Combined effect of cadmium and lead on durum wheat

Cadmium (Cd) and lead (Pb) are two toxic heavy metals (HMs) whose presence in soil is generally low. However, industrial and agricultural activities in recent years have significantly raised their levels, causing progressive accumulations in plant edible tissues, and stimulating research in this field. Studies on toxic metals are commonly focused on a single metal, but toxic metals occur simultaneously. The understanding of the mechanisms of interaction between HMs during uptake is important to design agronomic or genetic strategies to limit contamination of crops. To study the single and combined effect of Cd and Pb on durum wheat, a hydroponic experiment was established to examine the accumulation of the two HMs. Moreover, the molecular mechanisms activated in the roots were investigated paying attention to transcription factors (bHLH family), heavy metal transporters and genes involved in the biosynthesis of metal chelators (nicotianamine and mugineic acid). Cd and Pb are accumulated following different molecular strategies by durum wheat plants, even if the two metals interact with each other influencing their respective uptake and translocation. Finally, we demonstrated that some genes (bHLH 29, YSL2, ZIF1, ZIFL1, ZIFL2, NAS2 and NAAT) were induced in the durum wheat roots only in response to Cd

A Flexible and Reconfigurable 5G Networking Architecture Based on Context and Content Information

The need for massive content delivery is a consolidated trend in mobile communications, and will even increase for next years. Moreover, while 4G maturity and evolution is driven by video contents, next generation (5G) networks will be dominated by heterogeneous data and additional massive diffusion of Internet of Things (IoT). The current network architecture is not sufficient to cope with such traffic, which is heterogeneous in terms of latency and QoS requirements, and variable in space and time. This paper proposes architectural advances to endow the network with the necessary flexibility helping to adapt to these varying traffic needs by providing content and communication services where and when actually needed. Our functional hardware/software (HW/SW) architecture aims at influencing future system standardization and leverage the benefits of some key 5G networking enablers described in the paper. Preliminary results demonstrate the potential of these key technologies to support the evolution toward content-centric and context-aware 5G systems

Lung carcinoid tumours: histology and Ki-67, the eternal rivalry

WHO classification of Thoracic Tumours defines lung carcinoid tumours (LCTs) as well-differentiated neuroendocrine neoplasms (NENs) classified in low grade typical (TC) and intermediate grade atypical carcinoids (AC). Limited data exist concerning protein expression and morphologic factors able to predict disease aggressiveness. Though Ki-67 has proved to be a powerful diagnostic and prognostic factor for Gastro-entero-pancreatic NENs, its role in lung NENs is still debated. A retrospective series of 370 LCT from two oncology centers was centrally reviewed. Morphology and immunohistochemical markers (Ki-67, TTF-1, CD44, OTP, SSTR-2A, Ascl1, and p53) were studied and correlated with Overall Survival (OS), Cancer-specific survival (CSS) and Disease-free survival (DFS). Carcinoid histology was confirmed in 355 patients: 297 (83.7%) TC and 58 (16.3%) AC. Ki-67 at 3% was the best value in predicting DFS. Ki-67 ≥ 3% tumours were significantly associated with AC histology, stage III-IV, smoking, vascular invasion, tumour spread through air spaces OTP negativity, and TTF-1, Ascl1 and p53 positivity. After adjustment for center and period of diagnosis, both Ki-67 (≥3 versus <3) and histology (AC versus TC) alone significantly added prognostic information to OS and CSS multivariable model with age, stage and OTP; addition of both variables did not provide further prognostic information. Conversely, an improved significance of the DFS prediction model at multivariate analysis was seen by adding Ki-67 (≥3 versus <3, P adj = 0.01) to TC and AC histological distinction, age, lymph node involvement, residual tumour and OTP. Ki-67 ≥ 3% plays a potentially pivotal role in LCT prognosis, irrespective of histological grade

Concentration-Dependent, Size-Independent Toxicity of Citrate Capped AuNPs in Drosophila melanogaster

The expected potential benefits promised by nanotechnology in various fields have led to a rapid increase of the presence of engineered nanomaterials in a high number of commercial goods. This is generating increasing questions about possible risks for human health and environment, due to the lack of an in-depth assessment of the physical/chemical factors responsible for their toxic effects. In this work, we evaluated the toxicity of monodisperse citrate-capped gold nanoparticles (AuNPs) of different sizes (5, 15, 40, and 80 nm) in the model organism Drosophila melanogaster, upon ingestion. To properly evaluate and distinguish the possible dose- and/or size-dependent toxicity of the AuNPs, we performed a thorough assessment of their biological effects, using two different dose-metrics. In the first approach, we kept constant the total surface area of the differently sized AuNPs (Total Exposed Surface area approach, TES), while, in the second approach, we used the same number concentration of the four different sizes of AuNPs (Total Number of Nanoparticles approach, TNN). We observed a significant AuNPs-induced toxicity in vivo, namely a strong reduction of Drosophila lifespan and fertility performance, presence of DNA fragmentation, as well as a significant modification in the expression levels of genes involved in stress responses, DNA damage recognition and apoptosis pathway. Interestingly, we found that, within the investigated experimental conditions, the toxic effects in the exposed organisms were directly related to the concentration of the AuNPs administered, irrespective of their size

Combined Large Cell Neuroendocrine Carcinomas of the Lung: Integrative Molecular Analysis Identifies Subtypes with Potential Therapeutic Implications

Simple Summary In this manuscript, we offer an integrated molecular analysis of 44 combined large cell neuroendocrine carcinomas (CoLCNECs) in order to deepen the knowledge about these rare histotypes and to clarify their relationship with lung cancers. In the present state of research, molecular studies are still scant, consisting of small and heterogeneous cohorts, and the genomic landscape is poorly characterized. This study shows that CoLCNECs constitute a standalone group of neuroendocrine neoplasm, with three different molecular profiles, two of which overlap with pure LCNEC or adenocarcinoma. CoLCNECs can be considered an independent histologic category with specific genomic and transcriptomic features, different and therefore not comparable to other lung cancers. Indeed, in addition to a histological re-evaluation of lung cancer classification, our study may help to develop a new diagnostic approach for novel and personalized treatments in CoLCNECs. Background: Combined large cell neuroendocrine carcinoma (CoLCNEC) is given by the association of LCNEC with adeno or squamous or any non-neuroendocrine carcinoma. Molecular bases of CoLCNEC pathogenesis are scant and no standardized therapies are defined. Methods: 44 CoLCNECs: 26 with adenocarcinoma (CoADC), 7 with squamous cell carcinoma (CoSQC), 3 with small cell carcinoma (CoSCLC), 4 with atypical carcinoid (CoAC) and 4 napsin-A positive LCNEC (NapA+), were assessed for alterations in 409 genes and transcriptomic profiling of 20,815 genes. Results: Genes altered included TP53 (n = 30), RB1 (n = 14) and KRAS (n = 13). Targetable alterations included six KRAS G12C mutations and ALK-EML4 fusion gene. Comparison of CoLCNEC transcriptomes with 86 lung cancers of pure histology (8 AC, 19 ADC, 19 LCNEC, 11 SCLC and 29 SQC) identified CoLCNEC as a separate entity of neuroendocrine tumours with three different molecular profiles, two of which showed a non-neuroendocrine lineage. Hypomethylation, activation of MAPK signalling and association to immunotherapy signature specifically characterized each of three CoLCNEC molecular clusters. Prognostic stratification was also provided. Conclusions: CoLCNECs are an independent histologic category. Our findings support the extension of routine evaluation of KRAS mutations, fusion genes and immune-related markers to offer new perspectives in the therapeutic management of CoLCNEC

Perpetrators, victims, bystanders and up standers: cyber bullying in a special school context.

This study offers a multi-dimensional analysis of ‘real world’ cyberbullying between members of a special school community. The purpose of this article is to analyse the social and educational contexts within which interactions of this nature are embedded.The interview both illuminated a number of themes pertinent to the current literature and extended those related to the call for further analysis of the contextual determinants of cyberbullying.The influence of the conditions experienced by the children involved (Attention Deficit Hyperactivity Disorder (ADHD) and Autistic Spectrum Condition (ASC)) is discussed and demonstrated. This use of natural observation provides a current and ‘real world’ illustration of teacher perceptions of the complex behaviours and interactions occurring in cyberspace, which hold potential for grave consequences. A hopeful tone is maintained as the potential for selfless upstander behaviour and resolution via the involvement of supportive and knowledgeable pastoral staff is realised in the article’s conclusion.<br/

Monitoring Insulin Aggregation via Capillary Electrophoresis

Early stages of insulin aggregation, which involve the transient formation of oligomeric aggregates, are an important aspect in the progression of Type II diabetes and in the quality control of pharmaceutical insulin production. This study is the first to utilize capillary electrophoresis (CE) with ultraviolet (UV) detection to monitor insulin oligomer formation at pH 8.0 and physiological ionic strength. The lag time to formation of the first detected species in the aggregation process was evaluated by UV-CE and thioflavin T (ThT) binding for salt concentrations from 100 mM to 250 mM. UV-CE had a significantly shorter (5–8 h) lag time than ThT binding (15–19 h). In addition, the lag time to detection of the first aggregated species via UV-CE was unaffected by salt concentration, while a trend toward an increased lag time with increased salt concentration was observed with ThT binding. This result indicates that solution ionic strength impacts early stages of aggregation and β-sheet aggregate formation differently. To observe whether CE may be applied for the analysis of biological samples containing low insulin concentrations, the limit of detection using UV and laser induced fluorescence (LIF) detection modes was determined. The limit of detection using LIF-CE, 48.4 pM, was lower than the physiological insulin concentration, verifying the utility of this technique for monitoring biological samples. LIF-CE was subsequently used to analyze the time course for fluorescein isothiocyanate (FITC)-labeled insulin oligomer formation. This study is the first to report that the FITC label prevented incorporation of insulin into oligomers, cautioning against the use of this fluorescent label as a tag for following early stages of insulin aggregation