Residual fibroglandular breast tissue after mastectomy is associated with an increased risk of a local recurrence or a new primary breast cancer".

BACKGROUND: Residual fibroglandular breast tissue (RFGT) following a mastectomy has been claimed to be associated with the occurrence of an in-breast local recurrence (IBLR) or new primary tumor (NP). Yet, scientific evidence proving this assumption is lacking. The primary aim of the study was to verify whether RFGT following a mastectomy is a risk factor for an IBLR or NP. METHODS: This retrospective analysis included all patients that underwent a mastectomy and were followed up at the Department of Obstetrics and Gynecology of the Medical University of Vienna between 01.01.2015 and 26.02.2020. RFGT volume (assessed on magnetic resonance imaging) was correlated with the prevalence of an IBLR and a NP. RESULTS: A total of 105 patients (126 breasts) following a therapeutic mastectomy were included. After a mean follow-up of 46.0 months an IBLR had occurred in 17 breasts and a NP in 1 breast. A significant difference in RFGT volume was observed between the disease-free cohort and the subgroup with an IBLR or NP (p = .017). A RFGT volume of ≥ 1153 mm3 increased the risk by the factor 3.57 [95%CI 1.27; 10.03]. CONCLUSIONS: RFGT volume is associated with an increased risk for an IBLR or NP.

Warmth and competence perceptions of key protagonists are associated with containment measures during the COVID-19 pandemic: Evidence from 35 countries.

It is crucial to understand why people comply with measures to contain viruses and their effects during pandemics. We provide evidence from 35 countries (Ntotal = 12,553) from 6 continents during the COVID-19 pandemic (between 2021 and 2022) obtained via cross-sectional surveys that the social perception of key protagonists on two basic dimensions-warmth and competence-plays a crucial role in shaping pandemic-related behaviors. Firstly, when asked in an open question format, heads of state, physicians, and protest movements were universally identified as key protagonists across countries. Secondly, multiple-group confirmatory factor analyses revealed that warmth and competence perceptions of these and other protagonists differed significantly within and between countries. Thirdly, internal meta-analyses showed that warmth and competence perceptions of heads of state, physicians, and protest movements were associated with support and opposition intentions, containment and prevention behaviors, as well as vaccination uptake. Our results have important implications for designing effective interventions to motivate desirable health outcomes and coping with future health crises and other global challenges.

The Ptr1 Locus of Solanum lycopersicoides Confers Resistance to Race 1 Strains of Pseudomonas syringae pv. tomato and to Ralstonia pseudosolanacearum by Recognizing the Type III Effectors AvrRpt2 and RipBN.

Race 1 strains of Pseudomonas syringae pv. tomato, which cause bacterial speck disease of tomato, are becoming increasingly common and no simply inherited genetic resistance to such strains is known. We discovered that a locus in Solanum lycopersicoides, termed Pseudomonas tomato race 1 (Ptr1), confers resistance to race 1 P. syringae pv. tomato strains by detecting the activity of type III effector AvrRpt2. In Arabidopsis, AvrRpt2 degrades the RIN4 protein, thereby activating RPS2-mediated immunity. Using site-directed mutagenesis of AvrRpt2, we found that, like RPS2, activation of Ptr1 requires AvrRpt2 proteolytic activity. Ptr1 also detected the activity of AvrRpt2 homologs from diverse bacteria, including one in Ralstonia pseudosolanacearum. The genome sequence of S. lycopersicoides revealed no RPS2 homolog in the Ptr1 region. Ptr1 could play an important role in controlling bacterial speck disease and its future cloning may shed light on an example of convergent evolution for recognition of a widespread type III effector.

In vivo imaging of epithelial wound healing in the cnidarian Clytia hemisphaerica demonstrates early evolution of purse string and cell crawling closure mechanisms.

BACKGROUND: All animals have mechanisms for healing damage to the epithelial sheets that cover the body and line internal cavities. Epithelial wounds heal either by cells crawling over the wound gap, by contraction of a super-cellular actin cable ("purse string") that surrounds the wound, or some combination of the two mechanisms. Both cell crawling and purse string closure of epithelial wounds are widely observed across vertebrates and invertebrates, suggesting early evolution of these mechanisms. Cnidarians evolved ~600 million years ago and are considered a sister group to the Bilateria. They have been much studied for their tremendous regenerative potential, but epithelial wound healing has not been characterized in detail. Conserved elements of wound healing in bilaterians and cnidarians would suggest an evolutionary origin in a common ancestor. Here we test this idea by characterizing epithelial wound healing in live medusae of Clytia hemisphaerica. RESULTS: We identified cell crawling and purse string-mediated mechanisms of healing in Clytia epithelium that appear highly analogous of those seen in higher animals, suggesting that these mechanisms may have emerged in a common ancestor. Interestingly, we found that epithelial wound healing in Clytia is 75 to >600 times faster than in cultured cells or embryos of other animals previously studied, suggesting that Clytia may provide valuable clues about optimized healing efficiency. Finally, in Clytia, we show that damage to the basement membrane in a wound gap causes a rapid shift between the cell crawling and purse string mechanisms for wound closure. This is consistent with work in other systems showing that cells marginal to a wound choose between a super-cellular actin cable or lamellipodia formation to close wounds, and suggests a mechanism underlying this decision. CONCLUSIONS: 1. Cell crawling and purse string mechanisms of epithelial wound healing likely evolved before the divergence of Cnidaria from the bilaterian lineage ~ 600mya 2. In Clytia, the choice between cell crawling and purse string mechanisms of wound healing depends on interactions between the epithelial cells and the basement membrane.

The Tomato Kinase Pti1 Contributes to Production of Reactive Oxygen Species in Response to Two Flagellin-Derived Peptides and Promotes Resistance to Pseudomonas syringae Infection.

The Pti1 kinase was identified from a reverse genetic screen as contributing to pattern-triggered immunity (PTI) against Pseudomonas syringae pv. tomato (Pst). The tomato genome has two Pti1 genes, referred to as Pti1a and Pti1b. A hairpin-Pti1 (hpPti1) construct was developed and was used to generate two independent stable transgenic tomato lines that had reduced transcript abundance of both genes. In response to P. syringae pv. tomato inoculation, these hpPti1 plants developed more severe disease symptoms, supported higher bacterial populations, and had reduced transcript accumulation of PTI-associated genes, as compared with wild-type plants. In response to two flagellin-derived peptides, the hpPti1 plants produced lesser amounts of reactive oxygen species (ROS) but showed no difference in mitogen-activated protein kinase (MAPK). Synthetic Pti1a and Pti1b genes designed to avoid silencing were transiently expressed in the hpPti1 plants and restored the ability of the plants to produce wild-type levels of ROS. Our results identify a new component of PTI in tomato that, because it affects ROS production but not MAPK signaling, appears to act early in the immune response.

Pseudomonas syringae pv. tomato Strains from New York Exhibit Virulence Attributes Intermediate Between Typical Race 0 and Race 1 Strains.

Bacterial speck disease, caused by Pseudomonas syringae pv. tomato, is a persistent problem for fresh-market tomato growers in New York. Race 0 strains of this pathogen express either or both of the type III effectors AvrPto or AvrPtoB, which are recognized by tomato varieties expressing the Pto resistance gene. Pto encodes a protein kinase that activates the host immune system, thereby inhibiting bacterial multiplication and preventing disease development. Race 1 P. syringae pv. tomato strains do not express these effectors and are virulent on tomato whether or not the variety expresses Pto. Very few fresh-market tomato varieties have the Pto gene. We collected six P. syringae pv. tomato strains from naturally infected tomato plants across New York in 2015 and characterized them for their virulence and for the presence of specific effectors. In experiments conducted in the greenhouse, all strains reached population sizes in Pto-expressing tomato leaves that were intermediate between typical race 0 and race 1 strains. This phenotype has not been observed previously and suggests that the strains are recognized by Pto but such recognition is compromised by another P. syringae pv. tomato factor. The strains were found to encode avrPto, which is transcribed and translated. They also express avrPtoB although, as reported for other P. syringae pv. tomato strains, protein expression for this effector was not detectable. Deletion of avrPto from a representative New York strain allowed it to reach high populations in Pto-expressing tomato varieties, without compromising its virulence on susceptible tomato plants. Collectively, our data suggest that introgression of the Pto gene into fresh-market tomato varieties could enhance protection against extant P. syringae pv. tomato strains.

Detecting N-myristoylation and S-acylation of host and pathogen proteins in plants using click chemistry.

BACKGROUND: The plant plasma membrane is a key battleground in the war between plants and their pathogens. Plants detect the presence of pathogens at the plasma membrane using sensor proteins, many of which are targeted to this lipophilic locale by way of fatty acid modifications. Pathogens secrete effector proteins into the plant cell to suppress the plant's defense mechanisms. These effectors are able to access and interfere with the surveillance machinery at the plant plasma membrane by hijacking the host's fatty acylation apparatus. Despite the important involvement of protein fatty acylation in both plant immunity and pathogen virulence mechanisms, relatively little is known about the role of this modification during plant-pathogen interactions. This dearth in our understanding is due largely to the lack of methods to monitor protein fatty acid modifications in the plant cell. RESULTS: We describe a rapid method to detect two major forms of fatty acylation, N-myristoylation and S-acylation, of candidate proteins using alkyne fatty acid analogs coupled with click chemistry. We applied our approach to confirm and decisively demonstrate that the archetypal pattern recognition receptor FLS2, the well-characterized pathogen effector AvrPto, and one of the best-studied intracellular resistance proteins, Pto, all undergo plant-mediated fatty acylation. In addition to providing a means to readily determine fatty acylation, particularly myristoylation, of candidate proteins, this method is amenable to a variety of expression systems. We demonstrate this using both Arabidopsis protoplasts and stable transgenic Arabidopsis plants and we leverage Agrobacterium-mediated transient expression in Nicotiana benthamiana leaves as a means for high-throughput evaluation of candidate proteins. CONCLUSIONS: Protein fatty acylation is a targeting tactic employed by both plants and their pathogens. The metabolic labeling approach leveraging alkyne fatty acid analogs and click chemistry described here has the potential to provide mechanistic details of the molecular tactics used at the host plasma membrane in the battle between plants and pathogens.

Natural Variation in Tomato Reveals Differences in the Recognition of AvrPto and AvrPtoB Effectors from Pseudomonas syringae.

The Pto protein kinase from Solanum pimpinellifolium interacts with Pseudomonas syringae effectors AvrPto or AvrPtoB to activate effector-triggered immunity. The previously solved crystal structures of the AvrPto-Pto and AvrPtoB-Pto complexes revealed that Pto binds each effector through both a shared and a unique interface. Here we use natural variation in wild species of tomato to further investigate Pto recognition of these two effectors. One species, Solanum chmielewskii, was found to have many accessions that recognize only AvrPtoB. The Pto ortholog from one of these accessions was responsible for recognition of AvrPtoB and it differed from Solanum pimpinellifolium Pto by only 14 amino acids, including two in the AvrPto-specific interface, glutamate-49/glycine-51. Converting these two residues to those in Pto (histidine-49/valine-51) did not restore recognition of AvrPto. Subsequent experiments revealed that a single substitution of a histidine-to-aspartate at position 193 in Pto, which is not near the AvrPto-specific interface, was sufficient for conferring recognition of AvrPto in plant cells. The reciprocal substitution of aspartate-to-histidine-193 in Pto abolished AvrPto recognition, confirming the importance of this residue. Our results reveal new aspects about effector recognition by Pto and demonstrate the value of using natural variation to understand the interaction between resistance proteins and pathogen effectors.