Endometrial receptivity testing is purported to improve live birth following frozen embryo transfer by identifying the optimal embryo transfer time for an individual patient; however, data are ...conflicting.
To compare live birth from single euploid frozen embryo transfer according to endometrial receptivity testing vs standardized timing.
Double-blind, randomized clinical trial at 30 sites within a multicenter private fertility practice in the Eastern US. Enrollment was from May 2018 to September 2020; follow-up concluded in August 2021. Participants underwent in vitro fertilization, preimplantation genetic testing for aneuploidy, endometrial receptivity testing, and frozen embryo transfer. Those with euploid blastocyst(s) and an informative receptivity result were randomized. Exclusion criteria included recurrent pregnancy loss, recurrent implantation failure, surgically aspirated sperm, donor egg(s), and unmitigated anatomic uterine cavity defects.
The intervention group (n = 381) underwent receptivity-timed frozen embryo transfer, with adjusted duration of progesterone exposure prior to transfer, if indicated by receptivity testing. The control group (n = 386) underwent transfer at standard timing, regardless of receptivity test results.
The primary outcome was live birth. There were 3 secondary outcomes, including biochemical pregnancy and clinical pregnancy.
Among 767 participants who were randomized (mean age, 35 years), 755 (98%) completed the trial. All randomized participants were analyzed. The primary outcome of live birth occurred in 58.5% of transfers (223 of 381) in the intervention group vs 61.9% of transfers (239 of 386) in the control group (difference, -3.4% 95% CI, -10.3% to 3.5%; rate ratio RR, 0.95 95% CI, 0.79 to 1.13; P = .38). There were no significant differences in the intervention vs the control group for the prespecified secondary outcomes, including biochemical pregnancy rate (77.2% vs 79.5%, respectively; difference, -2.3% 95% CI, -8.2% to 3.5%; RR, 0.97 95% CI, 0.83 to 1.14; P = .48) and clinical pregnancy rate (68.8% vs 72.8%, respectively; difference, -4.0% 95% CI, -10.4% to 2.4%; RR, 0.94 95% CI, 0.80 to 1.12; P = .25). There were no reported adverse events.
Among patients for whom in vitro fertilization yielded a euploid blastocyst, the use of receptivity testing to guide the timing of frozen embryo transfer, compared with standard timing for transfer, did not significantly improve the rate of live birth. The findings do not support routine use of receptivity testing to guide the timing of embryo transfer during in vitro fertilization.
ClinicalTrials.gov Identifier: NCT03558399.
Resident microbes play important roles in the development of the gastrointestinal tract, but their influence on other digestive organs is less well explored. Using the gnotobiotic zebrafish, we ...discovered that the normal expansion of the pancreatic β cell population during early larval development requires the intestinal microbiota and that specific bacterial members can restore normal β cell numbers. These bacteria share a gene that encodes a previously undescribed protein, named herein BefA (β Cell Expansion Factor A), which is sufficient to induce β cell proliferation in developing zebrafish larvae. Homologs of BefA are present in several human-associated bacterial species, and we show that they have conserved capacity to stimulate β cell proliferation in larval zebrafish. Our findings highlight a role for the microbiota in early pancreatic β cell development and suggest a possible basis for the association between low diversity childhood fecal microbiota and increased diabetes risk.
Fibrosis compromises pancreatic ductal carcinoma (PDAC) treatment and contributes to patient mortality, yet antistromal therapies are controversial. We found that human PDACs with impaired epithelial ...transforming growth factor-β (TGF-β) signaling have high epithelial STAT3 activity and develop stiff, matricellular-enriched fibrosis associated with high epithelial tension and shorter patient survival. In several KRAS-driven mouse models, both the loss of TGF-β signaling and elevated β1-integrin mechanosignaling engaged a positive feedback loop whereby STAT3 signaling promotes tumor progression by increasing matricellular fibrosis and tissue tension. In contrast, epithelial STAT3 ablation attenuated tumor progression by reducing the stromal stiffening and epithelial contractility induced by loss of TGF-β signaling. In PDAC patient biopsies, higher matricellular protein and activated STAT3 were associated with SMAD4 mutation and shorter survival. The findings implicate epithelial tension and matricellular fibrosis in the aggressiveness of SMAD4 mutant pancreatic tumors and highlight STAT3 and mechanics as key drivers of this phenotype.
Nearly every animal species on Earth contains a unique polyketide synthase (PKS) encoded in its genome, yet no animal-clade PKS has been biochemically characterized, and even the chemical products of ...these ubiquitous enzymes are known in only a few cases. The earliest animal genome-encoded PKS gene to be identified was SpPks1 from sea urchins. Previous genetic knockdown experiments implicated SpPks1 in synthesis of the sea urchin pigment echinochrome. Here, we express and purify SpPks1, performing biochemical experiments to demonstrate that the sea urchin protein is responsible for the synthesis of 2-acetyl-1,3,6,8-tetrahydroxynaphthalene (ATHN). Since ATHN is a plausible precursor of echinochromes, this result defines a biosynthetic pathway to the ubiquitous echinoderm pigments and rewrites the previous hypothesis for echinochrome biosynthesis. Truncation experiments showed that, unlike other type I iterative PKSs so far characterized, SpPks1 produces the naphthalene core using solely ketoacylsynthase (KS), acyltransferase, and acyl carrier protein domains, delineating a unique class of animal nonreducing aromatic PKSs (aPKSs). A series of amino acids in the KS domain define the family and are likely crucial in cyclization activity. Phylogenetic analyses indicate that SpPks1 and its homologs are widespread in echinoderms and their closest relatives, the acorn worms, reinforcing their fundamental importance to echinoderm biology. While the animal microbiome is known to produce aromatic polyketides, this work provides biochemical evidence that animals themselves also harbor ancient, convergent, dedicated pathways to carbocyclic aromatic polyketides. More fundamentally, biochemical analysis of SpPks1 begins to define the vast and unexplored biosynthetic space of the ubiquitous animal PKS family.
Abstract
A near-complete diploid nuclear genome and accompanying circular mitochondrial and chloroplast genomes have been assembled from the elite commercial diatom species
Nitzschia inconspicua
. ...The 50 Mbp haploid size of the nuclear genome is nearly double that of model diatom
Phaeodactylum tricornutum
, but 30% smaller than closer relative
Fragilariopsis cylindrus
. Diploid assembly, which was facilitated by low levels of allelic heterozygosity (2.7%), included 14 candidate chromosome pairs composed of long, syntenic contigs, covering 93% of the total assembly. Telomeric ends were capped with an unusual 12-mer, G-rich, degenerate repeat sequence. Predicted proteins were highly enriched in strain-specific marker domains associated with cell-surface adhesion, biofilm formation, and raphe system gliding motility. Expanded species-specific families of carbonic anhydrases suggest potential enhancement of carbon concentration efficiency, and duplicated glycolysis and fatty acid synthesis pathways across cytosolic and organellar compartments may enhance peak metabolic output, contributing to competitive success over other organisms in mixed cultures. The
N. inconspicua
genome delivers a robust new reference for future functional and transcriptomic studies to illuminate the physiology of benthic pennate diatoms and harness their unique adaptations to support commercial algae biomass and bioproduct production.
Abstract
Earth’s mineral deposits show a non-uniform spatial distribution from the craton-scale, to the scale of individual mineral districts. Although this pattern of differential metal endowment is ...underpinned by lithospheric-scale processes the geological features that cause clustering of deposits remains enigmatic. The integration of geological and geophysical (seismic, gravity, and magnetotelluric) features has produced the first whole-of-crust image through an iconic Neoarchean volcanic complex and mineral district in the Abitibi Greenstone Belt, Superior Province, Canada. Observations indicate an asymmetry in surface geology, structure, and crustal architecture that defines deep transcrustal magmatic-hydrothermal upflow zones and the limits of the Noranda District ore system. Here, extreme volcanogenic massive sulfide (VMS) endowment is confined to a smaller area adjacent to an ancestral transcrustal structure interpreted to have localized and optimized magmatic and ore forming processes. Although lithospheric-scale evolutionary processes might act as the fundamental control on metal endowment, the new crustal reconstruction explains the clustering of deposits on both belt and district scales. The results highlight a strong magmatic control on metal and in particular Au endowment in VMS systems. Overprinting by clusters of ca. 30 Ma younger orogenic Au deposits suggest the ore systems accessed an upper lithospheric mantle enriched in Au and metals.
•A co-cultivation technology that converts, CH4 and CO2, into microbial biomass.•Robust bacterial growth on biogas and natural gas feedstocks.•Continuous co-cultivation without air or O2 feed to ...support CH4 oxidation.•A flexible co-culture technology constructed from genetically tractable bacteria.
A new co-cultivation technology is presented that converts greenhouse gasses, CH4 and CO2, into microbial biomass. The methanotrophic bacterium, Methylomicrobium alcaliphilum 20z, was coupled to a cyanobacterium, Synechococcus PCC 7002 via oxygenic photosynthesis. The system exhibited robust growth on diverse gas mixtures ranging from biogas to those representative of a natural gas feedstock. A continuous processes was developed on a synthetic natural gas feed that achieved steady-state by imposing coupled light and O2 limitations on the cyanobacterium and methanotroph, respectively. Continuous co-cultivation resulted in an O2 depleted reactor and does not require CH4/O2 mixtures to be fed into the system, thereby enhancing process safety considerations over traditional methanotroph mono-culture platforms. This co-culture technology is scalable with respect to its ability to utilize different gas streams and its biological components constructed from model bacteria that can be metabolically customized to produce a range of biofuels and bioproducts.
Shewanella oneidensis MR-1 produced electrically conductive pilus-like appendages called bacterial nanowires in direct response to electron-acceptor limitation. Mutants deficient in genes for c-type ...decaheme cytochromes MtrC and OmcA, and those that lacked a functional Type II secretion pathway displayed nanowires that were poorly conductive. These mutants were also deficient in their ability to reduce hydrous ferric oxide and in their ability to generate current in a microbial fuel cell. Nanowires produced by the oxygenic phototrophic cyanobacterium Synechocystis PCC6803 and the thermophilic, fermentative bacterium Pelotomaculum thermopropionicum reveal that electrically conductive appendages are not exclusive to dissimilatory metal-reducing bacteria and may, in fact, represent a common bacterial strategy for efficient electron transfer and energy distribution.
The COVID crisis hit during the interview season for the Complex General Surgical Oncology (CGSO) fellowship. With minimal time to adapt, all programs transitioned to virtual interviews. Here we ...describe the experience of both program directors (PDs) and candidates with virtual interviews, and provide guidelines for implementation based on the results.
Surveys regarding interview day specifics and perceptions were created for CGSO fellowship PDs and candidates. They were distributed at the conclusion of the season, prior to match.
Thirty (94%) PDs and 64 (79%) candidates responded. Eighty-three% of PDs and 79% of candidates agreed or strongly agreed that they felt comfortable creating a rank list. If given the choice, 60% of PDs and 45% of candidates would choose virtual interviews over in-person interviews. The majority of candidates found PD overviews, fellows only sessions and pre-interview materials helpful.
Overall, the majority of PDs and candidates felt comfortable creating a rank list; however, more PDs preferred virtual interviews for the future. Our results also confirm key components of a virtual interview day.
•The COVID pandemic hit during the CGSO interview season, mandating a transition to virtual interviews.•Survey results of program directors and candidates show ease in using a virtual platform.•Both program directors and candidates felt comfortable making rank lists at the conclusion of the interview season.•If given the choice, candidates would prefer in-person interviews over virtual interviews more than program directors.
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