Subjective Cognitive Complaints in Participants of the Healthy Brain Ageing Study (HeBA)

Subjective cognitive complaints (SCC) have the potential for earlier detection of Alzheimer’s disease and Parkinson’s disease. Currently, the results of the completed online survey in the frame of the HeBA study reveal that 23% of the Luxembourgish participants have SCC with the SCC group having a higher prevalence rate of depression

A Deep Insight into the Sialome of Rhodnius neglectus, a vector of chagas disease

Background Triatomines are hematophagous insects that act as vectors of Chagas disease. Rhodnius neglectus is one of these kissing bugs found, contributing to the transmission of this American trypanosomiasis. The saliva of hematophagous arthropods contains bioactive molecules responsible for counteracting host haemostatic, inflammatory, and immuneresponses. Methods/Principal Findings Next generation sequencing and mass spectrometry-based protein identification were performed to investigate the content of triatomine R. neglectus saliva.We deposited 4,230 coding DNA sequences (CDS) in GenBank. A set of 636 CDS of proteins of putative secretory nature was extracted from the assembled reads, 73 of them confirmed by proteomic analysis. The sialome of R. neglectus was characterized and serine protease transcripts detected. The presence of ubiquitous protein families was revealed, including lipocalins, serine protease inhibitors, and antigen-5. Metalloproteases, disintegrins, and odorant binding protein families were less abundant. Conclusions/Significance The data presented improve our understanding of hematophagous arthropod sialomes, and aid in understanding hematophagy and the complex interplay among vectors and their vertebrate hosts

Comprehensive blood metabolomics profiling of Parkinson’s disease reveals coordinated alterations in xanthine metabolism

Abstract Parkinson’s disease (PD) is a highly heterogeneous disorder influenced by several environmental and genetic factors. Effective disease-modifying therapies and robust early-stage biomarkers are still lacking, and an improved understanding of the molecular changes in PD could help to reveal new diagnostic markers and pharmaceutical targets. Here, we report results from a cohort-wide blood plasma metabolic profiling of PD patients and controls in the Luxembourg Parkinson’s Study to detect disease-associated alterations at the level of systemic cellular process and network alterations. We identified statistically significant changes in both individual metabolite levels and global pathway activities in PD vs. controls and significant correlations with motor impairment scores. As a primary observation when investigating shared molecular sub-network alterations, we detect pronounced and coordinated increased metabolite abundances in xanthine metabolism in de novo patients, which are consistent with previous PD case/control transcriptomics data from an independent cohort in terms of known enzyme-metabolite network relationships. From the integrated metabolomics and transcriptomics network analysis, the enzyme hypoxanthine phosphoribosyltransferase 1 (HPRT1) is determined as a potential key regulator controlling the shared changes in xanthine metabolism and linking them to a mechanism that may contribute to pathological loss of cellular adenosine triphosphate (ATP) in PD. Overall, the investigations revealed significant PD-associated metabolome alterations, including pronounced changes in xanthine metabolism that are mechanistically congruent with alterations observed in independent transcriptomics data. The enzyme HPRT1 may merit further investigation as a main regulator of these network alterations and as a potential therapeutic target to address downstream molecular pathology in PD

Early-to-mid stage idiopathic Parkinson's disease shows enhanced cytotoxicity and differentiation in CD8 T-cells in females.

peer reviewedNeuroinflammation in the brain contributes to the pathogenesis of Parkinson's disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral cytotoxic immune milieu, with more terminally-differentiated effector memory (TEMRA) CD8 T, CD8+ NKT cells and circulating cytotoxic molecules in fresh blood of patients with early-to-mid iPD, especially females, after analyzing > 700 innate and adaptive immune features. This profile, also reflected by fewer CD8+FOXP3+ T cells, was confirmed in another subcohort. Co-expression between cytotoxic molecules was selectively enhanced in CD8 TEMRA and effector memory (TEM) cells. Single-cell RNA-sequencing analysis demonstrated the accelerated differentiation within CD8 compartments, enhanced cytotoxic pathways in CD8 TEMRA and TEM cells, while CD8 central memory (TCM) and naïve cells were already more-active and transcriptionally-reprogrammed. Our work provides a comprehensive map of dysregulated peripheral immunity in iPD, proposing candidates for early diagnosis and treatments

Phylogram of lipocalin containing triabin domain from <i>R</i>. <i>neglectus</i> SG transcriptome.

<p>Phylogenetic tree derived from the alignment of <i>R</i>. <i>neglectus</i> CDS and other triatomine lipocalin sequences as described in Methods section. The bar at the bottom represents 20% amino acid substitution. The colored circles indicate each species whose sequences were used: blue, <i>R</i>. <i>neglectus</i> sequences from SG transcriptome; red, <i>R</i>. <i>prolixus</i>; yellow, <i>Triatoma dimidiata</i>; green, <i>Triatoma brasiliensis</i>; dark green, <i>Triatoma matogrossensis</i>; dark blue, <i>T</i>. <i>pallidipennis</i>; purple, <i>Triatoma protacta</i>; magenta, <i>Triatoma infestans</i>; gray, <i>Dipetalogaster maxima</i>.</p

Classification and abundance of coding sequences of putative housekeeping function extracted from the sialotranscriptome of <i>R</i>. <i>neglectus</i>.

<p>Classification and abundance of coding sequences of putative housekeeping function extracted from the sialotranscriptome of <i>R</i>. <i>neglectus</i>.</p

Phylogram of lipocalin containing nitrophorin domain from <i>R</i>. <i>neglectus</i> SG transcriptome.

<p>Phylogenetic tree derived from the alignment of <i>R</i>. <i>neglectus</i> CDS and <i>R</i>. <i>prolixus</i> nitrophorin sequences as described in Methods section. The bar at the bottom represents 20% amino acid substitution. The colored circles indicate each species whose sequences were used: blue, <i>R</i>. <i>neglectus</i> sequences from SG transcriptome and red, <i>R</i>. <i>prolixus</i> sequences from NCBI.</p

Kazal-type members from <i>R</i>. <i>neglectus</i> SG transcriptome.

<p>ClustalW alignment of Kazal-type domain-containing members from <i>R</i>. <i>neglectus</i> salivary transcriptome (RN_5563 and RN_549) and other insect kazal-type sequences, identified as described in Methods section. The alignment indicates conserved residues in black and similar residues in gray background, the six conserved cysteines (boxes) and the blue bar indicates the signal peptide indicative of secretion.</p

Classification and abundance of proteins from the salivary proteome of <i>R</i>. <i>neglectus</i> based on LC-MS/MS.

<p>Classification and abundance of proteins from the salivary proteome of <i>R</i>. <i>neglectus</i> based on LC-MS/MS.</p

Phylogram of Antigen-5 proteins from <i>R</i>. <i>neglectus</i> SG transcriptome.

<p>Phylogenetic tree derived from the alignment of <i>R</i>. <i>neglectus</i> CDS and other insect antigen-5 sequences as described in Methods section. The bar represents 10% amino acid substitution.</p