Next generation sequencing technologies to address aberrant mRNA translation in cancer.

In this review, we explore the transformative impact of next generation sequencing technologies in the realm of translatomics (the study of how translational machinery acts on a genome-wide scale). Despite the expectation of a direct correlation between mRNA and protein content, the complex regulatory mechanisms that affect this relationship remark the limitations of standard RNA-seq approaches. Then, the review characterizes crucial techniques such as polysome profiling, ribo-seq, trap-seq, proximity-specific ribosome profiling, rnc-seq, tcp-seq, qti-seq and scRibo-seq. All these methods are summarized within the context of cancer research, shedding light on their applications in deciphering aberrant translation in cancer cells. In addition, we encompass databases and bioinformatic tools essential for researchers that want to address translatome analysis in the context of cancer biology.

Variations in Fruit Ploidy Level and Cell Size between Small- and Large-Fruited Olive Cultivars during Fruit Ontogeny.

Olive (Olea europaea L.) is one of the major oil fruit tree crops worldwide. However, the mechanisms underlying olive fruit growth remain poorly understood. Here, we examine questions regarding the interaction of endoreduplication, cell division, and cell expansion with olive fruit growth in relation to the final fruit size by measuring fruit diameter, pericarp thickness, cell area, and ploidy level during fruit ontogeny in three olive cultivars with different fruit sizes. The results demonstrate that differences in the fruit size are related to the maximum growth rate between olive cultivars during early fruit growth, about 50 days post-anthesis (DPA). Differences in fruit weight between olive cultivars were found from 35 DPA, while the distinctive fruit shape became detectable from 21 DPA, even though the increase in pericarp thickness became detectable from 7 DPA in the three cultivars. During early fruit growth, intense mitotic activity appeared during the first 21 DPA in the fruit, whereas the highest cell expansion rates occurred from 28 to 42 DPA during this phase, suggesting that olive fruit cell number is determined from 28 DPA in the three cultivars. Moreover, olive fruit of the large-fruited cultivars was enlarged due to relatively higher cell division and expansion rates compared with the small-fruited cultivar. The ploidy level of olive fruit pericarp between early and late growth was different, but similar among olive cultivars, revealing that ploidy levels are not associated with cell size, in terms of different 8C levels during olive fruit growth. In the three olive cultivars, the maximum endoreduplication level (8C) occurred just before strong cell expansion during early fruit growth in fruit pericarp, whereas the cell expansion during late fruit growth occurred without preceding endoreduplication. We conclude that the basis for fruit size differences between olive cultivars is determined mainly by different cell division and expansion rates during the early fruit growth phase. These data provide new findings on the contribution of fruit ploidy and cell size to fruit size in olive and ultimately on the control of olive fruit development.

Immunomodulatory effects of inactivated Ligilactobacillus salivarius CECT 9609 on respiratory epithelial cells.

The microbiota in humans and animals play crucial roles in defense against pathogens and offer a promising natural source for immunomodulatory products. However, the development of physiologically relevant model systems and protocols for testing such products remains challenging. In this study, we present an experimental condition where various natural products derived from the registered lactic acid bacteria Ligilactobacillus salivarius CECT 9609, known for their immunomodulatory activity, were tested. These products included live and inactivated bacteria, as well as fermentation products at different concentrations and culture times. Using our established model system, we observed no morphological changes in the airway epithelium upon exposure to Pasteurella multocida, a common respiratory pathogen. However, early molecular changes associated with the innate immune response were detected through transcript analysis. By employing diverse methodologies ranging from microscopy to next-generation sequencing (NGS), we characterized the interaction of these natural products with the airway epithelium and their potential beneficial effects in the presence of P. multocida infection. In particular, our discovery highlights that among all Ligilactobacillus salivarius CECT 9609 products tested, only inactivated cells preserve the conformation and morphology of respiratory epithelial cells, while also reversing or altering the natural immune responses triggered by Pasteurella multocida. These findings lay the groundwork for further exploration into the protective role of these bacteria and their derivatives.

METTL3 regulates breast cancer-associated alternative splicing switches.

Alternative splicing (AS) enables differential inclusion of exons from a given transcript, thereby contributing to the transcriptome and proteome diversity. Aberrant AS patterns play major roles in the development of different pathologies, including breast cancer. N6-methyladenosine (m6A), the most abundant internal modification of eukaryotic mRNA, influences tumor progression and metastasis of breast cancer, and it has been recently linked to AS regulation. Here, we identify a specific AS signature associated with breast tumorigenesis in vitro. We characterize for the first time the role of METTL3 in modulating breast cancer-associated AS programs, expanding the role of the m6A-methyltransferase in tumorigenesis. Specifically, we find that both m6A deposition in splice site boundaries and in splicing and transcription factor transcripts, such as MYC, direct AS switches of specific breast cancer-associated transcripts. Finally, we show that five of the AS events validated in vitro are associated with a poor overall survival rate for patients with breast cancer, suggesting the use of these AS events as a novel potential prognostic biomarker.

Esrrb Regulates Specific Feed-Forward Loops to Transit From Pluripotency Into Early Stages of Differentiation.

Characterization of pluripotent states, in which cells can both self-renew or differentiate, with the irreversible loss of pluripotency, are important research areas in developmental biology. Although microRNAs (miRNAs) have been shown to play a relevant role in cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these early stages of embryonic stem cell (ESC) differentiation remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of stem cells that incorporate protein-coding and miRNA genes based on miRNA array expression and quantitative sequencing of short transcripts upon the downregulation of the Estrogen Related Receptor Beta (Esrrb). The data reveals how Esrrb, a key stem cell transcription factor, regulates a specific stem cell miRNA expression program and integrates dynamic changes of feed-forward loops contributing to the early stages of cell differentiation upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in embryonic stem cells.

In Silico Research of New Therapeutics Rotenoids Derivatives against Leishmania amazonensis Infection.

Yearly, 1,500,000 cases of leishmaniasis are diagnosed, causing thousands of deaths. To advance in its therapy, we present an interdisciplinary protocol that unifies ethnobotanical knowledge of natural compounds and the latest bioinformatics advances to respond to an orphan disease such as leishmaniasis and specifically the one caused by Leishmania amazonensis. The use of ethnobotanical information serves as a basis for the development of new drugs, a field in which computer-aided drug design (CADD) has been a revolution. Taking this information from Amazonian communities, located in the area with a high prevalence of this disease, a protocol has been designed to verify new leads. Moreover, a method has been developed that allows the evaluation of lead molecules, and the improvement of their affinity and specificity against therapeutic targets. Through this approach, deguelin has been identified as a good lead to treat the infection due to its potential as an ornithine decarboxylase (ODC) inhibitor, a key enzyme in Leishmania development. Using an in silico-generated combinatorial library followed by docking approaches, we have found deguelin derivatives with better affinity and specificity against ODC than the original compound, suggesting that this approach could be adapted for developing new drugs against leishmaniasis.

ZFP207 sustains pluripotency by coordinating OCT4 stability, alternative splicing and RNA export.

The pluripotent state is not solely governed by the action of the core transcription factors OCT4, SOX2, and NANOG, but also by a series of co-transcriptional and post-transcriptional events, including alternative splicing (AS) and the interaction of RNA-binding proteins (RBPs) with defined subpopulations of RNAs. Zinc Finger Protein 207 (ZFP207) is an essential transcription factor for mammalian embryonic development. Here, we employ multiple functional analyses to characterize its role in mouse embryonic stem cells (ESCs). We find that ZFP207 plays a pivotal role in ESC maintenance, and silencing of Zfp207 leads to severe neuroectodermal differentiation defects. In striking contrast to human ESCs, mouse ZFP207 does not transcriptionally regulate neuronal and stem cell-related genes but exerts its effects by controlling AS networks and by acting as an RBP. Our study expands the role of ZFP207 in maintaining ESC identity, and underscores the functional versatility of ZFP207 in regulating neural fate commitment.

Predictors for mortality due to acute exacerbation of COPD in primary care: Derivation of a clinical prediction rule in a multicentre cohort study.

BACKGROUND: In primary care (PC), 80% of the acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are treated. However, no predictive model has been derived or validated for use in PC to help general practitioners make decisions about these patients. OBJECTIVES: To derive a clinical prediction rule for mortality from any cause 30 days after the last PC visit. METHODS: Between December 2013 and November 2014, we performed a cohort study with people aged 40 and over who were treated for AECOPD in 148 health centres in Spain. We recorded demographic variables, past medical history, signs, and symptoms of the patients and derived a logistic regression model. RESULTS: In the analysis, 1,696 cases of AECOPD were included and 17 patients (1%) died during follow-up. A clinical prediction rule was derived based on the exacerbations suffered in the last 12 months, age, and heart rate, displaying an area under the receiver operating characteristic curve of 0.792 (95% confidence interval, 0.692-0.891) and good calibration. CONCLUSION: This rule stratifies patients into three categories of risk and suggests to the physician a different action for each category: managing low-risk patients in PC, referring high-risk patients to hospitals and taking other criteria into account for decision-making in patients with moderate risk. These findings suggest that it is possible to accurately estimate the risk of death due to AECOPD without complex devices. Future studies on external validation and impact assessment are needed before this prediction rule may be used in clinical practice.

Junctional Adhesion Molecule 3 Expression in the Mouse Airway Epithelium Is Linked to Multiciliated Cells.

Tight-junction (TJ) proteins are essential for establishing the barrier function between neighbor epithelial cells, but also for recognition of pathogens or cell migration. Establishing the expression pattern and localization of different TJ proteins will help to understand the development and physiology of the airway. Here we identify that the junctional adhesion molecule 3 (Jam3) expression is restricted to multiciliated cells (MCCs) in the airway epithelium. In vitro, Jam3 expression varies along airway basal stem cell (BSC) differentiation and upon DAPT treatment or IL6 exposure. However, Jam3 is not required for BSC differentiation to specific cell types. In addition, we found that MCC lacking Jam3 display normal cilia morphology and cilia beating frequency with a delay in BB assembly/positioning in MCCs during differentiation. Remarkably, Jam3 in MCC is mostly localized to subapical organelles, which are negative for the apical recycling endosome marker Rab11 and positive for EEA1. Our data show that Jam3 expression is connected to mature MCC in the airway epithelium and suggest a Jam3 role unrelated to its known barrier function.

p53 regulation by MDM2 contributes to self-renewal and differentiation of basal stem cells in mouse and human airway epithelium.

Proper physiological function of mammalian airways requires the differentiation of basal stem cells into secretory or multiciliated cells, among others. In addition, the self-renewal ability of these basal stem cells is crucial for developing a quick response to toxic agents in order to re-establish the epithelial barrier function of the airways. Although these epithelial missions are vital, little is known about those mechanism controlling airway epithelial regeneration in health and disease. p53 has been recently proposed as the guardian of homeostasis, promoting differentiation programs, and antagonizing a de-differentiation program. Here, we exploit mouse and human tracheal epithelial cell culture models to study the role of MDM2-p53 signaling in self-renewal and differentiation in the airway epithelium. We show that p53 protein regulation by MDM2 is crucial for basal stem cell differentiation and to keep proper cell proliferation. Therefore, we suggest that MDM2/p53 interaction modulation is a potential target to control regeneration of the mammalian airway epithelia without massively affecting the epithelium integrity and differentiation potential.

Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function.

Skin integrity requires constant maintenance of a quiescent, yet responsive, population of stem cells. While interfollicular epidermal progenitors control normal homeostasis, hair follicle stem cells residing within the bulge provide regenerative potential during hair cycle and in response to wounding. The aryl hydrocarbon receptor (AhR) modulates cell plasticity and differentiation and its overactivation results in severe skin lesions in humans. However, its physiological role in skin homeostasis and hair growth is unknown. Reconstitution assays grafting primary keratinocytes and dermal fibroblasts into nude mice and 3-D epidermal equivalents revealed a positive role for AhR in skin regeneration, epidermal differentiation, and stem cell maintenance. Furthermore, lack of receptor expression in AhR-/- mice delayed morphogenesis and impaired hair regrowth with a phenotype closely correlating with a reduction in suprabasal bulge stem cells (α6low CD34+ ). Moreover, RNA-microarray and RT-qPCR analyses of fluorescence-activated cell sorting (FACS)-isolated bulge stem cells revealed that AhR depletion impaired transcriptional signatures typical of both epidermal progenitors and bulge stem cells but upregulated differentiation markers likely compromising their undifferentiated phenotype. Altogether, our findings support that AhR controls skin regeneration and homeostasis by ensuring epidermal stem cell identity and highlights this receptor as potential target for the treatment of cutaneous pathologies.

Distribution of planar cell polarity proteins in the developing avian retina.

Planar cell polarity (PCP) is evolutionary conserved and play a critical role in proper tissue development and function. During central nervous system development, PCP proteins exhibit specific patterns of distribution and are indispensable for axonal growth, dendritogenesis, neuronal migration, and neuronal differentiation. The retina constitutes an excellent model in which to study molecular mechanisms involved in neural development. The analysis of the spatiotemporal expression of PCP proteins in this model constitutes an useful histological approach in order to identify possible roles of these proteins in retinogenesis. Immunohistochemical techniques revealed that Frz6, Celsr1, Vangl1, Pk1, Pk3, and Fat1 were present in emerging axons from recently differentiated ganglion cells in the chicken retina. Except for Vangl1, they were also asymmetrically distributed in differentiated amacrine cells. Pk1 and Pk3 were restricted in the outer nuclear layer to the outer segment of photoreceptors. Vangl1 was also located in the cell somata of Müller glia. Given these findings together, the distribution of PCP proteins in the developing chicken retina suggest essential roles in axonal guidance during early retinogenesis and a possible involvement in the establishment of cell asymmetry and maintenance of retinal cell phenotypes.

Title: p38δ Regulates IL6 Expression Modulating ERK Phosphorylation in Preadipocytes.

IL6 is an essential cytokine in metabolism regulation and for intercommunication among different organs and tissues. IL6 produced by different tissues has different functions and therefore it is very important to understand the mechanism of its expression in adipose tissue. In this work we demonstrated that IL6 expression in mouse preadipocytes, like in human, is partially dependent on Wnt5a and JNK. Using mouse preadipocytes lacking each one of the p38 SAPK family members, we have shown that IL6 expression is also p38γ and p38δ dependent. In fact, the lack of some of these two kinases increases IL6 expression without altering that of Wnt5a. Moreover, we show that the absence of p38δ promotes greater ERK1/2 phosphorylation in a MEK1/2 independent manner, and that this increased ERK1/2 phosphorylation state is contributing to the higher IL6 expression in p38δ-/- preadipocytes. These results suggest a new crosstalk between two MAPK signaling pathway, p38δ and ERK1/2, where p38δ modulates the phosphorylation state of ERK1/2.

O esporte e o lazer em contextos de medidas socioeducativas no Brasil: panorama e análise da produção científica / Sport and leisure in contexts of educational correctional measures in Brazil: overview and analysis of scientific production

Este estudo tem por objetivo evidenciar o panorama de pesquisas relacionadas ao esporte e o lazer em contextos de medidas socioeducativas no Brasil. Para tal, foram selecionados 9 artigos científicos e 5 dissertações através de busca nos Periódicos da CAPES, Base de dados SciELO, Google Acadêmico e Banco de Teses e Dissertações da CAPES. Os resultados das pesquisas foram analisados a partir da análise de conteúdo. Através das categorias de análise, observou-se que o esporte e o lazer, quando tratados como vias e objetos de educação, propiciam ambientes favoráveis ao desenvolvimento positivo dos adolescentes, ainda que sejam concebidos na lógica funcional e utilitarista por uma grande parte das Instituições e adolescentes. Conclui-se que o restrito entendimento dos adolescentes sobre os potenciais do esporte e do lazer está intimamente ligado a falta de acesso a essas políticas em suas trajetórias.

This study aims to highlight the panorama of research related to sport and leisure for juvenile offenders, who are in youth detention center in Brazil. Therefore, we selected 9 scientific papers and 5 Master thesis by a targeted search in the journals of CAPES, SciELO Database, Google Academics and Banco de Teses e Dissertações of CAPES. The results of the research were analyzed with the method of content analysis. Through the categories of analysis, it was observed that sport and leisure, when treated as pathways and objects of education provide environments favorable to the positive development of adolescents, although they are conceived in functional and utilitarian logic by a large part of the institutions and adolescents. It is concluding that the restricted understanding from adolescents about the potentials of sport and leisure is closely linked to the lack of access to these policies in their trajectories.

Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor.

Transcriptional repression of Nanog is an important hallmark of stem cell differentiation. Chromatin modifications have been linked to the epigenetic profile of the Nanog gene, but whether chromatin organization actually plays a causal role in Nanog regulation is still unclear. Here, we report that the formation of a chromatin loop in the Nanog locus is concomitant to its transcriptional downregulation during human NTERA-2 cell differentiation. We found that two Alu elements flanking the Nanog gene were bound by the aryl hydrocarbon receptor (AhR) and the insulator protein CTCF during cell differentiation. Such binding altered the profile of repressive histone modifications near Nanog likely leading to gene insulation through the formation of a chromatin loop between the two Alu elements. Using a dCAS9-guided proteomic screening, we found that interaction of the histone methyltransferase PRMT1 and the chromatin assembly factor CHAF1B with the Alu elements flanking Nanog was required for chromatin loop formation and Nanog repression. Therefore, our results uncover a chromatin-driven, retrotransposon-regulated mechanism for the control of Nanog expression during cell differentiation.

Esporte e lazer no plano individual de atendimento de adolescentes em cumprimento de medida socioeducativa de internação / Sport and leisure in the individual plan of adolescent care in compliance with court-mandated social-educative internment / Deporte y recreación en el plan individual de asistencia para adolescentes en cumplimiento de medida socioeducativa de internación

Esta pesquisa documental tem por objetivo compreender o acesso ao esporte e lazer na trajetória de adolescentes em cumprimento de medida socioeducativa de internação no estado de Mato Grosso. Foram analisados 36 Planos Individuais de Atendimento (PIA) de sete Centros de Atendimento Socioeducativo, elaborados entre os anos de 2017-2018 e disponibilizados pela Gestão Estadual do Sistema para Infância e Adolescência - SIPIA/SINASE/MT. Os dados relacionados aos eixos esporte e lazer foram analisados através da análise de conteúdo. O perfil dos adolescentes retrata os problemas socioeconômicos e de vulnerabilidade social presentes na contemporaneidade. A partir das categorias de análise observou-se a restrita oferta dessas políticas de atendimento na trajetória dos adolescentes. Conclui-se que o cumprimento da medida socioeducativa de internação propiciou maior acesso aos espaços, equipamentos e conteúdos de esporte e lazer aos adolescentes, se comparado com suas vivências anteriores à aplicação da medida.

This research aims to understand the access to sports and leisure in adolescents' lives in compliance with court-mandated social-educative internment in the state of Mato Grosso. Thirty-six Individual Care Plans of seven Socio-Educational Care Centers were examined, which had been created between 2017-2018 and publicized by the State Management of the System for Childhood and Adolescence - SIPIA/SINASE/MT. Data related to sports and leisure were submitted to content analysis. The adolescents' profiles show today's socioeconomic problems and social vulnerability. Based on the categories of analysis, the offer of these care policies in the adolescents' lives was observed to be restricted. Compliance to court-mandated social-educative internment is found to provide greater access to sports and leisure spaces, equipment and contents to the adolescents when compared to their experiences before the sentence.

Este estudio tiene por objetivo comprender el acceso al deporte y a la recreación de adolescentes que cumplen medidas socioeducativas de internación en el Estado de Mato Grosso. Se analizaron 36 Planes Individuales de Asistencia (PIA) de siete Centros de Asistencia Socioeducativa, elaborados en los años 2017 y 2018 y puestos a disposición por la Administración Estatal del Sistema para la Infancia y Adolescencia - SIPIA/SINASE/MT. Los datos relacionados a los ejes deportes y recreación se analizaron a través de la metodología de análisis de contenido. El perfil de los adolescentes retrata los problemas socioeconómicos y de vulnerabilidad social presentes actualmente. A partir de las categorías de análisis, se observó una oferta limitada de estas políticas de asistencia en la trayectoria de los adolescentes. Se concluye que el cumplimiento de medidas socioeducativas de internación propició un mayor acceso a los espacios y contenidos de deporte y recreación a los adolescentes, en comparación con sus experiencias previas a la aplicación de las medidas.

Adolescentes e conduta infracional: espaços, equipamentos e conteúdos de esporte e lazer / Adolescents and infraction conduct: sport and leisure spaces, equipment and content / Adolescentes y conducta infractora: espacios, equipos y contenidos de deporte y recreación

Este estudo exploratório e descritivo tem por objetivo identificar os espaços, equipamentos e conteúdos de esporte e lazer de um município do estado de Mato Grosso, com maior incidência de adolescentes em cumprimento de medida socioeducativa de internação nos anos de 2017 e 2018. Os dados foram disponibilizados pela Gestão Estadual do Sistema de Informação para Infância e Adolescência (SIPIA). Realizaram-se observações in loco em oito bairros, utilizando categorias de análise predefinidas para registros em diário de campo. Os resultados demonstram a escassa oferta de espaços, equipamentos e conteúdos de esporte e lazer disponibilizados aos adolescentes dessas comunidades. Diante desse cenário, a falta de acesso às políticas de esporte e lazer pode configurar como possível fator de risco ao cometimento de ato infracional no contexto pesquisado, além da exposição dos jovens ao mesmo risco ao retornarem à comunidade.

This exploratory and descriptive study aims to identify sports and leisure spaces, equipment and contents of a municipality in the Brazilian state of Mato Grosso with higher incidence of adolescents sentenced to socio-educational internment in 2017 and 2018. Data were provided by the State Management of the Children and Adolescents Information System (SIPIA). On-site observation was carried out in eight neighborhoods, using predefined analytical categories for field diary records. The results point to scarce offer of sport and leisure spaces, equipment and content in those communities. In view of this scenario, the study concludes that the lack of access to sports and leisure policies is seen as a possible risk factor for committing infractions in the context researched, in addition to exposing young people to the same risk when they return to their communities.

Este estudio exploratorio y descriptivo tiene por objetivo identificar los espacios, equipos y contenidos de deporte y recreación de un municipio del estado de Mato Grosso que tiene mayor incidencia de adolescentes en cumplimiento de medida socioeducativa de internación durante los años 2017 y 2018. Los datos fueron puestos a disposición por la Administración Estatal del Sistema de Información para Infancia y Adolescencia (SIPIA). Se realizaron observaciones in situ en ocho barrios, utilizando categorías de análisis predefinidas para registros en diario de campo. Los resultados demuestran la escasa oferta de espacios, equipos y contenidos de deporte y recreación que se ofrece a los adolescentes de esas comunidades. Ante este escenario, la falta de acceso a políticas de deporte y recreación puede configurarse como posible factor de riesgo para cometer infracciones en el contexto investigado, además de exponer a los jóvenes al mismo riesgo cuando regresan a la comunidad.

Centriole Positioning: Not Just a Little Dot in the Cell.

Organelle positioning as many other morphological parameters in a cell is not random. Centriole positioning as centrosomes or ciliary basal bodies is not an exception to this rule in cell biology. Indeed, centriole positioning is a tightly regulated process that occurs during development, and it is critical for many organs to function properly, not just during development but also in the adulthood. In this book chapter, we overview our knowledge on centriole positioning in different and highly specialized animal cells like photoreceptor or ependymal cells. We will also discuss recent advances in the discovery of molecular pathways involved in this process, mostly related to the cytoskeleton and the cell polarity pathways. And finally, we present quantitative methods that have been used to assess centriole positioning in different cell types although mostly in epithelial cells.

Tracing the Lineage of Two Traits Associated with the Coat Protein of the Tombusviridae: Silencing Suppression and HR Elicitation in Nicotiana Species.

In this paper we have characterized the lineage of two traits associated with the coat proteins (CPs) of the tombusvirids: Silencing suppression and HR elicitation in Nicotiana species. We considered that the tombusvirid CPs might collectively be considered an effector, with the CP of each CP-encoding species comprising a structural variant within the family. Thus, a phylogenetic analysis of the CP could provide insight into the evolution of a pathogen effector. The phylogeny of the CP of tombusvirids indicated that CP representatives of the family could be divided into four clades. In two separate clades the CP triggered a hypersensitive response (HR) in Nicotiana species of section Alatae but did not have silencing suppressor activity. In a third clade the CP had a silencing suppressor activity but did not have the capacity to trigger HR in Nicotiana species. In the fourth clade, the CP did not carry either function. Our analysis illustrates how structural changes that likely occurred in the CP effector of progenitors of the current genera led to either silencing suppressor activity, HR elicitation in select Nicotiana species, or neither trait.

Diminished Expression of Fat and Dachsous PCP Proteins Impaired Centriole Planar Polarization in Drosophila.

Proper ciliary basal body positioning within a cell is key for cilia functioning. Centriole and basal body positioning depends on signaling pathways such as the planar cell polarity pathway (PCP) governed by Frizzled (Fz-PCP). There have been described two PCP pathways controlled by different protein complexes, the Frizzled-PCP and the Fat-PCP pathway. Centriole planar polarization in non-dividing cells is a dynamic process that depends on the Fz-PCP pathway to properly occur during development from flies to humans. However, the function of the Ft-PCP pathway in centrioles polarization is elusive. Here, we present a descriptive initial analysis of centrioles polarization in Fat-PCP loss of function (LOF) conditions. We found that Fat (Ft) and Dachsous (Ds) LOF showed a marked centrioles polarization defect similar to what we have previously reported in Fz-PCP alterations. Altogether, our data suggest that centriole planar polarization in Drosophila wings depends on both Ft-PCP and Fz-PCP pathways. Further analyses in single and double mutant conditions will be required to address the functional connection between PCP and centriole polarization in flies.