Johansensalomonsen1023
DNA binding metal complexes are synonymous with anticancer drug discovery. Given the array of structural and chemical reactivity properties available through careful design, metal complexes have been directed to bind nucleic acid structures through covalent or noncovalent binding modes. Several recognition modes - including crosslinking, intercalation, and oxidation - are central to the clinical success of broad-spectrum anticancer metallodrugs. However, recent progress in nucleic acid click chemistry coupled with advancement in our understanding of metal complex-nucleic acid interactions has opened up new avenues in genetic engineering and targeted therapies. Several of these applications are enabled by the hybridisation of oligonucleotide or polyamine probes to discrete metal complexes, which facilitate site-specific reactivity at the nucleic acid interface under the guidance of the probe. This Review focuses on recent advancements in hybrid design and, by way of an introduction to this topic, we provide a detailed overview of nucleic acid structures and metal complex-nucleic acid interactions. Our aim is to provide readers with an insight on the rational design of metal complexes with DNA recognition properties and an understanding of how the sequence-specific targeting of these interactions can be achieved for gene engineering applications.
Application of volatile organic compounds (VOCs) from Streptomyces salmonis PSRDC-09 (VOCs PSRDC-09) grown on sterile wheat seeds against chili anthracnose pathogen was investigated in vitro and in vivo.
Among 10 isolates of Colletotrichum species tested, Colletotrichum gloeosporioides PSU-03 was selected as the most aggressive anthracnose pathogenic strain on chili fruit against VOCs produced by Streptomyces species. Among 11 isolates, the strain PSRDC-09 exhibited the highest antifungal activity and was identified as S. salmonis PSRDC-09. The antagonistic mechanism of the VOCs PSRDC-09 on morphological of C. gloeosporioides PSU-03, observed by scanning electron microscope (SEM), revealed the irregular distortions in the fungal hyphae. The effect of inoculum size and spore concentration of S. salmonis PSRDC-09 prepared as a wheat seed inoculum on the suppression of C. gloeosporioides PSU-03 was studied both in vitro and on chili fruit. The optimum inoculum size (45g 0·31l
) and spore concentration (10
spores per ml) of the wheat seed culture of S. salmonis PSRDC-09 exhibited the complete suppression (100% inhibition) on C. gloeosporioides PSU-03. The optimum fumigation period of the VOCs PSRDC-09 (45g 1·38l
) was found to be 24h. Based on gas chromatography-mass spectrometry (GC-MS) analysis, 14 major VOCs (produced by the strain PSRDC-09) were detected and l-linalool was the main volatile component.
The results indicated that the VOCs from S. salmonis PSRDC-09 could effectively control the chili anthracnose disease caused by C. gloeosporioides.
These findings suggest that S. salmonis PSRDC-09 may have the potential to become a promising biofumigant for biocontrol of chili anthracnose disease in the postharvest system.
These findings suggest that S. salmonis PSRDC-09 may have the potential to become a promising biofumigant for biocontrol of chili anthracnose disease in the postharvest system.Bone is a dynamic tissue that constantly adapts to changing mechanical demands. The transforming growth factor beta (TGFβ) signaling pathway plays several important roles in maintaining skeletal homeostasis by both coupling the bone-forming and bone-resorbing activities of osteoblasts and osteoclasts and by playing a causal role in the anabolic response of bone to applied loads. However, the extent to which the TGFβ signaling pathway in osteocytes is directly regulated by fluid shear stress (FSS) is unknown, despite work suggesting that fluid flow along canaliculi is a dominant physical cue sensed by osteocytes following bone compression. To investigate the effects of FSS on TGFβ signaling in osteocytes, we stimulated osteocytic OCY454 cells cultured within a microfluidic platform with FSS. We find that FSS rapidly upregulates Smad2/3 phosphorylation and TGFβ target gene expression, even in the absence of added TGFβ. Indeed, relative to treatment with TGFβ, FSS induced a larger increase in levels of pSmad2/3 and Serpine1 that persisted even in the presence of a TGFβ receptor type I inhibitor. Our results show that FSS stimulation rapidly induces phosphorylation of multiple TGFβ family R-Smads by stimulating multimerization and concurrently activating several TGFβ and BMP type I receptors, in a manner that requires the activity of the corresponding ligand. While the individual roles of the TGFβ and BMP signaling pathways in bone mechanotransduction remain unclear, these results implicate that FSS activates both pathways to generate a downstream response that differs from that achieved by either ligand alone.
Literature on pacifier use remains controversial, but mostly suggests an inverse association with childhood intelligence.
The objective of this study was to assess the association between pacifier use and intelligence quotient (IQ) in six-year-old children from a birth cohort.
Data from 3532 children from the 2004 Pelotas (Brazil) Birth Cohort were analysed. ITD-1 cell line Children were recruited and assessed at birth and followed up at 3months, and 1, 2, 4, and 6years. Data on pacifier use duration and intensity were obtained via interviews with mothers in all six follow-up visits. IQ was estimated at 6years using the Wechsler Intelligence Scale for Children and standardised for the analyses. Crude and adjusted coefficients were calculated (linear regression) for all the data collected in follow-up assessments for pacifier use.
IQ was inversely associated with all pacifier use indicators. Children who used a pacifier all day long (ADL) at any follow-up showed an IQ 0.18 (95% confidence interval [CI] 0.11, 0.24) stad to be clarified. One hypothesis is that children using a pacifier, especially those who use it more intensely, are less stimulated.
Social isolation and quarantine are unusual precautions taken all over the world against the COVID-19 pandemic. Some legal sanctions were made in order to protect vulnerable age groups such as the geriatric population, to make them stay at home. These measures, which are vital for pandemic management, have negative psychological effects on elderly individuals. The aim of this study was to reveal how pandemic process affected individuals over 65years old psychosocially.
Socio-demographic characteristics questionnaire, the COVID-19 Phobia Scale (C19P-S) and the Loneliness Scale for the Elderly individuals were used. Descriptive analysis, Mann-Whitney U-test, Kruskal-Wallis test, Pearson correlation analysis were performed for data analysis.
A total of 130 elderly people (80 women, 50 men) were included in the study. Of the participants, 61.5% were women, 67.7% were married and mean age was 71.53±5.57 (min. 65-max. 87) years old. The C19P-S scores were significantly higher in women, singles, people living alone, those living in an apartment, and those with higher economic and educational level (P=.001). There was a strong positive correlation between age and total loneliness score. Loneliness scores were significantly higher in singles, those with higher levels of education and income, those who live alone, who was a relative of a healthcare worker, and whose relatives were infected with COVID-19 (P<.05).
Our study revealed that elderly individuals, who have to comply with social isolation rules, have increased fear and loneliness due to coronavirus. Considering this situation, timely psychological treatment and social support measures should be taken.
Our study revealed that elderly individuals, who have to comply with social isolation rules, have increased fear and loneliness due to coronavirus. Considering this situation, timely psychological treatment and social support measures should be taken.
The aim of this work was to determine the rate of incisional hernia (IH) repair and risk factors for IH repair after laparotomy.
This population-based study used data extracted from the French Programme de Médicalisation des Systèmes d'Informations (PMSI) database. All patients who had undergone a laparotomy in 2010, their hospital visits from 2010 to 2015 and patients who underwent a first IH repair in 2013 were included. Previously identified risk factors included age, gender, high blood pressure (HBP), obesity, diabetes and chronic obstructive pulmonary disease (COPD).
Among the 431619 patients who underwent a laparotomy in 2010, 5% underwent IH repair between 2010 and 2015. A high-risk list of the most frequent surgical procedures (>100) with a significant risk of IH repair (>10% at 5years) was established and included 71863 patients (17%; 65 procedures). The overall IH repair rate from this list was 17%. Gastrointestinal (GI) surgery represented 89% of procedures, with the majority of patienthigh-risk patients should be considered.Glia make up roughly half of all cells in the mammalian nervous system and play a major part in nervous system development, function, and disease. Although research in the past few decades has shed light on their morphological and functional diversity, there is still much to be known about key aspects of their development such as the generation of glial diversity and the factors governing proper morphogenesis. Glia of the nematode C. elegans possess many developmental and morphological similarities with their vertebrate counterparts and can potentially be used as a model to understand certain aspects of glial biology owing to advantages such as its genetic tractability and fully mapped cell lineage. In this review, we summarize recent progress in our understanding of genetic pathways that regulate glial development in C. elegans and discuss how some of these findings may be conserved.The capacity of working memory is limited and undergoes important developmental changes during childhood. One proposed reason for the expansion of working memory capacity during childhood is the emergence and increased efficiency of active maintenance mechanisms, such as that of refreshing. Refreshing is a proposed mechanism to keep information active in working memory by bringing memory items back into the focus of attention. One prevalent view is that the spontaneous use of refreshing emerges around the age of 7 and becomes more efficient during middle childhood and beyond. Using a novel approach to examine refreshing in children in Experiment 1, we show, against common conceptions, that simply giving free time in a basic working memory task does not lead to spontaneous refreshing in 9-12-year-old children. Instead, their focus of attention appears to linger on the last-presented memory item, even when ample time for refreshing is provided. Experimentally imposing the use of refreshing in Experiment 2, however, showed that children in this age range are able to switch their focus of attention away from the last-presented item in switch to another memory item. Thus, the current study uncovers that children in middle childhood do not always spontaneously switch attention away from the last-presented memory item to refresh the entire list, even though they are able to switch attention away from the last-presented memory item when instructed to do so. The theoretical implications of these findings are discussed.
