Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.

The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.

The renaissance and enlightenment of Marchantia as a model system.

The liverwort Marchantia polymorpha has been utilized as a model for biological studies since the 18th century. In the past few decades, there has been a Renaissance in its utilization in genomic and genetic approaches to investigating physiological, developmental, and evolutionary aspects of land plant biology. The reasons for its adoption are similar to those of other genetic models, e.g. simple cultivation, ready access via its worldwide distribution, ease of crossing, facile genetics, and more recently, efficient transformation, genome editing, and genomic resources. The haploid gametophyte dominant life cycle of M. polymorpha is conducive to forward genetic approaches. The lack of ancient whole-genome duplications within liverworts facilitates reverse genetic approaches, and possibly related to this genomic stability, liverworts possess sex chromosomes that evolved in the ancestral liverwort. As a representative of one of the three bryophyte lineages, its phylogenetic position allows comparative approaches to provide insights into ancestral land plants. Given the karyotype and genome stability within liverworts, the resources developed for M. polymorpha have facilitated the development of related species as models for biological processes lacking in M. polymorpha.

Painted flowers: Eluta generates pigment patterning in Antirrhinum.

In the early 1900s, Erwin Baur established Antirrhinum majus as a model system, identifying and characterising numerous flower colour variants. This included Picturatum/Eluta, which restricts the accumulation of magenta anthocyanin pigments, forming bullseye markings on the flower face. We identified the gene underlying the Eluta locus by transposon-tagging, using an Antirrhinum line that spontaneously lost the nonsuppressive el phenotype. A candidate MYB repressor gene at this locus contained a CACTA transposable element. We subsequently identified plants where this element excised, reverting to a suppressive Eluta phenotype. El alleles inhibit expression of anthocyanin biosynthetic genes, confirming it to be a regulatory locus. The modes of action of Eluta were investigated by generating stable transgenic tobacco lines, biolistic transformation of Antirrhinum petals and promoter activation/repression assays. Eluta competes with MYB activators for promoter cis-elements, and also by titrating essential cofactors (bHLH proteins) to reduce transcription of target genes. Eluta restricts the pigmentation established by the R2R3-MYB factors, Rosea and Venosa, with the greatest repression on those parts of the petals where Eluta is most highly expressed. Baur questioned the origin of heredity units determining flower colour variation in cultivated A. majus. Our findings support introgression from wild species into cultivated varieties.

A phosphatase gene is linked to nectar dihydroxyacetone accumulation in manuka (Leptospermum scoparium).

Floral nectar composition beyond common sugars shows great diversity but contributing genetic factors are generally unknown. Manuka (Leptospermum scoparium) is renowned for the antimicrobial compound methylglyoxal in its derived honey, which originates from the precursor, dihydroxyacetone (DHA), accumulating in the nectar. Although this nectar trait is highly variable, genetic contribution to the trait is unclear. Therefore, we investigated key gene(s) and genomic regions underpinning this trait. We used RNAseq analysis to identify nectary-associated genes differentially expressed between high and low nectar DHA genotypes. We also used a manuka high-density linkage map and quantitative trait loci (QTL) mapping population, supported by an improved genome assembly, to reveal genetic regions associated with nectar DHA content. Expression and QTL analyses both pointed to the involvement of a phosphatase gene, LsSgpp2. The expression pattern of LsSgpp2 correlated with nectar DHA accumulation, and it co-located with a QTL on chromosome 4. The identification of three QTLs, some of the first reported for a plant nectar trait, indicates polygenic control of DHA content. We have established plant genetics as a key influence on DHA accumulation. The data suggest the hypothesis of LsSGPP2 releasing DHA from DHA-phosphate and variability in LsSgpp2 gene expression contributing to the trait variability.

Comparative transcriptomics elucidates the cellular responses of an aeroterrestrial zygnematophyte to UV radiation.

The zygnematophytes are the closest relatives of land plants and comprise several lineages that adapted to a life on land. Species of the genus Serritaenia form colorful, mucilaginous capsules, which surround the cells and block harmful solar radiation, one of the major terrestrial stressors. In eukaryotic algae, this 'sunscreen mucilage' represents a unique photoprotective strategy, whose induction and chemical background are unknown. We generated a de novo transcriptome of Serritaenia testaceovaginata and studied its gene regulation under moderate UV radiation (UVR) that triggers sunscreen mucilage under experimental conditions. UVR induced the repair of DNA and the photosynthetic apparatus as well as the synthesis of aromatic specialized metabolites. Specifically, we observed pronounced expressional changes in the production of aromatic amino acids, phenylpropanoid biosynthesis genes, potential cross-membrane transporters of phenolics, and extracellular, oxidative enzymes. Interestingly, the most up-regulated enzyme was a secreted class III peroxidase, whose embryophyte homologs are involved in apoplastic lignin formation. Overall, our findings reveal a conserved, plant-like UVR perception system (UVR8 and downstream factors) in zygnematophyte algae and point to a polyphenolic origin of the sunscreen pigment of Serritaenia, whose synthesis might be extracellular and oxidative, resembling that of plant lignins.

Stress, senescence, and specialized metabolites in bryophytes.

Life on land exposes plants to varied abiotic and biotic environmental stresses. These environmental drivers contributed to a large expansion of metabolic capabilities during land plant evolution and species diversification. In this review we summarize knowledge on how the specialized metabolite pathways of bryophytes may contribute to stress tolerance capabilities. Bryophytes are the non-tracheophyte land plant group (comprising the hornworts, liverworts, and mosses) and rapidly diversified following the colonization of land. Mosses and liverworts have as wide a distribution as flowering plants with regard to available environments, able to grow in polar regions through to hot desert landscapes. Yet in contrast to flowering plants, for which the biosynthetic pathways, transcriptional regulation, and compound function of stress tolerance-related metabolite pathways have been extensively characterized, it is only recently that similar data have become available for bryophytes. The bryophyte data are compared with those available for angiosperms, including examining how the differing plant forms of bryophytes and angiosperms may influence specialized metabolite diversity and function. The involvement of stress-induced specialized metabolites in senescence and nutrient response pathways is also discussed.

Interferon and anti-TNF therapies differentially modulate amygdala reactivity which predicts associated bidirectional changes in depressive symptoms.

A third of patients receiving Interferon-α (IFN-α) treatment for Hepatitis-C develop major depressive disorder (MDD). Conversely, anti-Tumor Necrosis Factor (TNF) therapies improve depression providing key empirical support for the "inflammatory theory" of depression. Heightened amygdala reactivity (particularly to negatively valanced stimuli) is a consistent finding within MDD; can predict treatment efficacy and reverses following successful treatment. However, whether IFN-α and anti-TNF enhance/attenuate depressive symptoms through modulation of amygdala emotional reactivity is unknown. Utilizing a prospective study design, we recruited 30 patients (mean 48.0 ± 10.5 years, 21 male) initiating IFN-α treatment for Hepatitis-C and 30 (mean 50.4 ± 15.7 years, 10 male) anti-TNF therapy for inflammatory arthritis. All completed an emotional face-processing task during fMRI and blood sampling before and after their first IFN-α (4-h) or anti-TNF (24-h) injection and follow-up psychiatric assessments for 3 months of treatment. IFN-α significantly increased depression symptoms (Hamilton Depression Rating Scale HAM-D) at 4 weeks (p < 0.001) but not 4-h after first dose (p > 0.1). Conversely, anti-TNF significantly improved depressive symptoms (Hospital Anxiety and Depression Rating Scale HADS) at both 24-h (P = 0.015) and 12 weeks (p = 0.018). In support of our a-priori hypothesis, both IFN-α and anti-TNF significantly modulated amygdala reactivity with IFN-α acutely enhancing right amygdala responses to sad (compared with neutral) faces (p = 0.032) and anti-TNF conversely decreasing right amygdala reactivity (across emotional valence) (p = 0.033). Furthermore, these changes predicted IFN-induced increases in HAM-D 4 weeks later (R2 = 0.17, p = 0.022) and anti-TNF-associated decreases in HADS at 24-h (R2 = 0.23, p = 0.01) suggesting that actions of systemic inflammation on amygdala emotional reactivity play a mechanistic role in inflammation-associated depressive symptoms.

Evolution and function of red pigmentation in land plants.

BACKGROUND: Land plants commonly produce red pigmentation as a response to environmental stressors, both abiotic and biotic. The type of pigment produced varies among different land plant lineages. In the majority of species they are flavonoids, a large branch of the phenylpropanoid pathway. Flavonoids that can confer red colours include 3-hydroxyanthocyanins, 3-deoxyanthocyanins, sphagnorubins and auronidins, which are the predominant red pigments in flowering plants, ferns, mosses and liverworts, respectively. However, some flowering plants have lost the capacity for anthocyanin biosynthesis and produce nitrogen-containing betalain pigments instead. Some terrestrial algal species also produce red pigmentation as an abiotic stress response, and these include both carotenoid and phenolic pigments. SCOPE: In this review, we examine: which environmental triggers induce red pigmentation in non-reproductive tissues; theories on the functions of stress-induced pigmentation; the evolution of the biosynthetic pathways; and structure-function aspects of different pigment types. We also compare data on stress-induced pigmentation in land plants with those for terrestrial algae, and discuss possible explanations for the lack of red pigmentation in the hornwort lineage of land plants. CONCLUSIONS: The evidence suggests that pigment biosynthetic pathways have evolved numerous times in land plants to provide compounds that have red colour to screen damaging photosynthetically active radiation but that also have secondary functions that provide specific benefits to the particular land plant lineage.

Evidence of floral rewards in Brasiliorchis supports the convergent evolution of food-hairs in Maxillariinae.

PREMISE: Angiosperms distributed over a large geographical area may display considerable phenotypic variation that can be recognized at morphological and micromorphological levels. Here, we investigate the pollination biology and the presence of floral rewards in Brazilian populations of the widely distributed orchid, Brasiliorchis picta. Based on the new data presented here this study investigates the evolution of floral rewards in Maxillariinae, and tests for the occurrence of convergent evolution of food-hairs in this subtribe. METHODS: Micromorphological and histochemical analyses of the labellar tissues were conducted, together with chemical analysis of fragrance and experiments involving the use of chemical baits. The evolution of floral rewards in Maxillariinae were addressed. RESULTS: Microscopy revealed that B. picta offers food-hairs as a reward. Fragrance is produced by abaxially located labellar epidermal papillae. The main compound present in our samples (2-phenylethanol) also occurs in the aggregation pheromone produced by the mandible glands of pollinators, Meliponini bees. Our analyses indicate a high diversity of flower rewards and pollinators displayed by members of Maxillariinae, and support that edible trichomes evolved independently five times in the subtribe. CONCLUSIONS: The high diversity of floral rewards and pollinators displayed by members of Maxillariinae suggests that different pollinator pressures are involved in the evolution of this neotropical subtribe. In addition, the offering of food-hairs, which are generally infrequently encountered in Orchidaceae, arose by convergent evolution in Maxillariinae.

Auronidins are a previously unreported class of flavonoid pigments that challenges when anthocyanin biosynthesis evolved in plants.

Anthocyanins are key pigments of plants, providing color to flowers, fruit, and foliage and helping to counter the harmful effects of environmental stresses. It is generally assumed that anthocyanin biosynthesis arose during the evolutionary transition of plants from aquatic to land environments. Liverworts, which may be the closest living relatives to the first land plants, have been reported to produce red cell wall-bound riccionidin pigments in response to stresses such as UV-B light, drought, and nutrient deprivation, and these have been proposed to correspond to the first anthocyanidins present in early land plant ancestors. Taking advantage of the liverwort model species Marchantia polymorpha, we show that the red pigments of Marchantia are formed by a phenylpropanoid biosynthetic branch distinct from that leading to anthocyanins. They constitute a previously unreported flavonoid class, for which we propose the name "auronidin," with similar colors as anthocyanin but different chemistry, including strong fluorescence. Auronidins might contribute to the remarkable ability of liverworts to survive in extreme environments on land, and their discovery calls into question the possible pigment status of the first land plants.

Discrete bHLH transcription factors play functionally overlapping roles in pigmentation patterning in flowers of Antirrhinum majus.

Floral pigmentation patterning is important for pollinator attraction as well as aesthetic appeal. Patterning of anthocyanin accumulation is frequently associated with variation in activity of the Myb, bHLH and WDR transcription factor complex (MBW) that regulates anthocyanin biosynthesis. Investigation of two classic mutants in Antirrhinum majus, mutabilis and incolorata I, showed they affect a gene encoding a bHLH protein belonging to subclade bHLH-2. The previously characterised gene, Delila, which encodes a bHLH-1 protein, has a bicoloured mutant phenotype, with residual lobe-specific pigmentation conferred by Incolorata I. Both Incolorata I and Delila induce expression of the anthocyanin biosynthetic gene DFR. Rosea 1 (Myb) and WDR1 proteins compete for interaction with Delila, but interact positively to promote Incolorata I activity. Delila positively regulates Incolorata I and WDR1 expression. Hierarchical regulation can explain the bicoloured patterning of delila mutants, through effects on both regulatory gene expression and the activity of promoters of biosynthetic genes like DFR that mediate MBW regulation. bHLH-1 and bHLH-2 proteins contribute to establishing patterns of pigment distribution in A. majus flowers in two ways: through functional redundancy in regulating anthocyanin biosynthetic gene expression, and through differences between the proteins in their ability to regulate genes encoding transcription factors.

Expression of sterile-α and armadillo motif containing protein (SARM) in rheumatoid arthritis monocytes correlates with TLR2-induced IL-1ß and disease activity.

OBJECTIVE: Cartilage and bone damage in RA are associated with elevated IL-1ß. The effects of IL-1ß can be reduced by biological therapies that target IL-1ß or TNF-α. However, the mechanisms responsible for increased IL-1ß and the effect of anti-TNF-α have not been fully elucidated. Recently, sterile-α and armadillo motif containing protein (SARM) was identified as a negative regulator of toll-like receptor (TLR) induced IL-1ß secretion through an interaction with the inflammasome. This study set out to investigate SARM during TLR-induced IL-1ß secretion in RA peripheral blood monocytes and in patients commencing anti-TNF-α treatment. METHODS: Monocytes were isolated from RA patients and healthy controls; disease activity was measured by DAS28. IL-1ß secretion was measured by ELISA following TLR1/2, TLR4 and TLR7/8 stimulation. The mRNA expression of SARM1, IL-1ß and the components of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome were measured by quantitative PCR. SARM protein expression was measured by western blotting. RESULTS: TLR1/2 activation induced elevated IL-1ß in RA monocytes compared with healthy controls (P = 0.0009), which negatively correlated with SARM1 expression (P = 0.0086). Lower SARM expression also correlated with higher disease activity (P = 0.0246). Additionally, patients responding to anti-TNF-α treatment demonstrated a rapid upregulation of SARM, which was not observed in non-responders. CONCLUSION: Together, these data highlight a potential contribution from SARM to RA pathophysiology where decreased SARM may lead to elevated IL-1ß associated with RA pathogenesis. Furthermore, the data additionally present a potential mechanism by which TNF-α blockade can modify IL-1ß secretion.

The investigation of diabetes in people living with HIV: A systematic review.

AIMS: HbA1c is reported to underestimate glycaemia in people living with HIV (PLHIV). There is not an internationally agreed screening method for diabetes. The primary aim was to identify which tests are performed to diagnose and monitor diabetes in PLHIV. Secondary aims were to identify whether prevalence or incidence of diabetes differs according to marker of glycaemia and how figures compare in PLHIV compared to people without. METHODS: Electronic databases were searched for studies investigating diabetes in PLHIV, not pregnant, aged ≥18 years. Narrative analysis and descriptive statistics were used to describe which markers of glycaemia, and their frequency, were employed in the diagnosis and monitoring of diabetes in PLHIV. Diagnostic studies provided prevalence or incidence of diabetes. RESULTS: In all, 45 of 1028 studies were included. Oral glucose tolerance test (OGTT), fasting glucose (FG), HbA1c and Fructosamine were used to investigate diabetes. In total, 27 studies described diagnosing diabetes, 14 using OGTT, 12 FG and 7 HbA1c. All 18 studies monitoring diabetes used HbA1c. Prevalence ranged from 1.3% to 26% and incidence 2.9% to 12.8%. Studies using glucose and HbA1c reported HbA1c to diagnose fewer people with diabetes, monitoring studies found HbA1c to underestimate glycaemia levels. Controlled studies demonstrate diabetes was more common in PLHIV. CONCLUSION: OGTT was used most frequently to diagnose diabetes, and HbA1c to monitor known diabetes. Prevalence and incidence varied depending on marker of glycaemia used. Studies reported a discrepancy in accuracy of HbA1c in PLHIV, to address this, well-designed, prospective studies, providing individual-level data on HbA1c levels and an additional marker of glycaemia in PLHIV are needed.

Theory of signs and statistical approach to big data in assessing the relevance of clinical biomarkers of inflammation and oxidative stress.

Biomarkers are widely used not only as prognostic or diagnostic indicators, or as surrogate markers of disease in clinical trials, but also to formulate theories of pathogenesis. We identify two problems in the use of biomarkers in mechanistic studies. The first problem arises in the case of multifactorial diseases, where different combinations of multiple causes result in patient heterogeneity. The second problem arises when a pathogenic mediator is difficult to measure. This is the case of the oxidative stress (OS) theory of disease, where the causal components are reactive oxygen species (ROS) that have very short half-lives. In this case, it is usual to measure the traces left by the reaction of ROS with biological molecules, rather than the ROS themselves. Borrowing from the philosophical theories of signs, we look at the different facets of biomarkers and discuss their different value and meaning in multifactorial diseases and system medicine to inform their use in patient stratification in personalized medicine.

TLR1/2 and 5 induce elevated cytokine levels from rheumatoid arthritis monocytes independent of ACPA or RF autoantibody status.

OBJECTIVE: RA is an autoimmune inflammatory joint disease. Both RF and ACPA are associated with more progressive disease and higher levels of systemic inflammation. Monocyte activation of toll-like receptors (TLRs) by endogenous ligands is a potential source of increased production of systemic cytokines. RA monocytes have elevated TLRs, some of which are associated with the disease activity score using 28 joints (DAS28). The aim of this study was to measure TLR-induced cytokine production from monocytes, stratified by autoantibody status, to assess if their capacity to induce cytokines is related to autoantibody status or DAS28. METHODS: Peripheral blood monocytes isolated from RA patients and healthy controls were stimulated with TLR1/2, TLR2/6, TLR4, TLR5, TLR7, TLR8 and TLR9 ligands for 18 h before measuring IL-6, TNFα and IL-10. Serum was used to confirm the autoantibody status. Cytokine levels were compared with RF, ACPA and DAS28. RESULTS: RA monocytes demonstrated significantly increased IL-6 and TNFα upon TLR1/2 stimulation and IL-6 and IL-10 upon TLR5 activation. TLR7 and TLR9 activation did not induce cytokines and no significant differences were observed between RA and healthy control monocytes upon TLR2/6, TLR4 or TLR8 activation. When stratified by ACPA or RF status there were no correlations between autoantibody status and elevated cytokine levels. However, TLR1/2-induced IL-6 did correlate with DAS28. CONCLUSIONS: Elevated TLR-induced cytokines in RA monocytes were not related to ACPA or RF status. However, TLR1/2-induced IL-6 was associated with disease activity.

UVR8-mediated induction of flavonoid biosynthesis for UVB tolerance is conserved between the liverwort Marchantia polymorpha and flowering plants.

Damaging UVB radiation is a major abiotic stress facing land plants. In angiosperms the UV RESISTANCE LOCUS8 (UVR8) photoreceptor coordinates UVB responses, including inducing biosynthesis of protective flavonoids. We characterised the UVB responses of Marchantia polymorpha (marchantia), the model species for the liverwort group of basal plants. Physiological, chemical and transcriptomic analyses were conducted on wild-type marchantia exposed to three different UVB regimes. CRISPR/Cas9 was used to obtain plant lines with mutations for components of the UVB signal pathway or the flavonoid biosynthetic pathway, and transgenics overexpressing the marchantia UVR8 sequence were generated. The mutant and transgenic lines were analysed for changes in flavonoid content, their response to UVB exposure, and transcript abundance of a set of 48 genes that included components of the UVB response pathway characterised for angiosperms. The marchantia UVB response included many components in common with Arabidopsis, including production of UVB-absorbing flavonoids, the central activator role of ELONGATED HYPOCOTYL5 (HY5), and negative feedback regulation by REPRESSOR OF UV-B PHOTOMORPHOGENESIS1 (RUP1). Notable differences included the greater importance of CHALCONE ISOMERASE-LIKE (CHIL). Mutants disrupted in the response pathway (hy5) or flavonoid production (chalcone isomerase, chil) were more easily damaged by UVB. Mutants (rup1) or transgenics (35S:MpMYB14) with increased flavonoid content had increased UVB tolerance. The results suggest that UVR8-mediated flavonoid induction is a UVB tolerance character conserved across land plants and may have been an early adaptation to life on land.

Persistent Dysphagia Rate After Antireflux Surgery is Similar for Nissen Fundoplication and Partial Fundoplication.

BACKGROUND: Laparoscopic fundoplication is the gold standard operation for treatment of gastroesophageal reflux disease (GERD). It has been suggested that persistent postoperative dysphagia is increased following Nissen fundoplication compared to partial fundoplication. This study aimed to determine risk factors for persistent postoperative dysphagia, specifically examining the type of fundoplication. METHODS: Patients experiencing GERD symptoms who underwent laparoscopic Nissen, Toupet, or Dor fundoplication from 2009 to 2016 were identified from a single-institutional database. A dysphagia score was obtained as part of the GERD health-related quality of life questionnaire. Persistent dysphagia was defined as a difficulty swallowing score ≥1 (noticeable) on a scale from 0 to 5 at least 1 y postoperatively. Odds ratios of persistent dysphagia among those who underwent antireflux surgery were calculated in a multivariate logistic regression model adjusted for fundoplication type, sex, age, body mass index, and redo operation. RESULTS: Of the 441 patients who met inclusion criteria, 255 had ≥1 y of follow-up (57.8%). The median duration of follow-up was 3 y. In this cohort, 45.1% of patients underwent Nissen fundoplication and 54.9% underwent partial fundoplication. Persistent postoperative dysphagia was present in 25.9% (n = 66) of patients. On adjusted analysis, there was no statistically significant association between the type of fundoplication (Nissen versus partial) and the likelihood of postoperative dysphagia. CONCLUSIONS: Persistent postoperative dysphagia after antireflux surgery occurred in approximately one-quarter of patients and did not differ by the type of fundoplication. These findings suggest that both Nissen and partial fundoplication are reasonable choices for an antireflux operation for properly selected patients.

Latina/o Children Living With an Immigrant Mother With Depression: Developmental and Cultural Nuances in Recognition and Coping.

The psychological experience of maternal depression and its impact on immigrant Latina/o families often goes unrecognized and unaddressed. Children may feel especially helpless and confused about the changes they observe in their mothers' mood and behavior, and about the deterioration of family relationships. Given the interdependence of family structures of immigrant Latina/o households, maternal depression can be detrimental to Latina/o youth attributions and coping strategies, and to their relationship with their mothers. The quantitative focus of most research on maternal depression in Latina/o samples limits our understanding of family processes in maternal depression. The current qualitative study explores the perceived impact of maternal depression on Latina/o youths' attributions and coping strategies. This inquiry involved focus groups with 12 participants aged 9-16 years to explore their perspectives on maternal depression. All youth had participated in a 12-week multifamily group intervention focused on building family and cultural strengths to address maternal depression on immigrant Latina/o families. Findings of the focus groups illuminated the essential experience of youth living with maternal depression, and indicated that there are developmental considerations for how youth recognize and make meaning of maternal depression, and cope with disrupted family life. Additionally, youth reported engaging in these culture-specific ways of coping: using close sibling relationships and family structure as support, having fathers and extended family members engage in additional and restorative parenting practices, and participating in religious practices to seek refuge from family stress. We propose considerations for intervention and further areas of research.

La experiencia psicológica de la depresión materna y su efecto en las familias de inmigrantes latinos generalmente no se reconoce ni se trata. Los niños pueden sentirse especialmente desamparados y confundidos con respecto a los cambios que observan en el estado de ánimo y la conducta de sus madres, y con respecto al deterioro de las relaciones familiares. Dada la interdependencia de las estructuras familiares de los hogares de los inmigrantes latinos, la depresión materna puede ser perjudicial para las estrategias de adaptación y las atribuciones de los jóvenes latinos así como para sus relaciones con sus madres. El enfoque cuantitativo de la mayoría de las investigaciones sobre depresión materna en muestras de latinos limita nuestra comprensión de los procesos familiares en la depresión materna. El presente estudio cualitativo analiza el efecto percibido de la depresión materna en las estrategias de adaptación y las atribuciones de los jóvenes latinos. Esta investigación consistió en grupos focales con 12 participantes de entre 9 y 16 años para analizar sus perspectivas sobre la depresión materna. Todos los jóvenes habían participado en una intervención grupal multifamiliar de 12 semanas centrada en el refuerzo de los puntos fuertes familiares y culturales para abordar la depresión materna en las familias de inmigrantes latinos. Los resultados de los grupos focales aclararon la experiencia fundamental de los jóvenes que viven con depresión materna e indicaron que existen consideraciones del desarrollo en cuanto a cómo los jóvenes reconocen y entienden la depresión materna, y hacen frente a una vida familiar perturbada. Además, los jóvenes informaron que recurrieron a estas formas de afrontamiento propias de su cultura: usaron como apoyo las relaciones estrechas entre hermanos y la estructura familiar, pidieron a los padres y a parientes lejanos que participen en prácticas de crianza adicionales y fortalecedoras, y participaron en prácticas religiosas para refugiarse del estrés familiar. Proponemos consideraciones sobre intervenciones y otras áreas de investigación.

A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants.

BACKGROUND: Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. RESULTS: A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within 'Hongyang' The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned 'Hort16A' cDNAs and comparing with the predicted protein models for Red5 and both the original 'Hongyang' assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised 'Hongyang' annotation, respectively, compared with 90.9% to the Red5 models. CONCLUSIONS: Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis.

Effect of rituximab on a salivary gland ultrasound score in primary Sjögren's syndrome: results of the TRACTISS randomised double-blind multicentre substudy.

OBJECTIVES: To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren's syndrome (PSS) in a multicentre, multiobserver phase III trial substudy. METHODS: Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0-11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point. RESULTS: 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were -1.2 (95% CI -2.1 to -0.3; P=0.0099) and -1.2 (95% CI -2.0 to -0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48. CONCLUSIONS: We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker. TRIAL REGISTRATION NUMBER: 65360827, 2010-021430-64; Results.