The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells

Different from canonical ubiquitin-like proteins, Hub 1 does not form covalent conjugates with substrates but binds proteins non- covalently. In Saccharomyces cerevisiae , Hub 1 associates with spliceosomes and mediates alternative splicing of SRC 1 , without affecting pre-mRNA splicing generally. Human Hub 1 is highly similar to its yeast homolog, but its cellular function remains largely unexplored. Here, we show that human Hub 1 binds to the spliceosomal protein Snu 66 as in yeast; however, unlike its S. cerevisiae homolog, human Hub 1 is essential for viability. Prolonged in vivo depletion of human Hub 1 leads to various cellular defects, including splicing speckle abnormalities, partial nuclear retention of mRNAs, mitotic catastrophe, and consequently cell death by apoptosis. Early consequences of Hub 1 depletion are severe splicing defects, however, only for specific splice sites leading to exon skipping and intron retention. Thus, the ubiquitin-like protein Hub 1 is not a canonical spliceosomal factor needed generally for splicing, but rather a modulator of spliceosome performance and facilitator of alternative splicing

Enhancing Stability and Efficacy of Trichoderma Bio-Control Agents through Layer-by-Layer Encapsulation for Sustainable Plant Protection

Agricultural fungicide pollution poses a significant environmental challenge and carries adverse consequences for human health. Therefore, strategies to limit fungicide usage have gained paramount importance. Trichoderma fungi, owing to their antagonistic activity against various pathogenic fungi, have emerged as prospective candidates for enhancing both the effectiveness and sustainability of plant protection. Nevertheless, the utilization of bio-control agents like Trichoderma has unveiled new challenges, notably their vulnerability to physical stimuli and diminished efficacy during prolonged storage. To overcome these drawbacks, we present a mild and scalable encapsulation method for Trichoderma spores, employing a layer-by-layer (LbL) encapsulation approach using biobased lignin derivates. Our investigations demonstrate that the LbL-encapsulation technique imparts remarkable improvements in spore stability, even under adverse conditions such as variable temperature and prolonged exposure to UV irradiation compared to unencapsulated spores. Notably, encapsulated Trichoderma spores exhibit increased efficiency in the cultivation of tomato plants when compared to their unencapsulated counterparts. Additionally, our findings reveal that the in planta efficacy of encapsulated spores is contingent upon the specific Trichoderma strain employed. The results outlined herein suggest that Trichoderma spores, encapsulated within lignin through the LbL approach, exhibit potential as promising and sustainable alternative to chemical fungicides and potential commercialization

Dread in Academia – how COVID-19 affects science and scientists

In order to gain an insight into scholars’ concerns emerging from the COVID-19 crisis, we asked scientists from all over the world about their attitudes and predictions regarding the repercussions of this current crisis on academia. Our data showed that the academic world was placed in an unprecedented situation. Results further showed that everybody worked on-line, conducting studies was impossible or highly impeded, and lab work was difficult. Almost a quarter of all scientists participating in our survey were anxious about their scientific employment, and over 25% expected serious financial losses as a consequence of the pandemic. Moreover, we identified sex differences regarding the severity of the COVID-19 impact in the majority of questions. We inferred from this that women perceived to be in a worse situation than men

Assessment of the Concentration of 51 Elements in the Liver and in Various Parts of the Human Brain—Profiling of the Mineral Status

The anthropogenic environment and diet introduce many metals into the human body, both essential and toxic. Absorption leads to systemic exposure and accumulation in body fluids and tissues. Both excess and deficiency of trace elements are health hazards. The primary aim of the present study was to evaluate the concentration of 51 elements in liver samples and 11 selected brain regions obtained at post-mortem examination from a population of adults living in south-eastern Poland (n = 15). A total of 180 analyses were performed by inductively coupled plasma mass spectrometry in two independent replicates. The collected data show very high individual variability in the content of the investigated elements. Macroelements such as sodium, magnesium, phosphorus, potassium, calcium, iron, and zinc occurred in the highest concentrations and with the greatest statistically significant variations. Although the elemental content of the brain and liver differed significantly, the strongest positive correlation between liver and polus frontalis was observed for the essential element selenium (0.9338) and the strongest negative one for manganese (−0.4316) and lanthanum (−0.5110). The brain areas studied have different requirements for phosphorus, manganese, iron, and molybdenum. In addition, males had a significantly (p < 0.05) higher brain content of lanthanides and actinides than females. The results of this study show that the inhabitants of south-eastern Poland are exposed to a fairly uniform accumulation of aluminum and vanadium in the brain, which have the highest affinity to the thalamus dorsalis. This result proves that there is environmental exposure to these elements

No relationship between the digit ratios (2D:4D) and salivary testosterone change: Study on men under an acute exercise

Abstract The digit ratio (2D:4D) is said to be a potential marker of exposure to prenatal sex steroids. Some studies suggest that the 2D:4D is also linked with the testosterone response to challenging situations due to organizational effect of prenatal hormonal milieu on adult endocrine functioning. However, up to date, there were only four studies (conducted on small samples) that examined the 2D:4D and the testosterone response to a challenging situation (i.e. physical exertion or aggressive context). Here, we examined the relationship between the 2D:4D and the testosterone change under an acute exercise among 97 men. We found that the digit ratios (the right 2D:4D, the left 2D:4D, and the right minus left 2D:4D) were neither predictors of pre-exercise testosterone, nor the change in testosterone level after a cycling task. Our results add a contradictory to previous studies evidence in a discussion on the links of the 2D:4D and the testosterone change

Transient Protein States in Designing Inhibitors of the MDM2-p53 Interaction

<p>Reactivation of p53 by release of the functional protein from its inhibition by MDM2 provides an efficient, nongenotoxic approach to a wide variety of cancers. We present the cocrystal structures of two complexes of MDM2 with inhibitors based on 6-chloroindole scaffolds. Both molecules bound to a distinct conformational state of MDM2 with nM-mu M affinities. In contrast to other structurally characterized antagonists, which mimic three amino acids of p53 (Phe19, Trp23, and Leu26), the compounds induced an additional hydrophobic pocket on the MDM2 surface and unveiled a four-point binding mode. The enlarged interaction interface of the inhibitors resulted in extension of small molecules binding toward the "lid" segment of MDM2 (residues 19-23) a nascent element that interferes with p53 binding. As supported by protein engineering and molecular dynamics studies, employing these unstable elements of MDM2 provides an efficient and yet unexplored alternative in development of MDM2-p53 association inhibitors.</p>