly associated with better cardiometabolic health outcomes. The study also found that standing, and to a lesser extent light-intensity physical activity, may have some benefits. However, they found that increasing sedentary behaviour was consistently associated with poorer outcomes.
Research paper:
Blodgett JM, Ahmadi MN, Atkin AJ, Chastin S, Chan HW, Suorsa K, Bakker EA, Hettiarcachchi P, Johansson PJ, Sherar LB, Rangul V, Pulsford RM, Mishra G, Eijsvogels TMH, Stenholm S, Hughes AD, Teixeira-Pinto AM, Ekelund U, Lee IM, Holtermann A, Koster A, Stamatakis E, Hamer M; ProPASS Collaboration. Device-measured physical activity and cardiometabolic health: the Prospective Physical Activity, Sitting, and Sleep (ProPASS) consortium. Eur Heart J. 2024 Feb 7;45(6):458-471.
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This article discusses the shortcomings of current methods for recording harms in behavioural change intervention trials, which primarily rely on definitions designed for drug trials. The authors argue that these definitions can miss important harms specific to behavioural interventions, leading to inefficient recording practices. They propose evidence-based recommendations for identifying and recording potential harms, encompassing a multidisciplinary approach, involving stakeholders, and incorporating a range of data collection methods. These recommendations aim to improve transparency, efficiency, and the overall understanding of potential risks and benefits of these interventions.
Research paper:
Papaioannou D, Hamer-Kiwacz S, Mooney C, Sprange K, Cooper C, O'Cathain A et al. Recommendations on recording harms in randomised controlled trials of behaviour change interventions BMJ 2024; 387:e077418
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This research paper examines the current state of knowledge surrounding the evolution of eukaryotic cells, which are more complex than their prokaryotic counterparts. The paper focuses on the two key events involved in eukaryogenesis: the evolution of the host cell, which is now believed to be closely related to Asgard archaea, and the acquisition of mitochondria, which are thought to have originated from a free-living bacterium. The authors discuss the different hypotheses surrounding the timing and nature of these events and highlight the advancements made possible by metagenomic sequencing and phylogenetic analyses. They also explain the ongoing research on the functional roles of eukaryotic signature proteins (ESPs) found in Asgard archaea and propose future research avenues that will help us understand the enigmatic origins of the eukaryotic cell.
Research paper:
Vosseberg, J., van Hooff, J.J.E., Köstlbacher, S. et al. The emerging view on the origin and early evolution of eukaryotic cells. Nature 633, 295–305 (2024).
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This article examines the complex relationship between mobile connectivity and well-being. The author argues that achieving digital well-being requires a delicate balance between the benefits and drawbacks of ubiquitous connectivity. The article then proposes a dynamic systems model of digital wellbeing, suggesting that it is influenced by person, device, and context specific factors. This model highlights the importance of considering the interconnectedness of various elements, rather than focusing solely on-screen time as a primary cause of problems. The author also discusses the implications of this dynamic systems model for research methodologies and advocates for the use of more sophisticated approaches, such as device logging and mobile experience sampling, to capture the nuances of digital well-being.
Research paper:
Mariek M P Vanden Abeele, Digital Wellbeing as a Dynamic Construct, Communication Theory, Volume 31, Issue 4, November 2021, Pages 932–955.
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