The Ecology of Sandy Shores provides the students and researchers with a one- volume resource for understanding the conservation and management of the sandy shore ecosystem. Covering all beach types, ...and addressing issues from the behavioral and physiological adaptations of the biota to exploring the effects of pollution and the impact of man's activities, this book should become the standard reference for those interested in Sandy Shore study, management and preservation. * More than 25% expanded from the previous edition * Three entirely new chapters: Energetics and Nutrient Cycling, Turtles and Terrestrial Vertebrates, and Benthic Macrofauna Populations * New sections on the interstitial environment, seagrasses, human impacts and coastal zone management * Examples drawn from virtually all parts of the world, considering all beach types from the most exposed to the most sheltered
Sensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of ...these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway. We show that CC-projecting cells encompass a broad spectrum of selectivity to stimulus orientation and are predominantly innervated by deep layer V1 neurons. In contrast, CT-projecting cells are ultrasparse firing, exquisitely tuned to orientation and direction information, and receive long-range input from higher cortical areas. This segregation in function and connectivity indicates that L6 microcircuits route specific contextual and stimulus-related information within and outside the cortical network.
•L6 cortico-cortical neurons are broadly tuned to stimulus orientation•L6 cortico-thalamic neurons are sparse firing and highly tuned to stimulus orientation•L6 cortico-cortical neurons receive input from cells located mostly within V1•L6 cortico-thalamic neurons receive input from higher order cortical areas
Vélez-Fort et al. combine in vivo whole-cell recordings with transsynaptic retrograde tracing of monosynaptic connectivity from cortical layer six neurons to delineate functionally distinct microcircuits underlying sensory processing in the mouse primary visual cortex.
APOBEC cytidine deaminases are the second-most prominent source of mutagenesis in sequenced tumors. Previous studies have proposed that APOBEC3B (A3B) is the major source of mutagenesis in breast ...cancer (BRCA). We show that APOBEC3A (A3A) is the only APOBEC whose expression correlates with APOBEC-induced mutation load and that A3A expression is responsible for cytidine deamination in multiple BRCA cell lines. Comparative analysis of A3A and A3B expression by qRT-PCR, RSEM-normalized RNA-seq, and unambiguous RNA-seq validated the use of RNA-seq to measure APOBEC expression, which indicates that A3A is the primary correlate with APOBEC-mutation load in primary BRCA tumors. We also demonstrate that A3A has >100-fold more cytidine deamination activity than A3B in the presence of cellular RNA, likely explaining why higher levels of A3B expression contributes less to mutagenesis in BRCA. Our findings identify A3A as a major source of cytidine deaminase activity in breast cancer cells and possibly a prominent contributor to the APOBEC mutation signature.
Abstract
Aim
We tested the hypothesis that dapagliflozin may regress left ventricular hypertrophy (LVH) in people with type 2 diabetes (T2D).
Methods and results
We randomly assigned 66 people (mean ...age 67 ± 7 years, 38 males) with T2D, LVH, and controlled blood pressure (BP) to receive dapagliflozin 10 mg once daily or placebo for 12 months. Primary endpoint was change in absolute left ventricular mass (LVM), assessed by cardiac magnetic resonance imaging. In the intention-to-treat analysis, dapagliflozin significantly reduced LVM compared with placebo with an absolute mean change of −2.82g 95% confidence interval (CI): −5.13 to −0.51, P = 0.018. Additional sensitivity analysis adjusting for baseline LVM, baseline BP, weight, and systolic BP change showed the LVM change to remain statistically significant (mean change −2.92g; 95% CI: −5.45 to −0.38, P = 0.025). Dapagliflozin significantly reduced pre-specified secondary endpoints including ambulatory 24-h systolic BP (P = 0.012), nocturnal systolic BP (P = 0.017), body weight (P < 0.001), visceral adipose tissue (VAT) (P < 0.001), subcutaneous adipose tissue (SCAT) (P = 0.001), insulin resistance, Homeostatic Model Assessment of Insulin Resistance (P = 0.017), and high-sensitivity C-reactive protein (hsCRP) (P = 0.049).
Conclusion
Dapagliflozin treatment significantly reduced LVM in people with T2D and LVH. This reduction in LVM was accompanied by reductions in systolic BP, body weight, visceral and SCAT, insulin resistance, and hsCRP. The regression of LVM suggests dapagliflozin can initiate reverse remodelling and changes in left ventricular structure that may partly contribute to the cardio-protective effects of dapagliflozin.
ClinicalTrials.gov Identifier
NCT02956811
We have identified an enantioselective copper-catalyzed
-to-
formal 1,3-rearrangement to form
-propargylic-2-pyridones. This enantioconvergent
-to-
propargylic rearrangement occurs rapidly at ambient ...temperature and high enantioselectivity is observed for a range of 3-alkyl-substituted substrates. Stereochemical features include a mild kinetic enantioenrichment of the substrate and a non-linear relationship between product and ligand enantiopurity. Based on kinetic analyses and cross-over experiments, we put forward a mechanistic proposal involving Cu-acetylides as well as bimetallic intermediates in which coordination to the pyridyl nitrogen is likely a crucial binding interaction.
Hate speech law can be found throughout the world. But it is also the subject of numerous principled arguments, both for and against. These principles invoke a host of morally relevant features ...(e.g., liberty, health, autonomy, security, non-subordination, the absence of oppression, human dignity, the discovery of truth, the acquisition of knowledge, self-realization, human excellence, civic dignity, cultural diversity and choice, recognition of cultural identity, intercultural dialogue, participation in democratic self-government, being subject only to legitimate rule) and practical considerations (e.g., efficacy, the least restrictive alternative, chilling effects). The book develops and then critically examines these various principled arguments. It also attempts to de-homogenize hate speech law into different clusters of laws/regulations/codes that constrain uses of hate speech, so as to facilitate a more nuanced examination of the principled arguments.
Research summary
We examine the correlations between financial resource allocation flow between business segments and two measures of overall firm financial performance using a sample of Compustat ...firms. Our analysis finds a consistent inverted U‐shape (or alternatively, V‐shape) relationship between those measures and firm profitability. Interestingly, nearly all the data lie on the upward sloping part of the curve. Taken together, these results support the notion that flows of financial capital are most often positively correlated with financial performance.
Managerial summary
A key question for any organization is how reallocating capital across business units is related to overall firm performance. We examine the correlations of firm profitability with a measure of change in year‐to‐year allocations across business units in a data set of several thousand firms spanning 18 years. Except in cases of the most extreme reallocations, our measure of firm reallocation is positively correlated with firm performance. Because we cannot prove causality, we cautiously conclude that our findings are consistent with a story that, in most cases, firms would benefit from greater internal reallocation of capital. The managerial question then becomes “what dynamic capabilities are necessary to increase the flow of resources across business segments?” Policies aimed at increasing allocation flow are likely to be beneficial.
The validation of automated image registration and segmentation is crucial for accurate and reliable mapping of brain connectivity and function in three-dimensional (3D) data sets. While validation ...standards are necessarily high and routinely met in the clinical arena, they have to date been lacking for high-resolution microscopy data sets obtained from the rodent brain. Here we present a tool for optimized automated mouse atlas propagation (aMAP) based on clinical registration software (NiftyReg) for anatomical segmentation of high-resolution 3D fluorescence images of the adult mouse brain. We empirically evaluate aMAP as a method for registration and subsequent segmentation by validating it against the performance of expert human raters. This study therefore establishes a benchmark standard for mapping the molecular function and cellular connectivity of the rodent brain.
Why do individuals volunteer their time even when recipients receive far less value than the donor’s opportunity cost? Previous models of altruism that focus on the overall impact of a gift cannot ...rationalize this behavior, despite its prevalence. We develop a model that allows for differential warm glow depending on the form of the donation. In a series of laboratory experiments that control for other aspects of volunteering, such as its signaling value, subjects demonstrate behavior consistent with the theoretical assumption that gifts of time produce greater utility than the same transfers in the form of money. Subjects perform an effort task, accruing earnings at potentially different wage rates for themselves or a charity of their choice, with the ability to transfer any of their personal earnings to charity at the end of the experiment. Subjects exhibit strong preferences for donating time even when differential wage rates make it costly to do so. The results provide new insights on the nature of volunteering and gift giving.
Data, the online appendix, and the experimental instructions are available at
https://doi.org/10.1287/mnsc.2017.2951
.
This paper was accepted by Teck-Hua Ho, behavioral economics.
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