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There is compelling evidence that the human cerebellum is engaged in a wide array of motor and cognitive tasks. A fundamental question centers on whether the cerebellum is organized into distinct functional subregions. To address this question, we employed a rich task battery designed to tap into a broad range of cognitive processes. During four functional MRI sessions, participants performed a battery of 26 diverse tasks comprising 47 unique conditions. Using the data from this multi-domain task battery, we derived a comprehensive functional parcellation of the cerebellar cortex and evaluated it by predicting functional boundaries in a novel set of tasks. The new parcellation successfully identified distinct functional subregions, providing significant improvements over existing parcellations derived from task-free data. Lobular boundaries, commonly used to summarize functional data, did not coincide with functional subdivisions. The new parcellation provides a functional atlas to guide future neuroimaging studies.

One important approach to human brain mapping is to define a set of distinct regions that can be linked to unique functions. Numerous brain parcellations have been proposed, using cytoarchitectonic, structural, or functional magnetic resonance imaging (fMRI) data. The intrinsic smoothness of brain data, however, poses a problem for current methods seeking to compare different parcellations. For example, criteria that simply compare within‐parcel to between‐parcel similarity provide even random parcellations with a high value. Furthermore, the evaluation is biased by the spatial scale of the parcellation. To address this problem, we propose the distance‐controlled boundary coefficient (DCBC), an unbiased criterion to evaluate discrete parcellations. We employ this new criterion to evaluate existing parcellations of the human neocortex in their power to predict functional boundaries for an fMRI data set with many different tasks, as well as for resting‐state data. We find that common anatomical parcellations do not perform better than chance, suggesting that task‐based functional boundaries do not align well with sulcal landmarks. Parcellations based on resting‐state fMRI data perform well; in some cases, as well as a parcellation defined on the evaluation data itself. Finally, multi‐modal parcellations that combine functional and anatomical criteria perform substantially worse than those based on functional data alone, indicating that functionally homogeneous regions often span major anatomical landmarks. Overall, the DCBC advances the field of functional brain mapping by providing an unbiased metric that compares the predictive ability of different brain parcellations to define brain regions that are functionally maximally distinct. We propose a new unbiased evaluation criterion (distance‐controlled boundary coefficient [DCBC]) for brain parcellations to overcome the drawback of existing evaluation criteria that are biased by spatial smoothness. Using DCBC, task‐evoked, and resting‐state functional magnetic resonance imaging data, we found resting‐state group parcellations predict task‐based functional boundaries very well, anatomical atlases predict functional boundaries no better than chance, and multi‐modal parcellations do not improve on resting‐state parcellations.

It is a fact that the use of antibiotics is inducing a growing resistance on bacteria. This situation is not only the consequence of a drugs' misuse, but a direct consequence of a widespread and continuous use. Current studies suggest that this effect could be reversed by using abandoned antibiotics to which bacteria have lost their resistance, but this is only a temporary solution that in near future would lead to new resistance problems. Fortunately, current nanotechnology offers a new life for old and new antibiotics, which could have significantly different pharmacokinetics when properly delivered; enabling new routes able to bypass acquired resistances. In this contribution, we will focus on the use of porous silica nanoparticles as functional carriers for the delivery of antibiotics and biocides in combination with additional features like membrane sensitizing and heavy metal-driven metabolic-disrupting therapies as two of the most interesting combination therapies. Keywords: mesoporous silica, bacteria, infection, combination therapy, drug delivery

The enormous versatility of mesoporous silica nanoparticles permits the creation of a large number of nanotherapeutic systems for the treatment of cancer and many other pathologies. In addition to the controlled release of small drugs, these materials allow a broad number of molecules of a very different nature and sizes. In this review, we focus on biogenic species with therapeutic abilities (proteins, peptides, nucleic acids, and glycans), as well as how nanotechnology, in particular silica-based materials, can help in establishing new and more efficient routes for their administration. Indeed, since the applicability of those combinations of mesoporous silica with bio(macro)molecules goes beyond cancer treatment, we address a classification based on the type of therapeutic action. Likewise, as illustrative content, we highlight the most typical issues and problems found in the preparation of those hybrid nanotherapeutic materials.

Runners are often categorized as forefoot, midfoot or rearfoot strikers, but how much and why do individuals vary in foot strike patterns when running on level terrain? This study used general linear mixed-effects models to explore both intra- and inter-individual variations in foot strike pattern among 48 Kalenjin-speaking participants from Kenya who varied in age, sex, body mass, height, running history, and habitual use of footwear. High speed video was used to measure lower extremity kinematics at ground contact in the sagittal plane while participants ran down 13 meter-long tracks with three variables independently controlled: speed, track stiffness, and step frequency. 72% of the habitually barefoot and 32% of the habitually shod participants used multiple strike types, with significantly higher levels of foot strike variation among individuals who ran less frequently and who used lower step frequencies. There was no effect of sex, age, height or weight on foot strike angle, but individuals were more likely to midfoot or forefoot strike when they ran on a stiff surface, had a high preferred stride frequency, were habitually barefoot, and had more experience running. It is hypothesized that strike type variation during running, including a more frequent use of forefoot and midfoot strikes, used to be greater before the introduction of cushioned shoes and paved surfaces.

Declawing of pet cats is widely believed to cause chronic pain and negatively impact animal welfare, leading to bans in many jurisdictions. However, little is known on how post-declaw pain develops and affects feline well-being. Existing data often fail to account for other sources of chronic pain, such as osteoarthritis (OA), which affects most aging cats. Here, the aim was to distinguish chronic post-declaw pain from OA-related pain. A secondary analysis of eight studies on feline OA was conducted, comparing somatosensory, biomechanical and functional assessments between healthy control cats, declawed OA (DOA) cats, and non-declawed OA (NDOA) cats. DOA cats exhibited significant somatosensory alterations (hyperalgesia and allodynia) and greater biomechanical (worse in heavier cats) and functional impairments, compared to NDOA cats. The alterations were not dependent on the number of declawed paws (two forelimbs vs. four paws). This alarming phenotype was associated with objective nervous conduction abnormalities indicative of worsened axonopathy in DOA cats. Our findings highlight the impact of chronic post-declaw pain and support the need to develop therapeutic strategies to alleviate chronic pain in DOA cats and highlights the pertinence of establishing a global ban of this elective procedure.

This paper examines the performance of orthogonal frequency division multiplexing (OFDM) systems for vehicle-to-vehicle (V2V) communication channels. More specifically, a doubly selective channel under high intercarrier interference (ICI) is considered. Current solutions involve complex detection and/or reduced spectral efficiency receivers. This paper proposes the use of virtual carriers (VC) in an OFDM system with a low-complexity maximal ratio combining (MRC) detector to improve the bit error rate (BER) performance. The results show that VC provides diversity in received data, resulting in a ≥5 dB gain compared to previous OFDM systems with conventional linear/nonlinear detectors used as a reference. The detector presented in this paper has linear complexity, making it a suitable solution for real-time V2V communication systems.

The assembly of HIV-1 is mediated by oligomerization of the major structural polyprotein, Gag, into a hexameric protein lattice at the plasma membrane of the infected cell. This leads to budding and release of progeny immature virus particles. Subsequent proteolytic cleavage of Gag triggers rearrangement of the particles to form mature infectious virions. Obtaining a structural model of the assembled lattice of Gag within immature virus particles is necessary to understand the interactions that mediate assembly of HIV-1 particles in the infected cell, and to describe the substrate that is subsequently cleaved by the viral protease. An 8-Å resolution structure of an immature virus-like tubular array assembled from a Gag-derived protein of the related retrovirus Mason–Pfizer monkey virus (M-PMV) has previously been reported, and a model for the arrangement of the HIV-1 capsid (CA) domains has been generated based on homology to this structure. Here we have assembled tubular arrays of a HIV-1 Gag-derived protein with an immature-like arrangement of the C-terminal CA domains and have solved their structure by using hybrid cryo-EM and tomography analysis. The structure reveals the arrangement of the C-terminal domain of CA within an immature-like HIV-1 Gag lattice, and provides, to our knowledge, the first high-resolution view of the region immediately downstream of CA, which is essential for assembly, and is significantly different from the respective region in M-PMV. Our results reveal a hollow column of density for this region in HIV-1 that is compatible with the presence of a six-helix bundle at this position.

Abstract Study Objectives This study assessed changes in sleep quality before and after the peak of the SARS-CoV-2 pandemic in community dwellers enrolled in the Atahualpa Project. Methods Atahualpa residents aged ≥40 years were eligible if they had a Pittsburgh Sleep Quality Index (PSQI) 9 months before the pandemic and a lateral flow-based test for identification of SARS-CoV-2 antibodies during the peak of the pandemic. Six months later, individuals completed a follow-up PSQI. The independent relationship between SARS-CoV-2 infection and deterioration in sleep quality was assessed by fitting logistic mixed models for longitudinal data. Results Of 639 participants (mean age at baseline: 59 ± 12.8 years), 325 (51%) had SARS-CoV-2 antibodies. A total of 185 (29%) individuals at baseline and 311 (49%) at follow-up were poor sleepers (p < 0.001). Mixed logistic regression models demonstrated a significant increase in poor sleepers at follow-up (odds ratio [OR]: 2.85; 95% CI: 2.16 to 3.75), which was more marked among SARS-CoV-2 seropositive subjects (OR: 3.8; 95% CI: 2.48 to 5.81). The adjusted proportion of poor sleepers increased from 29% to 56.2% (95% CI: 50.9% to 61.6%) among SARS-CoV-2 seropositive individuals, but only to 40.7% (95% CI: 35.3% to 46.1%) in their seronegative counterparts (p < 0.001). Likewise, progression from a good to a poor sleeper status was higher among seropositive individuals than in their seronegative counterparts (38.1% vs 22.3%; p < 0.001), after adjusting for relevant covariates. Conclusions This study shows a deleterious effect of SARS-CoV-2 in sleep quality. An effect of SARS-CoV-2 in disrupting sleep-related pathways cannot be ruled out. Trial registration The Atahualpa Project has been registered at ClinicalTrials.gov; the identifier number is NCT01627600, and the date was: 10/02/2012 (https://clinicaltrials.gov/ct2/show/NCT01627600?cond=Atahualpa&draw=2&rank=1). The Sleep Disorders substudy has been registered at ClinicalTrials.gov; the identifier number is NCT01877616, and the date was: 06/13/2013 (https://clinicaltrials.gov/ct2/show/NCT01877616?cond=Atahualpa&draw=2&rank=4).

Claudins, the integral tight junction (TJ) proteins that regulate paracellular permeability and cell polarity, are frequently dysregulated in cancer; however, their role in neoplastic progression is unclear. Here, we demonstrated that knockout of Cldn18, a claudin family member highly expressed in lung alveolar epithelium, leads to lung enlargement, parenchymal expansion, increased abundance and proliferation of known distal lung progenitors, the alveolar epithelial type II (AT2) cells, activation of Yes-associated protein (YAP), increased organ size, and tumorigenesis in mice. Inhibition of YAP decreased proliferation and colony-forming efficiency (CFE) of Cldn18-/- AT2 cells and prevented increased lung size, while CLDN18 overexpression decreased YAP nuclear localization, cell proliferation, CFE, and YAP transcriptional activity. CLDN18 and YAP interacted and colocalized at cell-cell contacts, while loss of CLDN18 decreased YAP interaction with Hippo kinases p-LATS1/2. Additionally, Cldn18-/- mice had increased propensity to develop lung adenocarcinomas (LuAd) with age, and human LuAd showed stage-dependent reduction of CLDN18.1. These results establish CLDN18 as a regulator of YAP activity that serves to restrict organ size, progenitor cell proliferation, and tumorigenesis, and suggest a mechanism whereby TJ disruption may promote progenitor proliferation to enhance repair following injury.