An N-terminal motif in NLR immune receptors is functionally conserved across distantly related plant species

The molecular codes underpinning the functions of plant NLR immune receptors are poorly understood. We used in vitro Mu transposition to generate a random truncation library and identify the minimal functional region of NLRs. We applied this method to NRC4-a helper NLR that functions with multiple sensor NLRs within a Solanaceae receptor network. This revealed that the NRC4 N-terminal 29 amino acids are sufficient to induce hypersensitive cell death. This region is defined by the consensus MADAxVSFxVxKLxxLLxxEx (MADA motif) that is conserved at the N-termini of NRC family proteins and ~20% of coiled-coil (CC)-type plant NLRs. The MADA motif matches the N-terminal a1 helix of Arabidopsis NLR protein ZAR1, which undergoes a conformational switch during resistosome activation. Immunoassays revealed that the MADA motif is functionally conserved across NLRs from distantly related plant species. NRC-dependent sensor NLRs lack MADA sequences indicating that this motif has degenerated in sensor NLRs over evolutionary time

Multisystem autoimmune disease caused by increased STAT3 phosphorylation, and dysregulated gene expression

Signal transducer and activator of transcription (STAT) 3 is a member of the STAT family, and plays a major role in various immunological mechanisms.1 Mutations in STAT3 are associated with a broad spectrum of manifestations, including immunodeficiency, autoimmunity, and malignancy.2 In particular, heterozygous germline loss-of-function (LOF) mutations cause Hyper-IgE syndrome (HIES),3–5 while heterozygous germline gain-of-function (GOF) mutations have recently been associated to multi-organ autoimmune manifestations (i.e. type 1 diabetes, enteropathy, cytopenia, interstitial lung disease, hypothyroidism), lymphoproliferation, short stature, and recurrent infections (OMIM #615952).6–8 We report a 7-year-old boy who presented with early-onset severe enteropathy, and diffuse eczematous dermatitis since birth. During the first weeks of life, Hirschsprung disease was also suspected and surgically treated. Gastrointestinal and cutaneous manifestations were first ascribed to food allergy with quite a good response to amino acid-based formula. In the following months, the patient failed to thrive, and developed respiratory tract infections. At two years, the patient presented with progressive interstitial lung disease characterized by lymphocytic interstitial infiltration leading to pulmonary hypertension, tricuspid insufficiency, and right ventricular heart failure with hepatomegaly. Because of the increased risk of infections, he received intravenous (IV) immunoglobulin infusions (400 mg/kg), prophylaxis with cotrimoxazole and fluconazole. Methylprednisolone at 0.3 mg/kg/day was also given to treat autoimmune manifestations

Family and Educational Strategies for Cyberbullying Prevention: A Systematic Review

Cyberbullying can be described as a form of bullying carried out by an individual or a group through digital media with the intention to harm others. It has been recognized as a public health issue recently; however, of the vast literature published in recent years on the phenomenon, only a small part concerns strategies adopted to prevent and combat cyberbullying, and the effectiveness of these strategies appears to be scarce. We conducted a systematic review of the literature published in the last five years about different interventions studied to prevent and contrast cyberbullying. Our results show how most of the strategies currently developed focus on the educational aspect, involving schools and families. Other authors describe technology-based practices to set programs to reduce and prevent cyberbullying through the usage of digital instruments, the same used by minors themselves. Finally, remaining tactics use a more comprehensive approach, mixing tools already in use in the aforementioned strategies. Cyberbullying requires wide-ranging methods to combat it, involving the contribution of mental health professionals, educators, and digital experts cooperating synergically. Prevention and contrast instruments should be defined, implemented, tested, and combined in order to deal with cyberbullying

Microflora cultivable y endomicorrizas obtenidas en hojarasca de bosque (páramo Guerrero - finca Puente de Tierra) Zipaquirá, Colombia

Se realizó el recuento de microorganismos cultivables (bacterias y hongos), microorganismos celulolíticos y endomicorrizas presentes en la hojarasca de bosque (finca Puente de Tierra) en el páramo Guerrero, Colombia. Los microorganismos aislados con mayor frecuencia pertenecían a los géneros Staphylococcus, Bacillus, Pseudomonas, Micrococcus, Penicillium, Rhodotorula y se aisló una cepa de Cladosporium sp. en un medio selectivo con carboximetil celulosa. Así mismo, se encontraron ocho morfotipos de endomicorrizas, entre los cuales predominaron especies de Glomus y Acaulospora. Este estudio contribuye con el conocimiento de la microbiota cultivable de hojarasca, que ha sido poco explorada en ecosistemas de páramo

Dynamic localization of a helper NLR at the plant–pathogen interface underpins pathogen recognition

Plants employ sensor–helper pairs of NLR immune receptors to recognize pathogen effectors and activate immune responses. Yet, the subcellular localization of NLRs pre- and postactivation during pathogen infection remains poorly understood. Here, we show that NRC4, from the “NRC” solanaceous helper NLR family, undergoes dynamic changes in subcellular localization by shuttling to and from the plant–pathogen haustorium interface established during infection by the Irish potato famine pathogen Phytophthora infestans. Specifically, prior to activation, NRC4 accumulates at the extrahaustorial membrane (EHM), presumably to mediate response to perihaustorial effectors that are recognized by NRC4-dependent sensor NLRs. However, not all NLRs accumulate at the EHM, as the closely related helper NRC2 and the distantly related ZAR1 did not accumulate at the EHM. NRC4 required an intact N-terminal coiled-coil domain to accumulate at the EHM, whereas the functionally conserved MADA motif implicated in cell death activation and membrane insertion was dispensable for this process. Strikingly, a constitutively autoactive NRC4 mutant did not accumulate at the EHM and showed punctate distribution that mainly associated with the plasma membrane, suggesting that postactivation, NRC4 may undergo a conformation switch to form clusters that do not preferentially associate with the EHM. When NRC4 is activated by a sensor NLR during infection, however, NRC4 forms puncta mainly at the EHM and, to a lesser extent, at the plasma membrane. We conclude that following activation at the EHM, NRC4 may spread to other cellular membranes from its primary site of activation to trigger immune responses

Whole-exome sequencing identifies tetratricopeptide repeat domain 7A (TTC7A) mutations for combined immunodeficiency with intestinal atresias

BACKGROUND: Combined Immunodeficiency with Multiple Intestinal Atresias (CID-MIA) is a rare hereditary disease characterized by intestinal obstructions and profound immune defects. OBJECTIVE: We sought to determine the underlying genetic causes of CID-MIA by analyzing the exomic sequence of 5 patients and their healthy direct relatives from 5 unrelated families. METHODS: We performed whole exome sequencing on 5 CID-MIA patients and 10 healthy direct family members belonging to 5 unrelated families with CID-MIA. We also performed targeted Sanger sequencing for the candidate gene TTC7A on 3 additional CID-MIA patients. RESULTS: Through analysis and comparison of the exomic sequence of the individuals from these 5 families, we identified biallelic damaging mutations in the TTC7A gene, for a total of 7 distinct mutations. Targeted TTC7A gene sequencing in 3 additional unrelated patients with CID-MIA revealed biallelic deleterious mutations in two of them, as well as an aberrant splice product in the third patient. Staining of normal thymus showed that the TTC7A protein is expressed in thymic epithelial cells as well as in thymocytes. Moreover, severe lymphoid depletion was observed in the thymus and peripheral lymphoid tissues from two patients with CID-MIA. CONCLUSIONS: We identified deleterious mutations of the TTC7A gene in 8 unrelated patients with CID-MIA and demonstrated that the TTC7A protein is expressed in the thymus. Our results strongly suggest that TTC7A gene defects cause CID-MIA. CLINICAL IMPLICATIONS: Damaging mutations in the gene TTC7A should be scrutinized in patients with CID-MIA. Characterization of the role of this protein in the immune system and intestinal development, as well as in thymic epithelial cells may have important therapeutic implications

Interpretare da e verso l’italiano: didattica e innovazione per la formazione dell’interprete

Il volume composto da 28 capitoli raccoglie l’esperienza di ricerca e di didattica dei docenti del Dipartimento di Interpretazione e Traduzione dell’Università di Bologna - Campus di Forlì - istituita nel 1989 e ufficialmente attiva dal 1990, come pure di suoi allievi ora docenti in altri atenei. Offre pertanto una variegata panoramica della riflessione, delle problematiche disciplinari e dell’impostazione pedagogica della “Scuola di Forlì”, arricchita anche dal contributo di “ospiti esterni” nazionali e internazionali che rappresentano indiscusse autorità negli Interpreting Studies sulle tematiche trasversali che qui affrontano. In questo Testo per la formazione dell’interprete emerge l’intento di conciliare tradizione e innovazione in una didattica che rivisita il processo interpretativo. Viene proposto un approccio contrastivo per evidenziare problematiche fonologiche, morfosintattiche, lessicali, semantiche, pragmatiche e culturali che potrebbero inficiare una rapida e corretta trasposizione tra l’italiano e, per la prima volta, in una pluralità di altre lingue. La didattica risulta innovativa anche perché accoglie i nuovi apporti tra cui, corpora di interpretazione, CAI tools, avanzate metodologie per la documentazione e gestione terminologica, didattica multimediale e a distanza, l’uso dell’attività teatrale. Il volume si articola in quattro parti: (1) Aspetti teorici e metodologici; (2) Problemi, strategie ed esercitazioni per coppie di lingue: interpretare COME(BCMS/Cinese/Francese/Inglese/Polacco/Portoghese/Russo/Spagnolo/Tedesco - Italiano; (3) Ambiti professionali: interpretare PER CHI; (4) Aspetti generali.This volume, consisting of 28 chapters, brings together the research and teaching experience of the teachers of the Department of Interpretation and Translation of the University of Bologna - Forlì Campus - established in 1989 and officially active since 1990, as well as of its students now teaching at other universities. It therefore offers a varied overview of the thinking, disciplinary issues and pedagogical approach of the "Forlì School", enriched also by the contribution of national and international "external guests" who are undisputed authorities in Interpreting Studies on the cross-cutting issues addressed here. In this Text for Interpreter Training the intention emerges of reconciling tradition and innovation in a didactic that revisits the interpretative process. A contrastive approach is proposed in order to highlight phonological, morphosyntactic, lexical, semantic, pragmatic and cultural problems that could affect a rapid and correct transposition between Italian and, for the first time, in a plurality of other languages. The didactics is innovative also because it welcomes new features such as interpreting corpora, CAI tools, advanced methodologies for terminology documentation and management, multimedia and distance learning, the use of theatrical activity. The book is divided into four parts: (1) Theoretical and methodological aspects; (2) Problems, strategies and exercises for language pairs: interpreting HOW (BCMS/Chinese/French/English/Polish/Portuguese/Russian/Spanish/German - Italian; (3) Professional fields: interpreting FOR WHOM; (4) General aspects