The lncRNA Snhg11, a new candidate contributing to neurogenesis, plasticity, and memory deficits in Down syndrome.

Down syndrome (DS) stands as the prevalent genetic cause of intellectual disability, yet comprehensive understanding of its cellular and molecular underpinnings remains limited. In this study, we explore the cellular landscape of the hippocampus in a DS mouse model, the Ts65Dn, through single-nuclei transcriptional profiling. Our findings demonstrate that trisomy manifests as a highly specific modification of the transcriptome within distinct cell types. Remarkably, we observed a significant shift in the transcriptomic profile of granule cells in the dentate gyrus (DG) associated with trisomy. We identified the downregulation of a specific small nucleolar RNA host gene, Snhg11, as the primary driver behind this observed shift in the trisomic DG. Notably, reduced levels of Snhg11 in this region were also observed in a distinct DS mouse model, the Dp(16)1Yey, as well as in human postmortem brain tissue, indicating its relevance in Down syndrome. To elucidate the function of this long non-coding RNA (lncRNA), we knocked down Snhg11 in the DG of wild-type mice. Intriguingly, this intervention alone was sufficient to impair synaptic plasticity and adult neurogenesis, resembling the cognitive phenotypes associated with trisomy in the hippocampus. Our study uncovers the functional role of Snhg11 in the DG and underscores the significance of this lncRNA in intellectual disability. Furthermore, our findings highlight the importance of DG in the memory deficits observed in Down syndrome.

Exploring the link between hedonic overeating and prefrontal cortex dysfunction in the Ts65Dn trisomic mouse model.

Individuals with Down syndrome (DS) have a higher prevalence of obesity compared to the general population. Conventionally, this has been attributed to endocrine issues and lack of exercise. However, deficits in neural reward responses and dopaminergic disturbances in DS may be contributing factors. To investigate this, we focused on a mouse model (Ts65Dn) bearing some triplicated genes homologous to trisomy 21. Through detailed meal pattern analysis in male Ts65Dn mice, we observed an increased preference for energy-dense food, pointing towards a potential "hedonic" overeating behavior. Moreover, trisomic mice exhibited higher scores in compulsivity and inflexibility tests when limited access to energy-dense food and quinine hydrochloride adulteration were introduced, compared to euploid controls. Interestingly, when we activated prelimbic-to-nucleus accumbens projections in Ts65Dn male mice using a chemogenetic approach, impulsive and compulsive behaviors significantly decreased, shedding light on a promising intervention avenue. Our findings uncover a novel mechanism behind the vulnerability to overeating and offer potential new pathways for tackling obesity through innovative interventions.

Beyond Quiescent and Active: Intermediate Microglial Transcriptomic States in a Mouse Model of Down Syndrome.

Research on microglia in Down syndrome (DS) has shown that microglial activation, increased inflammatory gene expression, and oxidative stress occur at different ages in DS brains. However, most studies resulted in simplistic definitions of microglia as quiescent or active, ignoring potential intermediate states. Indeed, recent work on microglial cells in young DS brains indicated that those evolve through different intermediate activation phenotypes before reaching a fully activated state. Here we used single nucleus RNA sequencing, to examine how trisomy affects microglial states in the Ts65Dn mouse model of DS. Despite no substantial changes in the proportion of glial populations, differential expression analysis revealed cell type-specific gene expression changes, most notably in astroglia, microglia, and oligodendroglia. Focusing on microglia, we identified differential expression of genes associated with different microglial states, including disease-associated microglia (DAMs), activated response microglia (ARMs), and human Alzheimer's disease microglia (HAMs), in trisomic microglia. Furthermore, pseudotime analysis reveals a unique reactivity profile in Ts65Dn microglia, with fewer in a homeostatic state and more in an intermediate aberrantly reactive state than in euploid microglia. This comprehensive understanding of microglial transcriptional dynamics sheds light on potential pathogenetic mechanisms but also possible avenues for therapy for neurodevelopmental disorders.

Fano-Like Resonance from Disorder Correlation in Vacancy-Doped Photonic Crystals.

By preparing colloidal crystals with random missing scatterers, crystals are created where disorder is embodied as vacancies in an otherwise perfect lattice. In this special system, there is a critical defect concentration where light propagation undergoes a transition from an all but perfect reflector (for the spectral range defined by the Bragg condition), to a metamaterial exhibiting an enhanced transmission phenomenon. It is shown that this behavior can be phenomenologically described in terms of Fano-like resonances. The results show that the Fano's parameter q experiences a sign change signaling the transition from a perfect crystal exhibiting a reflectance Bragg peak, through a state where background scattering is maximum and Bragg reflectance reaches a minimum to a point where the system reenters a low scattering state recovering ordinary Bragg diffraction. A simple dipolar model considering the correlation between scatterers and vacancies is proposed and the reported evolution of the Fano-like scattering is explained in terms of the emerging covariance between the optical paths and polarizabilities and the effect of field enhancement in photonic crystal (PhC) defects.

Extrathoracic Aneurysms in Marfan Syndrome: A Systematic Review of the Literature.

BACKGROUND: Marfan syndrome (MS) most often shows as thoracic aortic aneurysm (TAA) or aortic dissection, but it may also involve other vascular territories. This study aimed to identify those extrathoracic vascular manifestations most frequently associated with MS. METHODS: A systematic review of the literature with Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was carried out. The following databases were included: MEDLINE, Embase, Web of Science, Cumulative Index of Nursing and Health Sciences Literature (CINHAL); Spanish database MEDESY Cochrane Central Register of Controlled Trials (CENTRAL). RESULTS: A total of 10,008 articles were identified, leaving 155 for the first stage of data analysis (total incidence of aneurysms) and 83 for the second (descriptive data analysis). Overall, 518 aneurysms were identified: 149 in the head and neck, 94 in the extremities, and 275 in the aortic, iliac, and visceral sectors. Mostly, they were simultaneously discovered during studies of the TAA. In the abdominal aorta, the presentation with rupture in 11 of 32 patients stands out. Resection and bypass were the most frequently used methods for repair in the treated cases. CONCLUSIONS: Although its frequency in the general population is unknown, this systematic review suggests that extrathoracic aneurysmal arterial involvement in the MS may be more frequent than expected. We believe screening for aneurysms in other vascular sectors may be advisable, especially in patients with MS and TAA.

Vacancies in Self-Assembled Crystals: An Archetype for Clusters Statistics at the Nanoscale.

Complex systems involving networks have attracted strong multidisciplinary attention since they are predicted to sustain fascinating phase transitions in the proximity of the percolation threshold. Developing stable and compact archetypes that allow one to experimentally study physical properties around the percolation threshold remains a major challenge. In nanoscale systems, this achievement is rare since it is tied to the ability to control the intentional disorder and perform a vast statistical analysis of cluster configurations. Here, a self-assembly method to fabricate perfectly ordered structures where random defects can be introduced is presented. Building binary crystals from two types of dielectric nanospheres and selectively removing one of them creates vacancies at random lattice positions that form a complex network of clusters. Vacancy content can be easily controlled and raised even beyond the percolation threshold. In these structures, the distribution of cluster sizes as a function of vacancy density is analyzed. For moderate concentrations, it is found to be homogeneous throughout the structure and in good agreement with the assumption of a random vacancy distribution.

Zika virus infection in chemosensory cells.

Zika virus (ZIKV) is an emerging virus belonging to the genus Flavivirus. ZIKV infection is a significant health concern, with increasing numbers of reports of microcephaly cases in fetuses and Guillain-Barré syndrome (GBS) in adults. Interestingly, chemosensory disturbances are also reported as one of the manifestations of GBS. ZIKV infects several human tissues and cell types in vitro and in vivo. However, there is no study demonstrating ZIKV infection and replication in chemosensory cells, including olfactory and taste cells. Taste papilla and olfactory cells are chemosensory receptor cells with unique histological, molecular, and physiological characteristics. Here we examined ZIKV infection (PRVABC59) in cultured human olfactory epithelial cells (hOECs) and fungiform taste papilla (HBO) cells in vitro, as well as in vivo mouse taste and olfactory epithelial and olfactory bulb tissues. Interestingly, while HBO cells showed resistance to ZIKV replication, hOECs were highly susceptible for ZIKV infection and replication. Further, we demonstrated the presence of ZIKV particles and expression of viral proteins in olfactory epithelium, as well as in olfactory bulb, but not in taste papillae, of immunocompromised mice (ifnar/-) infected with the PRVABC59 strain of ZIKV. These observations suggest that chemosensory cells in the olfactory neuroepithelium and olfactory bulb may be important tissues for ZIKV replication and dissemination.

Rethinking Intellectual Disability from Neuro- to Astro-Pathology.

Neurodevelopmental disorders arise from genetic and/or from environmental factors and are characterized by different degrees of intellectual disability. The mechanisms that govern important processes sustaining learning and memory, which are severely affected in intellectual disability, have classically been thought to be exclusively under neuronal control. However, this vision has recently evolved into a more integrative conception in which astroglia, rather than just acting as metabolic supply and structural anchoring for neurons, interact at distinct levels modulating neuronal communication and possibly also cognitive processes. Recently, genetic tools have made it possible to specifically manipulate astrocyte activity unraveling novel functions that involve astrocytes in memory function in the healthy brain. However, astrocyte manipulation has also underscored potential mechanisms by which dysfunctional astrocytes could contribute to memory deficits in several neurodevelopmental disorders revealing new pathogenic mechanisms in intellectual disability. Here, we review the current knowledge about astrocyte dysfunction that might contribute to learning and memory impairment in neurodevelopmental disorders, with special focus on Fragile X syndrome and Down syndrome.

Template-Free, Surfactant-Mediated Orientation of Self-Assembled Supercrystals of Metal-Organic Framework Particles.

Mesoscale self-assembly of particles into supercrystals is important for the design of functional materials such as photonic and plasmonic crystals. However, while much progress has been made in self-assembling supercrystals adopting diverse lattices and using different types of particles, controlling their growth orientation on surfaces has received limited success. Most of the latter orientation control has been achieved via templating methods in which lithographic processes are used to form a patterned surface that acts as a template for particle assembly. Herein, a template-free method to self-assemble (111)-, (100)-, and (110)-oriented face-centered cubic supercrystals of the metal-organic framework ZIF-8 particles by adjusting the amount of surfactant (cetyltrimethylammonium bromide) used is described. It is shown that these supercrystals behave as photonic crystals whose properties depend on their growth orientation. This control on the orientation of the supercrystals dictates the orientation of the composing porous particles that might ultimately facilitate pore orientation on surfaces for designing membranes and sensors.

A Self-Assembled 2D Thermofunctional Material for Radiative Cooling.

The regulation of temperature is a major energy-consuming process of humankind. Today, around 15% of the global-energy consumption is dedicated to refrigeration and this figure is predicted to triple by 2050, thus linking global warming and cooling needs in a worrying negative feedback-loop. Here, an inexpensive solution is proposed to this challenge based on a single layer of silica microspheres self-assembled on a soda-lime glass. This 2D crystal acts as a visibly translucent thermal-blackbody for above-ambient radiative cooling and can be used to improve the thermal performance of devices that undergo critical heating during operation. The temperature of a silicon wafer is found to be 14 K lower during daytime when covered with the thermal emitter, reaching an average temperature difference of 19 K when the structure is backed with a silver layer. In comparison, the soda-lime glass reference used in the measurements lowers the temperature of the silicon by just 5 K. The cooling power of this simple radiative cooler under direct sunlight is found to be 350 W m-2 when applied to hot surfaces with relative temperatures of 50 K above the ambient. This is crucial to radiatively cool down devices, i.e., solar cells, where an increase in temperature has drastic effects on performance.

Arteriocutaneous Fistula Associated with Bilateral Femoral Pseudoaneurysms Caused by Bacillus Calmette-Guérin. Apropos of a Case and Review of Literature.

Vascular complications of intravesical instillation of bacillus Calmette-Guérin (BCG) are rare. BCG is an attenuated strain of Mycobacterium bovis that was initially developed for vaccination against tuberculosis, but it has also been used as an adjuvant treatment for bladder transitional carcinoma. We report a patient with a history of instillation of BCG 2 years before, who underwent surgical treatment of 2 pseudoaneurysms. The first, located in the left superficial femoral artery (SFA), was resected, and the artery was ligated because he had a history of femoropopliteal occlusion. After 4 weeks, he presented another one associated with hemorrhage by cutaneous fistula, in the right common femoral artery. In this case, revascularization was performed by means a common-to-deep femoral artery bypass with polytetrafluorethylene graft and reimplantation of SFA. Initially, bacterial cultures were negative, but bacilli cultures identified M. bovis after 3 weeks. Antituberculosis therapy was administered. After 13 months, the patient was asymptomatic and duplex ultrasound showed no signs of recurrent infection. This exposure should be considered if presentation of the false aneurysm is spontaneous and there is a history of bladder carcinoma.

Seeded Synthesis of Monodisperse Core-Shell and Hollow Carbon Spheres.

Monodisperse carbon spheres between 500 and 900 nm are hydrothermally synthesized from glucose on polystyrene seeds. Control over temperature, time, glucose concentration, and seed size yields hybrid spheres without aggregation and no additional spheres population. Pyrolysis transforms the hybrid into hollow carbon spheres preserving monodispersity. This approach provides a basis for functional carbon spheres applicable in photonics and energy storage.

A Rare Complication After Endovascular Aneurysm Repair: Disconnection of the Suprarenal Stent of a Zenith Endograft.

PURPOSE: To report a disconnection between the bare suprarenal stent and the main body of a Zenith endograft. CASE REPORT: A 79-year-old man with a history of successful endovascular repair of an aortic aneurysm presented a sudden episode of hypotension and hematuria. He had undergone implantation of a Zenith bifurcated device 8 years earlier in 2006. Plain abdominal radiography and computed tomography showed disconnection of the uncovered proximal stent, which led to endograft migration and type Ia endoleak. The patient also presented with distal endoleaks at the attachment sites in both common iliac arteries. The aneurysm sac diameter had increased from 52 to 96 mm. A proximal aortic cuff and bilateral iliac extensions were deployed via a common femoral artery access. Completion angiography did not show endoleak. CONCLUSION: After publication of a few such cases with the older Zenith device, the union between the suprarenal stent and main body was reinforced in 2002 to prevent this complication. Since modification of the device, this sequela had not been described. The reappearance of this complication underscores the need for continued surveillance, considering that these late events may require a reintervention to maintain the clinical success of the procedure.

Rapidly expanding ulnar false aneurysm related to a tablet computer.

Aneurysms of the ulnar artery are rare, usually related to the hypothenar hammer syndrome and caused by repetitive blunt trauma over the hook of the hamate bone. However, rapidly expanding ulnar false aneurysms are extremely rare, and nearly all are caused by a penetrating injury. We report a singular case of rapidly expanding pseudoaneurysm caused by the repetitive use of the hypothenar eminence as the supporting point of a tablet computer. This tablet model has a notch on its posterior side that played an essential role in the pathogenesis. This report illustrate that even low-intensity trauma can be an exceptional cause of injury to the palmar portion of the ulnar artery, and subsequently, can lead to the development of these lesions. The false aneurysm was repaired by means of resection and reconstruction by an end-to-end anastomosis because a rapid diagnosis and surgical treatment can prevent further complications.

The Roadside Technique for Type II Endoleak Embolization 4 Years after Endovascular Aortic Aneurysm Repair.

Endoleaks are the most common cause of reintervention after endovascular aortic aneurysm repair (EVAR). Type II endoleaks have been implicated as a risk factor for expansion and rupture. Several techniques have been described to manage type II endoleaks, being transarterial catheterization the most commonly used. In some cases this technique can be difficult or impossible to achieve. We report the use of a technique that offers a direct access to the aneurysm sac and the possibility of catheterization of the involved vessels or the embolization of the communication between them, even 4 years after EVAR.

Functional rehabilitation based on therapeutic exercise training in patients with postacute COVID syndrome (RECOVER).

INTRODUCTION AND OBJECTIVES: Postacute COVID syndrome (PACS) is common after acute SARS-CoV-2 infection. One of the most frequent and disabling symptoms is exercise intolerance (EI). Recent evidence suggests that EI in PACS has a peripheral (metabolic-neuromuscular) origin, suggesting that exercise training may be an effective treatment. The aim of this study was to assess the role a therapeutic physical exercise program (TPEP) in PACS with EI. METHODS: This single-center, open-label, randomized clinical trial compared an exercise training program (intervention group) with regular physical activity recommendations (control group) in patients with PACS and EI. The intervention group underwent an 8-week TPEP. The primary endpoint was improvement in functional capacity, assessed as the change in peak VO2. RESULTS: We included 50 participants with PACS (73% women, mean age 47±7.1 years). The intervention group showed a 15% improvement in peak VO2 (peak VO2 pre- and postintervention: 25.5±7.7mL/kg/min and 29.3±4.7 mL/kg/min; P <.001) and a 13.2% improvement in predicted values (92.1±14.3% and 108.4±13.4%; P <.001). No significant changes in VO2 values were observed in the control group. Unlike the control group, the intervention group also showed improvements in all secondary outcomes: quality of life scales, muscle power, maximum inspiratory power, metabolic flexibility, and body fat percentage. CONCLUSIONS: The program improved functional capacity in patients with PACS and EI.

Water-dependent micromechanical and rheological properties of silica colloidal crystals studied by nanoindentation.

Here we show the suitability of nanoindentation to study in detail the micromechanical response of silica colloidal crystals (CCs). The sensitivity to displacements smaller than the submicrometer spheres size, even resolving discrete events and superficial features, revealed particulate features with analogies to atomic crystals. Significant robustness, long-range structural deformation, and large energy dissipation were found. Easily implemented temperature/rate-dependent nanoindentation quantified the paramount role of adsorbed water endowing silica CCs with properties of wet granular materials like viscoplasticity. A novel "nongranular" CC was fabricated by substituting capillary bridges with silica necks to directly test water-independent mechanical response. Silica CCs, as specific (nanometric, ordered) wet granular assemblies with well-defined configuration, may be useful model systems for granular science and capillary cohesion at the nanoscale.

The method behind the unprecedented production of indicators of the presence of languages in the Internet.

Reliable and updated indicators of the presence of languages in the Internet are required to drive efficiently policies for languages, to forecast e-commerce market or to support further researches on the field of digital support of languages. This article presents a complete description of the methodological elements involved in the production of an unprecedented set of indicators of the presence in the Internet of the 329 languages with more than 1 million L1 speakers. A special emphasis is given to the treatment of the comprehensive set of biases involved in the process, either from the method or the various sources used in the modeling process. The biases related to other sources providing similar data are also discussed, and in particular, it is shown how the lack of consideration of the high level of multilingualism of the Web leads to a huge overestimation of the presence of English. The detailed list of sources is presented in the various annexes. For the first time in the history of the Internet, the production of indicators about virtual presence of a large set of languages could allow progress in the fields of economy of languages, cyber-geography of languages and language policies for multilingualism.

Defective engram allocation contributes to impaired fear memory performance in Down syndrome.

Down syndrome (DS) is the most common genetic form of intellectual disability (ID). The cellular and molecular mechanisms contributing to ID in DS are not completely understood. Recent evidence indicates that a given memory is encoded by sparsely distributed neurons, highly activated during learning, the engram cells. Intriguingly, mechanisms that are of paramount importance for engram formation are impaired in DS. Here we explored engram formation in a DS mouse model, the Ts65Dn and we found a reduced number of engram cells in the dentate gyrus (DG), suggesting reduced neuronal allocation to engrams. We also show that trisomic engram cells present reduced number of mature spines than WT engram cells and their excitability is not enhanced during memory recall. In fact, activation of engram cells using a chemogenetic approach does not recover memory deficits in Ts65Dn. Altogether, our findings suggest that perturbations in engram neurons may play a significant role in memory alterations in DS.

The lncRNA Snhg11, a new candidate contributing to neurogenesis, plasticity and memory deficits in Down syndrome.

Down syndrome (DS) stands as the prevalent genetic cause of intellectual disability, yet comprehensive understanding of its cellular and molecular underpinnings remains limited. In this study, we explore the cellular landscape of the hippocampus in a DS mouse model through single-nuclei transcriptional profiling. Our findings demonstrate that trisomy manifests as a highly specific modification of the transcriptome within distinct cell types. Remarkably, we observed a significant shift in the transcriptomic profile of granule cells in the dentate gyrus (DG) associated with trisomy. We identified the downregulation of a specific small nucleolar RNA host gene, Snhg11, as the primary driver behind this observed shift in the trisomic DG. Notably, reduced levels of Snhg11 in this region were also observed in a distinct DS mouse model, the Dp(16)1Yey, as well as in human postmortem tissue, indicating its relevance in Down syndrome. To elucidate the function of this long non-coding RNA (lncRNA), we knocked down Snhg11 in the DG of wild-type mice. Intriguingly, this intervention alone was sufficient to impair synaptic plasticity and adult neurogenesis, resembling the cognitive phenotypes associated with trisomy in the hippocampus. Our study uncovers the functional role of Snhg11 in the DG and underscores the significance of this lncRNA in intellectual disability. Furthermore, our findings highlight the importance of the DG in the memory deficits observed in Down syndrome.