Bispyrene Functionalization Drives Self-Assembly of Graphite Nanoplates into Highly Efficient Heat Spreader Foils

Thermally conductive nanopapers fabricated from graphene and related materials are currently showing great potential in thermal management applications. However, thermal contacts between conductive plates represent the bottleneck for thermal conductivity of nanopapers prepared in the absence of a high temperature step for graphitization. In this work, the problem of ineffective thermal contacts is addressed by the use of bifunctional polyaromatic molecules designed to drive self-assembly of graphite nanoplates (GnP) and establish thermal bridges between them. To preserve the high conductivity associated to a defect-free sp2 structure, non-covalent functionalization with bispyrene compounds, synthesized on purpose with variable tethering chain length, was exploited. Pyrene terminal groups granted for a strong pi-pi interaction with graphene surface, as demonstrated by UV-Vis, fluorescence, and Raman spectroscopies. Bispyrene molecular junctions between GnP were found to control GnP organization and orientation within the nanopaper, delivering significant enhancement in both in-plane and cross-plane thermal diffusivities. Finally, nanopapers were validated as heat spreader devices for electronic components, evidencing comparable or better thermal dissipation performance than conventional Cu foil, while delivering over 90% weight reduction

The epileptology of Aicardi-Goutières syndrome: electro-clinical-radiological findings

Objective: Although epileptic seizures occur in approximately a quarter of patients with Aicardi-Goutie`res syndrome (AGS), their phenotypic and electrophysiological characterization remains elusive. The aim of our study was to characterize epilepsy phenotypes and electroencephalographic (EEG) patterns in AGS and look for possible correlations with clinical, genetic and neuroradiological features. Methods: We selected patients with an established AGS diagnosis followed at three Italian reference centers. Medical records, EEGs and MRI/CT findings were reviewed. EEGs were independently and blindly reviewed by three board-certified pediatric epileptologists. Chi square and Fisher?s exact tests were used to test associations between epilepsy and EEG feature categories and clinical, radiological and genetic variables. Results: Twenty-seven patients were enrolled. We reviewed 63 EEGs and at least one brain MRI scan per patient. Epilepsy, mainly in the form of epileptic spasms and focal seizures, was present in 37 % of the cohort; mean age at epilepsy onset was 9.5 months (range 1?36). The presence of epilepsy was associated with calcification severity (p = 0.016) and startle reactions (p = 0.05). Organization of EEG electrical activity appeared to be disrupted or markedly disrupted in 73 % of cases. Severe EEG disorganization correlated with microcephaly (p < 0.001) and highly abnormal MRI T2-weighted signal intensity in white matter (p = 0.022). Physiological organization of the EEG was found to be better preserved during sleep (87 %) than wakefulness (38 %). Focal slow activity was recorded in more than one third of cases. Fast activity, either diffuse or with frontal location, was more frequent in the awake state (78 %) than in sleep (50 %). Interictal epileptiform discharges (IEDs) were present in 33 % of awake and 45 % of sleep recordings. IEDs during sleep were associated with a higher risk of a epileptic seizures (p = 0.008). Significance: The hallmarks of EEG recordings in AGS were found to be: disruption of electrical organization, the presence of focal slow and fast activity, and the presence of IEDs, both in patients with and in those without epilepsy. The associations between epilepsy and calcification and between EEG pattern and the finding of a highly abnormal white matter T2 signal intensity suggest a common anatomical correlate. However, the complex anatomical-electroclinical basis of AGS-related epilepsy still requires further elucidation

Off-Target Inhibition of Human Dihydroorotate Dehydrogenase (hDHODH) Highlights Challenges in the Development of Fat Mass and Obesity-Associated Protein (FTO) Inhibitors

FTO, an N $^{6}$-methyladenosine (m$^{6}$A) and N $^{6}$,2'-O-dimethyladenosine (m$^{6}$A$_{m}$) RNA demethylase, is a promising target for treating acute myeloid leukemia (AML) due to the significant anticancer activity of its inhibitors in preclinical models. Here, we demonstrate that the FTO inhibitor FB23-2 suppresses proliferation across both AML and CML cell lines, irrespective of FTO dependency, indicating an alternative mechanism of action. Metabolomic analysis revealed that FB23-2 induces the accumulation of dihydroorotate (DHO), a key intermediate in pyrimidine nucleotide synthesis catalyzed by human dihydroorotate dehydrogenase (hDHODH). Notably, structural similarities between the catalytic pockets of FTO and hDHODH enabled FB23-2 to inhibit both enzymes. In contrast, the hDHODH-inactive FB23-2 analog, ZLD115, required FTO for its antiproliferative activity. Similarly, the FTO inhibitor CS2 (brequinar), known as one of the most potent hDHODH inhibitors, exhibited FTO-independent antileukemic effects. Uridine supplementation fully rescued leukemia cells from FB23-2 and CS2-induced growth inhibition, but not ZLD115, confirming the inhibition of pyrimidine synthesis as the primary mechanism of action underlying their antileukemic activity. These findings underscore the importance of considering off-target effects on hDHODH in the development of FTO inhibitors to optimize their therapeutic potential and minimize unintended consequences

Los mosaicos de vegetación y roca maximizan los servicios hídricos en las zonas altas de montaña del centro de la Argentina

En sistemas con lluvias estacionales, el rendimiento hídrico (caudal de salida del curso de agua relativo al área de la cuenca) en la estación seca depende de las lluvias previas y de la infiltración y la evapotranspiración, procesos que, a su vez, están afectados por las características del paisaje. Nuestro objetivo fue evaluar el efecto de distintas variables de paisaje sobre el rendimiento hídrico y la tasa de recesión (tasa a la que disminuye el caudal) durante la estación seca, en cuencas de alta montaña del centro de la Argentina. Seleccionamos 33 cuencas de 9-61 ha, y durante el final de la estación seca de 2017 medimos semanalmente el caudal en sus puntos de cierre durante siete semanas consecutivas. Para cada cuenca calculamos el rendimiento hídrico (mm/mes) promedio y un índice de recesión (adimensional) como la diferencia normalizada del rendimiento entre las últimas y las primeras fechas. Los paisajes extensamente ocupados por un mosaico de pajonal y roca, con pendiente y rugosidad intermedias, tuvieron los rendimientos hídricos máximos (>5 mm/mes). Por lo contrario, el rendimiento hídrico fue más bajo tanto en los paisajes suaves y cubiertos por vegetación, como en los muy ásperos (muy rugosos, escarpados y rocosos). Por su parte, la recesión fue lenta en los paisajes más ásperos y muy abrupta en los paisajes más suaves. Posiblemente, en los paisajes suaves y vegetados se pierde mucha agua por evapotranspiración, mientras que en los paisajes muy ásperos se pierde mucha agua por escorrentía después de las lluvias. Los paisajes con aspereza intermedia y un mosaico de vegetación y roca serían los que optimizan el almacenamiento, minimizando las pérdidas por evapotranspiración. Por lo tanto, para sostener el rendimiento hídrico es prioritario conservar este tipo de paisajes, evitando la erosión del suelo que genera un aumento de áreas rocosas.Fil: Cingolani, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Poca, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; ArgentinaFil: Whitworth Hulse, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi". Universidad Nacional de San Luis. Facultad de Ciencias Físico, Matemáticas y Naturales. Instituto de Matemática Aplicada de San Luis "Prof. Ezio Marchi"; ArgentinaFil: Giorgis, Melisa Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Vaieretti, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Herrero, María Lucrecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Navarro Ramos, Silvia Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Renison, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Global impoverishment of natural vegetation revealed by dark diversity

Anthropogenic biodiversity decline threatens the functioning of ecosystems and the many benefits they provide to humanity1. As well as causing species losses in directly affected locations, human influence might also reduce biodiversity in relatively unmodified vegetation if far-reaching anthropogenic effects trigger local extinctions and hinder recolonization. Here we show that local plant diversity is globally negatively related to the level of anthropogenic activity in the surrounding region. Impoverishment of natural vegetation was evident only when we considered community completeness: the proportion of all suitable species in the region that are present at a site. To estimate community completeness, we compared the number of recorded species with the dark diversity—ecologically suitable species that are absent from a site but present in the surrounding region2. In the sampled regions with a minimal human footprint index, an average of 35% of suitable plant species were present locally, compared with less than 20% in highly affected regions. Besides having the potential to uncover overlooked threats to biodiversity, dark diversity also provides guidance for nature conservation. Species in the dark diversity remain regionally present, and their local populations might be restored through measures that improve connectivity between natural vegetation fragments and reduce threats to population persistence

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Global impoverishment of natural vegetation revealed by dark diversity

Anthropogenic biodiversity decline threatens the functioning of ecosystems and the many benefits they provide to humanity . As well as causing species losses in directly affected locations, human influence might also reduce biodiversity in relatively unmodified vegetation if far-reaching anthropogenic effects trigger local extinctions and hinder recolonization. Here we show that local plant diversity is globally negatively related to the level of anthropogenic activity in the surrounding region. Impoverishment of natural vegetation was evident only when we considered community completeness: the proportion of all suitable species in the region that are present at a site. To estimate community completeness, we compared the number of recorded species with the dark diversity-ecologically suitable species that are absent from a site but present in the surrounding region . In the sampled regions with a minimal human footprint index, an average of 35% of suitable plant species were present locally, compared with less than 20% in highly affected regions. Besides having the potential to uncover overlooked threats to biodiversity, dark diversity also provides guidance for nature conservation. Species in the dark diversity remain regionally present, and their local populations might be restored through measures that improve connectivity between natural vegetation fragments and reduce threats to population persistence. [Abstract copyright: © 2025. The Author(s).

La lactancia como eje integrador de actividades en docencia, investigación y extensión

Promover la lactancia materna constituye una sencilla estrategia de prevención de la morbimortalidad infantil. Las decisiones y actitudes del equipo de salud condicionan los resultados de lactancia en una población. Por ello, capacitar a estudiantes de Medicina y motivarlos a participar en actividades diversas relacionadas con la lactancia constituye una estrategia de promoción a largoplazo. Se describen en este trabajo actividades encuadradas en la docencia, la extensión y la investigación que se realizan en la Facultad de Medicina de la Universidad Nacional de Tucumán tomando como eje a la lactancia. La docencia está representada por el Módulo Optativo Lactancia Materna, que se articula con el Voluntariado Universitario Apoyo a la Lactancia Materna y con el Proyecto de investigación sobre la misma temática. Se destaca la participación activa de los estudiantes y el valor de esta experiencia para su formación profesional y humana