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As our scientific and technical abilities expand at breathtaking speeds, concern that modern genetics and bioengineering are leading us to a posthuman future is growing. Is Human Nature Obsolete? poses the overarching question of what it is to be human against the background of these current advances in biotechnology. Its perspective is philosophical and interdisciplinary rather than technical; the focus is on questions of fundamental ontological importance rather than the specifics of medical or scientific practice.The authors -- all distinguished scholars in their fields -- take on questions about technology's goals and values that are often ignored or sidelined in the face of rapid scientific advances and the highly specialized nature of technical knowledge. The essays included represent a rich variety of thought, ranging from finely nuanced philosophical and theological arguments to historical studies and cultural commentaries. Several explore the historical background of today's biotechnology: Timothy Casey traces such developments as the emergence of cybernetic humanity from Cartesian dualism, and Diane Paul presents the history of \"positive\" versus coerced eugenics. Jean Bethke Elshtain discusses cloning as a \"messianic project\" to perfect the body and exclude natural diversity -- giving as an example the elimination of Down Syndrome as an acceptable human type -- while Harold Baillie calls for an examination of the metaphysical roots of personhood. Robert Proctor finds no evidence in paleontology for any \"essence of humanity,\" and Tom Shannon argues against materialist reductionism. Addressing social concerns, Lisa Sowle Cahill finds the possibility of a political solution to the problems raised by genetic engineering in Catholic teachings on social justice, and Langdon Winner looks critically at the \"scientific enthusiasts of a posthuman future.\" Taken as a whole, the book provides a humanistic overview of a subject too often considered only in its technological aspect.

The main objective of the multi-site Pediatric Imaging, Neurocognition, and Genetics (PING) study was to create a large repository of standardized measurements of behavioral and imaging phenotypes accompanied by whole genome genotyping acquired from typically-developing children varying widely in age (3 to 20years). This cross-sectional study produced sharable data from 1493 children, and these data have been described in several publications focusing on brain and cognitive development. Researchers may gain access to these data by applying for an account on the PING portal and filing a data use agreement. Here we describe the recruiting and screening of the children and give a brief overview of the assessments performed, the imaging methods applied, the genetic data produced, and the numbers of cases for whom different data types are available. We also cite sources of more detailed information about the methods and data. Finally we describe the procedures for accessing the data and for using the PING data exploration portal. •We provide a brief description of the Pediatric Imaging Neurocognition and Genetics (PING) Study.•We describe the data in the PING Data Repository.•We outline the methods used to generate the data.•We describe the procedure for accessing and exploring the data through the PING Portal.

The peptidoglycan cell wall is an integral organelle critical for bacterial cell shape and stability. Proper cell wall construction requires the interaction of synthesis enzymes and the cytoskeleton, but it is unclear how the activities of individual proteins are coordinated to preserve the morphology and integrity of the cell wall during growth. To elucidate this coordination, we used single-molecule imaging to follow the behaviours of the two major peptidoglycan synthases in live, elongating Escherichia coli cells and after perturbation. We observed heterogeneous localization dynamics of penicillin-binding protein (PBP) 1A, the synthase predominantly associated with cell wall elongation, with individual PBP1A molecules distributed between mobile and immobile populations. Perturbations to PBP1A activity, either directly through antibiotics or indirectly through PBP1A’s interaction with its lipoprotein activator or other synthases, shifted the fraction of mobile molecules. Our results suggest that multiple levels of regulation control the activity of enzymes to coordinate peptidoglycan synthesis. The bacterial cell wall is important for cell shape and stability, but how the activities of the biosynthetic machinery are coordinated are not clear. Here the authors use single-molecule imaging and chemical perturbations to determine factors that affect the localization dynamics of penicillin-binding proteins (PBP)1A and PBP1B.

When Staphylococcus aureus undergoes cytokinesis, it builds a septum, generating two hemispherical daughters whose cell walls are only connected via a narrow peripheral ring. We found that resolution of this ring occurred within milliseconds (\"popping\"), without detectable changes in cell volume. The likelihood of popping depended on cell-wall stress, and the separating cells split open asymmetrically, leaving the daughters connected by a hinge. An elastostatic model of the wall indicated high circumferential stress in the peripheral ring before popping. Last, we observed small perforations in the peripheral ring that are likely initial points of mechanical failure. Thus, the ultrafast daughter cell separation in S. aureus appears to be driven by accumulation of stress in the peripheral ring and exhibits hallmarks of mechanical crack propagation.

We previously reported the results of a randomized phase II trial (NCT02904954) in patients with early-stage non-small cell lung cancer (NSCLC) who were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation (DRT). The trial met its primary endpoint of major pathological response, which was significantly higher following DRT with no new safety signals. Here, we report on the prespecified secondary endpoint of disease-free survival (DFS) regardless of treatment assignment and the prespecified exploratory analysis of DFS in each arm of the trial. DFS at 2 and 3 years across patients in both arms of the trial were 73% (95% CI: 62.1–84.5) and 65% (95% CI: 52.5–76.9) respectively. For the exploratory endpoint of DFS in each arm of the trial, three-year DFS was 63% (95% CI: 46.0–80.4) in the durvalumab monotherapy arm compared to 67% (95% CI: 49.6–83.4) in the dual therapy arm. In addition, we report post hoc exploratory analysis of progression-free survival as well as molecular correlates of response and recurrence through high-plex immunophenotyping of sequentially collected peripheral blood and gene expression profiles from resected tumors in both treatment arms. Together, our results contribute to the evolving landscape of neoadjuvant treatment regimens for NSCLC and identify easily measurable potential biomarkers of response and recurrence. The authors previously reported the primary outcomes of a randomized phase II trial comparing neoadjuvant durvalumab (anti-PD-L1) alone or in combination with stereotactic radiotherapy in patients with early-stage NSCLC. Here, the authors report the secondary outcomes of the trial and post hoc analysis.

Background The determination and regulation of cell morphology are critical components of cell-cycle control, fitness, and development in both single-cell and multicellular organisms. Understanding how environmental factors, chemical perturbations, and genetic differences affect cell morphology requires precise, unbiased, and validated measurements of cell-shape features. Results Here we introduce two software packages, Morphometrics and BlurLab , that together enable automated, computationally efficient, unbiased identification of cells and morphological features. We applied these tools to bacterial cells because the small size of these cells and the subtlety of certain morphological changes have thus far obscured correlations between bacterial morphology and genotype. We used an online resource of images of the Keio knockout library of nonessential genes in the Gram-negative bacterium Escherichia coli to demonstrate that cell width, width variability, and length significantly correlate with each other and with drug treatments, nutrient changes, and environmental conditions. Further, we combined morphological classification of genetic variants with genetic meta-analysis to reveal novel connections among gene function, fitness, and cell morphology, thus suggesting potential functions for unknown genes and differences in modes of action of antibiotics. Conclusions Morphometrics and BlurLab set the stage for future quantitative studies of bacterial cell shape and intracellular localization. The previously unappreciated connections between morphological parameters measured with these software packages and the cellular environment point toward novel mechanistic connections among physiological perturbations, cell fitness, and growth.

SLIP is a high-throughput, automated microscopy workflow for large strain collections. Bacterial cultures are transferred to large agar pads using replicator pins, and thousands of images are automatically acquired for single-cell quantification. Single-cell microscopy is a powerful tool for studying gene functions using strain libraries, but it suffers from throughput limitations. Here we describe the Strain Library Imaging Protocol (SLIP), which is a high-throughput, automated microscopy workflow for large strain collections that requires minimal user involvement. SLIP involves transferring arrayed bacterial cultures from multiwell plates onto large agar pads using inexpensive replicator pins and automatically imaging the resulting single cells. The acquired images are subsequently reviewed and analyzed by custom MATLAB scripts that segment single-cell contours and extract quantitative metrics. SLIP yields rich data sets on cell morphology and gene expression that illustrate the function of certain genes and the connections among strains in a library. For a library arrayed on 96-well plates, image acquisition can be completed within 4 min per plate.

In this article, members of the Midwest Critical Whiteness Collective argue that Peggy McIntosh's seminal \"knapsack\" article acts as a synecdoche, or as a stand-in, for all the antiracist work to be done in teacher education and that this limits our understanding and possibilities for action. The authors develop this argument by questioning the lack of critique of McIntosh's 1988 classic \"invisible knapsack\" article and sharing two narratives by members of their collective that illustrate problems with both the acceptance and the rejection of McIntosh's conception of white privilege. This discussion illuminates how white privilege pedagogy demands confession and how confession is a dead end for antiracist action. The authors also explore how McIntosh's ideas can lead to dangerous misreadings of student resistance. Acknowledging the initial fruitfulness of McIntosh's ideas, it is time for us to move to more complex treatments of working with white people on questions of race, white supremacy, and antiracism.

Autophagy is an intracellular recycling process that degrades harmful molecules and enables survival during starvation, with implications for diseases including dementia, cancer and atherosclerosis. Previous studies demonstrate how a limited number of transcription factors (TFs) can increase autophagy. However, this knowledge has not resulted in translation into therapy, thus, to gain understanding of more suitable targets, we utilized a systems biology approach. We induced autophagy by amino acid starvation and mTOR inhibition in HeLa, HEK 293 and SH-SY5Y cells and measured temporal gene expression using RNA-seq. We observed 456 differentially expressed genes due to starvation and 285 genes due to mTOR inhibition (P FDR  < 0.05 in every cell line). Pathway analyses implicated Alzheimer’s and Parkinson’s diseases (P FDR  ≤ 0.024 in SH-SY5Y and HeLa) and amyotrophic lateral sclerosis (ALS, P FDR  < 0.05 in mTOR inhibition experiments). Differential expression of the Senataxin (SETX) target gene set was predicted to activate multiple neurodegenerative pathways (P FDR  ≤ 0.04). In the SH-SY5Y cells of neuronal origin, the E2F transcription family was predicted to activate Alzheimer’s disease pathway (P FDR  ≤ 0.0065). These exploratory analyses suggest that SETX and E2F may mediate transcriptional regulation of autophagy and further investigations into their possible role in neuro-degeneration are warranted.