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934 result(s) for "Alvarez, Xavier"
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Full-field thermal imaging of quasiballistic crosstalk reduction in nanoscale devices
Understanding nanoscale thermal transport is of substantial importance for designing contemporary semiconductor technologies. Heat removal from small sources is well established to be severely impeded compared to diffusive predictions due to the ballistic nature of the dominant heat carriers. Experimental observations are commonly interpreted through a reduction of effective thermal conductivity, even though most measurements only probe a single aggregate thermal metric. Here, we employ thermoreflectance thermal imaging to directly visualise the 2D temperature field produced by localised heat sources on InGaAs with characteristic widths down to 100 nm. Besides displaying effective thermal performance reductions up to 50% at the active junctions in agreement with prior studies, our steady-state thermal images reveal that, remarkably, 1–3 μm adjacent to submicron devices the crosstalk is actually reduced by up to fourfold. Submicrosecond transient imaging additionally shows responses to be faster than conventionally predicted. A possible explanation based on hydrodynamic heat transport, and some open questions, are discussed. When thermal fields in semiconductors approach the submicron scale, non-diffusive heat transport is observed where Fourier based heat transport models fail. Here, the authors use thermal imaging to visualise these thermal field variations and in turn derive a hydrodynamic heat transport model.
Cannabinoids modulate the microbiota–gut–brain axis in HIV/SIV infection by reducing neuroinflammation and dysbiosis while concurrently elevating endocannabinoid and indole-3-propionate levels
Background Although the advent of combination anti-retroviral therapy (cART) has transformed HIV into a manageable chronic disease, an estimated 30–50% of people living with HIV (PLWH) exhibit cognitive and motor deficits collectively known as HIV-associated neurocognitive disorders (HAND). A key driver of HAND neuropathology is chronic neuroinflammation, where proinflammatory mediators produced by activated microglia and macrophages are thought to inflict neuronal injury and loss. Moreover, the dysregulation of the microbiota–gut–brain axis (MGBA) in PLWH, consequent to gastrointestinal dysfunction and dysbiosis, can lead to neuroinflammation and persistent cognitive impairment, which underscores the need for new interventions. Methods We performed RNA-seq and microRNA profiling in basal ganglia (BG), metabolomics (plasma) and shotgun metagenomic sequencing (colon contents) in uninfected and SIV-infected rhesus macaques (RMs) administered vehicle (VEH/SIV) or delta-9-tetrahydrocannabinol (THC) (THC/SIV). Results Long-term, low-dose THC reduced neuroinflammation and dysbiosis and significantly increased plasma endocannabinoid, endocannabinoid-like, glycerophospholipid and indole-3-propionate levels in chronically SIV-infected RMs. Chronic THC potently blocked the upregulation of genes associated with type-I interferon responses ( NLRC5 , CCL2 , CXCL10 , IRF1 , IRF7 , STAT2 , BST2 ), excitotoxicity ( SLC7A11 ), and enhanced protein expression of WFS1 (endoplasmic reticulum stress) and CRYM (oxidative stress) in BG. Additionally, THC successfully countered miR-142-3p-mediated suppression of WFS1 protein expression via a cannabinoid receptor-1-mediated mechanism in HCN2 neuronal cells. Most importantly, THC significantly increased the relative abundance of Firmicutes and Clostridia including indole-3-propionate ( C. botulinum , C. paraputrificum , and C. cadaveris ) and butyrate ( C. butyricum , Faecalibacterium prausnitzii and Butyricicoccus pullicaecorum ) producers in colonic contents. Conclusion This study demonstrates the potential of long-term, low-dose THC to positively modulate the MGBA by reducing neuroinflammation, enhancing endocannabinoid levels and promoting the growth of gut bacterial species that produce neuroprotective metabolites, like indole-3-propionate. The findings from this study may benefit not only PLWH on cART, but also those with no access to cART and more importantly, those who fail to suppress the virus under cART.
Harnessing dairy wastewater to cultivate Scenedesmus sp. for biofertilizer applications in Phaseolus vulgaris L.: a sustainable agro-biotechnological approach
Transforming traditional linear production into sustainable circular processes is crucial, and integrating microalgae biomass production with wastewater recycling is a promising approach. This study addresses key challenges using dairy industry effluents as a nutrient-rich medium, achieving high biomass productivity and protein content with Scenedesmus sp. grown in an 80% wastewater-based medium. Impressive nutrient removal efficiencies were recorded for TN (79.24%) and PO 4 -3 (77.14%). The proposed culture medium achieved maximum productivity of 0.22 ± 0.05 g L −1 day −1 and a high protein concentration of 384.38 ± 34.06 mg g −1 , demonstrating the medium’s efficiency in promoting substantial biomass and nutritional quality. The application of Scenedesmus sp. biomass in treatment T 1 (extract) and T 2 (culture) in Phaseolus vulgaris significantly improved soil quality, increasing the concentration of organic matter (SOM), nitrates, phosphates, and microbial activity. Additionally, T 1 promoted the vegetative and reproductive development of P. vulgaris , as reflected in a germination index of 305.81%, an average height of 49.52 cm, higher leaf density, a greater number of floral buds, and enhanced floral development. These results demonstrate the bio-stimulatory potential of biomass and its role in practical bioremediation, highlighting the environmental and agricultural benefits of this innovative approach.
Antiretroviral therapy timing impacts latent tuberculosis infection reactivation in a Mycobacterium tuberculosis/SIV coinfection model
Studies using the nonhuman primate model of Mycobacterium tuberculosis/simian immunodeficiency virus coinfection have revealed protective CD4+ T cell-independent immune responses that suppress latent tuberculosis infection (LTBI) reactivation. In particular, chronic immune activation rather than the mere depletion of CD4+ T cells correlates with reactivation due to SIV coinfection. Here, we administered combinatorial antiretroviral therapy (cART) 2 weeks after SIV coinfection to study whether restoration of CD4+ T cell immunity occurred more broadly, and whether this prevented reactivation of LTBI compared to cART initiated 4 weeks after SIV. Earlier initiation of cART enhanced survival, led to better control of viral replication, and reduced immune activation in the periphery and lung vasculature, thereby reducing the rate of SIV-induced reactivation. We observed robust CD8+ T effector memory responses and significantly reduced macrophage turnover in the lung tissue. However, skewed CD4+ T effector memory responses persisted and new TB lesions formed after SIV coinfection. Thus, reactivation of LTBI is governed by very early events of SIV infection. Timing of cART is critical in mitigating chronic immune activation. The potential novelty of these findings mainly relates to the development of a robust animal model of human M. tuberculosis/HIV coinfection that allows the testing of underlying mechanisms.
Concurrent TB and HIV therapies control TB reactivation during co-infection but not chronic immune activation
Most HIV-negative individuals exposed to Mycobacterium tuberculosis ( Mtb ) control infection as latent TB infection (LTBI), but HIV co-infection greatly increases progression to tuberculosis (TB), the leading cause of death in people living with HIV (PLHIV). Although combination antiretroviral therapy (cART) reduces LTBI reactivation, immune control of Mtb is not fully restored, as shown by persistent TB incidence in PLHIV on cART. In macaques, skewed pulmonary effector memory CD4⁺ T-cell (T EM ) responses and new TB lesions persist despite cART. We hypothesize that concurrent anti-TB therapy with cART would improve bacterial control and immune restoration compared to cART alone. Using rhesus macaques (RM) with LTBI and Simian Immunodeficiency Virus (SIV) co-infection, we tested three months of weekly isoniazid and rifapentine (3HP) plus daily cART. Concurrent cART+3HP improves clinical and microbiological outcomes but fails to fully restore lung CD4⁺ T-cell immunity. Treated RMs retain caseous granulomas with high FDG uptake and incomplete CD4⁺ T-cell reconstitution, marked by persistent activation, exhaustion, and inflammation. CD4⁺ T EM cells remain depleted. Concurrent therapy induces Type I IFN signatures and enhances Mtb -specific T H1 /T H17 —but reduces TNFα—responses. These findings reveal persistent pulmonary immune defects underlying TB risk in HIV co-infection and identify potential targets for host-directed adjunctive therapies. The basis for inefficient Mtb control in PLWH despite treatment is unclear. Here, the authors show that combined TB/HIV therapy in Mtb/SIV co-infected macaques reduces bacterial and viral burden and improved lung pathology, but failed to fully restore immune balance, revealing persistent inflammation.
High Turnover of Tissue Macrophages Contributes to Tuberculosis Reactivation in Simian Immunodeficiency Virus-Infected Rhesus Macaques
Tuberculosis (TB) and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) profoundly affect the immune system and synergistically accelerate disease progression. It is believed that CD4+ T-cell depletion by HIV is the major cause of immunodeficiency and reactivation of latent TB. Previous studies demonstrated that blood monocyte turnover concurrent with tissue macrophage death from virus infection better predicted AIDS onset than CD4+ T-cell depletion in macaques infected with simian immunodeficiency virus (SIV). In this study, we describe the contribution of macrophages to the pathogenesis of Mycobacterium tuberculosis (Mtb)/SIV coinfection in a rhesus macaque model using in vivo BrdU labeling, immunostaining, flow cytometry, and confocal microscopy. We found that increased monocyte and macrophage turnover and levels of SIV-infected lung macrophages correlated with TB reactivation. All Mtb/SIV-coinfected monkeys exhibited declines in CD4+ T cells regardless of reactivation or latency outcomes, negating lower CD4+ T-cell levels as a primary cause of Mtb reactivation. Results suggest that SIV-related damage to macrophages contributes to Mtb reactivation during coinfection. This also supports strategies to target lung macrophages for the treatment of TB.
Resolving inflammation: The impact of antiretroviral therapy on macrophage traffic in and out of the CNS
The effects of antiretroviral therapy (ART) and treatment interruption on myeloid cell egress from the central nervous system (CNS) during human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection remain poorly defined. We hypothesized that CNS macrophages normally traffic out of the CNS, accumulate during viral infection and inflammation, and are released as inflammation resolves. To test this, we administered intracisternal (i.c.) injections of two different colored fluorescent superparamagnetic iron oxide nanoparticles (SPION) to SIV-infected macaques either early in infection (12-14 dpi) or 30 days before necropsy. SPION are preferentially taken up by perivascular, meningeal, and choroid plexus macrophages, enabling us to track macrophage turnover, infection, and migration. In non-infected macaques, SPION+ macrophages trafficked from the CNS to peripheral sites including the deep cervical lymph node (dCLN), lumbar lymph nodes, spleen, and dorsal root ganglia (DRG). With SIV infection, these cells accumulated in the CNS and showed reduced peripheral trafficking. ART decreased the number of SPION+ perivascular macrophages, and to a lesser extent, meningeal or choroid plexus macrophages. After ART interruption, SPION+ perivascular and choroid plexus macrophage numbers remained stable, whereas SPION+ meningeal macrophages increased. ART eliminated SIV-RNA+ perivascular macrophages, leaving few- scattered SIV-RNA+ cells in the meninges and choroid plexus. Following ART interruption, perivascular macrophages remained virus-negative, but scattered viral RNA+ meningeal macrophages persisted. In non-infected macaques, SPION+ macrophages trafficked to the dCLN, spleen, and DRG, but this trafficking diminished with SIV infection and AIDS with SIVE. Importantly, SIV-RNA+ SPION+ macrophages that exited the CNS were cleared by ART and did not reappear after treatment interruption. Using two differently colored SPION to assess establishment of CNS viral reservoirs, we observed higher numbers of early-labeled macrophages within and outside the CNS in animals with AIDS and SIVE, ART treatment, and ART interruption. These findings support a model in which SIV-infected perivascular macrophages seed an early CNS viral reservoir, while the meninges and choroid plexus undergo continual viral seeding during infection. ART reduces trafficking of infected macrophages out of the CNS and clears the perivascular macrophage reservoir, but SIV-RNA+ meningeal macrophages can persist, in low numbers, and can rebound after ART interruption.
Maternal CD4⁺ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission
Elucidation of maternal immune correlates of protection against congenital cytomegalovirus (CMV) is necessary to inform future vaccine design. Here, we present a novel rhesus macaque model of placental rhesus CMV (rhCMV) transmission and use it to dissect determinants of protection against congenital transmission following primary maternal rhCMV infection. In this model, asymptomatic intrauterine infection was observed following i.v. rhCMV inoculation during the early second trimester in two of three rhCMV-seronegative pregnant females. In contrast, fetal loss or infant CMV-associated sequelae occurred in four rhCMV-seronegative pregnant macaques that were CD4⁺ T-cell depleted at the time of inoculation. Animals that received the CD4⁺ T-cell–depleting antibody also exhibited higher plasma and amniotic fluid viral loads, dampened virus-specific CD8⁺ T-cell responses, and delayed production of autologous neutralizing antibodies compared with immunocompetent monkeys. Thus, maternal CD4⁺ T-cell immunity during primary rhCMV infection is important for controlling maternal viremia and inducing protective immune responses that prevent severe CMV-associated fetal disease.
Enhancement of Biomass and Lipid Productivities of Scenedesmus sp. Cultivated in the Wastewater of the Dairy Industry
Microalgae are photoautotrophic microorganisms capable of producing compounds with potential bioenergetic applications as an alternative energy source due to the imminent exhaustion of fossil fuels, their impact on the environment, and the constant population increase. The mass cultivation of these microorganisms requires high concentrations of nutrients, which is not profitable if analytical grade culture media are used. A viable alternative is the use of agro-industrial wastewater, due to the metabolic flexibility of these microorganisms and their ability to take advantage of the nutrients present in these substrates. For the reasons mentioned above, the effect of the cultivation in wastewater from cheese processing on the growth parameters and biomass composition of Scenedesmus sp. was evaluated, and its nutrient removal capacity determined. A high lipid concentration was obtained in the cultures with the dairy effluent (507.81 ± 19.09 mg g−1) compared to the standard culture medium, while the growth parameters remained similar to the control medium. Scenedesmus sp. achieved high percentages of nutrient assimilation of the wastewater used (88.41% and 97.07% for nitrogen and phosphorus, respectively). With the results obtained, the feasibility of cultivating microalgae in agro-industrial wastewater as an alternative culture medium that induces the accumulation of compounds with potential bioenergetic applications was verified.