Publisher's Note: Continued Publication of Current Issues in Molecular Biology by MDPI.

Current Issues in Molecular Biology (ISSN 1467-3045) was launched in 1999 and has published international and multidisciplinary articles on all aspects of molecular biology spanning from basic mechanisms to applications in fields primarily, but not exclusively, relevant to microbiology and virology [...].

Publisher's Note: Continued Publication of Tomography by MDPI.

Tomography was launched in 2015 and has published international and multidisciplinary research on all aspects of imaging science, spanning from basic research to clinical trials [...].

Publisher's Note: Continued Publication of Infectious Disease Reports by MDPI.

Infectious Disease Reports was launched in 2009 and it has been published over the past eleven years by PAGEPress Publications [...].

Publisher's Note: Continued Publication of Neurology International by MDPI.

Neurology International was launched in 2009 and it has been published over the past eleven years by PAGEPress Publications [...].

Publisher's Note: Continued Publication of Audiology Research by MDPI.

Audiology Research (ISSN 2039-4349) was launched in 2011 and published over the past nine years by PAGEPress Publications [...].

Publisher's Note: Continued Publication of Pediatric Reports by MDPI.

Pediatric Reports was launched in 2009 and it has been published over the past eleven years by PAGEPress Publications [...].

Medicine 4.0: New Technologies as Tools for a Society 5.0.

Are new technologies in the medicine sector a driver to support the development of a society 5.0? Innovation pushes the artisan to become smart and lean, customer-oriented but within a standardized environment of production, maintaining and ensuring the quality of the product. An artisan is a user and innovator, as an essential part of the industrial chain. In the healthcare sector, the doctor is the industrial artisan, and medicine can be considered as an example of a smart tool, strongly tailored, that embeds the innovation of materials, nano-devices, and smart technology (e.g., sensors and controllers). But how much of society is ready to host smart technology "on board", becoming "on life", constantly connected with remote controls that allow us to monitor, gather data, and, in any case, act, with preventive healthcare solutions? After a short overview of the medicine sector, a preliminary, tentative link between technological innovation and the healthcare sector allows us to adopt several outlooks on how to change research, always more transdisciplinary, combining science with social science in order to remain human-centered.

Publisher's Note: Continued Publication of Clinics and Practice by MDPI.

Clinics and Practice was launched in 2011 and it has been published over the past nine years by PAGEPress Publications [...].

Publisher's Note: Continued Publication of Nursing Reports by MDPI.

Nursing Reports was launched in 2011 and published over the past nine years by PAGEPress Publications [...].

Publisher's Note: Continued Publication of Pathophysiology, the Official Journal of the International Society of Pathophysiology, by MDPI.

Pathophysiology (ISSN 0928-4680) was launched in 1994 and has been published during the past 26 years by Elsevier [...].

Crosstalk between PTGS and TGS pathways in natural antiviral immunity and disease recovery.

Virus-induced diseases cause severe damage to cultivated plants, resulting in crop losses. Certain plant-virus interactions allow disease recovery at later stages of infection and have the potential to reveal important molecular targets for achieving disease control. Although recovery is known to involve antiviral RNA silencing1,2, the specific components of the many plant RNA silencing pathways 3 required for recovery are not known. We found that Arabidopsis thaliana plants infected with oilseed rape mosaic virus (ORMV) undergo symptom recovery. The recovered leaves contain infectious, replicating virus, but exhibit a loss of viral suppressor of RNA silencing (VSR) protein activity. We demonstrate that recovery depends on the 21-22 nt siRNA-mediated post-transcriptional gene silencing (PTGS) pathway and on components of a transcriptional gene silencing (TGS) pathway that is known to facilitate non-cell-autonomous silencing signalling. Collectively, our observations indicate that recovery reflects the establishment of a tolerant state in infected tissues and occurs following robust delivery of antiviral secondary siRNAs from source to sink tissues, and establishment of a dosage able to block the VSR activity involved in the formation of disease symptoms.

The 35-amino acid C2 protein of Cotton leaf curl Kokhran virus, Burewala, implicated in resistance breaking in cotton, retains some activities of the full-length protein.

With one exception, all the begomoviruses characterized so far encode an ~134-amino acid (aa) (A)C2 protein. The exception is the "Burewala" strain of Cotton leaf curl Kokhran virus (CLCuKoV-Bu), associated with resistance breaking in cotton across Pakistan and northwestern India, that encodes a truncated 35-aa C2. The C2 protein encoded by begomoviruses performs multiple functions including suppression of post-transcriptional gene silencing (PTGS), modulating microRNA (miRNA) expression and may be a pathogenicity determinant. The study described here was designed to investigate whether the CLCuKoV-Bu 35-aa C2 retains the activities of the full-length C2 protein. The results showed the 35-aa C2 of CLCuKoV-Bu acts as a pathogenicity determinant, suppresses PTGS and upregulates miRNA expression when expressed from a Potato virus X vector in Nicotiana benthamiana. The symptoms induced by expression of full-length C2 were more severe than those induced by the 35-aa C2. The accumulation of most developmental miRNAs decreases with the full-length C2 protein and increases with the 35-aa peptide of CLCuKoV-Bu. The study also revealed that 35-aa peptide of CLCuKoV-Bu maintains suppressor of silencing activity at a level equal to that of full-length C2. The significance of the results with respect to virus fitness and resistance breaking is discussed.

Arabidopsis microRNA expression regulation in a wide range of abiotic stress responses.

Arabidopsis microRNA expression regulation was studied in a wide array of abiotic stresses such as drought, heat, salinity, copper excess/deficiency, cadmium excess, and sulfur deficiency. A home-built RT-qPCR mirEX platform for the amplification of 289 Arabidopsis microRNA transcripts was used to study their response to abiotic stresses. Small RNA sequencing, Northern hybridization, and TaqMan® microRNA assays were performed to study the abundance of mature microRNAs. A broad response on the level of primary miRNAs (pri-miRNAs) was observed. However, stress response at the level of mature microRNAs was rather confined. The data presented show that in most instances, the level of a particular mature miRNA could not be predicted based on the level of its pri-miRNA. This points to an essential role of posttranscriptional regulation of microRNA expression. New Arabidopsis microRNAs responsive to abiotic stresses were discovered. Four microRNAs: miR319a/b, miR319b.2, and miR400 have been found to be responsive to several abiotic stresses and thus can be regarded as general stress-responsive microRNA species.

MiR393 regulation of auxin signaling and redox-related components during acclimation to salinity in Arabidopsis.

One of the most striking aspects of plant plasticity is the modulation of development in response to environmental changes. Plant growth and development largely depend on the phytohormone auxin that exerts its function through a partially redundant family of F-box receptors, the TIR1-AFBs. We have previously reported that the Arabidopsis double mutant tir1 afb2 is more tolerant to salt stress than wild-type plants and we hypothesized that down-regulation of auxin signaling might be part of Arabidopsis acclimation to salinity. In this work, we show that NaCl-mediated salt stress induces miR393 expression by enhancing the transcription of AtMIR393A and leads to a concomitant reduction in the levels of the TIR1 and AFB2 receptors. Consequently, NaCl triggers stabilization of Aux/IAA repressors leading to down-regulation of auxin signaling. Further, we report that miR393 is likely involved in repression of lateral root (LR) initiation, emergence and elongation during salinity, since the mir393ab mutant shows reduced inhibition of emergent and mature LR number and length upon NaCl-treatment. Additionally, mir393ab mutant plants have increased levels of reactive oxygen species (ROS) in LRs, and reduced ascorbate peroxidase (APX) enzymatic activity compared with wild-type plants during salinity. Thus, miR393 regulation of the TIR1 and AFB2 receptors could be a critical checkpoint between auxin signaling and specfic redox-associated components in order to coordinate tissue and time-specific growth responses and tolerance during acclimation to salinity in Arabidopsis.

miR393 is required for production of proper auxin signalling outputs.

Auxins are crucial for plant growth and development. Auxin signalling primarily depends on four partially redundant F-box proteins of the TIR1/AFB2 Auxin Receptor (TAAR) clade to trigger the degradation of AUX/IAA transcriptional repressors. Auxin signalling is a balanced system which involves complex feedback regulations. miR393 regulation of TAAR genes is important for different developmental programs and for responses to environment. However, so far, the relevance of the two MIR393 genes for Arabidopsis leaf development and their significance for auxin signalling homeostasis have not been evaluated. First, our analyses of mir393a-1 and mir393b-1 mutants and of mir393ab double mutant show that the two genes have only partially redundant functions for leaf development. Expression analyses of typical auxin-induced reporter genes have shown that the loss of miR393 lead to several unanticipated changes in auxin signalling. The expression of DR5pro:GUS is decreased, the expression of primary AUX/IAA auxin-responsive genes is slightly increased and the degradation of the AXR3-NT:GUS reporter protein is delayed in mir393ab mutants. Additional analyses using synthetic auxin and auxin antagonists indicated that miR393 deficient mutants have higher levels of endogenous AUX/IAA proteins, which in turn create a competition for degradation. We propose that the counter-intuitive changes in the expression of AUX/IAA genes and in the accumulation of AUX/IAA proteins are explained by the intrinsic nature of AUX/IAA genes which are feedback regulated by the AUX/IAA proteins which they produce. Altogether our experiments provide an additional highlight of the complexity of auxin signaling homeostasis and show that miR393 is an important component of this homeostasis.

Welcome to the New Journal Non-Coding RNA!

Dear colleagues and non-coding RNAs aficionados, you will probably ask 'why a new journal'?, these days when we are flooded not only by information of any type in any sector of our life, but also by so many new journals that come and disappear like comets in the summer sky! The answer is simple: because we believe that this field finally deserves to have a dedicated journal where its wide community will be able to communicate and exchange its latest findings in one centralized place. Moreover, with your outstanding contributions and by publishing papers that promulgate the 'thinking out of the box', we will be able to build a reputation for Non-Coding RNA to survive over the years to come. [...].

The crosstalk between plant microRNA biogenesis factors and the spliceosome.

Many of the plant microRNA (miRNA) genes contain introns. The miRNA-containing hairpin loop structure is predominantly located within the first exon of such pri-miRNAs. We have shown that the downstream intron and its splicing are important for the regulation of the processing of these pri-miRNAs. The 5' splice site in MIR genes is essential in the process of miRNA biogenesis. We postulate that the presence of yet undefined interactions between U1 snRNP and the pri-miRNA processing machinery leads to an increase in the efficiency of miRNA biogenesis. The 5' splice site also decreases the accessibility of the polyadenylation machinery to the pri-miRNA polyA signal located within the same intron. It is likely that the spliceosome assembly controls the length and structure of MIR primary transcripts, and regulates mature miRNA levels. The emerging picture shows that introns, splicing, and/or alternative splicing have highly relevant roles in regulating the miRNA levels in very specific conditions that contribute to proper plant response to stress conditions.

Biogenesis and Biological Activity of Secondary siRNAs in Plants.

Two important hallmarks of RNA silencing in plants are (1) its ability to self-amplify by using a mechanism called transitivity and (2) its ability to spread locally and systemically through the entire plant. Crucial advances have been made in recent years in understanding the molecular mechanisms of these phenomena. We review here these recent findings, and we highlight the recently identified endogenous small RNAs that use these advantageous properties to act either as patterning signals in important developmental programs or as a part of regulatory cascades.

Introns of plant pri-miRNAs enhance miRNA biogenesis.

Plant MIR genes are independent transcription units that encode long primary miRNA precursors, which usually contain introns. For two miRNA genes, MIR163 and MIR161, we show that introns are crucial for the accumulation of proper levels of mature miRNA. Removal of the intron in both cases led to a drop-off in the level of mature miRNAs. We demonstrate that the stimulating effects of the intron mostly reside in the 5'ss rather than on a genuine splicing event. Our findings are biologically significant as the presence of functional splice sites in the MIR163 gene appears mandatory for pathogen-triggered accumulation of miR163 and proper regulation of at least one of its targets.