Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Organometallic palladium reagents for cysteine bioconjugation

Reactions based on transition metals have found wide use in organic synthesis, in particular for the functionalization of small molecules. However, there are very few reports of using transition-metal-based reactions to modify complex biomolecules, which is due to the need for stringent reaction conditions (for example, aqueous media, low temperature and mild pH) and the existence of multiple reactive functional groups found in biomolecules. Here we report that palladium(II) complexes can be used for efficient and highly selective cysteine conjugation (bioconjugation) reactions that are rapid and robust under a range of bio-compatible reaction conditions. The straightforward synthesis of the palladium reagents from diverse and easily accessible aryl halide and trifluoromethanesulfonate precursors makes the method highly practical, providing access to a large structural space for protein modification. The resulting aryl bioconjugates are stable towards acids, bases, oxidants and external thiol nucleophiles. The broad utility of the bioconjugation platform was further corroborated by the synthesis of new classes of stapled peptides and antibody–drug conjugates. These palladium complexes show potential as benchtop reagents for diverse bioconjugation applications.National Institutes of Health (U.S.) (GM-58160)National Institutes of Health (U.S.) (GM-101762)MIT Faculty Start-up FundDamon Runyon Cancer Research FoundationSontag Foundation (Distinguished Scientist Award)Massachusetts Institute of Technology. Dept. of Chemistry (George Buchi Research Fellowship)David H. Koch Institute for Integrative Cancer Research at MIT (Graduate Fellowship in Cancer Research

Corporate Social Responsibility and Corporate Financial Performance: Evidence from Korea

This paper studies the empirical relation between corporate social responsibility (CSR) and corporate financial performance in Korea using a sample of 1122 firm-years during 2002-2008. We measure corporate social responsibility by both an equal-weighted CSR index and a stakeholder-weighted CSR index suggested by Akpinar et al. (2008). Corporate financial performance is measured by ROE, ROA and Tobin’s Q. We find a positive and significant relation between corporate financial performance and the stakeholder-weighted CSR index, but not the equal-weighted CSR index. This finding is robust to alternative model specifications and several additional tests, providing evidence in support of instrumental stakeholder theory

Surprised at All the Entropy: Hippocampal, Caudate and Midbrain Contributions to Learning from Prediction Errors

Influential concepts in neuroscientific research cast the brain a predictive machine that revises its predictions when they are violated by sensory input. This relates to the predictive coding account of perception, but also to learning. Learning from prediction errors has been suggested for take place in the hippocampal memory system as well as in the basal ganglia. The present fMRI study used an action-observation paradigm to investigate the contributions of the hippocampus, caudate nucleus and midbrain dopaminergic system to different types of learning: learning in the absence of prediction errors, learning from prediction errors, and responding to the accumulation of prediction errors in unpredictable stimulus configurations. We conducted analyses of the regions of interests' BOLD response towards these different types of learning, implementing a bootstrapping procedure to correct for false positives. We found both, caudate nucleus and the hippocampus to be activated by perceptual prediction errors. The hippocampal responses seemed to relate to the associative mismatch between a stored representation and current sensory input. Moreover, its response was significantly influenced by the average information, or Shannon entropy of the stimulus material. In accordance with earlier results, the habenula was activated by perceptual prediction errors. Lastly, we found that the substantia nigra was activated by the novelty of sensory input. In sum, we established that the midbrain dopaminergic system, the hippocampus, and the caudate nucleus were to different degrees significantly involved in the three different types of learning: acquisition of new information, learning from prediction errors and responding to unpredictable stimulus developments. We relate learning from perceptual prediction errors to the concept of predictive coding and related information theoretic accounts

Prevalence of mental disorders from adolescence through early adulthood in American Indian and First Nations communities

Indigenous communities lack representation in psychiatric epidemiology despite disproportionate exposure to risk factors. We document the cumulative and 12-month prevalence of psychiatric disorders across the early life course among a sample of Indigenous young adults and compare prospective and retrospective reporting of lifetime mental disorders. This community-based participatory research includes data from 735 Indigenous people from 8 reservations/reserves. Personal interviews were conducted between 2002–2010 and 2017–2018 totaling 9 waves; diagnostic assessments of DSM-IV-TR alcohol abuse/dependence, marijuana use/dependence, other substance abuse/dependence, generalized anxiety disorder, major depressive disorder, dysthymic disorder, and attention deficit/hyperactivity disorder occurred at waves 1 (mean age = 11.1 years), 4 (mean age = 14.3 years), 6 (mean age = 16.2 years), 8 (mean age = 18.3 years), and 9 (mean age = 26.3 years). Cumulative lifetime psychiatric disorders reached 77.3% and lifetime comorbidity 56.4% by wave 9. Past-year prevalence and comorbidity at wave 9 were 28.7% and 6.7%, respectively. Substance use disorders (SUDs) were most common with peak past-year prevalence observed when participants were on average 16.3 years old then declining thereafter. Trends in early life course psychiatric disorders in this study with Indigenous participants highlight cultural variations in psychiatric epidemiology including surprisingly low rates of internalizing disorders in the face of risk factors, disproportionately high rates of early-onset and lifetime SUD, and lower rates of past-year SUD in early adulthood compared with prior research.Peer reviewedSociolog