Lax eyelid condition (LEC) and floppy eyelid syndrome (FES) prevalence in obstructive sleep apnea syndrome (OSA) patients: a systematic review and meta-analysis.

PURPOSE: Lax eyelid condition (LEC) and floppy eyelid syndrome (FES) represent two distinct conditions which have been associated with several ocular and systemic comorbidities. The main aim of this systematic review and meta-analysis is to explore the available literature to estimate the prevalence rate of LEC and FES in obstructive sleep apnea (OSA). METHODS: The protocol of this systematic review and meta-analysis has been registered in PROSPERO. Four electronic databases (PubMed/MEDLINE, Google Scholar, Cochrane Library, Web of Science) were searched from inception to December 24, 2021. A random intercept logistic regression model was carried out for the analysis of overall proportions. Odds ratio and mean difference were reported as measures of the effect size in the presence of binary and continuous outcomes, respectively. The estimated numbers of LEC/FES patients in OSA were calculated by multiplying the prevalence rate determined by our random-effects model and the corresponding Benjafield et al.'s population prospect. RESULTS: We included 11 studies comprising 1225 OSA patients of whom 431 and 153 affected by LEC and FES, respectively. Our model estimated a pooled prevalence rate for LEC and FES in OSA patients of 40.2% (95%CI: 28.6-53.1%) and of 22.4% (95%CI: 13.8-34.2%), respectively. The number of LEC/FES affected individuals among OSA patients is expected to peak up to 376 and to 210 million, respectively. OSA patients appeared to have a 3.4 (95%CI: 2.2-5.2) and a 3.0 (95%CI: 1.7-5.5) increased risk of developing LEC and FES than the healthy counterpart. CONCLUSION: Prevalence of LEC and FES is higher in OSA-affected patients compared to controls. More studies are warranted to investigate the mechanisms leading to the development of LEC and/or FES in OSA patients, as well as the feasibility of the adoption of these clinical findings as screening tools for OSA.

Symplectic Geometry Aspects of the Parametrically-Dependent Kardar-Parisi-Zhang Equation of Spin Glasses Theory, Its Integrability and Related Thermodynamic Stability.

A thermodynamically unstable spin glass growth model described by means of the parametrically-dependent Kardar-Parisi-Zhang equation is analyzed within the symplectic geometry-based gradient-holonomic and optimal control motivated algorithms. The finitely-parametric functional extensions of the model are studied, and the existence of conservation laws and the related Hamiltonian structure is stated. A relationship of the Kardar-Parisi-Zhang equation to a so called dark type class of integrable dynamical systems, on functional manifolds with hidden symmetries, is stated.

Panicle Apical Abortion 7 Regulates Panicle Development in Rice (Oryza sativa L.).

The number of grains per panicle significantly contributes to rice yield, but the regulatory mechanism remains largely unknown. Here, we reported a loss-of-function mutant, panicle apical abortion 7 (paa7), which exhibited panicle abortion and degeneration of spikelets on the apical panicles during the late stage of young panicle development in rice. High accumulations of H2O2 in paa7 caused programmed cell death (PCD) accompanied by nuclear DNA fragmentation in the apical spikelets. Map-based cloning revealed that the 3 bp "AGC" insertion and 4 bp "TCTC" deletion mutation of paa7 were located in the 3'-UTR regions of LOC_Os07g47330, which was confirmed through complementary assays and overexpressed lines. Interestingly, LOC_Os07g47330 is known as FRIZZY PANICLE (FZP). Thus, PAA7 could be a novel allele of FZP. Moreover, the severe damage for panicle phenotype in paa7/lax2 double mutant indicated that PAA7 could crosstalk with Lax Panicle 2 (LAX2). These findings suggest that PAA7 regulates the development of apical spikelets and interacts with LAX2 to regulate panicle development in rice.

Cure of Interstitial Cystitis and Non-Ulcerating Hunner's Ulcer by Cardinal/Uterosacral Ligament Repair.

A serendipitous cure in a 73-year-old woman of Hunner's ulcer, urge, nocturia, apical prolapse by a tissue fixation system tensioned minisling (TFS) which reinforced the cardinal, and uterosacral ligaments (USLs) led us to analyse the relationship between Hunner's ulcer and known pain conditions associated with USL laxity. The original intention was to cure the "posterior fornix syndrome" (PFS), uterine prolapse, and associated pain and bladder symptoms by USL repair. A speculum inserted preoperatively into the posterior fornix alleviated pain and urge symptoms, by mechanically supporting USLs. Hunner's ulcer, along with pain and other PFS symptoms were cured by USL repair. The concept of USL laxity causing chronic pelvic pain and bladder problems is not new. It was published in the German literature by Heinrich Martius in 1938 and by Petros in the English literature in 1993. These findings raise important questions. As PFS symptoms are identical with those of interstitial cystitis (IC), are PFS and IC similar conditions? If so, then patients with IC who have a positive speculum test are at least theoretically, potentially curable by USL repair. These questions need to be explored.

Arabidopsis and sunflower plants with increased xylem area show enhanced seed yield.

Plant architecture plasticity determines the efficiency at harvesting and plays a major role defining biomass and seed yield. We observed that several previously described transgenic genotypes exhibiting increased seed yield also show wider stems and more vascular bundles than wild-type plants. Here, the relationship between these characteristics and seed yield was investigated. Hanging weight on the main stem of Arabidopsis plants provoked significant stem widening. Such widening was accompanied by an increase in the number of vascular bundles and about 100% of yield increase. In parallel, lignin deposition diminished. Vascular bundle formation started in the upper internode and continued downstream. AUX/LAX carriers were essential for this response. The increase of vascular bundles was reverted 3 weeks after the treatment leading to an enlarged xylem area. Aux1, lax1, and lax3 mutant plants were also able to enlarge their stems after the treatment, whereas lax2 plants did not. However, none of these mutants exhibited more vascular bundles or seed yield compared with untreated plants. Weight-induced xylem area enhancement and increased seed yield were also observed in sunflower plants. Altogether these results showed a strong correlation between the number of vascular bundles and enhanced seed yield under a long-day photoperiod. Furthermore, changes in the levels of auxin carriers affected both these processes in the same manner, suggesting that there may be an underlying causality.

AtHB23 participates in the gene regulatory network controlling root branching, and reveals differences between secondary and tertiary roots.

In Arabidopsis, lateral root (LR) development is mainly controlled by several known auxin-regulated transcription factors (TFs). Here, we show that AtHB23 (a homeodomain-leucine zipper I TF) participates in this intricate network. Our study of the expression pattern of AtHB23 revealed that it is transcriptionally activated in the early stages of secondary LR primordium (LRP). We found that AtHB23 directly limits the expression of LBD16, a key factor in LR initiation, and also directly induces the auxin transporter gene LAX3. We propose that this HD-Zip I mediates the regulation of LAX3 by ARF7/19. Furthermore, AtHB23 plays distinct roles during the formation of secondary and tertiary roots, exhibiting differential expression patterns. ATHB23 is expressed throughout the tertiary root primordium, whereas it is restricted to early stages in secondary primordia, likely later repressing LBD16 in tertiary LR development and further inhibiting root emergence. Our results suggest that different genetic programs govern the formation of LRP from the main or secondary roots, thereby shaping the global dynamic architecture of the root system.

Transcription of specific auxin efflux and influx carriers drives auxin homeostasis in tobacco cells.

Auxin concentration gradients are informative for the transduction of many developmental cues, triggering downstream gene expression and other responses. The generation of auxin gradients depends significantly on cell-to-cell auxin transport, which is supported by the activities of auxin efflux and influx carriers. However, at the level of individual plant cell, the co-ordination of auxin efflux and influx largely remains uncharacterized. We addressed this issue by analyzing the contribution of canonical PIN-FORMED (PIN) proteins to the carrier-mediated auxin efflux in Nicotiana tabacum L., cv. Bright Yellow (BY-2) tobacco cells. We show here that a majority of canonical NtPINs are transcribed in cultured cells and in planta. Cloning of NtPIN genes and their inducible overexpression in tobacco cells uncovered high auxin efflux activity of NtPIN11, accompanied by auxin starvation symptoms. Auxin transport parameters after NtPIN11 overexpression were further assessed using radiolabelled auxin accumulation and mathematical modelling. Unexpectedly, these experiments showed notable stimulation of auxin influx, which was accompanied by enhanced transcript levels of genes for a specific auxin influx carrier and by decreased transcript levels of other genes for auxin efflux carriers. A similar transcriptional response was observed upon removal of auxin from the culture medium, which resulted in decreased auxin efflux. Overall, our results revealed an auxin transport-based homeostatic mechanism for the maintenance of endogenous auxin levels. OPEN RESEARCH BADGES: This article has earned an Open Data Badge for making publicly available the digitally-shareable data necessary to reproduce the reported results. The data is available at http://osf.io/ka97b/.

The evolutionary origins of auxin transport: what we know and what we need to know.

Auxin, represented by indole-3-acetic acid (IAA), has for a long time been studied mainly with respect to the development of land plants, and recent evidence confirms that canonical nuclear auxin signaling is a land plant apomorphy. Increasing sequential and physiological data show that the presence of auxin transport machinery pre-dates the emergence of canonical signaling. In this review, we summarize the present state of knowledge regarding the origins of auxin transport in the green lineage (Viridiplantae), integrating both data from wet lab experiments and sequence evidence on the presence of PIN-FORMED (PIN), PIN-LIKES (PILS), and AUXIN RESISTANT 1/LIKE-AUX1 (AUX1/LAX) homologs. We discuss a high divergence of auxin carrier homologs among algal lineages and emphasize the urgent need for the establishment of good molecular biology models from within the streptophyte green algae. We further postulate and discuss two hypotheses for the ancestral role of auxin in the green lineage. First, auxin was present as a by-product of cell metabolism and the evolution of its transport was stimulated by the need for IAA sequestration and cell detoxification. Second, auxin was primarily a signaling compound, possibly of bacterial origin, and its activity in the pre-plant green algae was a consequence of long-term co-existence with bacteria in shared ecological consortia.

Potassium Stimulation of IAA Transport Mediated by the Arabidopsis Importer AUX1 Investigated in a Heterologous Yeast System.

Auxin regulates diverse processes involved in plant growth and development. AUX1 is the first identified and most widely investigated auxin importer, and plays an important role in root gravitropism and the development of lateral root and root hair. However, the regulation of auxin transport by AUX1 is still not well understood. In this study, we examined the effect of metal ions on AUX1 transport function and found that the activity could be specifically stimulated four times by K+. Further experiments revealed the preference of KF on the enhancement of transport activity of AUX1 over KCl, KBr, and KI. In addition, the interaction between K+ and AUX1 confers AUX1 more resistant to thermal stress but more vulnerable to proteolysis. Conventional chemical modification indicated that the extracellular acidic amino acids of AUX1 play a key role in the K+ stimulation. Site-specific mutagenesis showed that the replacement of Asp166, Asp293, and Asp312 of AUX1 to alanine deteriorated the K+-stimulated auxin transport. By contrast, when these residues were mutated to glutamate, lysine, or asparagine, only the D312E variant restored the IAA transport activity to the wild-type level. It is thus convinced that D312 is presumably the most promising residue for the K+ stimulation on AUX1.

Evaluating the Long-, Short-, and Oblique-Axis Approaches for Ultrasound-Guided Vascular Access Cannulation.

BACKGROUND: Our goal was to conduct a network meta-analysis of randomized controlled trials to compare the effects of the long-axis (LAX), short-axis (SAX), and oblique-axis (OAX) ultrasound guidance approaches for vascular access cannulation. METHODS: We searched 5 databases, including the Cochrane Central Register of Controlled Trials in the Cochrane Library, Embase, MEDLINE, CINAHL, and Web of Science. Seven randomized clinical trials assessing ultrasound guidance for vascular access cannulation via the LAX, SAX, or OAX approach were included. The primary end point was the first-pass success rate. Secondary end points included the mean time to success and average number of attempts until success. We used random-effects models to calculate weighted mean differences with 95% confidence intervals for continuous outcomes and relative risks with 95% confidence intervals for dichotomous outcomes. RESULTS: There were no significant differences between the LAX, SAX, and OAX techniques with respect to the first-pass success rate, mean time to success, average number of attempts until success, or the incidence of hematoma. CONCLUSION: There was insufficient evidence to definitively recommend the LAX, SAX, or OAX approach for patients undergoing ultrasound-guided vascular access cannulation.

Plant embryogenesis requires AUX/LAX-mediated auxin influx.

The plant hormone auxin and its directional transport are known to play a crucial role in defining the embryonic axis and subsequent development of the body plan. Although the role of PIN auxin efflux transporters has been clearly assigned during embryonic shoot and root specification, the role of the auxin influx carriers AUX1 and LIKE-AUX1 (LAX) proteins is not well established. Here, we used chemical and genetic tools on Brassica napus microspore-derived embryos and Arabidopsis thaliana zygotic embryos, and demonstrate that AUX1, LAX1 and LAX2 are required for both shoot and root pole formation, in concert with PIN efflux carriers. Furthermore, we uncovered a positive-feedback loop between MONOPTEROS (ARF5)-dependent auxin signalling and auxin transport. This MONOPTEROS-dependent transcriptional regulation of auxin influx (AUX1, LAX1 and LAX2) and auxin efflux (PIN1 and PIN4) carriers by MONOPTEROS helps to maintain proper auxin transport to the root tip. These results indicate that auxin-dependent cell specification during embryo development requires balanced auxin transport involving both influx and efflux mechanisms, and that this transport is maintained by a positive transcriptional feedback on auxin signalling.

Auxin enhances grafting success in Carya cathayensis (Chinese hickory).

MAIN CONCLUSION: Application of auxin to root stock and scion increases the success rate of grafting in Chinese hickory. The nuts of the Chinese hickory (Carya cathayensis) tree are considered both delicious and healthy. The popularity and high demand result is that the hickory nuts are of very high economical value for horticulture. This is particularly true for the Zhejiang province in eastern China where this tree is widely cultivated. However, there are several difficulties surrounding the hickory cultivation, such as for example long vegetative growth, tall trees, labour-intensive nut picking, and slow variety improvements. These complications form a great bottleneck in the expansion of the hickory industry. The development of an efficient grafting procedure could surpass at least some of these problems. In this study, we demonstrate that application of the auxin indole-3-acetic acid promotes the grafting process in hickory, whereas application of the auxin transport inhibitor 1-N-naphthylphthalamic acid inhibits the grafting process. Furthermore, we have identified hickory genes in the PIN, ABCB, and AUX/LAX-families known to encode influx and efflux carriers in the polar transport of auxin. We show that increased expression of several of these genes, such as CcPIN1b and CcLAX3, is correlating with successful grafting.

Genome-wide identification and expression analysis of the CaLAX and CaPIN gene families in pepper (Capsicum annuum L.) under various abiotic stresses and hormone treatments.

Auxin plays key roles in regulating plant growth and development as well as in response to environmental stresses. The intercellular transport of auxin is mediated by the following four gene families: ATP-binding cassette family B (ABCB), auxin resistant1/like aux1 (AUX/LAX), PIN-formed (PIN), and PIN-like (PILS). Here, the latest assembled pepper (Capsicum annuum L.) genome was used to characterise and analyse the CaLAX and CaPIN gene families. Genome-wide investigations into these families, including chromosomal distributions, phytogenic relationships, and intron/exon structures, were performed. In total, 4 CaLAX and 10 CaPIN genes were mapped to 10 chromosomes. Most of these genes exhibited varied tissue-specific expression patterns assessed by quantitative real-time PCR. The expression profiles of the CaLAX and CaPIN genes under various abiotic stresses (salt, drought, and cold), exogenous phytohormones (IAA, 6-BA, ABA, SA, and MeJA), and polar auxin transport inhibitor treatments were evaluated. Most CaLAX and CaPIN genes were altered by abiotic stress at the transcriptional level in both shoots and roots, and many CaLAX and CaPIN genes were regulated by exogenous phytohormones. Our study helps to identify candidate auxin transporter genes and to further analyse their biological functions in pepper development and in its adaptation to environmental stresses.

Should Authors be Requested to Suggest Peer Reviewers?

As part of a continuous process to explore the factors that might weaken or corrupt traditional peer review, in this paper, we query the ethics, fairness and validity of the request, by editors, of authors to suggest peer reviewers during the submission process. One of the reasons for the current crisis in science pertains to a loss in trust as a result of a flawed peer review which is by nature biased unless it is open peer review. As we indicate, the fact that some editors and journals rely on authors' suggestions in terms of who should peer review their paper already instills a potential way to abuse the trust of the submission and publishing system. An author-suggested peer reviewer choice might also tempt authors to seek reviewers who might be more receptive or sympathetic to the authors' message or results, and thus favor the outcome of that paper. Authors should thus not be placed in such a potentially ethically compromising situation, especially as a mandatory condition for submission. However, the fact that they do not have an opt-out choice during the submission process-especially when using an online submission system that makes such a suggestion compulsory-may constitute a violation of authors' rights.

Generalizations of the short pulse equation.

We classify integrable scalar polynomial partial differential equations of second order generalizing the short pulse equation.

Genome-wide identification and expression analysis of ClLAX, ClPIN and ClABCB genes families in Citrullus lanatus under various abiotic stresses and grafting.

BACKGROUND: Auxin plays an important role in regulating plant growth and development as well as in the response of plants to abiotic stresses. Auxin is transported by three kinds of major protein families, including the AUXIN RESISTANT 1/LIKE AUX1 (AUX/LAX) influx carriers, the PIN-FORMED (PIN) efflux carriers and the ATP binding cassette B/P-glycoprotein/Multidrug-resistance (ABCB/MDR/PGP) efflux/condition carriers. The biological function of several auxin transporter genes has been well characterized in Arabidopsis thaliana. However, their function in response to exogenous auxin and abiotic stresses in watermelon (Citrullus lanatus. L) remained unknown. RESULTS: Here, the latest updated watermelon genome was used to characterise the ClLAX, ClPIN and ClABCB family genes from watermelon. The genome-wide analysis of the ClLAX, ClPIN and ClABCB family genes, including chromosome localisation, gene structure, and phylogenic relationships, was carried out. Seven ClLAXs, 11 ClPINs and 15 ClABCBs were mapped on 10 watermelon chromosomes. The expression profiles of the ClLAX, ClPIN and ClABCB genes under exogenous indole-3-acetic acid and various abiotic stresses (salt, drought, and cold stresses) treatments were performed by quantitative real-time PCR (qRT-PCR). The transcriptional level of majority ClLAX, ClPIN and ClABCB genes were changed by abiotic stresses in both shoots and roots. We also analysed the expression levels of ClLAX, ClPIN and ClABCB genes in graft response. CONCLUSION: Analysis of the expression patterns of ClLAX, ClPIN and ClABCB genes under salt, drought, cold treatment and grafting response helps us to understand the possible roles of auxin transporter genes in watermelon adaptation to environmental stresses.

A role for LAX2 in regulating xylem development and lateral-vein symmetry in the leaf.

Background and Aims: The symmetry of venation patterning in leaves is highly conserved within a plant species. Auxins are involved in this process and also in xylem vasculature development. Studying transgenic Arabidopsis plants ectopically expressing the sunflower transcription factor HaHB4, it was observed that there was a significant lateral-vein asymmetry in leaves and in xylem formation compared to wild type plants. To unravel the molecular mechanisms behind this phenotype, genes differentially expressed in these plants and related to auxin influx were investigated. Methods: Candidate genes responsible for the observed phenotypes were selected using a co-expression analysis. Single and multiple mutants in auxin influx carriers were characterized by morphological, physiological and molecular techniques. The analysis was further complemented by restoring the wild type (WT) phenotype by mutant complementation studies and using transgenic soybean plants ectopically expressing HaHB4 . Key Results: LAX2 , down-regulated in HaHB4 transgenic plants, was bioinformatically chosen as a candidate gene. The quadruple mutant aux1 lax1 lax2 lax3 and the single mutants, except lax1, presented an enhanced asymmetry in venation patterning. Additionally, the xylem vasculature of the lax2 mutant and the HaHB4 -expressing plants differed from the WT vasculature, including increased xylem length and number of xylem cell rows. Complementation of the lax2 mutant with the LAX2 gene restored both lateral-vein symmetry and xylem/stem area ratio in the stem, showing that auxin homeostasis is required to achieve normal vascular development. Interestingly, soybean plants ectopically expressing HaHB4 also showed an increased asymmetry in the venation patterning, accompanied by the repression of several GmLAX genes. Conclusions: Auxin influx carriers have a significant role in leaf venation pattering in leaves and, in particular, LAX2 is required for normal xylem development, probablt controlling auxin homeostasis.

Redirection of auxin flow in Arabidopsis thaliana roots after infection by root-knot nematodes.

Plant-parasitic root-knot nematodes induce the formation of giant cells within the plant root, and it has been recognized that auxin accumulates in these feeding sites. Here, we studied the role of the auxin transport system governed by AUX1/LAX3 influx proteins and different PIN efflux proteins during feeding site development in Arabidopsis thaliana roots. Data generated via promoter-reporter line and protein localization analyses evoke a model in which auxin is being imported at the basipetal side of the feeding site by the concerted action of the influx proteins AUX1 and LAX3, and the efflux protein PIN3. Mutants in auxin influx proteins AUX1 and LAX3 bear significantly fewer and smaller galls, revealing that auxin import into the feeding sites is needed for their development and expansion. The feeding site development in auxin export (PIN) mutants was only slightly hampered. Expression of some PINs appears to be suppressed in galls, probably to prevent auxin drainage. Nevertheless, a functional PIN4 gene seems to be a prerequisite for proper nematode development and gall expansion, most likely by removing excessive auxin to stabilize the hormone level in the feeding site. Our data also indicate a role of local auxin peaks in nematode attraction towards the root.

Mitogen Activated Protein Kinase (MPK) Interacts With Auxin Influx Carrier (OsAux/LAX1) Involved in Auxin Signaling in Plant.

BACKGROUND: Mitogen activated protein kinases (MPKs) are serine/threonine protein kinases that contain characteristic T-x-Y motif in the activation loop region. MPKs are important signaling molecules involved in diverse signaling cascades that regulate plant growth, development and stress responses by conducting phosphorylation events in their target proteins. MPKs phosphorylate their target proteins at either S-P/T-P (Serine/Proline/Threonine) amino acid. To understand, if MPKs are involved in the auxin signaling cascade, we identified probable target proteins of MPKs involved in auxin signaling or transport processes. RESULTS: A genome-wide search of the rice genome database led us to identification of the OsAux/LAX1 gene as a potential downstream target protein of MPKs. In-silico analysis predicted that MPKs interact with OsAux/LAX1 proteins which were validated by a yeast two-hybrid assay that showed OsMPK3, OsMPK4 and OsMPK6 are physically interact with OsAux/LAX1 protein. CONCLUSION: The yeast two-hybrid interaction showed that MPKs are directly involved in auxin signaling events in plants. This is the first study to report direct involvement of MPKs in the auxin signaling pathway.

Functions for rice RFL in vegetative axillary meristem specification and outgrowth.

Axillary meristems (AMs) are secondary shoot meristems whose outgrowth determines plant architecture. In rice, AMs form tillers, and tillering mutants reveal an interplay between transcription factors and the phytohormones auxin and strigolactone as some factors that underpin this developmental process. Previous studies showed that knockdown of the transcription factor gene RFL reduced tillering and caused a very large decrease in panicle branching. Here, the relationship between RFL, AM initiation, and outgrowth was examined. We show that RFL promotes AM specification through its effects on LAX1 and CUC genes, as their expression was modulated on RFL knockdown, on induction of RFL:GR fusion protein, and by a repressive RFL-EAR fusion protein. Further, we report reduced expression of auxin transporter genes OsPIN1 and OsPIN3 in the culm of RFL knockdown transgenic plants. Additionally, subtle change in the spatial pattern of IR4 DR5:GFP auxin reporter was observed, which hints at compromised auxin transport on RFL knockdown. The relationship between RFL, strigolactone signalling, and bud outgrowth was studied by transcript analyses and by the tillering phenotype of transgenic plants knocked down for both RFL and D3. These data suggest indirect RFL-strigolactone links that may affect tillering. Further, we show expression modulation of the auxin transporter gene OsPIN3 upon RFL:GR protein induction and by the repressive RFL-EAR protein. These modified forms of RFL had only indirect effects on OsPIN1. Together, we have found that RFL regulates the LAX1 and CUC genes during AM specification, and positively influences the outgrowth of AMs though its effects on auxin transport.