The Influence of the Hudson's Bay Company in the Exploration and Settlement of the Red River Valley of the North

As beaver became scarcer in the east, the quest for Castor Canadensis sent traders into the northern plains. Reluctant explorers, traders looked for easier access and cheaper means of transport. Initially content to wait on the shores of the Bay, HBC was forced to meet their competitors in the natives? homelands. The Red River Valley was easily accessed from Hudson?s Bay, becoming the center of the fur trade in the northern plains. HBC helped colonize the first permanent settlement west of the Great Lakes in the Red River Valley. Allowing white women and introducing cultivation into the area was a necessary change. The influence of the fur trade in North Dakota and of the Hudson?s Bay Company on the exploration and settlement of the Red River Valley cannot be overemphasized

Mechanism of the Mitsunobu Reaction: An Ongoing Mystery.

The Mitsunobu reaction is one the most widely known reactions in the organic chemistry canon. Despite its fame, some aspects of the mechanism remain poorly understood, 55 years after its initial discovery. This short review collates the findings of several publications focused on the mechanism of the Mitsunobu reaction, highlighting both the current state of knowledge and the remaining missing pieces

Rural Implications of Geographic Rating of Health Insurance Premiums

This brief examines how and to what extent states allow health plans to vary premiums by geographic rating area and, using insurance data from selected states, assesses the direction and magnitude of variations in rural and urban geographic rating factors. The authors conclude with a discussion of strategies that federal and state policymakers might use to help ensure that premium variations based on geography are justified. KEY POINTS: There is no clear pattern of geographic rating factors favoring rural or urban areas. This lack of a clear pattern suggests that health plans may use geographic rating for business purposes other than adjusting for underlying cost/price differences. Geographic rating could reduce insurance risk pooling and be used as a proxy for experience rating. To limit the effect of market segmentation resulting from geographic rating, rate bands could be imposed on area rating factors

Cryo-EM structure of the monomeric Rhodobacter sphaeroides RC-LH1 core complex at 2.5Å

Reaction centre light-harvesting 1 (RC-LH1) complexes are the essential components of bacterial photosynthesis. The membrane-intrinsic LH1 complex absorbs light and the energy migrates to an enclosed RC where a succession of electron and proton transfers conserves the energy as a quinol, which is exported to the cytochrome bc1 complex. In some RC-LH1 variants quinols can diffuse through small pores in a fully circular, 16- subunit LH1 ring, while in others missing LH1 subunits create a gap for quinol export. We used cryogenic electron microscopy to obtain a 2.5 Å resolution structure of one such RC-LH1, a monomeric complex from Rhodobacter sphaeroides. The structure shows that the RC is partly enclosed by a 14-subunit LH1 ring in which each αβ heterodimer binds two bacteriochlorophylls and, unusually for currently reported complexes, two carotenoids rather than one. Although the extra carotenoids confer an advantage in terms of photoprotection and light harvesting, they could impede passage of quinones through small, transient pores in the LH1 ring, necessitating a mechanism to create a dedicated quinone channel. The structure shows that two transmembrane proteins play a part in stabilising an open ring structure; one of these components, the PufX polypeptide, is augmented by a hitherto undescribed protein subunit we designate as protein-Y, which lies against the transmembrane regions of the thirteenth and fourteenth LH1α polypeptides. Protein-Y prevents LH1 subunits 11-14 adjacent to the RC QB site from bending inwards towards the RC and, with PufX preventing complete encirclement of the RC, this pair of polypeptides ensures unhindered quinone diffusion

Coalition-building for labor actions in life sciences departments: lessons from the largest academic strike in history

Abstract: In life sciences graduate programs in the United States, efforts are underway to address barriers to academic success—namely, using interventions targeted at addressing inclusivity and diversity concerns. However, graduate students are typically simultaneously workers for their institutions, where they face workplace challenges such as low wages, inadequate benefits, and vulnerability to harassment and abuse. These challenges may disproportionately affect workers with excluded identities and are thereby barriers to diversity and equity. In recent years, graduate student unionization has expanded. The outcomes of these movements may improve pay, benefits, and working conditions for graduate workers; however, labor organizing presents numerous challenges in academic environments. We reflect on our experiences in a life sciences department at the University of California, Santa Cruz, in 2022 during the largest graduate labor strike to date. We summarize the challenges and discuss successful interventions, including communication strategies for cross-stage coalition building at the departmental level

Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property–free knowledge base for future anticoronavirus drug discovery