Taste and smell : a unifying chemosensory theory

Since antiquity, the sense of smell (olfaction) is considered as a distance sense, just like sight and hear-ing. Conversely, the sense of taste (gustation) is thought to operate by direct contact, similarly to touch.With the progress of natural sciences, information at molecular, anatomical, and neurobiological levelshas also contributed to the taste-smell dichotomy, but much evidence inconsistent with a sharp differenti-ation of these two senses has emerged, especially when considering species other than humans. In spite ofthis, conflicting information has been interpreted so that it could conform to the traditional differentia-tion. As a result, a confirmation bias is currently affecting scientific research on chemosensory systemsand is also hindering the development of a satisfactory narrative of the evolution of chemical communi-cation across taxa. From this perspective, the chemosensory dichotomy loses its validity and usefulness. Wethus propose the unification of all chemosensory modalities into a single sense, moving toward a synthetic,complex, and interconnected perspective on the gradual processes by which a vast variety of chemicals havebecome signals that are crucially important to communication among and within cells, organs, and or-ganisms in a wide variety of environmental conditions

Taste and Smell: A Unifying Chemosensory Theory

Since antiquity, the sense of smell (olfaction) is considered as a distance sense, just like sight and hearing. Conversely, the sense of taste (gustation) is thought to operate by direct contact, similarly to touch. With the progress of natural sciences, information at molecular, anatomical, and neurobiological levels has also contributed to the taste-smell dichotomy, but much evidence inconsistent with a sharp differentiation of these two senses has emerged, especially when considering species other than humans. In spite of this, conflicting information has been interpreted so that it could conform to the traditional differentiation. As a result, a confirmation bias is currently affecting scientific research on chemosensory systems and is also hindering the development of a satisfactory narrative of the evolution of chemical communication across taxa. From this perspective, the chemosensory dichotomy loses its validity and usefulness. We thus propose the unification of all chemosensory modalities into a single sense, moving toward a synthetic, complex, and interconnected perspective on the gradual processes by which a vast variety of chemicals have become signals that are crucially important to communication among and within cells, organs, and organisms in a wide variety of environmental condition

Taste and Smell: A Unifying Chemosensory Theory

Since antiquity, the sense of smell (olfaction) is considered as a distance sense, just like sight and hear- ing. Conversely, the sense of taste (gustation) is thought to operate by direct contact, similarly to touch. With the progress of natural sciences, information at molecular, anatomical, and neurobiological levels has also contributed to the taste-smell dichotomy, but much evidence inconsistent with a sharp differenti- ation of these two senses has emerged, especially when considering species other than humans. In spite of this, conflicting information has been interpreted so that it could conform to the traditional differentia- tion. As a result, a confirmation bias is currently affecting scientific research on chemosensory systems and is also hindering the development of a satisfactory narrative of the evolution of chemical communi- cation across taxa. From this perspective, the chemosensory dichotomy loses its validity and usefulness. We thus propose the unification of all chemosensory modalities into a single sense, moving toward a synthetic, complex, and interconnected perspective on the gradual processes by which a vast variety of chemicals have become signals that are crucially important to communication among and within cells, organs, and or- ganisms in a wide variety of environmental conditions

Restoration of replication fork stability in BRCA1- and BRCA2-deficient cells by inactivation of SNF2-family fork remodelers

To ensure the completion of DNA replication and maintenance of genome integrity, DNA repair factors protect stalled replication forks upon replication stress. Previous studies have identified a critical role for the tumor suppressors BRCA1 and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease after replication stress. Here we show that depletion of SMARCAL1, a SNF2-family DNA translocase that remodels stalled forks, restores replication fork stability and reduces the formation of replication stress-induced DNA breaks and chromosomal aberrations in BRCA1/2-deficient cells. In addition to SMARCAL1, other SNF2-family fork remodelers, including ZRANB3 and HLTF, cause nascent DNA degradation and genomic instability in BRCA1/2-deficient cells upon replication stress. Our observations indicate that nascent DNA degradation in BRCA1/2-deficient cells occurs as a consequence of MRE11-dependent nucleolytic processing of reversed forks generated by fork remodelers. These studies provide mechanistic insights into the processes that cause genome instability in BRCA1/2- deficient cells

Potent Antioxidant and Genoprotective Effects of Boeravinone G, a Rotenoid Isolated from Boerhaavia diffusa

Background and Aims: Free radicals are implicated in the aetiology of some gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. In the present study we investigated the antioxidant and genoprotective activity of some rotenoids (i.e. boeravinones) isolated from the roots of Boerhaavia diffusa, a plant used in the Ayurvedic medicine for the treatment of diseases affecting the gastrointestinal tract. Methods/Principal Findings: Antioxidant activity has been evaluated using both chemical (Electron Spin Resonance spectroscopy, ESR) and Caco-2 cells-based (TBARS and ROS) assays. DNA damage was evaluated by Comet assay, while pERK 1/2 and phospho-NF-kB p65 levels were estimated by western blot. Boeravinones G, D and H significantly reduced the signal intensity of ESR induced by hydroxyl radicals, suggesting a scavenging activity. Among rotenoids tested, boeravinone G exerted the most potent effect. Boeravinone G inhibited both TBARS and ROS formation induced by Fenton's reagent, increased SOD activity and reduced H 2O 2-induced DNA damage. Finally, boeravinone G reduced the levels of pERK 1 and phospho-NF-kB p65 (but not of pERK 2) increased by Fenton's reagent. Conclusions: It is concluded that boeravinone G exhibits an extraordinary potent antioxidant activity (significant effect in the nanomolar range). The MAP kinase and NF-kB pathways seem to be involved in the antioxidant effect of boeravinone G. Boeravinone G might be considered as lead compound for the development of drugs potentially useful against those pathologies whose aetiology is related to ROS-mediated injuries

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

La misura dell’attaccamento materno prenatale: un confronto psicometrico di tre strumenti di valutazione

RIASSUNTO: Obiettivi: Questo studio confronta le proprietà psicometriche dei rating di attaccamento prenatale, misurati dalle scale Maternal Foetal Attachment Scale (MFAS), Prenatal Attachment Scale (PAI) e Maternal Antenatal Attachment Scale (MAAS), tenendo in considerazione l’età gestazionale. Metodo: 254 donne (età 31±5 anni; età gestazionale 24±11 settimane) hanno compilato i tre strumenti presentati in ordine casuale. L’attendibilità e la validità dei punteggi totali e parziali è stata valutata in funzione dell’età gestazionale. Risultati: I punteggi totali, in particolare quelli di MFAS e PAI, raggiungono gli standard di attendibilità, specialmente se i rating sono stati raccolti entro la 20-esima settimana. I punteggi parziali hanno una buona validità convergente, ma la loro attendibilità è minacciata dal ridotto numero di item, specialmente per i rating raccolti oltre la 21-esima settimana. Tutti i punteggi correlano con l’età gestazionale, mentre quelli del PAI erano i più correlati con le caratteristiche del campione. Conclusioni: I punteggi totali sono più attendibili dei punteggi parziali, ma essi colgono meno aspetti specifici del costrutto. Le proprietà psicometriche tendono a peggiorare nella seconda metà della gravidanza, presumibilmente a causa di un ‘effetto tetto’ nella valutazione materna. L’analisi fattoriale confermativa ha dimostrato che nessuno dei modelli ipotizzati nella letteratura raggiunge un fit accettabile. Ulteriori studi dovranno indagare la caratteristiche strutturali dei rating di attaccamento, per distinguere fattori comuni e specifici utili per le applicazioni cliniche e di ricerca