Activity

Cooperation within and across borders is of paramount importance for the provision of public goods. Parochialism – the tendency to cooperate more with ingroup than outgroup members – limits contributions to global public goods. National parochialism (i.e., greater cooperation among members of the same nation) could vary across nations and has been hypothesized to be associated with rule of law, exposure to world religions, relational mobility and pathogen stress. We conduct an experiment in participants from 42 nations (N = 18,411), and observe cooperation in a prisoner’s dilemma with ingroup, outgroup, and unidentified partners. TAK-243 clinical trial We observe that national parochialism is a ubiquitous phenomenon it is present to a similar degree across the nations studied here, is independent of cultural distance, and occurs both when decisions are private or public. These findings inform existing theories of parochialism and suggest it may be an obstacle to the provision of global public goods.Metaplastic breast carcinoma (MpBC) is a rare special histologic subtype of breast carcinoma characterized by the presence of squamous and/or mesenchymal differentiation. Most MpBCs are of triple-negative phenotype and neoadjuvant chemotherapy (NAC) is frequently utilized in patients with MpBC. The aim of this study was to evaluate response to NAC in a retrospective cohort of MpBCs. We identified 44 patients with MpBC treated with NAC at our center between 2002 and 2018. Median age was 48 years, 86% were clinical stage II-III, and 36% were clinically node-positive. Most (80%) MpBCs were triple-negative or low (1-10%) hormonal receptor positive and HER2 negative on pre-NAC biopsy. While on NAC, 49% showed no clinical response or clinico-radiological progression. Matrix-producing subtype was associated with clinico-radiological response (p = 0.0036). Post NAC, two patients initially ineligible for breast-conserving surgery (BCS) were downstaged to be eligible for BCS, whereas three patients potentially eligible for BCS before treatment became ineligible due to disease progression. Only one (2%) patient had a pathologic complete response (pCR). Among the 16 patients presenting with biopsy-proven clinical node-positive disease, 3 (19%) had nodal pCR. Axillary lymph node dissection was avoided in 3 (19%) patients who had successful axillary downstaging. Residual cancer burden (RCB) was assessed in 22 patients and was significantly associated with disease-free survival and overall survival. We observed a poor response or even disease progression on NAC among patients with MpBC, suggesting that NAC should be reserved for patients with inoperable MpBC.CRISPR-Cas12j is a recently identified family of miniaturized RNA-guided endonucleases from phages. These ribonucleoproteins provide a compact scaffold gathering all key activities of a genome editing tool. We provide the first structural insight into the Cas12j family by determining the cryoEM structure of Cas12j3/R-loop complex after DNA cleavage. The structure reveals the machinery for PAM recognition, hybrid assembly and DNA cleavage. The crRNA-DNA hybrid is directed to the stop domain that splits the hybrid, guiding the T-strand towards the catalytic site. The conserved RuvC insertion is anchored in the stop domain and interacts along the phosphate backbone of the crRNA in the hybrid. The assembly of a hybrid longer than 12-nt activates catalysis through key functional residues in the RuvC insertion. Our findings suggest why Cas12j unleashes unspecific ssDNA degradation after activation. A site-directed mutagenesis analysis supports the DNA cutting mechanism, providing new avenues to redesign CRISPR-Cas12j nucleases for genome editing.Plant sulfate transporters (SULTR) mediate absorption and distribution of sulfate (SO42-) and are essential for plant growth; however, our understanding of their structures and functions remains inadequate. Here we present the structure of a SULTR from Arabidopsis thaliana, AtSULTR4;1, in complex with SO42- at an overall resolution of 2.8 Å. AtSULTR4;1 forms a homodimer and has a structural fold typical of the SLC26 family of anion transporters. The bound SO42- is coordinated by side-chain hydroxyls and backbone amides, and further stabilized electrostatically by the conserved Arg393 and two helix dipoles. Proton and SO42- are co-transported by AtSULTR4;1 and a proton gradient significantly enhances SO42- transport. Glu347, which is ~7 Å from the bound SO42-, is required for H+-driven transport. The cytosolic STAS domain interacts with transmembrane domains, and deletion of the STAS domain or mutations to the interface compromises dimer formation and reduces SO42- transport, suggesting a regulatory function of the STAS domain.The basal body of the bacterial flagellum is a rotary motor that consists of several rings (C, MS and LP) and a rod. The LP ring acts as a bushing supporting the distal rod for its rapid and stable rotation without much friction. Here, we use electron cryomicroscopy to describe the LP ring structure around the rod, at 3.5 Å resolution, from Salmonella Typhimurium. The structure shows 26-fold rotational symmetry and intricate intersubunit interactions of each subunit with up to six partners, which explains the structural stability. The inner surface is charged both positively and negatively. Positive charges on the P ring (the part of the LP ring that is embedded within the peptidoglycan layer) presumably play important roles in its initial assembly around the rod with a negatively charged surface.Feedback in the brain is thought to convey contextual information that underlies our flexibility to perform different tasks. Empirical and computational work on the visual system suggests this is achieved by targeting task-relevant neuronal subpopulations. We combine two tasks, each resulting in selective modulation by feedback, to test whether the feedback reflected the combination of both selectivities. We used visual feature-discrimination specified at one of two possible locations and uncoupled the decision formation from motor plans to report it, while recording in macaque mid-level visual areas. Here we show that although the behavior is spatially selective, using only task-relevant information, modulation by decision-related feedback is spatially unselective. Population responses reveal similar stimulus-choice alignments irrespective of stimulus relevance. The results suggest a common mechanism across tasks, independent of the spatial selectivity these tasks demand. This may reflect biological constraints and facilitate generalization across tasks.