Nueva información palinológica sobre la Formación Poti (Viseano superior) en el arroyo Roncador, Cuenca Parnaíba, noreste de Brasil

Se presenta el resultado del análisis palinológico de seis muestras de superficie de la Formación Poti expuesta en el arroyo Roncador (Jerumenha, Piauí), noreste de Brasil. Esta unidad sobreyace en discordancia a la Formación Longá (Famenniano superior-Tournaisiano) y sobre ella se dispone en discordancia la Formación Piaui (Pennsylvaniano inferior). Lutitas carbonosas y limolitas brindaron una diversa asociación de palinomorfos bien preservados, compuesta por 95 especies: 58 especies autóctonas de esporas y 5 de algas, y 9 especies de esporas y 23 especies de microplancton retrabajados principalmente de depósitos del Devónico. Se describen tres nuevas especies (Verrucosisporites iannuzzii, V. roncadorense, V. souzai). Se documenta el primer registro de 24 especies para el Mississippiano de Brasil y 7 especies para América del Sur. Entre las especies con valor estratigráfico registradas en la sección aquí estudiada Anapiculatisporites amplus, A. concinnus, Foveosporites pellucidus, Grandispora maculosa, Reticulatisporites magnidictyus, Verrucosisporites morulatus, Waltzispora polita, junto con otras no registradas previamente en la Formación Poti (Apiculiretusispora microseta, Densosporites spinosus, Knoxisporites ruhlandi, Punctatisporites subvaricosus, Retusotriletes mirabilis, Tricidarisporites phippsae), confirman una edad Viseano tardío y su correlación con la Zona R. magnidictyus (Mag) Melo y Loboziak. La comparación mundial del presente conjunto palinológico indica una gran afinidad con palinofloras coetáneas distribuidas en paleolatitudes similares en América del Sur, Norte de África y Australia (Reino Paracas). Las características sedimentológicas (e.g., areniscas con estratificación cruzada sigmoidal y ondulitas) y paleontológicas (e.g., restos de plantas y abundante materia orgánica terrestre) de la sección indican que la depositación ocurrió en un ambiente de estuario de baja profundidad.This contribution presents the results of the palynological analysis of six surface samples of the Poti Formation cropping out at the Roncador creek (Jerumenha, Piauí), northeastern Brazil. This unit unconformable overlies the upper Famennian-Tournaisian Longá Formation and it is unconformable overlain by the lower Pennsylvanian Piaui Formation. Carbonaceous shales and siltstones yielded a diverse assemblage of well-preserved palynomorphs, composed of 95 species: 58 indigenous spore, and 5 algal species, and 9 reworked spore and 23 reworked microplankton species mostly from Devonian strata. Three new species are described (Verrucosisporites iannuzzii, V. roncadorense, V. souzai). First records for the Mississippian of Brazil (24 species) and South America (7 species) are also documented. Several age diagnostic species recorded in the Poti Formation (Anapiculatisporites amplus, A. concinnus, Foveosporites pellucidus, Grandispora maculosa, Reticulatisporites magnidictyus, Verrucosisporites morulatus and Waltzispora polita), completed with others not previously documented in subsurface deposits of this unit (Apiculiretusispora microseta, Densosporites spinosus, Knoxisporites ruhlandi, Punctatisporites subvaricosus, Retusotriletes mirabilis and Tricidarisporites phippsae), confirms a late Visean age and its correlation to the R. magnidictyus Melo and Loboziak Zone. Worldwide comparison of the Roncador association indicates greater affinity with coeval palynofloras with similar paleolatitudinal position in South America, North Africa and Australia (Paracas Realm). Sedimentologic (e.g., sandstones with sigmoidal cross and wave ripples beddings) and paleontological features (e.g., plant remains and abundant terrestrial organic matter) along this section document a shallow estuarine depositional environment.Fil: Di Pasquo Lartigue, Maria. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Iannuzzi, R.. Universidade Federal do Rio Grande do Sul; Brasi

hMENA11a contributes to HER3-mediated resistance to PI3K inhibitors in HER2-overexpressing breast cancer cells.

Human Mena (hMENA), an actin regulatory protein of the ENA/VASP family, cooperates with ErbB receptor family signaling in breast cancer. It is overexpressed in high-risk preneoplastic lesions and in primary breast tumors where it correlates with HER2 overexpression and an activated status of AKT and MAPK. The concomitant overexpression of hMENA and HER2 in breast cancer patients is indicative of a worse prognosis. hMENA is expressed along with alternatively expressed isoforms, hMENA11a and hMENAΔv6 with opposite functions. A novel role for the epithelial-associated hMENA11a isoform in sustaining HER3 activation and pro-survival pathways in HER2-overexpressing breast cancer cells has been identified by reverse phase protein array and validated in vivo in a series of breast cancer tissues. As HER3 activation is crucial in mechanisms of cell resistance to PI3K inhibitors, we explored whether hMENA11a is involved in these resistance mechanisms. The specific hMENA11a depletion switched off the HER3-related pathway activated by PI3K inhibitors and impaired the nuclear accumulation of HER3 transcription factor FOXO3a induced by PI3K inhibitors, whereas PI3K inhibitors activated hMENA11a phosphorylation and affected its localization. At the functional level, we found that hMENA11a sustains cell proliferation and survival in response to PI3K inhibitor treatment, whereas hMENA11a silencing increases molecules involved in cancer cell apoptosis. As shown in three-dimensional cultures, hMENA11a contributes to resistance to PI3K inhibition because its depletion drastically reduced cell viability upon treatment with PI3K inhibitor BEZ235. Altogether, these results indicate that hMENA11a in HER2-overexpressing breast cancer cells sustains HER3/AKT axis activation and contributes to HER3-mediated resistance mechanisms to PI3K inhibitors. Thus, hMENA11a expression can be proposed as a marker of HER3 activation and resistance to PI3K inhibition therapies, to select patients who may benefit from these combined targeted treatments. hMENA11a activity could represent a new target for antiproliferative therapies in breast cancer

GALNT2 as a novel modulator of adipogenesis and adipocyte insulin signaling

Background/objectives: A better understanding of adipose tissue biology is crucial to tackle insulin resistance and eventually coronary heart disease and diabetes, leading causes of morbidity and mortality worldwide. GALNT2, a GalNAc-transferase, positively modulates insulin signaling in human liver cells by down-regulating ENPP1, an insulin signaling inhibitor. GALNT2 expression is increased in adipose tissue of obese as compared to that of non-obese individuals. Whether this association is secondary to a GALNT2-insulin sensitizing effect exerted also in adipocytes is unknown. We then investigated in mouse 3T3-L1 adipocytes the GALNT2 effect on adipogenesis, insulin signaling and expression levels of both Enpp1 and 72 adipogenesis-related genes. Methods: Stable over-expressing GALNT2 and GFP preadipocytes (T 0 ) were generated. Adipogenesis was induced with (R+) or without (R−) rosiglitazone and investigated after 15 days (T 15 ). Lipid accumulation (by Oil Red-O staining) and intracellular triglycerides (by fluorimetric assay) were measured. Lipid droplets (LD) measures were analyzed at confocal microscope. Gene expression was assessed by RT-PCR and insulin-induced insulin receptor (IR), IRS1, JNK and AKT phosphorylation by Western blot. Results: Lipid accumulation, triglycerides and LD measures progressively increased from T 0 to T 15 R- and furthermore to T 15 R+. Such increases were significantly higher in GALNT2 than in GFP cells so that, as compared to T 15 R+GFP, T 15 R- GALNT2 cells showed similar (intracellular lipid and triglycerides accumulation) or even higher (LD measures, p < 0.01) values. In GALNT2 preadipocytes, insulin-induced IR, IRS1 and AKT activation was higher than that in GFP cells. GALNT2 effect was totally abolished during adipocyte maturation and completely reversed at late stage maturation. Such GALNT2 effect trajectory was paralleled by coordinated changes in the expression of Enpp1 and adipocyte-maturation key genes. Conclusions: GALNT2 is a novel modulator of adipogenesis and related cellular phenotypes, thus becoming a potential target for tackling the obesity epidemics and its devastating sequelae

Oxysterol-Binding Protein-1 (OSBP1) Modulates Processing and Trafficking of the Amyloid Precursor Protein

BACKGROUND Evidence from biochemical, epidemiological and genetic findings indicates that cholesterol levels are linked to amyloid-β (Aβ) production and Alzheimer's disease (AD). Oxysterols, which are cholesterol-derived ligands of the liver X receptors (LXRs) and oxysterol binding proteins, strongly regulate the processing of amyloid precursor protein (APP). Although LXRs have been studied extensively, little is known about the biology of oxysterol binding proteins. Oxysterol-binding protein 1 (OSBP1) is a member of a family of sterol-binding proteins with roles in lipid metabolism, regulation of secretory vesicle generation and signal transduction, and it is thought that these proteins may act as sterol sensors to control a variety of sterol-dependent cellular processes. RESULTS We investigated whether OSBP1 was involved in regulating APP processing and found that overexpression of OSBP1 downregulated the amyloidogenic processing of APP, while OSBP1 knockdown had the opposite effect. In addition, we found that OSBP1 altered the trafficking of APP-Notch2 dimers by causing their accumulation in the Golgi, an effect that could be reversed by treating cells with OSBP1 ligand, 25-hydroxycholesterol. CONCLUSION These results suggest that OSBP1 could play a role in linking cholesterol metabolism with intracellular APP trafficking and Aβ production, and more importantly indicate that OSBP1 could provide an alternative target for Aβ-directed therapeutic.National Institute on Aging (AG/NS17485

Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation

The aberrant activation of hedgehog (HH) signaling is a leading cause of the development of medulloblastoma, a pediatric tumor of the cerebellum. The FDA‑approved HH inhibitor, Vismodegib, which targets the transmembrane transducer SMO, has shown limited efficacy in patients with medulloblastoma, due to compensatory mechanisms that maintain an active HH‑GLI signaling status. Thus, the identification of novel actionable mechanisms, directly affecting the activity of the HH‑regulated GLI transcription factors is an important goal for these malignancies. In this study, using gene expression and reporter assays, combined with biochemical and cellular analyses, we demonstrate that mitogen‑activated kinase kinase kinase 1 (MEKK1), the most upstream kinase of the mitogen‑activated protein kinase (MAPK) phosphorylation modules, suppresses HH signaling by associating and phosphorylating GLI1, the most potent HH‑regulated transcription factor. Phosphorylation occurred at multiple residues in the C‑terminal region of GLI1 and was followed by an increased association with the cytoplasmic proteins 14‑3‑3. Of note, the enforced expression of MEKK1 or the exposure of medulloblastoma cells to the MEKK1 activator, Nocodazole, resulted in a marked inhibitory effect on GLI1 activity and tumor cell proliferation and viability. Taken together, the results of this study shed light on a novel regulatory mechanism of HH signaling, with potentially relevant implications in cancer therapy

Correlation between parodontal indexes and orthodontic retainers: prospective study in a group of 16 patients

Purpose. Fixed retainers are used to stabilize dental elements after orthodontic treatment. Being it a permanent treatment, it is necessary to instruct patients about a constant and continuous monitoring of their periodontal conditions and a correct oral hygiene. The aim of this study was to highlight the possible adverse effects of bonded retainers on parameters correlated to the health conditions of periodontal tissues. Materials and methods. We selected 16 patients, under treatment in the Orthodontics Department of University of Bari Dental School, who had undergone a lingual retainer insertion at the end of the orthodontic treatment. The patients were then divided into two groups (Control Group and Study Group) and monitored for 3 and 36 months, respectively. The following indexes were taken into consideration: gingival index (GI), plaque index (PI) and the presence of calculus (Calculus Index, CI), the probing depth and the presence of gingival recession on the six inferior frontal dental elements. Results. After the observation was carried out, any of the patients showed periodontal sockets and gingival recession. In the Study Group, only 1 patient had a PI score=3, the 7 left had scores between 0.66 and 2.83. In the Control Group, one patient had score=0, the other ones showed values between 0.5 and 1.66. The mean GI in the Study Group peaked at a score of 2.83, the minimum was 0.66; whereas in the Control Group the maximum value was 2 and the minimum 0.66. The CI in the Group Study was between 1 and 2. In the Control Group it was absent in only 1 patient, whereas in the remaining 7, it had a value between 0.3 and 1. The clinical data were studied by means of the Wilcoxon test. We found a statistically significant difference for what concerns the Plaque Indexes (PI) (P>0.05) and Calculus Indexes (CI) (P>0.1) in both groups, with higher scores in the Study Group, having retainers for 36 months. Any statistically significant difference was calculated for the GI. Conclusions. We can therefore conclude that patients with lingual retainers need periodontal hygiene and treatment as to prevent, in the course of time, periodontal damages non-detectable in short-term

Genome Sequencing of Ancient Plant Remains: Findings, Uses and Potential Applications for the Study and Improvement of Modern Crops

The advent of new sequencing technologies is revolutionizing the studies of ancient DNA (aDNA). In the last 30 years, DNA extracted from the ancient remains of several plant species has been explored in small-scale studies, contributing to understand the adaptation, and migration patterns of important crops. More recently, NGS technologies applied on aDNA have opened up new avenues of research, allowing investigation of the domestication process on the whole-genome scale. Genomic approaches based on genome-wide and targeted sequencing have been shown to provide important information on crop evolution and on the history of agriculture. Huge amounts of next-generation sequencing (NGS) data offer various solutions to overcome problems related to the origin of the material, such as degradation, fragmentation of polynucleotides, and external contamination. Recent advances made in several crop domestication studies have boosted interest in this research area. Remains of any nature are potential candidates for aDNA recovery and almost all the analyses that can be made on fresh DNA can also be performed on aDNA. The analysis performed on aDNA can shed light on many phylogenetic questions concerning evolution, domestication, and improvement of plant species. It is a powerful instrument to reconstruct patterns of crop adaptation and migration. Information gathered can also be used in many fields of modern agriculture such as classical breeding, genome editing, pest management, and product promotion. Whilst unlocking the hidden genome of ancient crops offers great potential, the onus is now on the research community to use such information to gain new insight into agriculture

Nurturing International Business research through Global Value Chains literature: A review and discussion of future research opportunities

This article offers a comprehensive and systematic review of the literature on Global Value Chains (GVCs). The GVC framework has received growing attention in the last decade, providing theoretical concepts and analytical tools to understand and assess patterns of value creation in view of the new international division of labour. In this area, a broad overlap of research interest exists with the international business (IB) literature. Yet, few interactions between the two fields of study have been recorded so far. Performing a quantitative content analysis on all academic publications on GVCs in the period 1994−2018, this paper describes the evolution of GVC studies, emphasizing points of contact and potential synergies with the IB literature. It also identifies research opportunities along the four key dimensions of the GVC framework: geographical and industrial scope, governance, upgrading, and institutional context