The Zymoseptoria tritici Avirulence Factor AvrStb6 Accumulates in Hyphae Close to Stomata and Triggers a Wheat Defense Response Hindering Fungal Penetration.

Zymoseptoria tritici, the causal agent of Septoria tritici blotch, is one of Europe's most damaging wheat pathogens, causing significant economic losses. Genetic resistance is a common strategy to control the disease, Stb6 being a resistance gene used for more than 100 years in Europe. This study investigates the molecular mechanisms underlying Stb6-mediated resistance. Utilizing confocal microscopy imaging, we determined that Z. tritici epiphytic hyphae mainly accumulate the corresponding avirulence factor AvrStb6 in close proximity to stomata. Consequently, the progression of AvrStb6-expressing avirulent strains is hampered during penetration. The fungal growth inhibition co-occurs with a transcriptional reprogramming in wheat characterized by an induction of immune responses, genes involved in stomatal regulation, and cell wall-related genes. Overall, we shed light on the gene-for-gene resistance mechanisms in the wheat-Z. tritici pathosystem at the cytological and transcriptomic level, and our results highlight that stomatal penetration is a critical process for pathogenicity and resistance. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Linear ß-1,2-glucans trigger immune hallmarks and enhance disease resistance in plants.

Immune responses in plants are triggered by molecular patterns or elicitors, recognized by plant pattern recognition receptors. Such molecular patterns are consequence of host-pathogen interactions and the response cascade activated after their perception is known as pattern-triggered immunity (PTI). Glucans have emerged as key players in PTI, but the ability of certain glucans to stimulate defensive responses in plants remains understudied. This work focused on identifying novel glucan oligosaccharides as molecular patterns. The ability of various microorganism-derived glucans to prompt PTI responses was tested, revealing that specific microbial-derived molecules, such as short linear ß-1,2-glucans, trigger this response in plants by increasing the production of reactive oxygen species (ROS), MAP kinase phosphorylation, and differential expression of defence-related genes in Arabidopsis thaliana. Pretreatments with ß-1,2-glucan trisaccharide (B2G3) improved Arabidopsis defence against bacterial and fungal infections in a hypersusceptible genotype. The knowledge generated was then transferred to the monocotyledonous model species maize and wheat, confirming that these plants also respond to ß-1,2-glucans, with increased ROS production and improved protection against fungal infections following B2G3 pretreatments. In summary, as with other ß-glucans, plants perceive ß-1,2-glucans as warning signals and stimulate defence responses against phytopathogens.

A Review of the Concept of Time Reversal and the Direction of Time.

In the debate about the direction of time in physics, the concept of time reversal has been central. Tradition has it that time-reversal invariant laws are sufficient to state that the direction of time is non-fundamental or emergent. In this paper, we review some of the debates that have gravitated around the concept of time reversal and its relation to the direction of time. We also clarify some of the central concepts involved, showing that the very concept of time reversal is more complex than frequently thought.

The metaphysical underdetermination of time-reversal invariance.

In this paper I argue that the concept of time-reversal invariance in physics suffers from metaphysical underdetermination, that is, that the concept may be understood differently depending on one's metaphysics about time, laws, and a theory's basic properties. This metaphysical under-determinacy also affects subsidiary debates in philosophy of physics that rely on the concept of time-reversal invariance, paradigmatically the problem of the arrow of time. I bring up three cases that, I believe, fairly illustrate my point. I conclude, on the one hand, that any formal representation of time reversal should be explicit about the metaphysical assumptions of the concept that it intends to represent; on the other, that philosophical arguments that rely on time reversal to argue against a direction of time require additional premises.

Humean time-reversal symmetry.

In this paper, we put forward an alternative interpretation of time-reversal symmetry in philosophy of physics: Humean time-reversal symmetry. According to it, time-reversal symmetry is understood as a heuristic, epistemic virtue of the best system, not as a property of the Humean mosaic. One of the consequences of this view is that one of the main arguments against a primitive direction of time is rendered harmless, which paves the way for primitivism about the direction of time.

A genetic approach reveals different modes of action of prefoldins.

The prefoldin complex (PFDc) was identified in humans as a co-chaperone of the cytosolic chaperonin T-COMPLEX PROTEIN RING COMPLEX (TRiC)/CHAPERONIN CONTAINING TCP-1 (CCT). PFDc is conserved in eukaryotes and is composed of subunits PFD1-6, and PFDc-TRiC/CCT folds actin and tubulins. PFDs also participate in a wide range of cellular processes, both in the cytoplasm and in the nucleus, and their malfunction causes developmental alterations and disease in animals and altered growth and environmental responses in yeast and plants. Genetic analyses in yeast indicate that not all of their functions require the canonical complex. The lack of systematic genetic analyses in plants and animals, however, makes it difficult to discern whether PFDs participate in a process as the canonical complex or in alternative configurations, which is necessary to understand their mode of action. To tackle this question, and on the premise that the canonical complex cannot be formed if one subunit is missing, we generated an Arabidopsis (Arabidopsis thaliana) mutant deficient in the six PFDs and compared various growth and environmental responses with those of the individual mutants. In this way, we demonstrate that the PFDc is required for seed germination, to delay flowering, or to respond to high salt stress or low temperature, whereas at least two PFDs redundantly attenuate the response to osmotic stress. A coexpression analysis of differentially expressed genes in the sextuple mutant identified several transcription factors, including ABA INSENSITIVE 5 (ABI5) and PHYTOCHROME-INTERACTING FACTOR 4, acting downstream of PFDs. Furthermore, the transcriptomic analysis allowed assigning additional roles for PFDs, for instance, in response to higher temperature.

Prefoldins contribute to maintaining the levels of the spliceosome LSM2-8 complex through Hsp90 in Arabidopsis.

Although originally identified as the components of the complex aiding the cytosolic chaperonin CCT in the folding of actins and tubulins in the cytosol, prefoldins (PFDs) are emerging as novel regulators influencing gene expression in the nucleus. Work conducted mainly in yeast and animals showed that PFDs act as transcriptional regulators and participate in the nuclear proteostasis. To investigate new functions of PFDs, we performed a co-expression analysis in Arabidopsis thaliana. Results revealed co-expression between PFD and the Sm-like (LSM) genes, which encode the LSM2-8 spliceosome core complex, in this model organism. Here, we show that PFDs interact with and are required to maintain adequate levels of the LSM2-8 complex. Our data indicate that levels of the LSM8 protein, which defines and confers the functional specificity of the complex, are reduced in pfd mutants and in response to the Hsp90 inhibitor geldanamycin. We provide biochemical evidence showing that LSM8 is a client of Hsp90 and that PFD4 mediates the interaction between both proteins. Consistent with our results and with the role of the LSM2-8 complex in splicing through the stabilization of the U6 snRNA, pfd mutants showed reduced levels of this snRNA and altered pre-mRNA splicing patterns.

Swimmers Heal on the Move Following Catastrophic Damage.

Herein, we describe the development of 2D self-healing small-scale swimmers capable of autonomous propulsion and "on-the-fly" structural recovery in large containers. Incorporation of magnetic Nd2Fe14B microparticles in specialized printed strips results in rapid reorientation and reattachment of the moving tail to its complementary broken static piece to restore the original swimmer structure and propulsion behavior. The swimmers display functional recovery independent of user input. Measurements of the magnetic hysteresis and fields were used to assess the behavior of the healing mechanism in real swimming situations. Damage position and multiple magnetic strip patterns have been examined and their influence upon the recovery efficiency has been compared. Owing to its versatility, fast response, and simplicity the new self-healing strategy represents an important step toward the development of new "on-the-fly" repairing strategies for small-scale swimmers and robots.

Connective Tissue Graft vs Platelet-rich Fibrin in the Treatment of Gingival Recessions: A Randomized Split-mouth Case Series.

AIM AND OBJECTIVE: Coronally advanced flap (CAF) with connective tissue graft (CTG) has been considered the gold standard for obtaining complete root coverage. However, some limitations have been reported with the use of CTG, especially because it increases morbidity and leads to postoperative pain and bleeding. Recently, platelet-rich fibrin (PRF) has been used in periodontal plastic surgery for the treatment of gingival recessions (GRs). The aim of this study was to evaluate the outcome of PRF combined with a CAF (test) compared to de-epithelialized connective tissue graft (DeCTG) + CAF (control) for GR coverage. MATERIALS AND METHODS: Ten healthy patients exhibiting mandibular or maxillary Miller class I and II were treated with PRF + CAF or DeCTG + CAF. GR, probing depth (PD), and gingival thickness (GT) were evaluated at baseline, 6 weeks, and 28 weeks postoperatively. RESULTS: GR, PD, and GT differences between the test and control groups at 28 weeks were not statistically significant. GR was 3.30 ± 1.25 mm and 3.00 ± 1.63 mm (control vs test) group (baseline) and -0.10 ± 0.32 vs -0.20 ± 0.42 mm (7 months), respectively. CONCLUSION: Within the limitations of the present study, it can be concluded that localized gingival recessions could be successfully treated with CAF + PRF or CAF + DeCTG. CLINICAL SIGNIFICANCE: This study suggests that PRF membrane may be an alternative and valid graft material for treating localized gingival recessions Miller class I and II.

The LSM1-7 Complex Differentially Regulates Arabidopsis Tolerance to Abiotic Stress Conditions by Promoting Selective mRNA Decapping.

In eukaryotes, the decapping machinery is highly conserved and plays an essential role in controlling mRNA stability, a key step in the regulation of gene expression. Yet, the role of mRNA decapping in shaping gene expression profiles in response to environmental cues and the operating molecular mechanisms are poorly understood. Here, we provide genetic and molecular evidence that a component of the decapping machinery, the LSM1-7 complex, plays a critical role in plant tolerance to abiotic stresses. Our results demonstrate that, depending on the stress, the complex from Arabidopsis thaliana interacts with different selected stress-inducible transcripts targeting them for decapping and subsequent degradation. This interaction ensures the correct turnover of the target transcripts and, consequently, the appropriate patterns of downstream stress-responsive gene expression that are required for plant adaptation. Remarkably, among the selected target transcripts of the LSM1-7 complex are those encoding NCED3 and NCED5, two key enzymes in abscisic acid (ABA) biosynthesis. We demonstrate that the complex modulates ABA levels in Arabidopsis exposed to cold and high salt by differentially controlling NCED3 and NCED5 mRNA turnover, which represents a new layer of regulation in ABA biosynthesis in response to abiotic stress. Our findings uncover an unanticipated functional plasticity of the mRNA decapping machinery to modulate the relationship between plants and their environment.

Environment-dependent regulation of spliceosome activity by the LSM2-8 complex in Arabidopsis.

Spliceosome activity is tightly regulated to ensure adequate splicing in response to internal and external cues. It has been suggested that core components of the spliceosome, such as the snRNPs, would participate in the control of its activity. The experimental indications supporting this proposition, however, remain scarce, and the operating mechanisms poorly understood. Here, we present genetic and molecular evidence demonstrating that the LSM2-8 complex, the protein moiety of the U6 snRNP, regulates the spliceosome activity in Arabidopsis, and that this regulation is controlled by the environmental conditions. Our results show that the complex ensures the efficiency and accuracy of constitutive and alternative splicing of selected pre-mRNAs, depending on the conditions. Moreover, miss-splicing of most targeted pre-mRNAs leads to the generation of nonsense mediated decay signatures, indicating that the LSM2-8 complex also guarantees adequate levels of the corresponding functional transcripts. Interestingly, the selective role of the complex has relevant physiological implications since it is required for adequate plant adaptation to abiotic stresses. These findings unveil an unanticipated function for the LSM2-8 complex that represents a new layer of posttranscriptional regulation in response to external stimuli in eukaryotes.

Intraoperative Indocyanine Green Angiography for Fat Necrosis Reduction in the Deep Inferior Epigastric Perforator (DIEP) Flap.

BACKGROUND: Fat necrosis is a frequent complication (up to 62.5%) of microsurgical breast reconstruction using the deep inferior epigastric perforator (DIEP) flap. This could have important clinical and psychological repercussions, deteriorating the results and increasing reconstruction costs. OBJECTIVES: The aim of this study was to demonstrate the intraoperative use of indocyanine green angiography (ICGA) to reduce fat necrosis in DIEP flap. METHODS: Sixty-one patients who underwent unilateral DIEP flap procedures for breast reconstruction after oncological mastectomy were included (24 cases with intraoperative use of ICGA during surgery, 37 cases in the control group). The follow-up period was 1 year after surgery. The association between the use of ICGA and the incidence of fat necrosis in the first postoperative year, differences in fat necrosis grade (I-V), differences in fat necrosis requiring reoperation, quality of life, and patient satisfaction were analyzed. RESULTS: The incidence of fat necrosis was reduced from 59.5% (control group) to 29% (ICG-group) (P = 0.021) (relative risk = 0.49 [95% CI, 0.25-0.97]). The major difference was in grade II (27% vs 2.7%, P = 0.038). The number of second surgeries for fat necrosis treatment was also reduced (45.9% vs 20.8%, P = 0.046). The ICG group had higher scores on the BREAST-Q. CONCLUSIONS: Intraoperative ICGA is a useful technique for reconstructive microsurgery that might improve patient satisfaction and reduce the incidence of fat necrosis by half as well as reduce its grade, especially in small fat necrosis cases; consequently, ICGA could reduce the number of secondary surgeries for treatment of fat necrosis.

No communication without manipulation: A causal-deflationary view of information.

In this paper, we shall describe a new account of information in communicational contexts, namely, a causal-deflationary one. Our approach draws from Timpson's deflationary view and supplies the field of philosophy of information with new tools that will help to clarify the underlying structure of communication: information is an abstract entity that must be involved in a causal link in order to achieve communication. In light of our account, communication is not merely the existence of statistical correlations between source and receiver, as usually understood from a purely formal view. Instead, communication is an asymmetric phenomenon involving causal notions: the destination system must be able to be causally manipulated by intervening on the source for successful communication. In a nutshell, we shall support the following lemma: no communication without manipulation.

Noninvasive Transdermal Delivery System of Lidocaine Using an Acoustic Droplet-Vaporization Based Wearable Patch.

Current technologies for managing acute and chronic pain have focused on reducing the time required for achieving high therapeutic efficiency. Herein a wearable transdermal patch is introduced, employing an acoustic droplet vaporization (ADV) methodology, as an effective noninvasive transdermal platform, for a fast local delivery of the anesthetic agent lidocaine. The skin-worn patch consists of a flexible drug reservoir containing hundreds of micropores loaded with lidocaine, and mixed with the perfluorocarbon (PFC) emulsion. The ultrasound-triggered vaporization of the PFC emulsion provides the necessary force to breach dermal barriers. The drug release kinetics of our model was investigated by measuring the amount of lidocaine that passed through phantom tissue and pigskin barriers. The ADV platform increases the payload skin penetration resulting in shorter treatment times compared to passive diffusion or ultrasound alone, holding considerable promise for addressing the delayed therapeutic action and slow pain relief of existing delivery protocols. It is envisioned that the integration of ADV-based transdermal devices could be expanded to the depth-dependent delivery of other pain management, vaccines, and gene therapy modalities.

Synthesis and Characterization of Poly(Vinyl Alcohol)-Chitosan-Hydroxyapatite Scaffolds: A Promising Alternative for Bone Tissue Regeneration.

Scaffolds can be considered as one of the most promising treatments for bone tissue regeneration. Herein, blends of chitosan, poly(vinyl alcohol), and hydroxyapatite in different ratios were used to synthesize scaffolds via freeze-drying. Mechanical tests, FTIR, swelling and solubility degree, DSC, morphology, and cell viability were used as characterization techniques. Statistical significance of the experiments was determined using a two-way analysis of variance (ANOVA) with p < 0.05. Crosslinked and plasticized scaffolds absorbed five times more water than non-crosslinked and plasticized ones, which is an indicator of better hydrophilic features, as well as adequate resistance to water without detriment of the swelling potential. Indeed, the tested mechanical properties were notably higher for samples which were undergone to crosslinking and plasticized process. The presence of chitosan is determinant in pore formation and distribution which is an imperative for cell communication. Uniform pore size with diameters ranging from 142 to 519 µm were obtained, a range that has been described as optimal for bone tissue regeneration. Moreover, cytotoxicity was considered as negligible in the tested conditions, and viability indicates that the material might have potential as a bone regeneration system.

What Does 'Information' Mean in Integrated Information Theory?

Integrated Information Theory (IIT) intends to provide a principled theoretical approach able to characterize consciousness both quantitatively and qualitatively. By starting off identifying the fundamental properties of experience itself, IIT develops a formal framework that relates those properties to the physical substratum of consciousness. One of the central features of ITT is the role that information plays in the theory. On the one hand, one of the self-evident truths about consciousness is that it is informative. On the other hand, mechanisms and systems of mechanics can contribute to consciousness only if they specify systems' intrinsic information. In this paper, we will conceptually analyze the notion of information underlying ITT. Following previous work on the matter, we will particularly argue that information within ITT should be understood in the light of a causal-manipulabilist view of information (López and Lombardi 2018), conforming to which information is an entity that must be involved in causal links in order to be precisely defined. Those causal links are brought to light by means of interventionist procedures following Woodward's and Pearl's version of the manipulability theories of causation.

Outcomes of Gastro-omental Free Flap Reconstruction for Salvage Laryngopharyngectomy for Pharyngeal and Laryngeal Cancer After Concurrent Chemoradiotherapy.

BACKGROUND: In the case of salvage laryngopharyngectomy, replacement of the pharyngoesophageal segment is mostly performed with fasciocutaneous or jejunal flaps. However, these options do not represent the best surgical technique of reconstruction in some occasions. Thus, the gastro-omental free flap could serve as an alternative procedure. METHODS: A retrospective review was conducted on patients who underwent pharyngoesophageal reconstruction using gastro-omental free flap after salvage laryngopharyngectomy for recurrent pharyngeal or laryngeal carcinoma between 1992 and 2012 at Bellvitge Universitary Hospital. The perioperative morbidity, mortality, functional outcomes, and oncological outcomes were evaluated. RESULTS: Twenty-six patients were included and followed up at our hospital for a mean of 43.4 months (range, 12-184 months). Survival rate was 94% after 1-year follow-up and 89% after 3 years. Abdominal evisceration was observed in 2 cases, whereas no abdominal complications occurred to the other patients. Total flap necrosis was observed in 3 (11.5%) patients. Postoperative course was uneventful in 20 patients. Moreover, esophageal continuity without fistula was confirmed by barium swallow test. CONCLUSIONS: The gastro-omental flap represents a useful method for reconstruction of the pharyngoesophageal segment in a surgical field compromised by previous multimodal therapy. Despite being useful, the complication rate is relevant.

Anterior intercostal artery perforator flap in immediate breast reconstruction: Anatomical study and clinical application.

BACKGROUND: Although the use of lateral intercostal artery perforator (ICAP) flaps for immediate breast reconstruction has been widely described, data on the use of the anterior ICAP (AICAP) flaps for this indication are limited. In this context, we describe the results of anatomical study and our clinical experience with AICAP flaps for breast reconstruction. METHODS: In this study, the location and characteristics of the AICAPs were dissected in 12 female adult formalin-preserved hemitrunks and two fresh-frozen cadavers. Fourteen patients (mean BMI 23) underwent partial breast resection for a quadrant breast cancer followed by breast reconstruction with an intercostal perforator flap. The mean resection size was 6 × 5 × 5.5 cm (range 3-8 × 3.5-7 × 4-8 cm).The main outcome measures were pre-operative and postradiotherapy health-related quality of life assessed with the BREAST-Q reconstruction survey. RESULTS: According to anatomical study, at least one perforator was found in each third of hemitrunks dissected. The mean of perforator size was in diameter 0.42 ± 0.05 mm and in length 3.1 ± 0.36 cm. In clinical outcomes, the mean of flap size was 16 × 5 × 3 cm (range 14-19 × 3-8 × 2-5 cm). The mean surgical time was 120 min (range 109-125 min). Only one partial flap failure was detected. No postoperative changes in breast size were observed, although soft tissue changes were observed in four patients after radiotherapy. The mean BREAST-Q scores changes were 0 in satisfaction with the breast, 5 in satisfaction with outcome, 0 in psychosocial well-being, 6.15 in sexual well being, and 34.69 in physical well-being. CONCLUSIONS: Based on this anatomical and clinical study, we found AICAP flap has a consistent vascularization with good perforators. And moreover, it is suitable for partial breast reconstruction (quadrantectomy) and does not appear to negatively impact patient satisfaction.

Use of fibula flaps to treat persistent talonavicular nonunion: A report of three cases.

Owing to the limited blood supply in the midfoot, multiple arthrodesis attempts in midfood joints may result in severe osteonecrosis, leading to a difficult scenario for bone reconstruction. This article describes the use of fibula flaps (two free and one pedicled flap) to reconstruct bone defects in three cases of persistent nonunion in midfoot joints. Before admission, all patients (aged 32-56 years old) had undergone multiple arthrodesis attempts (range 3-4) aimed at treating joint diseases associated with flatfoot or Müller-Weiss syndrome. All inserted flaps were stable, and bone fusion was confirmed by X-ray examination at month 4. After the follow-up period (range 1-4 years), all patients showed normal, painless gait. No foot deformities or further complications were observed. Our report suggests that fibula flap transfer may be a good alternative for treating persistent nonunion in midfoot joints involving bone loss, and may prevent the osteonecrosis associated with limited blood supply. © 2016 Wiley Periodicals, Inc. Microsurgery 36:430-434, 2016.