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Hereditary spastic paraplegia (HSP) encompasses a group of rare genetic diseases primarily affecting motor neurons. Among these, spastic paraplegia type 11 (SPG11) represents a complex form of HSP caused by deleterious variants in the SPG11 gene, which encodes the spatacsin protein. Previous studies have described several potential roles for spatacsin, including its involvement in lysosome and autophagy mechanisms, neuronal and neurites development or mitochondria function. Despite these findings, the precise function of the spatacsin protein remains elusive. To elucidate its function, we conducted an extensive RNA sequencing (RNAseq) experiment and transcriptomic analysis in three distinct neural structures (cerebellum, cortex and hippocampus) and at three different ages (6 weeks, 4 months and 8 months) in both wild type and Spg11 −/− mice. Our functional analysis of differentially expressed genes (DEGs) and Gene Set Enrichment Analysis (GSEA) revealed dysregulation in pathways related to inflammation, RNA metabolism and neuronal and neurite development, factors frequently implicated in neurodegenerative disorders. Notably, we also observed early deregulation in cellular pathways related to cell proliferation. Our results represent a significant step towards a better understanding of the functions of spatacsin in the cell and the underlying cellular mechanisms disrupted by its absence.

TimSort is an intriguing sorting algorithm designed in 2002 for Python, whose worst-case complexity was announced, but not proved until our recent preprint. In fact, there are two slightly different versions of TimSort that are currently implemented in Python and in Java respectively. We propose a pedagogical and insightful proof that the Python version runs in \\(O(n n)\\). The approach we use in the analysis also applies to the Java version, although not without very involved technical details. As a byproduct of our study, we uncover a bug in the Java implementation that can cause the sorting method to fail during the execution. We also give a proof that Python's TimSort running time is in \\(O(n + n )\\), where \\(\\) is the number of runs (i.e. maximal monotonic sequences), which is quite a natural parameter here and part of the explanation for the good behavior of TimSort on partially sorted inputs.

The topic of the article is the parametric study of the complexity of algorithms on arrays of pairwise distinct integers. We introduce a model that takes into account the non-uniformness of data, which we call the Ewens-like distribution of parameter \\(\\) for records on permutations: the weight \\(^r\\) of a permutation depends on its number \\(r\\) of records. We show that this model is meaningful for the notion of presortedness, while still being mathematically tractable. Our results describe the expected value of several classical permutation statistics in this model, and give the expected running time of three algorithms: the Insertion Sort, and two variants of the Min-Max search.

Magnetic resonance imaging (MRI) can be used to identify biomarkers in Parkinson's disease (PD); R2* values reflect iron content related to high levels of oxidative stress, whereas volume and/or shape changes reflect neuronal death. We sought to assess iron overload in the nigrostriatal system and characterize its relationship with focal and overall atrophy of the striatum in the pivotal stages of PD. Twenty controls and 70 PD patients at different disease stages (untreated de novo patients, treated early-stage patients and advanced-stage patients with L-dopa-related motor complications) were included in the study. We determined the R2* values in the substantia nigra, putamen and caudate nucleus, together with striatal volume and shape analysis. We also measured R2* in an acute MPTP mouse model and in a longitudinal follow-up two years later in the early-stage PD patients. The R2* values in the substantia nigra, putamen and caudate nucleus were significantly higher in de novo PD patients than in controls. Early-stage patients displayed significantly higher R2* values in the substantia nigra (with changes in striatal shape), relative to de novo patients. Measurements after a two-year follow-up in early-stage patients and characterization of the acute MPTP mouse model confirmed that R2* changed rapidly with disease progression. Advanced-stage patients displayed significant atrophy of striatum, relative to earlier disease stages. Each pivotal stage in PD appears to be characterized by putative nigrostriatal MRI biomarkers: iron overload at the de novo stage, striatal shape changes at early-stage disease and generalized striatal atrophy at advanced disease.

It has been documented that up to 22% of all soccer injuries are concussions. This is in part due to players purposely using their head to direct the ball during play. To provide a more complete understanding of head trauma in soccer athletes, this study characterized the effects of four soccer ball characteristics (size, inflation pressure, mass, velocity) on the resulting peak impact force as it relates to the potential for incurring neurophysiological changes. A total of six hundred trials were performed on size 4 and 5 soccer balls as well as a novel lightweight soccer ball. Impact force was measured with a force plate and ball velocity was determined using motion capture. These data were used, in conjunction with dimensional analysis to relate impact force to ball size, mass, velocity, and pressure. Reasonable reductions in allowable ball parameters resulted in a 19.7% decrease in peak impact force. Adjustments to ball parameters could reduce a high cumulative peak translational acceleration soccer athlete down into a previously defined safer low loading range. In addition, it was noted that water absorption by soccer balls can result in masses that substantially increase impact force and quickly surpass the NCAA weight limit for game play. Additional research is required to determine whether varying soccer ball characteristics will enable soccer players to avoid persistent neurophysiological deficits or what additional interventions may be necessary and the legal implications of these data are discussed.

Black soldier fly larvae (BSF, Hermetia illucens ) have gained much attention for their industrial use as biowaste recyclers and as a new source of animal proteins. The functional effect that microbiota has on insect health and growth performance remains largely unknown. This study clarifies the role of microbiota in BSF ontogeny by investigating the differential genomic expression of BSF larvae in axenic conditions (i.e., germfree) relative to non-axenic (conventional) conditions. We used RNA-seq to measure differentially expressed transcripts between axenic and conventional condition using DESeq2 at day 4, 12 and 20 post-hatching. Gene expression was significantly up or down-regulated for 2476 transcripts mapped in gene ontology functions, and axenic larvae exhibited higher rate of down-regulated functions. Up-regulated microbiota-dependant transcriptional gene modules included the immune system, the lipid metabolism, and the nervous system. Expression profile showed a shift in late larvae (day 12 and 20), exposing a significant temporal effect on gene expression. These results provide the first evidence of host functional genes regulated by microbiota in the BSF larva, further demonstrating the importance of host-microbiota interactions on host ontogeny and health. These results open the door to optimization of zootechnical properties in alternative animal protein production, biowaste revalorization and recycling.

Streptococcus suis serotype 2 is an important porcine pathogen and zoonotic agent causing sudden death, septic shock and meningitis, with exacerbated inflammation being a hallmark of the infection. A rapid, effective and balanced innate immune response against S. suis is critical to control bacterial growth without causing excessive inflammation. Even though interleukin (IL)-1 is one of the most potent and earliest pro-inflammatory mediators produced, its role in the S. suis pathogenesis has not been studied. We demonstrated that a classical virulent European sequence type (ST) 1 strain and the highly virulent ST7 strain induce important levels of IL-1 in systemic organs. Moreover, bone marrow-derived dendritic cells and macrophages contribute to its production, with the ST7 strain inducing higher levels. To better understand the underlying mechanisms involved, different cellular pathways were studied. Independently of the strain, IL-1β production required MyD88 and involved recognition via TLR2 and possibly TLR7 and TLR9. This suggests that the recognized bacterial components are similar and conserved between strains. However, very high levels of the pore-forming toxin suilysin, produced only by the ST7 strain, are required for efficient maturation of pro-IL-1β via activation of different inflammasomes resulting from pore formation and ion efflux. Using IL-1R −/− mice, we demonstrated that IL-1 signaling plays a beneficial role during S. suis systemic infection by modulating the inflammation required to control and clear bacterial burden, thus promoting host survival. Beyond a certain threshold, however, S. suis -induced inflammation cannot be counterbalanced by this signaling, making it difficult to discriminate its role.

Black soldier fly larvae (BSF, Hermetia illucens) have gained much attention for their industrial use as biowaste recyclers and as a new source of animal proteins. The functional effect that microbiota has on insect health and growth performance remains largely unknown. This study clarifies the role of microbiota in BSF ontogeny by investigating the differential genomic expression of BSF larvae in axenic conditions (i.e., germfree) relative to non-axenic (conventional) conditions. We used RNA-seq to measure differentially expressed transcripts between axenic and conventional condition using DESeq2 at day 4, 12 and 20 post-hatching. Gene expression was significantly up or down-regulated for 2476 transcripts mapped in gene ontology functions, and axenic larvae exhibited higher rate of down-regulated functions. Up-regulated microbiota-dependant transcriptional gene modules included the immune system, the lipid metabolism, and the nervous system. Expression profile showed a shift in late larvae (day 12 and 20), exposing a significant temporal effect on gene expression. These results provide the first evidence of host functional genes regulated by microbiota in the BSF larva, further demonstrating the importance of host-microbiota interactions on host ontology and health. These results open the door to optimization of zootechnical properties in alternative animal protein production, biowaste revalorization and recycling.