The nuclear organization of tightly condensed heterochromatin plays important roles in regulating gene transcription and genome integrity. Heterochromatic domains are usually present at chromosomal regions containing a large array of repeated DNA sequences. We previously showed that integration of a 1,000-copy tandem array of an inducible reporter gene into the genome of mammalian cells induces the formation of a highly compact heterochromatic domain enriched in heterochromatin protein 1 (HP1). It remains to be determined how these DNA repeats are packaged into a heterochromatic form and are silenced. Here, we show that HP1-mediated transgene condensation and silencing require the interaction with PxVxL motif-containing proteins. The chromatin assembly factor 1 (CAF-1) complex concentrates at the transgenic locus through the interaction of its PxVxL motif-containing p150 subunit with HP1. Knockdown of p150 relieves HP1-mediated transgene compaction and repression. When targeted to the transgenic locus, p150 mutants defective in binding HP1 cause transgene decondensation and activation. Taken together, these results suggest that HP1 cooperates with CAF-1 to compact transgene repeats. This study provides important insight into how heterochromatin is maintained at chromosomal regions with abundant DNA repeats.

The physiological roles of Zn transporter (ZNT) proteins are being increasingly recognized, and three dimensional structures of ZNT bacterial homologs have facilitated our understanding of their biochemical characteristics at the molecular level. However, the biological role of the unique structural features of vertebrate ZNTs, which are absent in their bacterial homologues, is not completely understood. These ZNT sequences include a cytosolic His-rich loop between transmembrane helices IV and V and the cytosolic N-terminus. This study investigated the contribution of these features to zinc transport by ZNT proteins. The importance of the His residues in the cytosolic His-rich loop was investigated using ZNT2 Ala substitution and deletion mutants. The presence of His residues was not essential for zinc transport, even though they possibly participate in modulation of zinc transport activity. Furthermore, we determined the role of the N-terminus by characterizing ZNT2 and ZNT3 domain-swapped and deletion mutants. Unexpectedly, the N-terminus was also not essential for zinc transport by ZNT2 and the domain-swapped ZNT2 mutant, in which the cytosolic His-rich loop was substituted with that of ZNT3. These results provide molecular insights into understanding the roles of the cytosolic parts of ZNT2, ZNT3, and probably other members of their subgroup.

The continuing rise of infections caused by multi-drug resistant bacteria has led to a renewed interest in bacteriophage therapy. Here we characterize phage vB_AbaM-KARL-1 with lytic activity against multi-drug resistant clinical isolates of Acinetobacter baumannii (AB). Besides genomic and phenotypic phage analysis, the objective of our study was to investigate the antibacterial outcome when the phage acts in concert with distinct antibiotics. KARL-1 belongs to the family of Myoviridae and is able to lyse 8 of 20 (40%) tested clinical isolates. Its double-stranded DNA genome consists of 166,560 bp encoding for 253 open reading frames. Genome wide comparison suggests that KARL-1 is a novel species within the subfamily Tevenvirinae, sharing 77% nucleotide identity (coverage 58%) with phage ZZ1. The antibacterial efficacy at various multiplicities of infection (MOI) was monitored either alone or in combination with meropenem, ciprofloxacin, and colistin. A complete clearance of liquid cultures was achieved with KARL-1 at an MOI of 10-1 and meropenem (>128 mg/l). KARL-1 was still effective at an MOI of 10-7, but antibacterial activity was significantly augmented with meropenem. While ciprofloxacin did generally not support phage activity, the application of KARL-1 at an MOI of 10-7 and therapeutic doses of colistin significantly elevated bacterial suppression. Hence, KARL-1 represents a novel candidate for use against multi-drug resistant AB and the therapeutic outcome may be positively influenced by the addition of traditional antibiotics.

Non-small cell lung cancer (NSCLC) is characterized by hyperexpression and/or gain-of-function mutations of the epidermal growth factor receptor (EGFR), resulting in an elevated overall kinase activity. Gefitinib is remarkably effective in patients with the L858R or ΔE746-A750-mutated of EGFR. However, drug resistance tends to develop because of the emergence of T790M mutation on EGFR. New strategies other than repressing kinase activity are thus required to treat NSCLC, thereby circumventing the resistance. In this study, arsenic trioxide (ATO) at 2 μM significantly inhibited the proliferation of the gefitinib-resistant NCI-H1975 cells of the EGFR L858R/T790M mutant compared with a modest inhibition in the gefitinib-sensitive HCC827 cells of ΔE746-A750 mutant and A549 cells of wild-type EGFR. Moreover, ATO significantly inhibited the overall kinase activity of EGFR primarily through quantitatively diminishing the EGFR in NCI-H1975 cells to an extent comparable with that reached by gefitinib in HCC827 cells. Furthermore, ATO promoted autophagic degradation of EGFR in NSCLC cells by directly binding to P62, which interacted with EGFR, preferentially the L858R/T790M mutant providing a plausible explanation for a more favorable effect of ATO on NCI-H1975 cells. Accordingly, the effect of ATO was further confirmed in the NSCLC xenograft mouse models. Our results reveal a new target for ATO with a unique molecular mechanism, i.e., ATO suppresses the overall catalytic potential of EGFR, significantly those with the L858R/T790M mutant in NCI-H1975 cells, through an autophagic degradation by interacting with P62. This study potentially offers an innovative therapeutic avenue for the NSCLC with L858R/T790M-mutated EGFR.

Based on confocal fluorescence and bright field video microscopy, we present detailed observations on the processes of invasion and egress of erythrocytes by the apicomplexan parasite Babesia divergens. Time-lapse images reveal numerous unexpected findings associated with the dynamics of B. divergens and its ability to manipulate the erythrocyte during both processes in its asexual cycle under in vitro conditions. Despite the speed at which these processes occur and the small size of the parasite, we capture infective merozoites moving vigorously and causing striking deformations in the erythrocyte's plasma membrane during an active invasion. We also observed intraerythrocytic dynamic stages as paired pyriforms, double paired pyriforms, tetrads, unattached pyriform sister cells and multiple parasite stages resulting in the release of large numbers of merozoites over a short period. Of considerable interest is that time-lapse images reveal a novel mechanism of egress used by B. divergens to exit the human erythrocyte. The release occurs when B. divergens parasites establish contacts with the plasma membrane of the erythrocyte from within, before exiting the cell. Visualization and analysis of the images enabled us to obtain useful information and broaden our knowledge of complex and crucial events involved with parasitisation of human erythrocytes by B. divergens.

Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have broader functions including potent antioxidant, anti-inflammatory and neuroprotective properties. Considerable researches have demonstrated that AXT shows preventive and therapeutic properties against for Diabetes, Osteoarthritis and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease has not yet been reported. In this study, we investigated effects of AXT on ethanol-induced liver injury in chronic plus binge alcohol feeding model. The hepatic steatosis and inflammation induced by ethanol administration were alleviated by AXT. Serum levels of aspartate transaminase and alanine transaminase were decreased in the livers of AXT administrated group. The ethanol-induced expression of cytochrome P450 2E1 (CYP2E1), pro-inflammatory proteins, cytokines, chemokines and reactive oxygen species (ROS) levels were also reduced in the livers of AXT administrated group. Moreover, ethanol-induced infiltration of neutrophils was decreased in the livers of AXT administrated group. Docking model and pull-down assay showed that AXT directly binds to the DNA binding site of STAT3. Moreover, AXT decreased STAT3 phosphorylation in the liver of AXT administration group. Therefore, these results suggest that AXT could prevent ethanol-induced hepatic injury via inhibition of oxidant and inflammatory responses via blocking of STAT3 activity.

The clinical presentation and diagnostic workup in pediatric cervical spine injuries (CSI) are different from adults owing to the unique anatomy and relative immaturity. The current article reviews the existing literature regarding the uniqueness of these injuries and discusses the current guidelines of radiological evaluation. A PubMed search was conducted using keywords "paediatric cervical spine injuries" or "paediatric cervical spine trauma." Six hundred and ninety two articles were available in total. Three hundred and forty three articles were considered for the review after eliminating unrelated and duplicate articles. Further screening was performed and 67 articles (original articles and review articles only) related to pediatric CSI were finally included. All articles were reviewed for details regarding epidemiology, injury patterns, anatomic considerations, clinical, and radiological evaluation protocols. CSIs are the most common level (60%-80%) for pediatric Spinal Injuries (SI). Children suffer from atlantoaxial injuries 2.5 times more often than adults. Children's unique anatomical features (large head size and highly flexible spine) predispose them to such a peculiar presentation. The role of National Emergency X-Ray Utilization Study, United State (NEXUS) and Canadian Cervical Spine Rule criteria in excluding pediatric cervical injury is questionable but cannot be ruled out completely. The minimum radiological examination includes 2- or 3-view cervical X-rays (anteroposterior, lateral ± open-mouth odontoid views). Additional radiological evaluations, including computerized tomography (CT) and magnetic resonance imaging (MRI) are obtained in situations of abnormal physical examination, abnormal X-rays, inability to obtain adequate X-rays, or to assess cord/soft-tissue status. The clinical criteria for cervical spine injury clearance can generally be applied to children older than 2 years of age. Nevertheless, adequate caution should be exercised before applying these rules in younger children. Initial radiographic investigation should be always adequate plain radiographs of cervical spine. CT and MRI scans should only be performed in an appropriate group of pediatric patients.

It is uncertain whether single bone fixation is comparable to both bone fixation in the treatment of unstable both bone forearm fractures in children.

Regular exercise is an exogenous factor of gene regulation with numerous health benefits. The study aimed to evaluate human genes linked to physical exercise in an 'omic scale, addressing biological questions to the generated database. Three literature databases were searched with the terms 'exercise', 'fitness', 'physical activity', 'genetics' and 'gene expression'. For additional references, papers were scrutinized and a text-mining tool was used. Papers linking genes to exercise in humans through microarray, RNA-Seq, RT-PCR and genotyping studies were included. Genes were extracted from the collected literature, together with information on exercise protocol, experimental design, gender, age, number of individuals, analytical method, fold change and statistical data. The 'omic scale dataset was characterized and evaluated with bioinformatics tools searching for gene expression patterns, functional meaning and gene clusters. As a result, a physical exercise-related human gene compendium was created, with data from 58 scientific papers and 5.147 genes functionally correlated with 17 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. While 50.9% of the gene set was up-regulated, 41.9% was down-regulated. 743 up- and 530 down-regulated clusters were found, some connected by regulatory networks. To summarize, up- and down-regulation was encountered, with a wide genomic distribution of the gene set and up- and down-regulated clusters possibly assembled by functional gene evolution. Physical exercise elicits a widespread response in gene expression.

Plants are rich in protease inhibitors (PI) and trypsin inhibitors are the most common. Therefore, it is of interest to screen PI from plant sources. We report the screening, purification and characterization of PI from Capsicum frutescenes. The partially purified PI showed bands corresponding to 21 KDa and was further confirmed using reverse zymography. The enzyme was stable at temperatures below 60°C and a wide range of pH with 65 folds purification. The effect of magnesium ions oxidizing and reducing agents on PI is reported. The large-scale isolation and purification of PI from Capsicum frutescenes is of commercial interest.

The DNA-protein interactions play vital roles in the central dogma of molecular biology. Proper interactions between DNA and protein would lead to the onset of various biological phenomena like transcription, translation, and replication. However, the mechanisms of these well-known processes vary between prokaryotic and eukaryotic organisms. The exact molecular mechanisms of these processes are unknown. Therefore, it is of interest to report the comparative estimate of the different properties of the DNA binding proteins from prokaryotic and eukaryotic organisms. We analyzed the different sequence-based features such as the frequency of amino acids and amino acid groups in the proteins of prokaryotes and eukaryotes by statistical measures. The general pattern of differences between the various DNA binding proteins for the development of a prediction system to discriminate between these proteins between prokaryotes and eukaryotes is documented.

To compare factors affecting patient satisfaction after femtosecond laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE) for myopia in the real-life situation study.

Programed cell death-1/programed death ligand-1 (PD-1/PD-L1) blockade represents an affirmed reality in the treatment of advanced non-small-cell lung cancer (NSCLC) patients. Atezolizumab, an anti-PD-L1 agent, figures among the drugs that provide previously unenvisaged outcomes in the pretreated setting of metastatic NSCLC. Increasing evidence vouches for the early administration of PD-1/PD-L1 blockers in untreated patients, encompassing atezolizumab combinations with chemotherapy and the anti-angiogenic agent bevacizumab. Moreover, the development of atezolizumab allowed to derive several hints regarding clinical and immunological factors predictive of its activity and efficacy, some of them exclusive among this class of drugs. This review provides an overview of atezolizumab development throughout clinical trials toward its applicability in the routine practice, with a particular focus on patient selection based on clinical and immune-related factors.

Mesenchymal stem cells (MSCs) possess inherent tropism towards tumor cells, and so have attracted increased attention as targeted-therapy vehicles for glioma treatment.

Circular RNAs represent a new class of noncoding RNAs involved in the development of cancer. However, little is known about their role in non-small cell lung cancer (NSCLC).

The usefulness of ribonucleotide reductase catalytic subunit M1 (RRM1) for predicting the therapeutic effects of gemcitabine-containing chemotherapy in patients with non-small cell lung cancer (NSCLC) remains controversial. RRM1-positive patients show unique clinicopathological features.

Although miR-221/222 cluster plays an important role in many human malignancies, the correlation between miR-221/222 cluster overexpression and tumor prognosis remains controversial. Therefore, an updated meta-analysis was conducted to clarify its prognostic value in malignancy.

The high content of carotenoids, sugars, dry matter, vitamins and minerals makes the fruit of winter squash (Cucurbita maxima Duchesne) a valuable fresh-market vegetable and an interesting material for the food industry. Due to their nutritional value, long shelf-life and health protective properties, winter squash fruits have gained increased interest from researchers in recent years. Despite these advantages, the genetic and genomic resources available for C. maxima are still limited. The aim of this study was to use the genetic mapping approach to map the ovary colour locus and to identify the quantitative trait loci (QTLs) for high carotenoid content and flesh colour. An F6 recombinant inbred line (RIL) mapping population was developed and used for evaluations of ovary colour, carotenoid content and fruit flesh colour. SSR markers and DArTseq genotyping-by-sequencing were used to construct an advanced genetic map that consisted of 1824 molecular markers distributed across linkage groups corresponding to 20 chromosomes of C. maxima. Total map length was 2208 cM and the average distance between markers was 1.21 cM. The locus affecting ovary colour was mapped at the end of chromosome 14. The identified QTLs for carotenoid content in the fruit and fruit flesh colour shared locations on chromosomes 2, 4 and 14. QTLs on chromosomes 2 and 4 were the most meaningful. A correlation was clearly confirmed between fruit flesh colour as described by the chroma value and carotenoid content in the fruit. A high-density genetic map of C. maxima with mapped loci for important fruit quality traits is a valuable resource for winter squash improvement programmes.

The purpose of this study was to screen the critical genes for future diagnosis and treatment of colon cancer by bioinformatics method.

Over the past few years, visual prostheses (namely, Argus II retinal implant) and gene therapy have obtained FDA approval in treating blindness resulting from retinitis pigmentosa. Compared to gene therapy; Argus II is less costly with a demonstrated favorable outcome, though the vision is yet artificial. To obtain better results, expectation counseling and preoperative retinal assessment are critical. The global experience with Argus II has enrolled no more than 300 cases so far. The first Argus II retinal prosthesis in Iran was successfully implanted in Shiraz (October 2017). To date, Argus II artificial retina is implanted in four patients in Iran. Beside successful surgery and post-operative care, rehabilitation efforts with validated outcome measures including visual rehabilitation together with neurovisual, visuo-constructive and cognitive rehabilitation/empowerment approaches are expected to boost the functional outcome. A multidisciplinary approach within a cross-functional team would optimize strategies toward better patient outcomes. As such, establishing a collaborative network will foster organized research efforts to better define outcome assessment and rehabilitation strategies. This technology report paper has been an attempt to provide an overview of Argus-II retinal implant global experience as well as the clinical outcome of the so far cases in Iran. Insights from this report were communicated during the first "Brain Engineering and Computational Neuroscience Conference," 31 January-2 February 2018 in Tehran.