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The War Lawyers: The United States, Israel, and Juridical Warfare. By Craig Jones. Oxford, UK: Oxford University Press, 2020. Pp. xxxii, 347. Index.

Heller, Kevin Jon

American Journal of International Law
Jan 14, 2022
10.1017/ajil.2021.66
Article

Lung emphysema and impaired macrophage elastase clearance in mucolipin 3 deficient mice

Barbara Spix, Elisabeth S. Butz, Cheng-Chang Chen, Anna Scotto Rosato, Rachel Tang, Ali Önder Yildirim, Martin Biel, Christian Grimm et 25 al.

Nature Communications
Jan 14, 2022
10.1038/s41467-021-27860-x
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Lung emphysema and chronic bronchitis are the two most common causes of chronic obstructive pulmonary disease. Excess macrophage elastase MMP-12, which is predominantly secreted from alveolar macrophages, is known to mediate the development of lung injury and emphysema. Here, we discovered the endolysosomal cation channel mucolipin 3 (TRPML3) as a regulator of MMP-12 reuptake from broncho-alveolar fluid, driving in two independently generated Trpml3−/− mouse models enlarged lung injury, which is further exacerbated after elastase or tobacco smoke treatment. Mechanistically, using a Trpml3IRES-Cre/eR26-τGFP reporter mouse model, transcriptomics, and endolysosomal patch-clamp experiments, we show that in the lung TRPML3 is almost exclusively expressed in alveolar macrophages, where its loss leads to defects in early endosomal trafficking and endocytosis of MMP-12. Our findings suggest that TRPML3 represents a key regulator of MMP-12 clearance by alveolar macrophages and may serve as therapeutic target for emphysema and chronic obstructive pulmonary disease.

High resolution in situ structure determination by cryo electron tomography and subtomogram averaging using emClarity

Tao Ni, Thomas Frosio, Luiza Mendonça, Yuewen Sheng, Daniel Clare, Benjamin A. Himes, Peijun Zhang

Nature Protocols
Jan 12, 2022
10.1038/s41596-021-00648-5
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Cryo-electron tomography and subtomogram averaging (STA) has developed rapidly in recent years. It provides structures of macromolecular complexes in situ and in cellular context at or below subnanometer resolution and has led to unprecedented insights into the inner working of molecular machines in their native environment, as well as their functional relevant conformations and spatial distribution within biological cells or tissues. Given the tremendous potential of cryo-electron tomography STA in in situ structural cell biology, we previously developed emClarity, a graphics processing unit-accelerated image-processing software that offers STA and classification of macromolecular complexes at high resolution. However, the workflow remains challenging, especially for newcomers to the field. In this protocol, we describe a detailed workflow, processing and parameters associated with each step, from initial tomography tilt-series data to the final 3D density map, with several features unique to emClarity. We use four different samples, including human immunodeficiency virus type 1 Gag assemblies, ribosome and apoferritin, to illustrate the procedure and results of STA and classification. Following the processing steps described in this protocol, along with a comprehensive tutorial and guidelines for troubleshooting and parameter optimization, one can obtain density maps up to 2.8 Å resolution from six tilt series by cryo-electron tomography STA.

Shirley McGreal, Champion of Primates Under Threat, Dies at 87

Richard Sandomir

The New York Times: Science
Jan 11, 2022
Article

She exposed smuggling rings and research laboratories and built a sanctuary for gibbons in South Carolina.

Atlas of exercise metabolism reveals time dependent signatures of metabolic homeostasis

Shogo Sato, Kenneth A. Dyar, Jonas T. Treebak, Sara L. Jepsen, Amy M. Ehrlich, Dominik Lutter, Juleen R. Zierath, Paolo Sassone-Corsi et 14 al.

Cell Metabolism
Jan 13, 2022
10.1016/j.cmet.2021.12.016
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Tissue sensitivity and response to exercise vary according to time of day. Sato et al. present an atlas of exercise metabolism, including global metabolomics profiling of multiple tissues, combined with arteriovenous sampling of hindlimb muscle and sampling across the liver to verify net uptake and release of time and exercise dependent signaling biochemicals.

Pericentriolar matrix integrity relies on cenexin and Polo-Like Kinase (PLK)1

Aljiboury, A. A. Mujcic, A. Curtis, E. Cammerino, T. Magny, D. Lan, Y. Bates, M. Freshour, J. Ahmed-Braimah, Y. H. Hehnly, H.

Biorxiv
Jan 11, 2022
10.1101/2022.01.09.475500
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Polo-Like-Kinase (PLK) 1 activity is associated with maintaining the functional and physical properties of the centrosomes pericentriolar matrix (PCM). In this study, we use a multimodal approach of human cells (HeLa) and zebrafish embryos in parallel to phylogenic analysis to test the role of a PLK1 binding protein, cenexin, in regulating the PCM. Our studies identify that cenexin is required for tempering microtubule nucleation and that a conserved C-terminal PLK1 binding site between humans and zebrafish is needed for PCM maintenance through mediating PLK1-dependent substrate phosphorylation events. PCM architecture in cenexin-depleted zebrafish embryos was rescued with wild-type human cenexin, but not with a C-terminal cenexin mutant (S796A) deficient in PLK1 binding. We propose a model where cenexins C-terminus acts in a conserved manner in eukaryotes, excluding nematodes and arthropods, to anchor PLK1 moderating its potential to phosphorylate PCM substrates required for PCM maintenance and function.

An investigation of structural violence in the lived experience of food insecurity

Rebecca Lindberg, Hayley McKenzie, Brontë Haines, Fiona H McKay

Critical Public Health
Jan 11, 2022
10.1080/09581596.2021.2019680
Article

Diverse Views in the Assignment of Credit for Research Discoveries.

Jeffrey I Seeman

ACS omega
Jan 11, 2022
10.1021/acsomega.1c04845

Closed-loop recruitment of striatal parvalbumin interneurons prevents the onset of compulsive behaviors

Mondragon-Gonzalez, S. L. Schreiweis, C. BURGUIERE, E.

Biorxiv
Jan 11, 2022
10.1101/2022.01.10.475745
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A prominent electrophysiological feature of compulsive behaviours is striatal hyperactivity; but its underlying dysfunctional cellular mechanisms still need to be characterized. Within the striatum, parvalbumin-positive interneurons (PVI) exert a powerful feedforward inhibition essential for the regulation of striatal activity. To investigate the potential implication of striatal PVI in aberrant repetitive behaviors, we used the Sapap3 mutant mice which exhibit compulsive-like behaviours characterized by excessive self-grooming. When striatal PVI in the centromedial striatum of Sapap3 mice were we optogenetically activated, we first showed that the number of compulsive-like events were greatly reduced. To investigate further the critical time-window when striatal PVI needed to be recruited for the behavioural regulation of compulsive-like grooming, we then designed a novel closed-loop stimulation pipeline. We identified a transient 1-4 Hz oscillations in the orbitofrontal cortex that temporally predicted grooming onsets. Exploiting this delta band signal as a biomarker, we were able to provide on-demand stimulation of striatal PVI shortly before predicted grooming events. This targeted closed-loop optogenetics approach greatly reduced grooming events and demonstrated that the recruitment of striatal PVI regulated the initiations of compulsive-like behaviours.

The science behind the first successful pig to human heart transplant

The Economist: Science
Jan 15, 2022
Article

Uncovering the reaction mechanism behind CoO as active phase for CO2 hydrogenation

Iris C. ten Have, Josepha J. G. Kromwijk, Matteo Monai, Davide Ferri, Ellen B. Sterk, Florian Meirer, Bert M. Weckhuysen

Nature Communications
Jan 14, 2022
10.1038/s41467-022-27981-x
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Transforming carbon dioxide into valuable chemicals and fuels, is a promising tool for environmental and industrial purposes. Here, we present catalysts comprising of cobalt (oxide) nanoparticles stabilized on various support oxides for hydrocarbon production from carbon dioxide. We demonstrate that the activity and selectivity can be tuned by selection of the support oxide and cobalt oxidation state. Modulated excitation (ME) diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) reveals that cobalt oxide catalysts follows the hydrogen-assisted pathway, whereas metallic cobalt catalysts mainly follows the direct dissociation pathway. Contrary to the commonly considered metallic active phase of cobalt-based catalysts, cobalt oxide on titania support is the most active catalyst in this study and produces 11% C2+ hydrocarbons. The C2+ selectivity increases to 39% (yielding 104 mmol h−1 gcat−1 C2+ hydrocarbons) upon co-feeding CO and CO2 at a ratio of 1:2 at 250 °C and 20 bar, thus outperforming the majority of typical cobalt-based catalysts.

NFAT: platelet stickiness regulator

Lucy Bird

Nature Reviews Immunology
Jan 14, 2022
10.1038/s41577-022-00677-5
Article

Rumination syndrome: pathophysiology, diagnosis and practical management

Sasegbon, A., Hasan, S. S., Disney, B. R., Vasant, D. H.

Frontline Gastroenterology
Jan 11, 2022
10.1136/flgastro-2021-101856
Article

Key messagesRumination syndrome should be considered in any patient who presents with recurrent regurgitation without associated retching or significant nausea. Behavioural therapies including diaphragmatic breathing and biofeedback are effective treatments for rumination syndrome and have the largest evidence bases. Following treatment, most patients have large reductions in their frequency of regurgitation.
Introduction When translated into English, the Latin word ruminor means to chew over again.1 This word has been used to describe the behaviour of a class of herbivorous mammals who, due to the indigestibility of the foods they eat, require that food is regurgitated and rechewed before being reswallowed to aid its breakdown and subsequent digestion.2 3 In certain herbivorous animals,3-5 rumination is, therefore, a normal, voluntary activity whereby gastric contents are brought up and rechewed as often as needed to optimise digestion.2 6...

Disentangling help seeking and giving up: differential human directed gazing by dogs in a modified unsolvable task paradigm

Animal Cognition
Jan 12, 2022
10.1007/s10071-021-01595-0
Article

Dogs are renowned for ‘looking back’ at humans when confronted with a problem, but it has been questioned whether this implies help seeking or giving up. We tested 56 pet dogs from two breed groups (herding dogs and terriers) in a modified unsolvable task paradigm. One reward type (food or toy) was enclosed in a box, while the respective other reward was accessible. With both reward types, human directed gazing in relation to the box was significantly positively correlated with interaction with the box, as long as an alternative was available. This suggests that both behaviours served to attain the unavailable reward and reflected individual motivation for the inaccessible vs the accessible reward. Furthermore, we varied whether the owner or the experimenter was responsible for handling the rewards. In the owner responsible group, dogs rarely gazed at the experimenter. In the experimenter responsible group, dogs preferentially directed box related gazing (prior to or after looking at or interacting with the box) at the owner. Still, they gazed at the experimenter significantly longer than the owner responsible group. Conversely, toy related gazing was directed significantly more at the experimenter. Thus, dogs adjust their gazing behaviour according to the people’s responsibility and their current goal (help seeking vs play). Gaze duration did not differ between herding dogs and terriers. We conclude that dogs use gazing at humans’ faces as a social problem solving strategy, but not all gazing can be classified as such. Dogs’ human directed gazing is influenced by the social relationships with the persons, situational associations, and context (unsolvable problem vs play).

Drug fuelled parties helped ancient Andean rulers to hold power

Nature
Jan 12, 2022
10.1038/d41586-022-00066-x
Article

One Size Does Not Fit All: Diversifying Immune Function in the Skin

Naik, S.

The Journal of Immunology
Jan 11, 2022
10.4049/jimmunol.2100758
Article

Our bodys most outward facing epithelial barrier, the skin, serves as the frontline defense against myriad environmental assailants. To combat these motley threats, the skin has evolved a sophisticated immunological arsenal. In this article, I provide an overview of the skins complex architecture and the distinct microniches in which immune cells reside and function. I review burgeoning literature on the synchronized immune, stromal, epithelial, and neuronal cell responses in healthy and inflamed skin. Next, I delve into the distinct requirement and mechanisms of long term immune surveillance and tissue adaptation at the cutaneous frontier. Finally, by discussing the contributions of immune cells in maintaining and restoring tissue integrity, I underscore the constellation of noncanonical functions undertaken by the skin immune system. Just as our skins immune system benefits from embracing diverse defense strategies, so, too, must we in the immunology research community support disparate perspectives and people from all walks of life.

Modular evolution of secretion systems and virulence plasmids in a bacterial species complex

Lin Chou, Yu-Chen Lin, Mindia Haryono, Mary Nia M. Santos, Shu-Ting Cho, Alexandra J. Weisberg, Chih-Feng Wu, Jeff H. Chang, Erh-Min Lai and Chih-Horng Kuo

BMC Biology
Jan 13, 2022
10.1186/s12915-021-01221-y
Article

Many named species as defined in current bacterial taxonomy correspond to species complexes. Uncertainties regarding the organization of their genetic diversity challenge research efforts. We utilized the Agrobac...

The CLASSY family controls tissue-specific DNA methylation patterns in Arabidopsis.

Ming Zhou, Ceyda Coruh, Guanghui Xu, Laura M Martins, Clara Bourbousse, Alice Lambolez, Julie A Law

Nature communications
Jan 11, 2022
10.1038/s41467-021-27690-x

DNA methylation shapes the epigenetic landscape of the genome, plays critical roles in regulating gene expression, and ensures transposon silencing. As is evidenced by the numerous defects associated with aberrant DNA methylation landscapes, establishing proper tissue-specific methylation patterns is critical. Yet, how such differences arise remains a largely open question in both plants and animals. Here we demonstrate that CLASSY1-4 (CLSY1-4), four locus-specific regulators of DNA methylation, also control tissue-specific methylation patterns, with the most striking pattern observed in ovules where CLSY3 and CLSY4 control DNA methylation at loci with a highly conserved DNA motif. On a more global scale, we demonstrate that specific clsy mutants are sufficient to shift the epigenetic landscape between tissues. Together, these findings reveal substantial epigenetic diversity between tissues and assign these changes to specific CLSY proteins, elucidating how locus-specific targeting combined with tissue-specific expression enables the CLSYs to generate epigenetic diversity during plant development.

Endothelial Piezo1 sustains muscle capillary density and contributes to physical activity.

Fiona Bartoli, Marjolaine Debant, Eulashini Chuntharpursat-Bon, Elizabeth L Evans, Katie E Musialowski, Gregory Parsonage, Lara C Morley, T Simon Futers, Piruthivi Sukumar, T Scott Bowen, Mark T Kearney, Laeticia Lichtenstein, Lee D Roberts, David J Beech

The Journal of clinical investigation
Jan 13, 2022
10.1172/jci141775
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Piezo1 forms mechanically-activated non-selective cation channels that contribute to endothelial response to fluid flow. Here we reveal an important role in the control of capillary density. Conditional endothelial-specific deletion of Piezo1 in adult mice depressed physical performance. Muscle microvascular endothelial cell apoptosis and capillary rarefaction were evident and sufficient to account for the effect on performance. There was selective upregulation of thrombospondin-2 (TSP2), an inducer of endothelial apoptosis, with no effect on thrombospondin-1 (TSP1), a related important player in muscle physiology. TSP2 was poorly expressed in muscle endothelial cells but robustly expressed in muscle pericytes, in which nitric oxide (NO) repressed the Tsp2 gene without effect on Tsp1. In the endothelial cells, Piezo1 was required for normal expression of endothelial nitric oxide synthase (eNOS). The data suggest an endothelial-pericyte partnership of muscle in which endothelial Piezo1 senses blood flow to sustain capillary density and thereby maintain physical capability.