Soluble Vascular Adhesion Protein 1 (sVAP-1) as a biomarker for pregnancy complications: A pilot study.

BACKGROUND: Vascular adhesion protein 1 (VAP-1) has been implicated in a wide range of clinical conditions. Moreover, serum levels are associated with disease prediction and progression in several clinical studies. There is a paucity of data on VAP-1 and pregnancy. Given the emerging role of VAP-1 in pregnancy, the aim of this study was to examine sVAP-1 as an early biomarker of pregnancy complications, especially hypertension during pregnancy. The objectives of the study are to associate sVAP-1 levels with other pregnancy complications, patient demographics and blood tests performed throughout pregnancy. METHODS: We conducted a pilot study in a cohort of pregnant women (gestational week lower than 20 at the time of recruitment) attending their first antenatal ultrasound scan at the Leicester Royal Infirmary (LRI, UK). Data were both prospectively generated (from blood sample analysis) and retrospectively collected (from hospital records). RESULTS: From July and October 2021, a total of 91 participants were enrolled. Using ELISA (enzyme-linked immunosorbent assay), we found reduced serum levels of sVAP-1 in pregnant women with either pregnancy induced hypertension (PIH) (310 ng/mL) or GDM (366.73 ng/mL) as compared to controls (427.44 ng/mL and 428.34 ng/mL, respectively). No significant difference was found between women with FGR compared to controls (424.32 ng/mL vs 424.52 ng/mL), and patients with any pregnancy complications compared to healthy pregnancies (421.28 ng/mL vs 428.34 ng/mL). CONCLUSION: Further studies are needed to establish whether or not sVAP-1 might be considered as an early, non-invasive, and affordable biomarker to screen women who will develop PIH or GDM. Our data will aid sample size calculations for such larger studies.

Altered expression of SELF-PRUNING disrupts homeostasis and facilitates signal delivery to meristems.

Meristem maintenance, achieved through the highly conserved CLAVATA-WUSCHEL (CLV-WUS) regulatory circuit, is fundamental in balancing stem cell proliferation with cellular differentiation. Disruptions to meristem homeostasis can alter meristem size, leading to enlarged organs. Cotton (Gossypium spp.), the world's most important fiber crop, shows inherent variation in fruit size, presenting opportunities to explore the networks regulating meristem homeostasis and to impact fruit size and crop value. We identified and characterized the cotton orthologs of genes functioning in the CLV-WUS circuit. Using virus-based gene manipulation in cotton, we altered the expression of each gene to perturb meristem regulation and increase fruit size. Targeted alteration of individual components of the CLV-WUS circuit modestly fasciated flowers and fruits. Unexpectedly, controlled expression of meristem regulator SELF-PRUNING (SP) increased the impacts of altered CLV-WUS expression on flower and fruit fasciation. Meristem transcriptomics showed SP and genes of the CLV-WUS circuit are expressed independently from each other, suggesting these gene products are not acting in the same path. Virus-induced silencing of GhSP facilitated the delivery of other signals to the meristem to alter organ specification. SP has a role in cotton meristem homeostasis, and changes in GhSP expression increased access of virus-derived signals to the meristem.

Blood biomarkers to predict the onset of pre-eclampsia: A systematic review and meta-analysis.

Pre-eclampsia is one of the most common pregnancy complications, and a major cause of fetal and maternal morbidity and mortality globally. Diagnosis currently takes place in the third trimester based on clinical symptoms. This systematic review and meta-analysis sought to determine the blood biomarkers that are associated with pre-eclampsia, and in particular, the biomarkers that could predict pre-eclampsia in early pregnancy. We searched the electronic databases (Medline, Embase, Cochrane Library) from inception up to March 2022. Prospective studies with 1000 or more participants that measured blood biomarkers to predict or diagnose pre-eclampsia have been included in this systematic review. Biomarkers' measurements were considered from the first up to the third trimester, but not during labor. Data concerning pre-eclampsia, biomarker measurements and study characteristics were extracted. Meta-analysis was performed when possible. We found a total of 43 studies (assessing 62 different biomarkers in 18,170 pregnancies, have been included in this systematic review, and a total of 6 studies (assessing 2 biomarkers have been included in the meta-analysis). Statistical analysis was performed for PlGF and sFlt-1. Mean difference in PlGF levels between pre-eclampsia and healthy pregnancies, appear to increase as the pregnancy progresses. Results of sFlt-1 meta-analysis were inconclusive. No significant publication bias was identified. This is the most comprehensive and up to date systematic review and meta-analysis on this important topic on blood biomarkers for the early prediction of pre-eclampsia. Further This research highlights the urgent needed for further discovery research to identify blood biomarkers that could predict the development of pre-eclampsia.

Cotton architecture: examining the roles of SINGLE FLOWER TRUSS and SELF-PRUNING in regulating growth habits of a woody perennial crop.

By specifying patterns of determinate and indeterminate growth, FLOWERING LOCUS T/SINGLE FLOWER TRUSS (SFT) and TERMINAL FLOWER 1/SELF-PRUNING (SP) regulate plant architecture. Though well characterized in Arabidopsis, the impacts of these genes on the architectures of diverse crops cultivated in different environments, and their potential to enhance crop productivity and management, are less well addressed. Cotton (Gossypium spp.) is naturally a short-day photoperiodic perennial that is now grown primarily as a day-neutral, annual row crop. Different environments and cultivation practices favor specific growth habits to optimize yield, and in cotton, especially in regions that rely heavily on mechanized harvest, the trend has been to more determinate varieties. Identifying and functionally characterizing SFT and SP homologs in cotton uncovered new aspects of how ratios of indeterminate and determinate growth are balanced, and unraveling their genetic networks emphasized how broadly these gene products affect cotton growth habits.

Complement Properdin Determines Disease Activity in MRL/lpr Mice.

Background and objects: In systemic lupus erythematosus, circulating immune complexes activate complement and, when trapped in renal capillaries, cause glomerulonephritis. Mouse models have been used in the preclinical assessment of targeting complement activation pathways to manage chronic inflammation in lupus. Properdin is the only known positive regulator of complement activation, but its role in the severity of lupus nephritis has not been studied yet. Materials and Methods: Fully characterized properdin-deficient mice were crossed with lupus prone MRL/lpr mice on C57Bl/6 background. Results: Compared to MRL/lpr properdin wildtype mice, MRL/lpr properdin-deficient mice had significantly lower anti-DNA antibody titres, TNFα and BAFF levels in serum. The qualitative glomerulonephritic score was less severe and there was significantly less serum creatinine in MRL/lpr properdin-deficient mice compared to MRL/lpr properdin wildtype littermate mice. Conclusion: Properdin plays a significant role in the severity of lupus overall and specifically in the extent of glomerulonephritis observed in MRL/lpr mice. Because MRL/lpr properdin-deficient mice had lower levels of anti-DNA antibodies, inflammatory mediators and markers of renal impairment, the study implies that properdin could constitute a novel therapy target in lupus disease.

SINGLE FLOWER TRUSS and SELF-PRUNING signal developmental and metabolic networks to guide cotton architectures.

Patterns of indeterminate and determinate growth specify plant architecture and influence crop productivity. In cotton (Gossypium hirsutum), SINGLE FLOWER TRUSS (SFT) stimulates the transition to flowering and determinate growth, while its closely related antagonist SELF-PRUNING (SP) maintains meristems in indeterminate states to favor vegetative growth. Overexpressing GhSFT while simultaneously silencing GhSP produces highly determinate cotton with reduced foliage and synchronous fruiting. These findings suggest that GhSFT, GhSP, and genes in these signaling networks hold promise for enhancing 'annualized' growth patterns and improving cotton productivity and management. To identify the molecular programs underlying cotton growth habits, we used comparative co-expression networks, differential gene expression, and phenotypic analyses in cotton varieties expressing altered levels of GhSFT or GhSP. Using multiple cotton and tomato datasets, we identified diverse genetic modules highly correlated with SFT or SP orthologs which shared related Gene Ontologies in different crop species. Notably, altering GhSFT or GhSP levels in cotton affected the expression of genes regulating meristem fate and metabolic pathways. Further phenotypic analyses of gene products involved in photosynthesis, secondary metabolism, and cell wall biosynthesis showed that early changes in GhSFT and GhSP levels profoundly impacted later development in distal tissues. Identifying the molecular underpinnings of GhSFT and GhSP activities emphasizes their broad actions in regulating cotton architecture.

Cotton CENTRORADIALIS/TERMINAL FLOWER 1/SELF-PRUNING genes functionally diverged to differentially impact plant architecture.

Genes of the CENTRORADIALIS/TERMINAL FLOWER 1/SELF-PRUNING (CETS) family influence meristem identity by controlling the balance between indeterminate and determinate growth, thereby profoundly impacting plant architecture. Artificial selection during cotton (Gossypium hirsutum) domestication converted photoperiodic trees to the day-neutral shrubs widely cultivated today. To understand the regulation of cotton architecture and exploit these principles to enhance crop productivity, we characterized the CETS gene family from tetraploid cotton. We demonstrate that genes of the TERMINAL FLOWER 1 (TFL1)-like clade show different roles in regulating growth patterns. Cotton has five TFL1-like genes: SELF-PRUNING (GhSP) is a single gene whereas there are two TFL1-like and BROTHER OF FT (BFT)-like genes, and these duplications are specific to the cotton lineage. All genes of the cotton TFL1-like clade delay flowering when ectopically expressed in transgenic Arabidopsis, with the strongest phenotypes failing to produce functional flowers. GhSP, GhTFL1-L2, and GhBFT-L2 rescue the early flowering Attfl1-14 mutant phenotype, and the encoded polypeptides interact with a cotton FD protein. Heterologous promoter::GUS fusions illustrate differences in the regulation of these genes, suggesting that genes of the GhTFL1-like clade may not act redundantly. Characterizations of the GhCETS family provide strategies for nuanced control of plant growth.

Impact of a fatigue management in work programme on meeting work demands of individuals with rheumatic diseases: A pilot study.

INTRODUCTION: Work disability and job loss are serious consequences of rheumatic diseases (RDs), and fatigue is a symptom of RDs commonly reported to have an impact on work performance. A FAtigue ManagEment in Work (FAME-W) programme was developed to facilitate the self-management of fatigue in work. The present pilot study explored if FAME-W could facilitate individuals with RDs to manage fatigue in work and improve their ability to meet work demands. METHODS: Twenty-seven individuals with a variety of rheumatic diagnoses completed a 4-week, 2-h occupational therapy-led self-management programme. Each week focused on fatigue-related topics, including fatigue and activity management, pain management and joint protection, mental well-being, effective communication with employers and work colleagues, and employment legislation. Individual workplace ergonomic assessments were also offered. Study measures (work function, fatigue, pain, mood and self-efficacy) were completed prior to starting FAME-W, immediately post-intervention and 12 weeks post-intervention. RESULTS: Participants (56% male) had a mean age of 43 years. No significant improvements were observed immediately post-programme. However, at the 12-week follow-up, significant improvements were reported in meeting work demands (scheduling [p = 0.046], output [p = 0.002], physical [p = 0.003], mental [p = 0.016]), fatigue [p = 0.001], pain [p = 0.01], anxiety [p = 0.001], depression [p < 0.001], self-efficacy [p < 0.001] and Arthritis Impact Measurement Scales 2-Short Form (physical: p = 0.005; symptoms: p = 0.010; affect: p = 0.010; social: p = 0.001). CONCLUSIONS: Significant improvements were reported in participants' ability to meet various demands of their work 3 months post-FAME-W. These findings suggest that FAME-W has the potential to assist individuals with RDs to meet the demands of their work, although further research is required to test the effectiveness of this intervention.

Monopodial and sympodial branching architecture in cotton is differentially regulated by the Gossypium hirsutum SINGLE FLOWER TRUSS and SELF-PRUNING orthologs.

Domestication of upland cotton (Gossypium hirsutum) converted it from a lanky photoperiodic perennial to a day-neutral annual row-crop. Residual perennial traits, however, complicate irrigation and crop management, and more determinate architectures are desired. Cotton simultaneously maintains robust monopodial indeterminate shoots and sympodial determinate shoots. We questioned if and how the FLOWERING LOCUS T/SINGLE FLOWER TRUSS (SFT)-like and TERMINAL FLOWER1/SELF-PRUNING (SP)-like genes control the balance of monopodial and sympodial growth in a woody perennial with complex growth habit. Virus-based manipulation of GhSP and GhSFT expression enabled unprecedented functional analysis of cotton development. GhSP maintains growth in all apices; in its absence, both monopodial and sympodial branch systems terminate precociously. GhSFT encodes a florigenic signal stimulating rapid onset of sympodial branching and flowering in side shoots of wild photoperiodic and modern day-neutral accessions. High florigen concentrations did not alter monopodial apices, implying that once a cotton apex is SP-determined, it cannot be reset by florigen. GhSP is also essential to establish and maintain cambial activity. Dynamic changes in GhSFT and GhSP levels navigate meristems between monopodial and sympodial programs in a single plant. SFT and SP influenced cotton domestication and are ideal targets for further agricultural optimization.

Dual tasking with the timed "up & go" test improves detection of risk of falls in people with Parkinson disease.

BACKGROUND: Falls are a common and disabling feature of Parkinson disease (PD). Early identification of patients at greatest risk of falling is a key goal of physical therapy assessment. The Timed "Up & Go" Test (TUG), a frequently used mobility assessment tool, has moderate sensitivity and specificity for identifying fall risk. OBJECTIVE: The study objective was to investigate whether adding a task (cognitive or manual) to the TUG (TUG-cognitive or TUG-manual, respectively) increases the utility of the test for identifying fall risk in people with PD. DESIGN: This was a retrospective cohort study of people with PD (N=36). METHODS: Participants were compared on the basis of self-reported fall exposure in the preceding 6 months (those who had experienced falls ["fallers"] versus those who had not ["nonfallers"]). The time taken to complete the TUG, TUG-cognitive, and TUG-manual was measured for both groups. Between-group differences were calculated with the Mann-Whitney U test. The discriminative performance of the test at various cutoff values was examined, and estimates of sensitivity and specificity were based on receiver operating characteristic curve plots. RESULTS: Fallers took significantly longer than nonfallers (n=19) to complete the TUG under all 3 conditions. The TUG-cognitive showed optimal discriminative performance (receiver operating characteristic area under the curve=0.82; 95% confidence interval [CI]=0.64, 0.92) at a cutoff of 14.7 seconds. The TUG-cognitive was more likely to correctly classify participants with a low risk of falling (positive likelihood ratio=2.9) (<14.7 seconds) and had higher estimates of sensitivity (0.76; 95% CI=0.52, 0.90) than of specificity (0.73; 95% CI=0.51, 0.88) at this threshold (negative likelihood ratio=0.32). LIMITATIONS: Retrospective classification of fallers and nonfallers was used. CONCLUSIONS: The addition of a cognitive task to the TUG enhanced the identification of fall risk in people with PD. The TUG-cognitive should be considered a component of a multifaceted fall risk assessment in people with PD.

Exploring LPS-induced sepsis in rats and mice as a model to study potential protective effects of the nociceptin/orphanin FQ system.

The nociceptin receptor (NOP) and its ligand nociceptin/orphanin FQ (N/OFQ) have been shown to exert a modulatory effect on immune cells during sepsis. We evaluated the suitability of an experimental lipopolysaccharide (LPS)-induced sepsis model for studying changes in the nociceptin system. C57BL/6 mice BALB/c mice and Wistar rats were inoculated with different doses of LPS with or without a nociceptin receptor antagonist (UFP-101 or SB-612111). In C57BL/6 mice LPS 0.85 mg/kg injection produced no septic response, whereas 1.2mg/kg produced a profound response within 5h. In BALB/c mice, LPS 4 mg/kg produced no response, whereas 7 mg/kg resulted in a profound response within 24h. In Wistar rats LPS 15 mg/kg caused no septic response in 6/10 animals, whereas 25mg/kg resulted in marked lethargy before 24h. Splenic interleukin-1ß mRNA in BALB/c mice, and serum TNF-α concentrations in Wistar rats increased after LPS injection in a dose-dependent manner, but were undetectable in control animals, indicating that LPS had stimulated an inflammatory reaction. IL-1ß and TNF-α concentrations in LPS-treated animals were unaffected by administration of a NOP antagonist. Similarly NOP antagonists had no effect on survival or expression of mRNA for NOP or ppN/OFQ (the N/OFQ precursor) in a variety of tissues. In these animal models, the dose-response curve for LPS was too steep to allow use in survival studies and no changes in the N/OFQ system occurred within 24h. We conclude that LPS-inoculation in rodents is an unsuitable model for studying possible changes in the NOP-N/OFQ system in sepsis.

Phloem-mobile signals affecting flowers: applications for crop breeding.

Transport of endogenous macromolecules within and between tissues serves as a signaling pathway to regulate numerous aspects of plant growth. The florigenic FT gene product moves via the phloem from leaves to apical tissues and induces the flowering program in meristems. Similarly, short interfering RNA (siRNA) signals produced in source or sink tissues move cell-to-cell and long distance via the phloem to apical tissues. Recent advances in identifying these mobile signals regulating flowering or the epigenetic status of targeted tissues can be applicable to crop-breeding programs. In this review, we address the identity of florigen, the mechanism of allocation, and how virus-induced flowering and grafting of transgenes producing siRNA signals affecting meiosis can produce transgene-free progenies useful for agriculture.

Overexpression of FT in cotton affects architecture but not floral organogenesis.

Flowering marks the change from indeterminate to determinate plant growth, and this developmental transition involves the activity of the Arabidopsis FLOWERING LOCUS T (FT) gene product and its orthologs. We demonstrated that when FT is ectopically expressed from a viral vector in cotton, a process referred to as virus induced flowering (VIF), it uncouples flowering from photoperiodic regulation and promotes determinate growth in aerial organs. The accelerated switch to determinate growth affected cotton floral buds and sympodial growth, but did not disrupt floral organogenesis. These results can be interpreted in the context of the balance model, which argues that the balance of indeterminate and determinate growth is influenced by the relative abundance of indeterminate and determinate factors in the growing apices. These results emphasize the expanding role of FT in affecting general determinate growth.

Geminivirus-mediated delivery of florigen promotes determinate growth in aerial organs and uncouples flowering from photoperiod in cotton.

BACKGROUND: Plant architecture and the timing and distribution of reproductive structures are fundamental agronomic traits shaped by patterns of determinate and indeterminate growth. Florigen, encoded by FLOWERING LOCUS T (FT) in Arabidopsis and SINGLE FLOWER TRUSS (SFT) in tomato, acts as a general growth hormone, advancing determinate growth. Domestication of upland cotton (Gossypium hirsutum) converted it from a lanky photoperiodic perennial to a highly inbred, compact day-neutral plant that is managed as an annual row-crop. This dramatic change in plant architecture provides a unique opportunity to analyze the transition from perennial to annual growth. METHODOLOGY/PRINCIPAL FINDINGS: To explore these architectural changes, we addressed the role of day-length upon flowering in an ancestral, perennial accession and in a domesticated variety of cotton. Using a disarmed Cotton leaf crumple virus (CLCrV) as a transient expression system, we delivered FT to both cotton accessions. Ectopic expression of FT in ancestral cotton mimicked the effects of day-length, promoting photoperiod-independent flowering, precocious determinate architecture, and lanceolate leaf shape. Domesticated cotton infected with FT demonstrated more synchronized fruiting and enhanced "annualization". Transient expression of FT also facilitated simple crosses between wild photoperiodic and domesticated day-neutral accessions, effectively demonstrating a mechanism to increase genetic diversity among cultivated lines of cotton. Virus was not detected in the F(1) progeny, indicating that crosses made by this approach do not harbor recombinant DNA molecules. CONCLUSIONS: These findings extend our understanding of FT as a general growth hormone that regulates shoot architecture by advancing organ-specific and age-related determinate growth. Judicious manipulation of FT could benefit cotton architecture to improve crop management.

Manipulating plant architecture with members of the CETS gene family.

The shape or architecture of a plant is specified through the activities of indeterminate and determinate meristems, and the sum of these events sharply impacts plant growth habit, productivity, and crop management. The CENTRORADIALIS/TERMINAL FLOWER 1/SELF-PRUNING (CETS) gene family shares homology to phosphatidylethanolamine binding protein (PEBP) genes and is prominent in controlling the timing and location of the developmental transition from indeterminate to determinate growth, with different family members balancing the activities of others through antagonistic functions. The CETS members FLOWERING LOCUS T (FT) of Arabidopsis and related genes (e.g. SINGLE FLOWER TRUSS, SFT, in tomato) are important in promoting the transition to determinate growth while TERMINAL FLOWER 1 (TFL1) and its homologs (e.g. tomato SELF PRUNING, SP) oppose this activity by maintaining meristems in an indeterminate state. FT orthologs, and perhaps other CETS family members, act as mobile proteinaceous hormones, and can amplify their impact by accumulating in recipient organs. A universal model is emerging for the timing and placement of determinate and indeterminate growth through a balance of FT-like and TFL1-like gene activities, and it is now clear that the domestication of many wild exotics into crops with desired growth habits resulted from selection of altered FT/TFL1 balances. Manipulating this ratio further, through transgenic or viral-based technologies, holds promise for improved agricultural sustainability.

Arabidopsis plants harbouring a mutation in AtSUC2, encoding the predominant sucrose/proton symporter necessary for efficient phloem transport, are able to complete their life cycle and produce viable seed.

BACKGROUND AND AIMS: AtSUC2 encodes a sucrose/proton symporter that localizes throughout the collection and transport phloem and is necessary for efficient transport of sucrose from source to sink tissues in Arabidopsis thaliana. Plants harbouring homozygous AtSUC2 null alleles accumulate sugar, starch, and anthocyanin in mature leaves, have severely delayed development and stunted growth and, in previous studies, failed to complete their life cycle by producing viable seed. METHODS: An AtSUC2 allele with a T-DNA insertion in the second intron was analysed. Full-length transcript from this allele is not produced, and a truncated protein translated from sequences upstream of the insertion site did not catalyse sucrose uptake into yeast, supporting the contention that this is a null allele. Mutant plants were grown in a growth chamber with a diurnal light/dark cycle, and growth patterns recorded. KEY RESULTS: This allele (SALK_038124, designated AtSUC2-4) has the hallmarks of previously described null alleles but, despite compromised carbon partitioning and growth, produces viable seeds. The onset of flowering was chronologically delayed but occurred at the same point in the plastochron index as wild type. CONCLUSIONS: AtSUC2 is important for phloem loading and is therefore fundamental to phloem transport and plant productivity, but plants can complete their life cycle and produce viable seed in its absence. Arabidopsis appears to have mechanisms for mobilizing reduced carbon from the phloem into developing seeds independent of AtSUC2.

A DNA element between At4g28630 and At4g28640 confers companion-cell specific expression following the sink-to-source transition in mature minor vein phloem.

The collection phloem in minor veins is distinct from other vein classes in that the minor veins mature during the sink to source transition and are the primary sites of phloem loading. After maturation, minor vein phloem maintains its character in part through minor-vein specific regulatory cascades; however despite its physiological significance, little of these developmental programs is understood. From an Arabidopsis enhancer trap screen, we identified MATURE MINOR VEIN ELEMENT1 (MMVE1) in the intergenic region between two oppositely oriented genes, the ABC transporter ATM1 (At4g28630) and IAA11 (At4g28640). MMVE1 promotes reporter gene activity in minor vein phloem in a pattern resembling the sink to source transition. Promoter truncation experiments and phylogenetic footprinting demonstrate sequences proximal to ATM1 promote minor vein expression whereas sequences closer to IAA11 repress it. Both orientations of the promoter were used to drive expression of CONSTANS to generate a phloem mobile signal conferring early flowering under non-inductive conditions. Tandem copies of MMVE1 increase minor vein expression strength and specificity. MMVE1 is the first minor vein enhancer characterized from a species that loads from the apoplast, and supports the presence of unique regulatory cascades operating in minor vein phloem.