The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression

Ion channels regulate cell proliferation, differentiation, and migration in normal and neoplastic cells through cell-cell and cell-extracellular matrix (ECM) transmembrane receptors called integrins. K+ flux through the human ether-\ue0-gogo- related gene 1 (hERG1) channel shapes action potential firing in excitable cells such as cardiomyocytes. Its abundance is often aberrantly high in tumors, where it modulates integrin-mediated signaling. We found that hERG1 interacted with the \u3b21 integrin subunit at the plasma membrane of human cancer cells. This interaction was not detected in cardiomyocytes because of the presence of the hERG1 auxiliary subunit KCNE1 (potassium voltage-gated channel subfamily E regulatory subunit 1), which blocked the \u3b21 integrin-hERG1 interaction. Although open hERG1 channels did not interact as strongly with \u3b21 integrins as did closed channels, current flow through hERG1 channelswas necessary to activate the integrin-dependent phosphorylation of Tyr397 in focal adhesion kinase (FAK) in both normal and cancer cells. In immunodeficient mice, proliferation was inhibited in breast cancer cells expressing forms of hERG1 with impaired K+ flow, whereas metastasis of breast cancer cells was reduced when the hERG1/\u3b21 integrin interaction was disrupted. We conclude that the interaction of \u3b21 integrins with hERG1 channels in cancer cells stimulated distinct signaling pathways that depended on the conformational state of hERG1 and affected different aspects of tumor progression

Inverse Association between Dietary Iron Intake and Gastric Cancer: A Pooled Analysis of Case-Control Studies of the Stop Consortium

Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 case-control studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83-0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77-0.94) and non-cardia GC (OR = 0.87, 95% CI = 0.81-0.94), and for diffuse (OR = 0.79, 95% CI = 0.69-0.89) and intestinal type (OR = 0.88, 95% CI = 0.79-0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis

Highly contiguous assemblies of 101 drosophilid genomes

Over 100 years of studies in Drosophila melanogaster and related species in the genus Drosophila have facilitated key discoveries in genetics, genomics, and evolution. While high-quality genome assemblies exist for several species in this group, they only encompass a small fraction of the genus. Recent advances in long-read sequencing allow high-quality genome assemblies for tens or even hundreds of species to be efficiently generated. Here, we utilize Oxford Nanopore sequencing to build an open community resource of genome assemblies for 101 lines of 93 drosophilid species encompassing 14 species groups and 35 sub-groups. The genomes are highly contiguous and complete, with an average contig N50 of 10.5 Mb and greater than 97% BUSCO completeness in 97/101 assemblies. We show that Nanopore-based assemblies are highly accurate in coding regions, particularly with respect to coding insertions and deletions. These assemblies, along with a detailed laboratory protocol and assembly pipelines, are released as a public resource and will serve as a starting point for addressing broad questions of genetics, ecology, and evolution at the scale of hundreds of species

Organic pumpkin production: comparison between different planting methods and planting spacings

openOriginaria dell’Asia Minore (Lageneria) e delle Americhe (Cucurbita), al giorno d’oggi la zucca è diffusa e utilizzata in tutto il mondo. Quando si parla di zucca in particolare ci si riferisce alle specie Cucurbita moschata e Cucurbita maxima che differiscono tra loro in quanto: la prima presenta semi bianchi e picciolo angoloso (es: Violina, Butternut, Moscata di Provenza), mentre la seconda è caratterizzata da semi con superficie bianco-gialla lucida e peduncolo cilindrico, morbido e spugnoso (es: Hokkaido, Delica, Marina di Chioggia, Grigia di Bologna, Mantovana, Quintale, Turbante). In Italia l’ortaggio ha un ruolo rilevante in ambito culinario poiché il gusto delicato e più o meno dolce a seconda della varietà si presta ai più svariati e numerosi utilizzi tanto che a tavola può benissimo accompagnarci dal primo piatto al dolce. La crescita della domanda di prodotto fresco e trasformato dalle agroindustrie e la carenza di informazioni precise relative alle tecniche di coltivazione più adeguate ed efficienti ci ha spinto ad effettuare una prova sperimentale al fine di poter ottenere dei primi rilevamenti per rispondere a quesiti in merito al metodo di insediamento dell’ortaggio e all’efficienza e efficacia del sesto d’impianto utilizzato. Sono state messe a confronto tre varietà di zucca: • Cultivar: Delica (Cucurbita maxima) ibrido F1 Violina (Cucurbita moschata) Hokkaido (Cucurbita maxima) • Metodo di insediamento: Semina in pieno campo (28 aprile) Trapianto da substrato 1 (5 maggio) Trapianto da substrato 2 (5 maggio) • Sesto d’impianto (variazione della distanza tra le piante sulla fila): 0,70 m 1 m 1,30 m La valutazione è stata scomposta in più fasi: FASE 1 (Vivaistica) • tempo necessario al germogliamento • germinabilità dei semi • caratteristiche delle plantule all’uscita dal vivaio: altezza, n° di foglie sviluppate, peso fresco, percentuale di clorofilla FASE 2 (Monitoraggi di crescita) • sopravvivenza post-trapianto delle plantule/germogliamento dei semi • caratteristiche delle piante: lunghezza del fusto principale, lunghezza del secondo fusto maggiore, n° fusti secondari, n° frutti, diametro frutti FASE 3 (Monitoraggi di produzione) • diametro e n° frutti (su parcella 3mx3m) FASE 4 (Raccolta) • caratteristiche del frutto: diametro, peso, rapporto peso/volume, colore Le analisi effettuate hanno evidenziato che: • la precocità di germinazione osservata da substrato Bioton, in particolare di Violina non ha influenzanto lo sviluppo successivo; • i semi di Hokkaido hanno evidenziato una germinabilità inferiore sia da substrato che da semina rispetto alle altre due varietà; • tra i due substrati utilizzati quello che ha incentivato maggiormente lo sviluppo è stato il Bioton, terriccio per orticoltura biologica della Vigor Plant; • trapianto da substrato Bioton e semina hanno prodotto risultati simili perciò si sostiene che la semina sia preferibile al trapianto se sono presenti fattori che possono decimare la popolazione trapiantata (es: grilli terricoli), al contrario, è necessario preferire il trapianto se si presume l’eventuale presenza di ristagni idrici; • come da aspettative, c’è una relazione diretta tra sviluppo e produzione che infatti è stata ottenuta dal sesto d’impianto con la distanza maggiore; • piante cresciute ad una distanza sulla fila di 0,7 m e da substrato Neutro hanno manifestato una minor crescita dell’apparato vegetativo e una produzione di frutti anticipata ma minore.Originally from Asia Minor (Lageneria) and the Americas (Cucurbita), pumpkin is now widespreadand used throughout the world. When we talk about pumpkin in particular we are referring to the species Cucurbita moschata and Cucurbita maxima which differ from each other in that: the first has white seeds and an angular peduncle (ex. Violina, Butternut, Moscata di Provenza), while the second is characterized by seeds with shiny white-yellow surface and cylindrical, soft and spongy peduncle (ex. Hokkaido, Delica, Marina di Chioggia, Grigia di Bologna, Mantovana, Quintale, Turbante). In Italy the vegetable plays an important role in the culinary field since the delicate and more or less sweet taste depending on the variety lends itself to the most varied an numerous uses, so much so that it can very well accompany at the table from the first course to the dessert. The growth in demand for fresh and processed products from agro-industries and the lack of precise information relating to the most appropriate and efficient cultivation technique has pushed us to carry out an experimental test in order to obtain the first findings to answer questions regarding the method ot establishment of the vegetable and efficiency and effectiveness of the planting layout used. Three varieties of pumpkin were compared: • Cultivars: Delica (Cucurbita maxima) hybrid F1 Violina (Cucurbita moschata) Hokkaido (Cucurbita maxima) • Establishment methods: Sow in open field (April 28) Substrate transplant 1 (May 5) Substrate transplant 2 (May 5) • Planting spacing (variation of the distance between the plants in the row): 0.70 m 1 m 1.30 m The evaluation was divide into different phases: PHASE 1 (Nursery) • time necessary for sprouting • germination of seeds • characteristics of the seedlings upon leaving the nursery: height, number of developed leaves, fresh weight, percentage of chlorophyll PHASE 2 (Growth monitoring) • post-transplant survival of seedlings/seed germination • characteristics of the plants: length of the main stem, length of the second major stem,number of secondary stems, number of fruits, diameter of fruits PHASE 3 (Production monitoring) • diameter and number of fruits (on a 3m x 3m plot) PHASE 4 (Picking) • characteristics of the fruit: diameter, weight, weight/volume ratio, colour The analyses carried out highlighted that: • the early germination observed with Bioton substrate, in particular with Violina, did not influence subsequent development; • Hokkaido seeds showed lower germination both from substrate and from sowing compared to the other two varieties; • of the two substrates used, the one that encouraged development the most was Bioton, soil for organic horticulture from Vigor Plant; • transplantation from Bioton substrate and sowing have produced similar resuls therefore it is argued that sowing is preferable to transplanting if there are factors that can decimate the transplanted population (ex. Ground crickets), on the contrary, it is necessary to prefer transplanting it it is presumed the possible presence of water stagnation; • as expected, there is a direct relationship between development and production which in fact was obtained from the plant layout with the biggest distance; • plants grown at a distance of 0.70 m in the row and on a Neutral substrate showed lower groth of the vegetative system and earlier but lower fruit production

The neuronal circuit of the dorsal circadian clock neurons in Drosophila melanogaster

Drosophila’s dorsal clock neurons (DNs) consist of four clusters (DN1as, DN1ps, DN2s, and DN3s) that largely differ in size. While the DN1as and the DN2s encompass only two neurons, the DN1ps consist of ∼15 neurons, and the DN3s comprise ∼40 neurons per brain hemisphere. In comparison to the well-characterized lateral clock neurons (LNs), the neuroanatomy and function of the DNs are still not clear. Over the past decade, numerous studies have addressed their role in the fly’s circadian system, leading to several sometimes divergent results. Nonetheless, these studies agreed that the DNs are important to fine-tune activity under light and temperature cycles and play essential roles in linking the output from the LNs to downstream neurons that control sleep and metabolism. Here, we used the Flybow system, specific split-GAL4 lines, trans-Tango, and the recently published fly connectome (called hemibrain) to describe the morphology of the DNs in greater detail, including their synaptic connections to other clock and non-clock neurons. We show that some DN groups are largely heterogenous. While certain DNs are strongly connected with the LNs, others are mainly output neurons that signal to circuits downstream of the clock. Among the latter are mushroom body neurons, central complex neurons, tubercle bulb neurons, neurosecretory cells in the pars intercerebralis, and other still unidentified partners. This heterogeneity of the DNs may explain some of the conflicting results previously found about their functionality. Most importantly, we identify two putative novel communication centers of the clock network: one fiber bundle in the superior lateral protocerebrum running toward the anterior optic tubercle and one fiber hub in the posterior lateral protocerebrum. Both are invaded by several DNs and LNs and might play an instrumental role in the clock network

Sleep Duration and Stress Level in the Risk of Gastric Cancer: A Pooled Analysis of Case-Control Studies in the Stomach Cancer Pooling (StoP) Project.

The association between sleep and stress and cancer is underinvestigated. We evaluated these factors in association with gastric cancer (GC). Five case-control studies from the Stomach Cancer Pooling (StoP) Project were included. We calculated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for sleep duration and stress level in association with GC through multiple logistic regression models adjusted for several lifestyle factors. The analysis included 1293 cases and 4439 controls, 215 cardia and 919 noncardia GC, and 353 diffuse and 619 intestinal types. Sleep duration of ≥9 h was associated with GC (OR =1.57, 95% CI = 1.23-2.00) compared to 8 h. This was confirmed when stratifying by subsite (noncardia OR = 1.59, 95% CI = 1.22-2.08, and cardia OR = 1.63, 95% CI = 0.97-2.72) and histological type (diffuse OR = 1.65, 95% CI = 1.14-2.40 and intestinal OR = 1.24, 95% CI = 0.91-1.67). Stress was associated with GC (OR = 1.33, 95% CI = 1.18-1.50, continuous). This relationship was selectively related to noncardia GC (OR = 1.28, 95% 1.12-1.46, continuous). The risk of diffuse (OR = 1.32, 95% CI = 1.11-1.58) and intestinal type (OR = 1.23, 95% CI = 1.07-1.42) were higher when stress was reported. Results for the association between increasing level of stress and GC were heterogeneous by smoking and socioeconomic status (p for heterogeneity = 0.02 and <0.001, respectively). In conclusion, long sleep duration (≥9 h) was associated with GC and its subtype categories. Stress linearly increased the risk of GC and was related to noncardia GC

The mediating role of combined lifestyle factors on the relationship between education and gastric cancer in the Stomach cancer Pooling (StoP) Project

BackgroundThe causal pathway between high education and reduced risk of gastric cancer (GC) has not been explained. The study aimed at evaluating the mediating role of lifestyle factors on the relationship between education and GC METHODS: Ten studies with complete data on education and five lifestyle factors (smoking, alcohol drinking, fruit and vegetable intake, processed meat intake and salt consumption) were selected from a consortium of studies on GC including 4349 GC cases and 8441 controls. We created an a priori score based on the five lifestyle factors, and we carried out a counterfactual-based mediation analysis to decompose the total effect of education on GC into natural direct effect and natural indirect effect mediated by the combined lifestyle factors. Effects were expressed as odds ratios (ORs) with a low level of education as the reference category.ResultsThe natural direct and indirect effects of high versus low education were 0.69 (95% CI: 0.62-0.77) and 0.96 (95% CI: 0.95-0.97), respectively, corresponding to a mediated percentage of 10.1% (95% CI: 7.1-15.4%). The mediation effect was limited to men.ConclusionsThe mediation effect of the combined lifestyle factors on the relationship between education and GC is modest. Other potential pathways explaining that relationship warrants further investigation

Inverse Association between Dietary Iron Intake and Gastric Cancer: A Pooled Analysis of Case-Control Studies of the Stop Consortium.

Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 case-control studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83-0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77-0.94) and non-cardia GC (OR = 0.87, 95% CI = 0.81-0.94), and for diffuse (OR = 0.79, 95% CI = 0.69-0.89) and intestinal type (OR = 0.88, 95% CI = 0.79-0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis

Yoghurt Intake and Gastric Cancer: A Pooled Analysis of 16 Studies of the StoP Consortium

BackgroundYoghurt can modify gastrointestinal disease risk, possibly acting on gut microbiota. Our study aimed at exploring the under-investigated association between yoghurt and gastric cancer (GC).MethodsWe pooled data from 16 studies from the Stomach Cancer Pooling (StoP) Project. Total yoghurt intake was derived from food frequency questionnaires. We calculated study-specific odds ratios (ORs) of GC and the corresponding 95% confidence intervals (CIs) for increasing categories of yoghurt consumption using univariate and multivariable unconditional logistic regression models. A two-stage analysis, with a meta-analysis of the pooled adjusted data, was conducted.ResultsThe analysis included 6278 GC cases and 14,181 controls, including 1179 cardia and 3463 non-cardia, 1191 diffuse and 1717 intestinal cases. The overall meta-analysis revealed no association between increasing portions of yoghurt intake (continuous) and GC (OR = 0.98, 95% CI = 0.94-1.02). When restricting to cohort studies, a borderline inverse relationship was found (OR = 0.93, 95% CI = 0.88-0.99). The adjusted and unadjusted OR were 0.92 (95% CI = 0.85-0.99) and 0.78 (95% CI = 0.73-0.84) for any vs. no yoghurt consumption and GC risk. The OR for 1 category of increase in yoghurt intake was 0.96 (95% CI = 0.91-1.02) for cardia, 1.03 (95% CI = 1.00-1.07) for non-cardia, 1.12 (95% CI = 1.07-1.19) for diffuse and 1.02 (95% CI = 0.97-1.06) for intestinal GC. No effect was seen within hospital-based and population-based studies, nor in men or women.ConclusionsWe found no association between yoghurt and GC in the main adjusted models, despite sensitivity analyses suggesting a protective effect. Additional studies should further address this association