Bermansimon9204
Many animals use visual cues to navigate their environment. To encode the large input ranges of natural signals optimally, their sensory systems have adapted to the stimulus statistics experienced in their natural habitats1. A striking example, shared across animal phyla, is the retinal tuning to the relative abundance of blue light from the sky, and green light from the ground, evident in the frequency of each photoreceptor type in the two retinal hemispheres2. By adhering only to specific regions of the visual field that contain the relevant information, as for the high-acuity dorsal regions in the eyes of male flies chasing females3, the neural investment can be further reduced. Regionalisation can even lead to activation of the appropriate visual pathway by target location, rather than by stimulus features. This has been shown in fruit flies, which increase their landing attempts when an expanding disc is presented in their frontal visual field, while lateral presentation increases obstacle avoidance responses4. We here report a similar switch in behavioural responses for extended visual scenes. Using a free-flight paradigm, we show that the hummingbird hawkmoth (Macroglossum stellatarum) responds with flight-control adjustments to translational optic-flow cues exclusively in their ventral and lateral visual fields, while identical stimuli presented dorsally elicit a novel directional flight response. This response split is predicted by our quantitative imaging data from natural visual scenes in a variety of habitats, which demonstrate higher magnitudes of translational optic flow in the ventral hemisphere, and the opposite distribution for contrast edges containing directional information.In the last ten years, the next generation sequencing revolution has multiplied the amount of genetic data for many organisms by orders of magnitude. This has not only led to evolutionary biologists having more data available but also to new and different types of data from a handful of allozyme markers in the 70s, we got dozens of restriction fragment length polymorphisms (RFLPs) in the 80s, hundreds of microsatellites in the 90s, thousands to hundreds of thousands of single nucleotide polymorphisms (SNPs) in the 2000s, a few full genomes in the 2010s, and thousands of full genomes in the 2020s. These data have provided information not only on the genetic diversity and evolution of the organisms studied but also on genome-wide patterns of selection, linkage disequilibrium, as well as recombination and mutation processes. Below, we will describe how these new genomic data can be used to infer the past demographic history of populations.Paul Hagerman and Randi Hagerman introduce the X-linked neurodevelopmental disorder Fragile X syndrome (FXS) and discuss what causes this disorder and how it can be treated.Interview with Lesley Weaver, who uses the Drosophila ovary as a model to study how inter-organ communication downstream of nuclear receptor signaling influences oogenesis at Indiana University.
During the early phase of the coronavirus disease 2019 (COVID-19) outbreak, many emergency departments (EDs) were exposed to COVID-19 and were temporarily closed according to national protocol of Korea. We aimed to evaluate the effect of concurrent and recurrent temporary closures of EDs on the clinical outcomes of patients who visited EDs during the COVID-19 outbreak.
This cross-sectional study used a nationwide emergency patient database. Patients who visited one of the 46 EDs in Daegu and Gyeongbuk between January 21 and April 14, 2020 were included. The main exposure variable was the first medical contact (ED visit or 119 call to emergency medical services (EMS)) during closure of at least one ED. There were 25 temporary closures of six Level-1 and Level-2 EDs between February 18 and March 17, 2020. We constructed a dataset by performing bidirectional crossover matching and conducted a conditional logistic regression analysis where the primary outcome was in-hospital mortality.
Of the 94,360 eligiblality rates irrespective of whether they used EMS. Preparing regional EMS systems to cope with new outbreaks is essential to protect the safety of all citizens.
Due to the unique nature of working in the field of emergency medicine (EM), physicians often find it difficult to engage in research and scholarly activity while also working clinical shifts. Barriers to engaging in both academic and clinical work include lack of time, resources, and incentives. EM physicians are familiar with the concept of scribes working alongside them in the emergency department, and there are multiple papers published that examine and advocate for their benefits.
This paper aims to introduce the concept of virtual research scribes in clinical research in EM to offer physicians an opportunity to alleviate the burdens of balancing clinical work and academia simultaneously.
A research scribe is a student who is interested in healthcare and research and aids the PI in literature reviews and manuscript writing and editing, completely remotely. Six research scribes were hired in a pilot program to test their efficacy in a clinical research setting. The scribes were assigned tasks including manuscript writing and editing, performing literature reviews, and writing newsletters.
The six research scribes in the pilot program proved to be beneficial for time management, collaboration, and editing in the research and scholarly process. The remote nature of the program allowed for flexibility in scheduling on both the PI and scribe's behalf.
By utilizing a research scribe in their academic career, EM physicians can increase efficiency and productivity in scholarly work.
By utilizing a research scribe in their academic career, EM physicians can increase efficiency and productivity in scholarly work.A health shock can have lasting consequences for the employment of not only the individuals experiencing it, but also their spouses. In this article, we complement the individual approach to the impact of health shocks with a dyadic perspective and show how employment opportunities and restrictions within couples are interdependent in the face of severe illness. We investigate whether the association between male spouses' health shocks and couples' employment trajectories depends on household specialization and both spouses' education. Multichannel sequence analysis is applied to retrospective life-course data from the Survey for Health, Ageing and Retirement in Europe for couples with health shocks and their matched controls (N = 1022). By identifying typical employment trajectories, we find that health shocks are negatively associated with trajectories where both spouses continue in full-time employment and positively with trajectories where the man retires while the woman continues working and where both spouses retire simultaneously. Couples' trajectories differ according to the spouses' combined education levels. Findings suggest that health shocks may exacerbate economic inequalities within and between couples.MicroRNAs (miRNAs/miRs) are small, non-coding RNAs that are reported to serve numerous important regulatory functions; however, the role of miRNAs in regulating breast cancer cell biology remains poorly understood. Accumulating evidence has demonstrated that miRNAs orchestrate multiple cellular functions and serve crucial roles in cell differentiation and cancer development, either by acting as tumor suppressors or oncogenes. In particular, miR-155-5p expression levels have been found to be upregulated and serve as a prognostic marker in numerous types of solid cancer, including human breast cancer. More than half of patients with breast cancer benefit from treatment with adjuvant paclitaxel chemotherapy following the early postoperative period. Despite the initial response to intensive combination chemotherapy, the majority of most patients will eventually acquire resistance to the drug and succumb to their disease. Therefore, further investigations into the association between miRNAs and the mechanism of paINP1, contributed to the re-sensitivity of drug-resistant cells to paclitaxel. The subsequent combination of the knockdown of miR-155-5p and the overexpression of TP53INP1 conferred paclitaxel sensitivity in resistant cells. These results may enhance the understanding of the molecular mechanisms underlying breast cancer progression and resistance to chemotherapy, and suggested that miR-155-5p or TP53INP1 may serve as novel therapeutic approaches to combat resistance to therapy, as well as the proliferation and evasion of apoptosis in breast cancer.Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC50 value of 0.95 μM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro, but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction.Emerging evidence suggests that cancer metabolism is closely associated to the serine biosynthesis pathway (SSP), in which glycolytic intermediate 3-phosphoglycerate is converted to serine through a three-step enzymatic transformation. As the rate-limiting enzyme in the first step of SSP, phosphoglycerate dehydrogenase (PHGDH) is overexpressed in various diseases, especially in cancer. Genetic knockdown or silencing of PHGDH exhibits obvious anti-tumor response both in vitro and in vivo, demonstrating that PHGDH is a promising drug target for cancer therapy. So far, several types of PHGDH inhibitors have been identified as a significant and newly emerging option for anticancer treatment. Herein, this comprehensive review summarizes the recent achievements of PHGDH, especially its critical role in cancer and the development of PHGDH inhibitors in drug discovery.Prostate cancer (PCa) is one of the most common malignancies affecting men worldwide. Androgen receptor (AR) has been a target of PCa treatment for nearly six decades. AR antagonists/degraders can effectively treat PCa caused by increased AR overexpression. However, all approved AR antagonists have similar chemical structures and exhibit the same mode of action on the protein. Although initially effective, resistance to these AR antagonists usually develops. Y-27632 solubility dmso Therefore, this calls for the identification of novel chemical structures of AR antagonists to overcome the resistance. Herein, we employed the synergetic combination of virtual and experimental screening to identify a flavonoid compound which not only effectively inhibits AR transcriptional activity, but also induces the degradation of the protein. Based on this compound, we designed and synthesized a series of derivatives. We discovered that the most potent compound 10e could effectively inhibit AR transcriptional activity, and possessed a profound ability to cause degradation of both full length- and ARv7 truncated forms of human AR.