Fossil Mice and Rats Show Isotopic Evidence of Niche Partitioning and Change in Dental Ecomorphology Related to Dietary Shift in Late Miocene of Pakistan

Stable carbon isotope analysis in tooth enamel is a well-established approach to infer C3 and C4 dietary composition in fossil mammals. The bulk of past work has been conducted on large herbivorous mammals. One important finding is that their dietary habits of fossil large mammals track the late Miocene ecological shift from C3 forest and woodland to C4 savannah. However, few studies on carbon isotopes of fossil small mammals exist due to limitations imposed by the size of rodent teeth, and the isotopic ecological and dietary behaviors of small mammals to climate change remain unknown. Here we evaluate the impact of ecological change on small mammals by fine-scale comparisons of carbon isotope ratios (δ13C) with dental morphology of murine rodents, spanning 13.8 to ∼2.0 Ma, across the C3 to C4 vegetation shift in the Miocene Siwalik sequence of Pakistan. We applied in-situ laser ablation GC-IRMS to lower first molars and measured two grazing indices on upper first molars. Murine rodents yield a distinct, but related, record of past ecological conditions from large herbivorous mammals, reflecting available foods in their much smaller home ranges. In general, larger murine species show more positive δ13C values and have higher grazing indices than smaller species inhabiting the same area at any given age. Two clades of murine rodents experienced different rates of morphological change. In the faster-evolving clade, the timing and trend of morphological innovations are closely tied to consumption of C4 diet during the vegetation shift. This study provides quantitative evidence of linkages among diet, niche partitioning, and dental morphology at a more detailed level than previously possible

Regioselective thermal [3+2]-dipolar cycloadditions of α-diazoacetates with α-sulfenyl/sulfinyl/sulfonyl-β-chloroacrylamide derivatives to form densely functionalised pyrazoles

Highly regioselective synthetic methodology leading to densely functionalised C(3), C(4) and C(5) substituted pyrazoles 10a–q, 14a‐i and 16a–g via thermal [3+2]‐dipolar cycloaddition, of α‐diazoacetates and α‐thio‐β‐chloroacrylamides, at the sulfide, sulfoxide and sulfone levels of oxidation, is described. This method allows access to C(4)‐sulfenyl or sulfonyl pyrazoles, through migration of the sulfur substituent at the sulfide and sulfone oxidation levels, while elimination of the sulfinyl group leading to 3,5‐disubstituted pyrazoles, is observed. While the sulfide migration is readily rationalised, the carbon to carbon 1,2‐sulfonyl migration is unprecedented and mechanistically intriguing. The synthetically versatile generation of densely functionalised pyrazoles containing substituents amenable to further modification offers advantages over alternative synthetic routes. Isolation of the N‐alkylated pyrazoles 11a and 12a as by‐products from the cycloaddition through further reaction of the pyrazoles 10 with excess α‐diazoacetate, proved useful in rationalising the tautomeric behaviour evident in the NMR spectra of the pyrazoles, with the position of tautomeric equilibrium influenced by solvent and substituents

Substrate and catalyst effects in the enantioselective copper catalysed C–H insertion reactions of α-diazo-β-oxo sulfones

Excellent enantioselectivities of up to 98% ee are achieved employing the copper‐bis(oxazoline)‐NaBARF catalyst system in the C‐H insertion reactions of α‐diazo‐β‐oxo sulfones. The influence of variation of the bis(oxazoline) ligand, copper salt, additive and substrate on both the efficiency and the enantioselectivities of these intramolecular C‐H insertion reactions has been explored. Optimum enantioselectivities are achieved with the phenyl and diphenyl ligands across the substrate series

Systemic immunity is required for effective cancer immunotherapy

Immune responses involve coordination across cell types and tissues. However, studies in cancer immunotherapy have focused heavily on local immune responses in the tumor microenvironment. To investigate immune activity more broadly, we performed an organism-wide study in genetically engineered cancer models using mass cytometry. We analyzed immune responses in several tissues after immunotherapy by developing intuitive models for visualizing single-cell data with statistical inference. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. However, during tumor rejection, only peripheral immune cells sustained their proliferation. This systemic response was coordinated across tissues and required for tumor eradication in several immunotherapy models. An emergent population of peripheral CD4 T cells conferred protection against new tumors and was significantly expanded in patients responding to immunotherapy. These studies demonstrate the critical impact of systemic immune responses that drive tumor rejection

No straight lines – young women’s perceptions of their mental health and wellbeing during and after pregnancy: a systematic review and meta-ethnography

Background: Young mothers face mental health challenges during and after pregnancy including increased rates of depression compared to older mothers. While the prevention of teenage pregnancy in countries such as the United States and the United Kingdom has been a focus for policy and research in recent decades, the need to understand young women’s own experiences has been highlighted. The aim of this meta-ethnography was to examine young women’s perceptions of their mental health and wellbeing during and after pregnancy to provide new understandings of those experiences. Methods: A systematic review and meta-ethnographic synthesis of qualitative research was conducted. Seven databases were systematically searched and forward and backward searching conducted. Papers were included if they were from Organisation for Economic Co-operation and Development countries and explored mental health and wellbeing experiences of young mothers (age under 20 in pregnancy; under 25 at time of research) as a primary research question – or where evidence about mental health and wellbeing from participants was foregrounded. Nineteen papers were identified and the Critical Appraisal Skills Programme checklist for qualitative research used to appraise the evidence. Following the seven-step process of meta-ethnography, key constructs were examined within each study and then translated into one another. Results: Seven translated themes were identified forming a new line of argument wherein mental health and wellbeing was analysed as relating to individual bodily experiences; tied into past and present relationships; underpinned by economic insecurity and entangled with feelings of societal surveillance. There were ‘no straight lines’ in young women’s experiences, which were more complex than dominant narratives around overcoming adversity suggest. Conclusions: The synthesis concludes that health and social care professionals need to reflect on the operation of power and stigma in young women’s lives and its impact on wellbeing. It adds to understanding of young women’s mental health and wellbeing during and after pregnancy as located in physical and structural factors rather than individual capacities alone

Plasmas and Controlled Nuclear Fusion

Contains research objectives and reports on three research projects.National Science Foundation (Grant GK-1165

Plasmas and Controlled Nuclear Fusion

Contains research objectives and reports on three research projects.National Science Foundation (Grant GK-1165)National Science Foundation (Grant GK-57

Paradox as a Metatheoretical Perspective

Organizations are rife with tensions – flexibility vs. control, exploration vs. exploitation, autocracy vs. democracy, social vs. financial, global vs. local. Researchers have long responded using contingency theory, asking “under what conditions should managers emphasize either A or B?” Yet increasingly studies apply a paradox perspective, shifting the question to: “how can we engage both A and B simultaneously?” Despite accumulating exemplars, commonalities across paradox studies remain unclear, and ties unifying this research community weak. To energize further uses of a paradox perspective, we build from past reviews to explicate its role as a metatheory. Contrasting this lens to contingency theory, we illustrate its meta-theoretical nature. We then dive deeper to sharpen the focus and widen the scope of a paradox perspective. Identifying core elements viewed from a paradox perspective – underlying assumptions, central concepts, nature of interrelationships and boundary conditions – offers a guide, informing the practice of paradox research. Next, we illustrate diverse uses of this lens. We conclude by exploring implications and next steps, stressing the rising need for paradox research, as complexity, change and ambiguity intensify demands for both/and approaches in theory and practice

Inflammatory chemokine receptors regulate CD8+ T cell contraction and memory generation following infection

CD8+ T cells lacking CXCR3 and CCR5 expression have impaired contraction and generate an increased number of memory cells after virus infection