The United States currently has the largest prison population on the planet. Over the last four decades, structural unemployment, concentrated urban poverty, and mass homelessness have also become ...permanent features of the political economy. These developments are without historical precedent, but not without historical explanation. In this searing critique, Jordan T. Camp traces the rise of the neoliberal carceral state through a series of turning points in U.S. history including the Watts insurrection in 1965, the Detroit rebellion in 1967, the Attica uprising in 1971, the Los Angeles revolt in 1992, and events in post-Katrina New Orleans in 2005.
Fe(II) is an excellent promoter for advanced oxidation processes (AOPs) because of its environmental ubiquity and low toxicity. This study is among the first to characterize the reaction of ...peracetic acid (PAA) with Fe(II) ion and apply the Fe(II)/PAA AOP for degradation of micropollutants. PAA reacts with Fe(II) (k = 1.10 × 105–1.56 × 104 M–1 s–1 at pH 3.0–8.1) much more rapidly than H2O2 and outperforms the coexistent H2O2 for reaction with Fe(II). While PAA alone showed minimal reactivity with methylene blue, naproxen, and bisphenol-A, significant abatement (48–98%) of compounds was observed by Fe(II)/PAA at initial pH of 3.0–8.2. The micropollutant degradation by Fe(II)/PAA exhibited two kinetic phases (very rapid then slow) related to PAA and H2O2, respectively. Based on experimental evidence, formation of carbon-centered radicals (CH3C(O)O•, CH3C(O)•, and •CH3), •OH, and Fe(IV) reactive intermediate species from the PAA and Fe(II) reactions in the presence of H2O2 is hypothesized. The carbon-centered radicals and/or Fe(IV) likely played an important role in micropollutant degradation in the initial kinetic phase, while •OH was important in the second reaction phase. The transformation products of micropollutants showed lower model-predicted toxicity than their parent compounds. This study significantly advances the understanding of PAA and Fe(II) reaction and demonstrates Fe(II)/PAA to be a feasible advanced oxidation technology.
The left and right rodent hippocampi exhibit striking lateralization in some of the very neural substrates considered to be critical for hippocampal cognitive function. Despite this, there is an ...overwhelming lack of consideration for hemispheric differences in studies of the rodent hippocampus. Asymmetries identified so far suggest that a bilateral model of the hippocampus will be essential for an understanding of this brain region, and perhaps of the brain more widely. Although hypotheses have been proposed to explain how the left and right hippocampi contribute to behavior and cognition, these hypotheses have either been refuted by more recent studies or have been limited in the scope of data they explain. Here, I will first review data on human and rodent hippocampal lateralization. The implications of these data suggest that considering the hippocampus as a bilateral structure with functional lateralization will be critical moving forward in understanding the function and mechanisms of this brain region. In exploring these implications, I will then propose a hypothesis of the hippocampus as a bilateral structure. This discrete‐continuous hypothesis proposes that the left and right hippocampi contribute to spatial memory and navigation in a complementary manner. Specifically, the left hemisphere stores spatial information as discrete, salient locations, and the right hemisphere represents space continuously, contributing to route computation and flexible spatial navigation. Consideration of hippocampal lateralization in designing future studies may provide insight into the function of the hippocampus and resolve debates concerning its function.
For more than 50 years, investigators have considered a malignant stem cell as the potential origin of and a key therapeutic target for acute myeloid leukemia (AML) and other forms of cancer.1-4 The ...nature and existence of tumor-initiating cells for leukemia and other malignancies have long been the subject of intense and rigorous study; indeed, the promise of the potential to eradicate such cells is clear. However, until recently, deficiencies in our understanding of the nature of these cell populations, coupled with a limited ability to therapeutically exploit their weaknesses, have been limiting factors in realizing the goal of targeting leukemic stem cells (LSCs). Exciting new insights into the fundamental underpinnings of LSCs are now being made in an era in which drug development pipelines offer the potential to specifically target pathways of significance. Therefore, the focus in this new era, characterized by the confluence of understanding LSCs and the ability to target them, is shifting from “if it can be done” to “how it will be done.” Moving from a theoretical stage to this hopeful era of possibilities, new challenges expectedly arise, and our focus now must shift to determining the best strategy by which to target LSCs, with their well-documented heterogeneity and readily evident intra- and interpatient variability. The purpose of this review is therefore both to summarize the key scientific findings pertinent to AML LSC targeting and to consider methods of clinical evaluation that will be most effective for identifying successful LSC-directed therapies.
Recent studies have implicated microglia-the resident immune cells of the brain-in the pathophysiology of alcoholism. Indeed, post-mortem alcoholic brains show increased microglial markers and ...increased immune gene expression; however, the effects of ethanol on microglial functioning and how this impacts the brain remain unclear. In this present study, we investigate the effects of acute binge ethanol on microglia and how microglial depletion changes the brain neuroimmune response to acute binge ethanol withdrawal.
C57BL/6J mice were treated intragastrically with acute binge ethanol for time course and dose-response studies. Cultured mouse BV2 microglia-like cells were treated with ethanol in vitro for time course studies. Mice were also administered the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia from the brain. These mice were subsequently treated with acute binge ethanol and sacrificed during withdrawal. Brain and BV2 mRNA were isolated and assessed using RT-PCR to examine expression of microglial and neuroimmune genes.
Acute binge ethanol biphasically changed microglial (e.g., Iba1, CD68) gene expression, with initial decreases during intoxication and subsequent increases during withdrawal. Acute ethanol withdrawal dose dependently increased neuroimmune gene (e.g., TNFα, Ccl2, IL-1ra, IL-4) expression beginning at high doses. BV2 cells showed biphasic changes in pro-inflammatory (e.g., TNFα, Ccl2) gene expression following ethanol treatment in vitro. Administration of PLX5622 depleted microglia from the brains of mice. Although some neuroimmune genes were reduced by microglial depletion, many others were unchanged. Microglial depletion blunted pro-inflammatory (e.g., TNFα, Ccl2) gene expression and enhanced anti-inflammatory (e.g., IL-1ra, IL-4) gene expression during acute binge ethanol withdrawal.
These studies find acute binge ethanol withdrawal increases microglial and neuroimmune gene expression. Ethanol exposure also increases microglial pro-inflammatory gene expression in vitro. Furthermore, microglial depletion decreases expression of microglia-specific genes but has little effect on expression of many other neuroimmune signaling genes. Microglial depletion blunted the acute binge ethanol withdrawal induction of pro-inflammatory genes and enhanced induction of anti-inflammatory genes. These findings indicate microglia impact the brain response to acute binge ethanol withdrawal.
To quantify and contextualize the risk for coronavirus disease 2019 (COVID-19)-related hospitalization and illness severity in type 1 diabetes.
We conducted a prospective cohort study to identify ...case subjects with COVID-19 across a regional health care network of 137 service locations. Using an electronic health record query, chart review, and patient contact, we identified clinical factors influencing illness severity.
We identified COVID-19 in 6,138, 40, and 273 patients without diabetes and with type 1 and type 2 diabetes, respectively. Compared with not having diabetes, people with type 1 diabetes had adjusted odds ratios of 3.90 (95% CI 1.75-8.69) for hospitalization and 3.35 (95% CI 1.53-7.33) for greater illness severity, which was similar to risk in type 2 diabetes. Among patients with type 1 diabetes, glycosylated hemoglobin (HbA
), hypertension, race, recent diabetic ketoacidosis, health insurance status, and less diabetes technology use were significantly associated with illness severity.
Diabetes status, both type 1 and type 2, independently increases the adverse impacts of COVID-19. Potentially modifiable factors (e.g., HbA
) had significant but modest impact compared with comparatively static factors (e.g., race and insurance) in type 1 diabetes, indicating an urgent and continued need to mitigate severe acute respiratory syndrome coronavirus 2 infection risk in this community.
Quantum processing architectures that include multiple qubit modalities offer compelling strategies for high-fidelity operations and readout, quantum error correction, and a path for scaling to large ...system sizes. Such hybrid architectures have been realized for leading platforms, including superconducting circuits and trapped ions. Recently, a new approach for constructing large, coherent quantum processors has emerged based on arrays of individually trapped neutral atoms. However, these demonstrations have been limited to arrays of a single atomic element where the identical nature of the atoms makes crosstalk-free control and nondemolition readout of a large number of atomic qubits challenging. Here we introduce a dual-element atom array with individual control of single rubidium and cesium atoms. We demonstrate their independent placement in arrays with up to 512 trapping sites and observe negligible crosstalk between the two elements. Furthermore, by continuously reloading one atomic element while maintaining an array of the other, we demonstrate a new continuous operation mode for atom arrays without any off-time. Our results enable avenues for auxiliary-qubit-assisted quantum protocols such as quantum nondemolition measurements and quantum error correction, as well as continuously operating quantum processors and sensors.
Initially identified as a T lymphocyte-elicited inhibitor of macrophage motility, macrophage migration inhibitory factor (MIF) has since been found to be expressed by nearly every immune cell type ...examined and overexpressed in most solid and hematogenous malignant cancers. It is localized to both extracellular and intracellular compartments and physically interacts with more than a dozen different cell surface and intracellular proteins. Although classically associated with and characterized as a mediator of pro-inflammatory innate immune responses, more recent studies demonstrate that, in malignant disease settings, MIF contributes to anti-inflammatory, immune evasive, and immune tolerant phenotypes in both innate and adaptive immune cell types. This review will summarize the studies describing MIF in tumor-specific innate and adaptive immune responses and attempt to reconcile these various pleiotropic functions in normal physiology.
The prevailing mid-latitude westerly winds, known as the westerlies, are a fundamental component of the climate system because they have a crucial role in driving surface ocean circulation
and ...modulating air-sea heat, momentum and carbon exchange
. Recent work suggests that westerly wind belts are migrating polewards in response to anthropogenic forcing
. Reconstructing the westerlies during past warm periods such as the Pliocene epoch, in which atmospheric carbon dioxide (CO
) was about 350 to 450 parts per million
and temperatures were about 2 to 4 degrees Celsius higher than today
, can improve our understanding of changes in the position and strength of these wind systems as the climate continues to warm. Here we show that the westerlies were weaker and more poleward during the warm Pliocene than during glacial periods after the intensification of Northern Hemisphere glaciation (iNHG), which occurred around 2.73 million years ago
. Our results, which are based on dust and export productivity reconstructions, indicate that major ice sheet development during the iNHG was accompanied by substantial increases in dust fluxes in the mid-latitude North Pacific Ocean, especially compared to those in the subarctic North Pacific. Following this shift, changes in dust and productivity largely track the glacial-interglacial cycles of the late Pliocene and early Pleistocene epochs. On the basis of this pattern, we infer that shifts in the westerlies were primarily driven by variations in Plio-Pleistocene thermal gradients and ice volume. By combining this relationship with other dust records
and climate modelling results
, we find that the proposed changes in the westerlies were globally synchronous. If the Pliocene is predictive of future warming, we posit that continued poleward movement and weakening of the present-day westerlies in both hemispheres can be expected.
Malignant stem cells have long been considered a key therapeutic target in leukemia. Therapeutic strategies designed to target the fundamental biology of leukemia stem cells while sparing normal ...hematopoietic cells may provide better outcomes for leukemia patients. One process in leukemia stem cell biology that has intriguing therapeutic potential is energy metabolism. In this article we discuss the metabolic properties of leukemia stem cells and how targeting energy metabolism may provide more effective therapeutic regimens for leukemia patients. In addition, we highlight the similarities and differences in energy metabolism between leukemia stem cells and malignant stem cells from solid tumors.
Cancer stem cells have unique metabolic biology that can in some instances be exploited for therapeutic intervention. This review summarizes the progress and challenges inherent to this field, including metabolic flexibility, inter and intra-patient heterogeneity, and commonalities and differences in energy metabolism between leukemia and solid tumors.
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