Guided by structural similarity between Kpn2I and the CCGG-family restriction endonucleases PfoI and AgeI, Kpn2I residues involved in the outer base pair recognition were proposed.
 
  Kpn2I is an orthodox Type IIP restriction endonuclease, which acts as a dimer. Kpn2I shares structural similarity to the CCGG-family restriction endonucleases PfoI, AgeI and PspGI.
 
  The Kpn2I structure concluded the studies of the CCGG-family, covering detailed structural and biochemical characterization of eleven restriction enzymes and their complexes with DNA.
 The Kpn2I structure concluded the studies of the CCGG-family, covering detailed structural and biochemical characterization of eleven restriction enzymes and their complexes with DNA.Marine microorganisms have been a resource for novel therapeutic drugs for decades. In addition to anticancer drugs, the drug acyclovir, derived from a marine sponge, is FDA-approved for the treatment of human herpes simplex virus-1 infections. Most alphaviruses that are infectious to terrestrial animals and humans, such as Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV), lack efficient antiviral drugs and it is imperative to develop these remedies. To push the discovery and development of anti-alphavirus compounds forward, this study aimed to isolate and screen for potential antiviral compounds from cultured marine microbes originating from the marine environment. Compounds from marine microbes were of interest as they are prolific producers of bioactive compounds across the spectrum of human diseases and infections. Homoseongomycin, an actinobacteria isolated from a marine sponge displayed impressive activity against VEEV from a total of 76 marine bioactive products. The 50% effective concentration (EC50) for homoseongomycin was 8.6 μM for suppressing VEEV TC-83 luciferase reporter virus replication. Homoseongomycin was non-toxic up to 50 μM and partially rescued cells from VEEV induced cell death. Homoseongomycin exhibited highly efficient antiviral activity with a reduction of VEEV infectious titers by 8 log10 at 50 μM. It also inhibited EEEV replication with an EC50 of 1.2 μM. Mechanism of action studies suggest that homoseongomycin affects both early and late stages of the viral life cycle. Cells treated with 25 μM of homoseongomycin had a ~90% reduction in viral entry. In comparison, later stages showed a more robust reduction in infectious titers (6 log10) and VEEV extracellular viral RNA levels (4 log10), but a lesser impact on intracellular viral RNA levels (1.5 log10). In sum, this work demonstrates that homoseongomycin is a potential anti-VEEV and anti-EEEV compound due to its low cytotoxicity and potent antiviral activity.There are well known phenotypic differences in sweet-liking across individuals, but it remains unknown whether these are related to broader underlying differences in interoceptive abilities (abilities to sense the internal state of the body). Here, healthy women (N = 64) classified as sweet likers (SLs) or sweet dislikers (SDs) completed a bimodal interoception protocol. A heartbeat tracking and a heartbeat discrimination task determined cardiac interoception; both were accompanied by confidence ratings.  https://www.selleckchem.com/products/imd-0354.html  A water load task, where participants consumed water to satiation and then to maximum fullness was used to assess gastric interoceptive abilities. Motivational state, psychometric characteristics and eating behaviour were also assessed. SLs performed significantly better than SDs on both heartbeat tasks, independently of impulsivity, anxiety, depression, and alexithymia. No differences in metacognitive awareness and subjective interoceptive measures were found. With gastric interoception, SLs were more sensitive to stomach distention, and they ingested less water than SDs to reach satiety when accounting for stomach capacity. SLs also scored higher on mindful and intuitive eating scales and on emotional eating particularly in response to negative stimuli; emotional overeating was fully mediated via interoceptive performance. Overall, our data suggest the SL phenotype may reflect enhanced responsiveness to internal cues more broadly.Meat consumption is increasingly seen as unsustainable, unhealthy, and unethical. Understanding what factors help people reduce their meat intake is urgently needed. One such factor is meat disgust, a feeling reported by many vegetarians, and which could be a promising basis for meat reduction interventions. However, meat disgust and its impact on meat consumption is poorly understood. We examined meat disgust and its role in vegetarianism and reducing meat intake in a cross-sectional and longitudinal online study. We measured self-reported meat consumption, meat disgust (by self-report and Implicit Association Test), meat liking, self-control, and disgust sensitivity in N = 711 adults (57% omnivores, 28% flexitarians, 15% vegetarians) recruited from a community cohort. Results showed that 73% of vegetarians can be classified as 'meat disgusted', and that meat disgust predicted meat intake better than self-control in omnivores and flexitarians at baseline. Following up a sub-sample of participants (N = 197) after six months revealed that changes in meat intake over time were also associated with changes in meat disgust. This is the first study to quantify the impact of meat disgust on (changes in) meat consumption and its prevalence in the vegetarian and the general population. Our findings advance research into meat disgust and encourage the development of disgust-based interventions to reduce meat intake.
  Aging is an inevitable physiological process, associated with a decline in cognitive function. Recently, metformin, as the first-line treatment for type II diabetes, has been shown to increase the life expectancy of diabetic patients. Therefore, researchers are paying increasing attention to its anti-aging properties. Oxygen free radicals are responsible for oxidative stress, which is a prominent factor in age-associated diseases. This study aimed to evaluate the effects of long-term administration of metformin on age-dependent oxidative stress and cognitive function.
 
  In this experimental study, 32 normal (nondiabetic) male Wistar rats were randomly assigned into control and metformin groups (n = 16 per group). The metformin group received 100 mg/kg of metformin in drinking water daily for six months. The shuttle box test was used for the passive avoidance task in 24-month-old rats. For the biochemical assay, the total antioxidant capacity (TAC) and malondialdehyde (MDA) level were measured. Nissl and TUNEL staining were also used for histopathological assessments.