Giovanna Masala | Search PubMed

PubMed2026

Mycoplasma and Bartonella in cats from the tropical tourist Gili Islands, Indonesia.

Bartonella spp. and haemotropic Mycoplasma spp. are important vector-borne bacteria of veterinary and zoonotic relevance, yet information on their circulation in Indonesian island ecosystems remains limited. We investigated their occurrence and molecular diversity in 117 domestic and free-roaming cats from the Gili Islands, Indonesia, using full-length 16S rRNA nanopore metagenomics followed by targeted PCR, sequencing, phylogenetic analysis and multilocus sequence typing (MLST). Bartonella DNA was detected in 18/117 (15.4%) cats and haemotropic Mycoplasma DNA in 40/117 (34.2%). Sequence analysis identified Bartonella henselae as the predominant species together with Bartonella clarridgeiae. MLST of B. henselae revealed three sequence types (ST1, ST16 and ST42), with ST1, a lineage reported in both feline and human isolates, predominating. Comparison with the PubMLST database showed significant geographical differences in the distribution of ST1 and ST42, supporting regional variation in the circulation of B. henselae lineages. Haemoplasma characterization identified Candidatus Mycoplasma haemominutum, Mycoplasma haemofelis, Candidatus Mycoplasma turicensis and a Mycoplasma feliminutum-like organism, comprising ten distinct sequence variants. Haemoplasma positivity was significantly associated with age, with adults showing higher positivity than younger animals (P < 0.001), whereas Bartonella infection was not associated with age, sex or island of origin. The detection of zoonotically relevant B. henselae lineages and the genetic diversity of feline haemoplasmas provide evidence of the circulation of vector-borne bacteria among cats in this tropical island ecosystem. These findings provide the first molecular epidemiological baseline for this region and contribute to understanding the circulation and genetic diversity of feline vector-borne pathogens in Southeast Asia.

Animals↗

PubMed2026

Proteomics of multimorbidity progression across cardiometabolic diseases and cancer in a multinational cohort.

BACKGROUND: Multimorbidity, defined here as the co-occurrence of cardiovascular disease (CVD), type 2 diabetes (T2D), and/or cancer is a major public health challenge. However, its underlying biological mechanisms remain unclear, limiting progress toward identifying shared interventional targets. METHODS: We applied large-scale plasma proteomics (SomaScan 7k; 7,289 aptamers) in 13,270 European Prospective Investigation into Cancer and Nutrition (EPIC) participants to identify protein signatures of multimorbidity. We modelled multimorbidity progression as sequential disease transitions, i.e., from the disease-free state at baseline to a first disease and from the first disease to a second disease. Using weighted multivariable Cox regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for risk of cancer, CVD, and T2D. Risk associations were replicated using Olink proteomics in UK Biobank (N = 44,567). RESULTS: We identified 422 aptamers associated with more than one disease (FDR-corrected P < 0.05), e.g., 265 aptamers were shared between CVD and T2D. Thirty-eight aptamers were associated with multimorbidity progression. Among these, 27 aptamers showed consistent positive associations across sequential disease transitions, including SEMA6A (disease-free to cancer HR: 1.14; 95% CI 1.05, 1.23; cancer to T2D HR: 2.61; 95% CI 1.76, 3.80). Four aptamers showed consistent inverse associations, including NLGN1 (disease-free to T2D HR: 0.72; 95% CI 0.61, 0.84; T2D to cancer HR: 0.57; 95% CI 0.43, 0.75). Nineteen of the identified proteins were also measured in UK Biobank, with broadly consistent associations. CONCLUSIONS: This study identifies candidate proteins that may indicate molecular pathways to multimorbidity of cardiometabolic diseases and cancer. Future studies should evaluate the causal roles of these proteins for targeted interventions and risk stratification.

Humans↗

PubMed2025

Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form. METHODS: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan). Cox proportional hazards models based on 4,567 participants (including 172 incident ALS cases) were used to identify protein biomarkers associated with future ALS diagnosis. Top results were indirectly validated in two independent case-control studies of prevalent ALS (n=417 ALS, 852 controls). Functional annotation included cross-disease comparisons, gene set and tissue enrichment testing, organ-specific proteomic clocks, and the application of large-language models (LLM). FINDINGS: Five proteins (SECTM1, CA3, THAP4, KLHL41, SLC26A7) were identified as significant pre-diagnostic ALS biomarkers (FDR=0.05), detectable approximately two decades before diagnosis. Of these, all except SECTM1 were indirectly validated in independent cohorts of prevalent ALS cases, supporting their clinical significance. Additionally, 22 nominally significant (p<0.05) pre-diagnostic biomarkers were FDR-significant in prevalent ALS with consistent effect directions. Cross-disease comparisons with pre-diagnostic Parkinson's and Alzheimer's disease suggested a largely specific pre-diagnostic ALS biomarker signature. Gene ontology and tissue enrichment highlighted early involvement of immune, muscle, metabolic, and digestive processes. Furthermore, analyses of proteomic clocks revealed accelerated aging in brain-cognition, immune, and muscle tissues before clinical diagnosis. Druggability and LLM analyses revealed possible therapeutic targets and novel strategies, emphasizing translational relevance. INTERPRETATION: Our study provides first evidence of ultra-early molecular changes in common ALS up to two decades prior to clinical onset, mainly affecting immune, muscle, metabolic, digestive, and cognitive systems. Our study nominates several compelling candidates for risk stratification studies and novel therapeutic targets for early intervention. FUNDING: Clinical Research in ALS and Related Disorders for Therapeutic Development (CreATe) Consortium, Cure Alzheimer's Fund, Michael J Fox Foundation, Interdisciplinary Centre for Clinical Research, University Münster.

Journal Article↗

PubMed2025

Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form. METHODS: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan). Cox proportional hazards models based on 4,567 participants (including 172 incident ALS cases) were used to identify protein biomarkers associated with future ALS diagnosis. Top results were indirectly validated in two independent case-control studies of prevalent ALS (n=417 ALS, 852 controls). Functional annotation included cross-disease comparisons, gene set and tissue enrichment testing, organ-specific proteomic clocks, and the application of large-language models (LLM). FINDINGS: Five proteins (SECTM1, CA3, THAP4, KLHL41, SLC26A7) were identified as significant pre-diagnostic ALS biomarkers (FDR=0.05), detectable approximately two decades before diagnosis. Of these, all except SECTM1 were indirectly validated in independent cohorts of prevalent ALS cases, supporting their clinical significance. Additionally, 22 nominally significant (p<0.05) pre-diagnostic biomarkers were FDR-significant in prevalent ALS with consistent effect directions. Cross-disease comparisons with pre-diagnostic Parkinson's and Alzheimer's disease suggested a largely specific pre-diagnostic ALS biomarker signature. Gene ontology and tissue enrichment highlighted early involvement of immune, muscle, metabolic, and digestive processes. Furthermore, analyses of proteomic clocks revealed accelerated aging in brain-cognition, immune, and muscle tissues before clinical diagnosis. Druggability and LLM analyses revealed possible therapeutic targets and novel strategies, emphasizing translational relevance. INTERPRETATION: Our study provides first evidence of ultra-early molecular changes in common ALS up to two decades prior to clinical onset, mainly affecting immune, muscle, metabolic, digestive, and cognitive systems. Our study nominates several compelling candidates for risk stratification studies and novel therapeutic targets for early intervention. FUNDING: Clinical Research in ALS and Related Disorders for Therapeutic Development (CreATe) Consortium, Cure Alzheimer's Fund, Michael J Fox Foundation, Interdisciplinary Centre for Clinical Research, University Münster.

Journal Article↗