Cooperative Stimulation of Dendritic Cells by Cryptococcus neoformans Mannoproteins and CpG Oligodeoxynucleotides

While mannosylation targets antigens to mannose receptors on dendritic cells (DC), the resultant immune response is suboptimal. We hypothesized that the addition of toll-like receptor (TLR) ligands would enhance the DC response to mannosylated antigens. Cryptococcus neoformans mannoproteins (MP) synergized with CpG-containing oligodeoxynucleotides to stimulate enhanced production of proinflammatory cytokines and chemokines from murine conventional and plasmacytoid DC. Synergistic stimulation required the interaction of mannose residues on MP with the macrophage mannose receptor (MR), CD206. Moreover, synergy with MP was observed with other TLR ligands, including tripalmitoylated lipopeptide (Pam3CSK4), polyinosine-polycytidylic acid (pI:C), and imiquimod. Finally, CpG enhanced MP-specific MHC II-restricted CD4+ T-cell responses by a mechanism dependent upon DC expression of CD206 and TLR9. These data suggest a rationale for vaccination strategies that combine mannosylated antigens with TLR ligands and imply that immune responses to naturally mannosylated antigens on pathogens may be greatly augmented if TLR and MR are cooperatively stimulated.National Institutes of Health (RO1 AI25780, RO1 AI37532, K08 AI 53542

Rethinking Criminal Law and Family Status

In our recent book, Privilege or Punish: Criminal Justice and the Challenge of Family Ties (OUP 2009), we examined and critiqued a number of ways in which the criminal justice system uses family status to distribute benefits or burdens to defendants. In their review essays, Professors Alafair Burke, Alice Ristroph & Melissa Murray identify a series of concerns with the framework we offer policymakers to analyze these family ties benefits or burdens. We think it worthwhile not only to clarify where those challenges rest on misunderstandings or confusions about the central features of our views, but also to show the deficiencies of the proposed alternatives. While we appreciate and admire the efforts of our critics to advance this important conversation, we hope this Essay will illuminate why the normative framework of Privilege or Punish remains a more helpful structure to policymakers assessing how family status should intersect with the criminal law within a liberal democracy such as our own

Criminal Justice and the Challenge of Family Ties

This Article asks two basic questions: When does, and when should, the state use the criminal justice apparatus to accommodate family ties, responsibilities, and interests? We address these questions by first revealing a variety of laws that together form a string of family ties subsidies and benefits pervading the criminal justice system. Notwithstanding our recognition of the important role family plays in securing the conditions for human flourishing, we then explain the basis for erecting a Spartan presumption against these family ties subsidies and benefits within the criminal justice system. We delineate the scope and rationale for the presumption and under what circumstances it might be overcome. When the presumption is overcome, we urge distributing the benefit on terms that are neutral to family status, if possible, with a focus instead on functions served by established relationships of care-giving responsibility

Ocular Coherence Tomography in the Evaluation of Anterior Eye Injuries in Space Flight

While Ocular Coherence Tomography (OCT) is not a first-line modality to evaluate anterior eye structures terrestrially, it is a resource already available on the International Space Station (ISS) that can be used in medical contingencies that involve the anterior eye. With remote guidance and subject matter expert (SME) support from the ground, a minimally trained crewmember can now use OCT to evaluate anterior eye pathologies on orbit. OCT utilizes low-coherence interferometry to produce detailed cross-sectional and 3D images of the eye in real time. Terrestrially, it has been used to evaluate macular pathologies and glaucoma. Since 2013, OCT has been used onboard the ISS as one part of a suite of hardware to evaluate the Visual Impairment/Intracranial Pressure risk faced by astronauts, specifically assessing changes in the retina and choroid during space flight. The Anterior Segment Module (ASM), an add-on lens, was also flown for research studies, providing an opportunity to evaluate the anterior eye in real time if clinically indicated. Anterior eye pathologies that could be evaluated using OCT were identified. These included corneal abrasions and ulcers, scleritis, and acute angle closure glaucoma. A remote guider script was written to provide ground specialists with step-by-step instructions to guide ISS crewmembers, who do not get trained on the ASM, to evaluate the anterior eye. The instructions were tested on novice subjects and/or operators, whose feedback was incorporated iteratively. The final remote guider script was reviewed by SME optometrists and NASA flight surgeons. The novel application of OCT technology to space flight allows for the acquisition of objective data to diagnose anterior eye pathologies when other modalities are not available. This demonstrates the versatility of OCT and highlights the advantages of using existing hardware and remote guidance skills to expand clinical capabilities in space flight

The neurobiology of methamphetamine induced psychosis

Chronic methamphetamine abuse commonly leads to psychosis, with positive and cognitive symptoms that are similar to those of schizophrenia. Methamphetamine induced psychosis (MAP) can persist and diagnoses of MAP often change to a diagnosis of schizophrenia over time. Studies in schizophrenia have found much evidence of cortical GABAergic dysfunction. Methamphetamine psychosis is a well studied model for schizophrenia, however there is little research on the effects of methamphetamine on cortical GABAergic function in the model, and the neurobiology of MAP is unknown. This paper reviews the effects of methamphetamine on dopaminergic pathways, with focus on its ability to increase glutamate release in the cortex. Excess cortical glutamate would likely damage GABAergic interneurons, and evidence of this disturbance as a result of methamphetamine treatment will be discussed. We propose that cortical GABAergic interneurons are particularly vulnerable to glutamate overflow as a result of subcellular location of NMDA receptors on interneurons in the cortex. Damage to cortical GABAergic function would lead to dysregulation of cortical signals, resulting in psychosis, and further support methamphetamine induced psychosis as a model for schizophrenia

Enhanced convection and fast plumes in the lower mantle induced by the spin transition in ferropericlase

Using a numerical model we explore the consequences of the intrinsic density change (Δρ/ρ ≈ 2–4%) caused by the Fe^(2+) spin transition in ferropericlase on the style and vigor of mantle convection. The effective Clapeyron slope of the transition from high to low spin is strongly positive in pressure-temperature space and broadens with high temperature. This introduces a net spin-state driving density difference for both upwellings and downwellings. In 2-D cylindrical geometry spin-buoyancy dominantly enhances the positive thermal buoyancy of plumes. Although the additional buoyancy does not fundamentally alter large-scale dynamics, the Nusselt number increases by 5–10%, and vertical velocities by 10–40% in the lower mantle. Advective heat transport is more effective and temperatures in the core-mantle boundary region are reduced by up to 12%. Our findings are relevant to the stability of lowermost mantle structures

Multi-omic Analyses of Extensively Decayed Pinus contorta Reveal Expression of a Diverse Array of Lignocellulose-Degrading Enzymes.

Fungi play a key role cycling nutrients in forest ecosystems, but the mechanisms remain uncertain. To clarify the enzymatic processes involved in wood decomposition, the metatranscriptomics and metaproteomics of extensively decayed lodgepole pine were examined by RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively. Following de novo metatranscriptome assembly, 52,011 contigs were searched for functional domains and homology to database entries. Contigs similar to basidiomycete transcripts dominated, and many of these were most closely related to ligninolytic white rot fungi or cellulolytic brown rot fungi. A diverse array of carbohydrate-active enzymes (CAZymes) representing a total of 132 families or subfamilies were identified. Among these were 672 glycoside hydrolases, including highly expressed cellulases or hemicellulases. The CAZymes also included 162 predicted redox enzymes classified within auxiliary activity (AA) families. Eighteen of these were manganese peroxidases, which are key components of ligninolytic white rot fungi. The expression of other redox enzymes supported the working of hydroquinone reduction cycles capable of generating reactive hydroxyl radicals. These have been implicated as diffusible oxidants responsible for cellulose depolymerization by brown rot fungi. Thus, enzyme diversity and the coexistence of brown and white rot fungi suggest complex interactions of fungal species and degradative strategies during the decay of lodgepole pine.IMPORTANCE The deconstruction of recalcitrant woody substrates is a central component of carbon cycling and forest health. Laboratory investigations have contributed substantially toward understanding the mechanisms employed by model wood decay fungi, but few studies have examined the physiological processes in natural environments. Herein, we identify the functional genes present in field samples of extensively decayed lodgepole pine (Pinus contorta), a major species distributed throughout the North American Rocky Mountains. The classified transcripts and proteins revealed a diverse array of oxidative and hydrolytic enzymes involved in the degradation of lignocellulose. The evidence also strongly supports simultaneous attack by fungal species employing different enzymatic strategies

New Criminal Law Review Symposium on Privilege or Punish: Criminal Justice and the Challenge of Family Ties

This symposium includes three review essays by Professors Doug Berman, Naomi Cahn, and Jack Chin. The review essays are focused on a recent book by Professors Dan Markel, Jennifer M. Collins and Ethan J. Leib entitled \u27Privilege or Punish: Criminal Justice and the Challenge of Family Ties\u27 (Oxford 2009). You can download the entire book for free at http://ssrn.com/abstract=1677503. In addition to the three review essays, the collection includes an essay by the book\u27s authors that serves as a reply to this set of critiques. Collectively, we are grateful to the New Criminal Law Review, which is hosting this collection in an upcoming issue. The essays are titled, respectively: Berman: Digging Deeper into, and Thinking Better about, the Interplay of Families and Criminal Justice Cahn: Protect and Preserve? Chin: Mandatory, Contingent, and Discretionary Policy Arguments Collins, Leib & Markel: (When) Should Family Status Matter in the Criminal Justice System

New Criminal Law Review Symposium on Privilege or Punish: Criminal Justice and the Challenge of Family Ties

This symposium includes three review essays by Professors Doug Berman, Naomi Cahn, and Jack Chin. The review essays are focused on a recent book by Professors Dan Markel, Jennifer M. Collins and Ethan J. Leib entitled \u27Privilege or Punish: Criminal Justice and the Challenge of Family Ties\u27 (Oxford 2009). You can download the entire book for free at http://ssrn.com/abstract=1677503. In addition to the three review essays, the collection includes an essay by the book\u27s authors that serves as a reply to this set of critiques. Collectively, we are grateful to the New Criminal Law Review, which is hosting this collection in an upcoming issue. The essays are titled, respectively: Berman: Digging Deeper into, and Thinking Better about, the Interplay of Families and Criminal Justice Cahn: Protect and Preserve? Chin: Mandatory, Contingent, and Discretionary Policy Arguments Collins, Leib & Markel: (When) Should Family Status Matter in the Criminal Justice System