METTL3 Is Suppressed by Circular RNA circMETTL3/miR-34c-3p Signaling and Limits the Tumor Growth and Metastasis in Triple Negative Breast Cancer

Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role in the underlying regulatory mechanism in TNBC are lacking. In this study, we investigate the pathological role and the underlying mechanism of the m6A methylated RNA level and its major methyltransferase METTL3 in the TNBC progression. We found that the m6A methylated RNA was dramatically decreased in TNBC tissues and cell lines. Functionally, we demonstrated that METTL3 inhibits the proliferation, migration, and invasion ability of TNBC cells. Moreover, we found METTL3 is repressed by miR-34c-3p in TNBC cells. On the mechanism, we found that circMETTL3 could act as a sponge for miR-34c-3p and inhibits cell proliferation, invasion, tumor growth and metastasis by up-regulating the expression of miR-34c-3p target gene METTL3. In conclusion, our study demonstrates the functional importance and regulatory mechanism of METTL3 in suppressing the tumor growth of TNBC.

Dichotomous Activity and Function of Neurons with Low- and High-Frequency Discharge in the External Globus Pallidus of Non-Human Primates

To date, there is a consensus that there are at least two neuronal populations in the non-human primate (NHP) external globus pallidus (GPe): the low- and high-frequency discharge (LFD and HFD) neurons. Nevertheless, almost all NHP physiological studies have neglected the functional importance of LFD neurons. This study examined the discharge features of these two GPe neuronal subpopulations recorded in four NHPs engaged in a classical conditioning task with cues predicting reward, neutral and aversive outcomes. The results show that LFD neurons tended to burst, encoded the salience of behavioral cues, and exhibited correlated spiking activity. By contrast, the HFD neurons tended to pause, encoded cue valence, and exhibited uncorrelated spiking activity. Overall, these findings point to the dichotomic organization of the NHP GPe which is likely to be critical to the implementation of normal basal ganglia functions and computations.

Genetic Diversity and Detection of Atypical Porcine Pestivirus Infections

Atypical porcine pestivirus (APPV), an RNA virus member of the Flaviviridae family, has been associated with congenital tremor in newborn piglets. Previously reported qPCR-based assays were unable to detect APPV in novel cases of congenital tremor originated from multiple farms from U.S. Midwest (MW). These assays targeted the viral polyprotein coding genes, which were shown to display substantial variation, with sequence identity ranging from 58.2 to 70.7% among 15 global APPV strains. In contrast, the 5’ UTR was found to have a much higher degree of sequence conservation. In order to obtain the complete 5’ UTR of the APPV strains originated from MW, the 5’ end of the viral cDNA was obtained by using template switching approach followed by amplification and dideoxy sequencing. Eighty one percent of the 5’UTR was identical across 14 global and 5 MW strains with complete, or relatively complete 5’ UTR. Notably, some of the most highly conserved 5’UTR segments overlapped with potentially important regions of an internal ribosome entry site (IRES), suggesting their functional role in viral protein translation. A newly designed single qPCR assay, targeting 100% conserved 5’UTR regions across 19 strains, was able to detect APPV in samples of well documented cases of congenital tremor which originated from five MW farm sites (1-18 samples/site). As these fully conserved 5’ UTR sequences may have functional importance, we expect that assays targeting this region would broadly detect APPV strains that are diverse in space and time.

Exploring New Forms with Parametric Patterns for Responsive Facades

Façades or building envelopes have always been the interface between the building and the environment. The effective and smart façades that are designed to adapt the environmental conditions date back to when windows and ventilators were designed carefully in response to the site conditions. Over recent decades, the emphasis on energy consumption and its reduction has increased drastically, as technology has evolved and increasingly new materials are used in buildings than ever. Due to the numerous significant roles that a facade plays, thermal comfort, aesthetics, acoustics and lighting, high-performance building facades have become one of the main focal points for researchers and designers. This study is based on the intersection of two main subjects of interest, the significance of jali/screens, as ornate architectural elements along with their functional importance and the integration of this knowledge with parametric design methods to achieve new design solutions in façade design. The study then demonstrates the kinetic façade concept through a jali. Two design exercises have been carried out and their kinetic systems explored, with the potential of a simple geometric design used as a module to generate the skin and its kinetic response. The investigations from this research open a gateway for further explorations in jali design, using parametric tools to develop kinetic responsive skins.

The Model of Digital Cartographic Layers of Different Scales to Calculate the Ratios of Cartographic Generalizations: An Applied Study to Anah City

The research aims to give an accurate perception of the role of modern technologies, represented by geographic information systems, in extracting data and information, and then building a geographical database for urban land uses in an Ana city to reach generalized models based on the source map with a scale of 1/5000 and then building generalized models through The application of digital generalization elements according to the different standards adopted in the research (1/10000, 1/25000, 1/50000, 1/100000) in order to reach the end to the best results in the cartographic production of these models in a way that facilitates the process of understanding and perception by finding The most appropriate way to represent this data on a map according For the functional importance of each of the uses through disposal to eliminate overlap between uses Depending on the generalization elements of selecting, deleting, simplifying, smoothing, coding and exaggeration, and finally, as The research showed that there is a difference in the areas, uses and preparation of methods when moving from one scale to another. the research concluded by building a three-dimensional model to simulate the natural process of generalizing digital cartography according to different scales.

Epithelial-Mesenchymal Transition Induces GSDME Transcriptional Activation for Inflammatory Pyroptosis

GSDME is a newly recognized executor of cellular pyroptosis, and has been recently implicated in tumor growth and immunity. However, knowledge about the molecular regulators underlying GSDME abundance remains limited. Here, we performed integrative bioinformatics analyses and identified that epithelial-mesenchymal transition (EMT) gene signatures exhibited positive correlation with GSDME levels across human cancers. A causal role was supported by the observation that EMT dictated GSDME reversible upregulation in multiple experimental models. Mechanistically, transcriptional activation of GSDME was directly driven by core EMT-activating transcription factors ZEB1/2, which bound to the GSDME promoter region. Of functional importance, elevated GSDME in mesenchymally transdifferentiated derivatives underwent proteolytic cleavage upon antineoplastic drug exposure, leading to pyroptotic cell death and consequent cytokine release. Taken together, our findings pinpointed a key transcriptional machinery controlling GSDME expression and indicated potential therapeutic avenues to exploit GSDME-mediated inflammatory pyroptosis for the treatment of mesenchymal malignancies.

Peroxisomal Membrane Contact Sites in Yeasts

Peroxisomes are ubiquitous, single membrane-bound organelles that play a crucial role in lipid metabolism and human health. While peroxisome number is maintained by the division of existing peroxisomes, nascent peroxisomes can be generated from the endoplasmic reticulum (ER) membrane in yeasts. During formation and proliferation, peroxisomes maintain membrane contacts with the ER. In addition to the ER, contacts between peroxisomes and other organelles such as lipid droplets, mitochondria, vacuole, and plasma membrane have been reported. These membrane contact sites (MCS) are dynamic and important for cellular function. This review focuses on the recent developments in peroxisome biogenesis and the functional importance of peroxisomal MCS in yeasts.

Jacques-Louis Reverdin - pioneer of transplantology, a surgeon who opened the veil of functional importance of the thyroid gland

Jacques-Louis Reverdin is a famous Swiss surgeon, scientist, and entomologist of the nineteenth century. He made a considerable contribution to the development of transplantology — he was one of the first to publish work on allotransplantation, performing the so — called “skin grafting”, urology — he defended his thesis on urethrotomy, endocrinology- he performed surgical operations for the treatment of goiter, observed and described the symptoms of iatrogenic hypothyroidism, introduced the concept of postoperative myxedema. For thirty-four years, he led an active surgical practice, thanks to which he described a large number of operations (the most famous are operations on the thyroid gland), introduced a surgical suture and needle, which are still used today. During the Franco-Prussian war, he commanded a Swiss ambulance. He was a proponent of Lister’s method of asepsis and antiseptics, and introduced it in hospitals in Geneva. He was engaged in teaching and research, and was nominated for the Nobel prize three times. He received the Amuss prize of the Academy of Medicine, the prize of the Paris Academy of medicine for his work on urethrotomy, founded the Revue Medicale de la Suisse Romande, and was a co-founder and later President of the Association of physicians of Geneva. Honorary member of the entomological societies of Switzerland, France, England and Brazil.