Loss of TJP1 disrupts gastrulation patterning and increases differentiation toward the germ cell lineage in human pluripotent stem cells.

Biological patterning events that occur early in development establish proper tissue morphogenesis. Identifying the mechanisms that guide these patterning events is necessary in order to understand the molecular drivers of development and disease and to build tissues in vitro. In this study, we use an in vitro model of gastrulation to study the role of tight junctions and apical/basolateral polarity in modulating bone morphogenic protein-4 (BMP4) signaling and gastrulation-associated patterning in colonies of human pluripotent stem cells (hPSCs). Disrupting tight junctions via knockdown (KD) of the scaffolding tight junction protein-1 (TJP1, also known as ZO1) allows BMP4 to robustly and ubiquitously activate pSMAD1/5 signaling over time, resulting in loss of the patterning phenotype and marked differentiation bias of pluripotent stem cells to primordial germ cell-like cells (PGCLCs). These findings give important insights into how signaling events are regulated and lead to spatial emergence of diverse cell types in vitro

The structural basis of bacterial manganese import

肺炎球菌が細胞内にマンガンイオンを取り込むしくみ --膜輸送体PsaBCの立体構造の解明--. 京都大学プレスリリース. 2021-09-15.Metal ions are essential for all forms of life. In prokaryotes, ATP-binding cassette (ABC) permeases serve as the primary import pathway for many micronutrients including the first-row transition metal manganese. However, the structural features of ionic metal transporting ABC permeases have remained undefined. Here, we present the crystal structure of the manganese transporter PsaBC from Streptococcus pneumoniae in an open-inward conformation. The type II transporter has a tightly closed transmembrane channel due to “extracellular gating” residues that prevent water permeation or ion reflux. Below these residues, the channel contains a hitherto unreported metal coordination site, which is essential for manganese translocation. Mutagenesis of the extracellular gate perturbs manganese uptake, while coordination site mutagenesis abolishes import. These structural features are highly conserved in metal-specific ABC transporters and are represented throughout the kingdoms of life. Collectively, our results define the structure of PsaBC and reveal the features required for divalent cation transport

The multidrug transporter ABCG2: still more questions than answers

ABCG2 is one of at least three human ATP binding cassette (ABC) transporters which can facilitate the export from cells of a wide range of chemically unrelated drug molecules. This capacity for multidrug transport is not only a confounding factor in chemotherapy, but is also one of the more perplexing phenomena in transporter biochemistry. Since its discovery in the last decade of the 20th century much has been revealed about ABCG2's localization, physiological function and its broad substrate range. There have also been many investigations of its structure and molecular mechanism. In this mini review article we take a Rumsfeldian approach to ABCG2 and essentially ask what we do know about this transporter, and what we will need to know about this transporter if we wish to use modulation of ABCG2 activity as a therapeutic approach

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

XML views of relational databases

Our goal was to create a program to link two existing algorithms to query relational databases in an XML format. The first algorithm, CoT, takes a relational schema and generates a corresponding XML schema represented in a proprietary grammar format, called XGrammar. The second algorithm, X2S, handles XPath queries over this XML schema. We wrote a program, G2D, that converts the schema in XGrammar into XML DTDs, annotated with key-foreign key information present in the relational schema. X2S was also modified to now work against these XML DTDs. To further the project, we recommend providing additional functionality allowing updates to occur in the relational databases using our software package

The Need for Speed: Demand, Regulation, and Welfare on the Margin of Alternative Financial Services

We use a nonlinear reduction in a bank\u27s check-cashing fees and variation in regulated check-clearing times to identify the elasticity of demand for cashing checks rather than depositing them. We find that an extra day of check-clearing time makes account holders 65.5% more likely to cash a check than deposit it, which implies they are willing to pay $11.17 per day for faster access to their funds – an effective annualized discount rate of 11,054% for the average check. We use this elasticity to evaluate recent proposals that mandate faster check-clearing times

Does Napping Boost Benefits of Brain-Training for Working Memory?

Working memory (WM) is engaged in most cognitive tasks deployed in the human brain. Braintrainingregimens that target WM may promote plasticity, leading to improved WM skills.Additionally, sleep is known to facilitate consolidation of newly learned information and skills. Here,we asked if napping could boost benefits of brain-training for WM. Participants completed ten days ofWM training on an N-back task; on each training day, a subset of participants were given a 30-minutenap opportunity (with EEG recording) immediately following their training session (training+nap).In Study 1 (n=10), we equated the amount of training (20-min training/day) in all participants andcompared training only to training+nap. In Study 2 (n=8), we asked if napping can effectively replaceadditional time spent training; we compared training+nap (20-min training/day) to double training(40-min training/day). On average, the nap group slept 16.0±5.77 minutes/nap in Study 1 and15.98±7.44 minutes/nap in Study 2. Our dependent measure of performance was the highest N-levelachieved on each day of training. In both studies, we found that performance improved across theten days of the study. However, there was no day x group interaction in either study, suggesting thatthe degree of improvement did not differ between training only vs. training+nap groups. In Study 2,there was a trend towards more improvement with double training compared to single training+nap.For people looking to dedicate time each day to improving their WM, it may be more beneficial tospend the entire time training rather than training+napping